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COVID-19 Clinical Research Studies

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This cluster of papers focuses on the clinical characteristics, epidemiology, immune response, and treatment of Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus. It covers topics such as thrombosis, ACE2 receptor, cytokine storm, and the pandemic's impact on various populations.

Keywords

Clinical Characteristics; SARS-CoV-2; Epidemiology; Thrombosis; Immune Response; ACE2 Receptor; Cytokine Storm; Antiviral Treatment; Pathophysiology; Pandemic

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

2020-02-14

Wenhua Liang , Wei‐jie Guan , Ruchong Chen +7 more

China and the rest of the world are experiencing an outbreak of a novel betacoronavirus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2).1Chen N Zhou M Dong X … China and the rest of the world are experiencing an outbreak of a novel betacoronavirus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2).1Chen N Zhou M Dong X et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; (published online Jan 29.)https://doi.org/10.1016/S0140-6736(20)30211-7Summary Full Text Full Text PDF Scopus (14363) Google Scholar By Feb 12, 2020, the rapid spread of the virus had caused 42 747 cases and 1017 deaths in China and cases have been reported in 25 countries, including the USA, Japan, and Spain. WHO has declared 2019 novel coronavirus disease (COVID-19), caused by SARS-CoV-2, a public health emergency of international concern. In contrast to severe acute respiratory system coronavirus and Middle East respiratory syndrome coronavirus, more deaths from COVID-19 have been caused by multiple organ dysfunction syndrome rather than respiratory failure,2Wang C Horby PW Hayden FG Gao GF A novel coronavirus outbreak of global health concern.Lancet. 2020; (published online Jan 24.)https://doi.org/10.1016/S0140-6736(20)30185-9Summary Full Text Full Text PDF Scopus (5019) Google Scholar which might be attributable to the widespread distribution of angiotensin converting enzyme 2—the functional receptor for SARS-CoV-2—in multiple organs.3Zhou P Yang XL Wang XG et al.A pneumonia outbreak associated with a new coronavirus of probable bat origin.Nature. 2020; (published online Feb 3.)DOI:10.1038/s41586-020-2012-7Crossref Scopus (14410) Google Scholar, 4Hamming I Timens W Bulthuis ML Lely AT Navis G van Goor H Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.J Pathol. 2004; 203: 631-637Crossref PubMed Scopus (4185) Google Scholar Patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments, such as chemotherapy or surgery.5Kamboj M Sepkowitz KA Nosocomial infections in patients with cancer.Lancet Oncol. 2009; 10: 589-597Summary Full Text Full Text PDF PubMed Scopus (249) Google Scholar, 6Li JY Duan XF Wang LP et al.Selective depletion of regulatory T cell subsets by docetaxel treatment in patients with nonsmall cell lung cancer.J Immunol Res. 2014; 2014286170Crossref PubMed Scopus (120) Google Scholar, 7Longbottom ER Torrance HD Owen HC et al.Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways.Ann Surg. 2016; 264: 370-377Crossref PubMed Scopus (55) Google Scholar, 8Sica A Massarotti M Myeloid suppressor cells in cancer and autoimmunity.J Autoimmun. 2017; 85: 117-125Crossref PubMed Scopus (137) Google Scholar Therefore, these patients might be at increased risk of COVID-19 and have a poorer prognosis. On behalf of the National Clinical Research Center for Respiratory Disease, we worked together with the National Health Commission of the People's Republic of China to establish a prospective cohort to monitor COVID-19 cases throughout China. As of the data cutoff on Jan 31, 2020, we have collected and analysed 2007 cases from 575 hospitals (appendix pp 4–9 for a full list) in 31 provincial administrative regions. All cases were diagnosed with laboratory-confirmed COVID-19 acute respiratory disease and were admitted to hospital. We excluded 417 cases because of insufficient records of previous disease history. 18 (1%; 95% CI 0·61–1·65) of 1590 COVID-19 cases had a history of cancer, which seems to be higher than the incidence of cancer in the overall Chinese population (285·83 [0·29%] per 100 000 people, according to 2015 cancer epidemiology statistics9Zheng RS Sun KX Zhang SW et al.Report of cancer epidemiology in China, 2015.Zhonghua Zhong Liu Za Zhi. 2019; 41 (in Chinese).: 19-28PubMed Google Scholar). Detailed information about the 18 patients with cancer with COVID-19 is summarised in the appendix (p 1). Lung cancer was the most frequent type (five [28%] of 18 patients). Four (25%) of 16 patients (two of the 18 patients had unknown treatment status) with cancer with COVID-19 had received chemotherapy or surgery within the past month, and the other 12 (25%) patients were cancer survivors in routine follow-up after primary resection. Compared with patients without cancer, patients with cancer were older (mean age 63·1 years [SD 12·1] vs 48·7 years [16·2]), more likely to have a history of smoking (four [22%] of 18 patients vs 107 [7%] of 1572 patients), had more polypnea (eight [47%] of 17 patients vs 323 [23%] of 1377 patients; some data were missing on polypnea), and more severe baseline CT manifestation (17 [94%] of 18 patients vs 1113 [71%] of 1572 patients), but had no significant differences in sex, other baseline symptoms, other comorbidities, or baseline severity of x-ray (appendix p 2). Most importantly, patients with cancer were observed to have a higher risk of severe events (a composite endpoint defined as the percentage of patients being admitted to the intensive care unit requiring invasive ventilation, or death) compared with patients without cancer (seven [39%] of 18 patients vs 124 [8%] of 1572 patients; Fisher's exact p=0·0003). We observed similar results when the severe events were defined both by the above objective events and physician evaluation (nine [50%] of 18 patients vs 245 [16%] of 1572 patients; Fisher's exact p=0·0008). Moreover, patients who underwent chemotherapy or surgery in the past month had a numerically higher risk (three [75%] of four patients) of clinically severe events than did those not receiving chemotherapy or surgery (six [43%] of 14 patients; figure). These odds were further confirmed by logistic regression (odds ratio [OR] 5·34, 95% CI 1·80–16·18; p=0·0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities. Cancer history represented the highest risk for severe events (appendix p 3). Among patients with cancer, older age was the only risk factor for severe events (OR 1·43, 95% CI 0·97–2·12; p=0·072). Patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (one [20%] of five patients with lung cancer vs eight [62%] of 13 patients with other types of cancer; p=0·294). Additionally, we used a Cox regression model to evaluate the time-dependent hazards of developing severe events, and found that patients with cancer deteriorated more rapidly than those without cancer (median time to severe events 13 days [IQR 6–15] vs 43 days [20–not reached]; p<0·0001; hazard ratio 3·56, 95% CI 1·65–7·69, after adjusting for age; figure). In this study, we analysed the risk for severe COVID-19 in patients with cancer for the first time, to our knowledge; only by nationwide analysis can we follow up patients with rare but important comorbidities, such as cancer. We found that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. Additionally, we showed that patients with cancer had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration. Therefore, we propose three major strategies for patients with cancer in this COVID-19 crisis, and in future attacks of severe infectious diseases. First, an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer should be considered in endemic areas. Second, stronger personal protection provisions should be made for patients with cancer or cancer survivors. Third, more intensive surveillance or treatment should be considered when patients with cancer are infected with SARS-CoV-2, especially in older patients or those with other comorbidities. We declare no competing interests. This study was approved by the ethics committee of the First Affiliated Hospital of Guangzhou Medical University. We thank all medical staff who are fighting against this public crisis. We also thank the hospital staff (see appendix pp 4–9 for a full list) for their efforts in collecting patient data. This study is supported by the China National Science Foundation (grant no 81871893) and the Key Project of Guangzhou Scientific Research Project (grant no 201804020030). Download .pdf (.27 MB) Help with pdf files Supplementary appendix Preparing African anticancer centres in the COVID-19 outbreakWe congratulate Wenhua Liang and colleagues for their Comment laying out the strategic policies against cancer during the COVID-19 outbreak.1 The disease is now spreading rapidly to and within Africa. Like other countries, Morocco had the opportunity to analyse early COVID-19 data and acknowledge that individual-scale policies such as isolation would not stop the pandemic. Morocco adopted large-scale drastic measures early, including constraining mobility with a mandatory restrictive housing and curfew, despite the low number of cases (starting from 60 cases) compared with Europe. Full-Text PDF Risk of COVID-19 for patients with cancerThe outbreak of coronavirus disease 2019 (COVID-19) is of international concern. We appreciated the Comment from Wenhua Liang and colleagues1 published in The Lancet Oncology on Feb 14, 2020, which, to the best of our knowledge, was the first to focus on COVID-19 infection in patients with cancer. Full-Text PDF Risk of COVID-19 for patients with cancerWe read the excellent Comment by Wenhua Liang and colleagues1 in The Lancet Oncology with great interest. Of 1590 cases with confirmed coronavirus disease 2019 (COVID-19), 18 patients had a history of cancer. The authors concluded that patients with cancer had a higher risk of COVID-19 and with a poorer prognosis than those without cancer. Full-Text PDF

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Time Course of Lung Changes at Chest CT during Recovery from Coronavirus Disease 2019 (COVID-19)

2020-02-13

Feng Pan , Tianhe Ye , Peng Sun +7 more

Background Chest CT is used to assess the severity of lung involvement in coronavirus disease 2019 (COVID-19). Purpose To determine the changes in chest CT findings associated with COVID-19 from … Background Chest CT is used to assess the severity of lung involvement in coronavirus disease 2019 (COVID-19). Purpose To determine the changes in chest CT findings associated with COVID-19 from initial diagnosis until patient recovery. Materials and Methods This retrospective review included patients with real-time polymerase chain reaction–confirmed COVID-19 who presented between January 12, 2020, and February 6, 2020. Patients with severe respiratory distress and/or oxygen requirement at any time during the disease course were excluded. Repeat chest CT was performed at approximately 4-day intervals. Each of the five lung lobes was visually scored on a scale of 0 to 5, with 0 indicating no involvement and 5 indicating more than 75% involvement. The total CT score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). Results Twenty-one patients (six men and 15 women aged 25–63 years) with confirmed COVID-19 were evaluated. A total of 82 chest CT scans were obtained in these patients, with a mean interval (±standard deviation) of 4 days ± 1 (range, 1–8 days). All patients were discharged after a mean hospitalization period of 17 days ± 4 (range, 11–26 days). Maximum lung involved peaked at approximately 10 days (with a calculated total CT score of 6) from the onset of initial symptoms (R2 = 0.25, P < .001). Based on quartiles of chest CT scans from day 0 to day 26 involvement, four stages of lung CT findings were defined. CT scans obtained in stage 1 (0–4 days) showed ground-glass opacities (18 of 24 scans [75%]), with a mean total CT score of 2 ± 2; scans obtained in stage 2 (5–8 days) showed an increase in both the crazy-paving pattern (nine of 17 scans [53%]) and total CT score (mean, 6 ± 4; P = .002); scans obtained in stage 3 (9–13 days) showed consolidation (19 of 21 scans [91%]) and a peak in the total CT score (mean, 7 ± 4); and scans obtained in stage 4 (≥14 days) showed gradual resolution of consolidation (15 of 20 scans [75%]) and a decrease in the total CT score (mean, 6 ± 4) without crazy-paving pattern. Conclusion In patients recovering from coronavirus disease 2019 (without severe respiratory distress during the disease course), lung abnormalities on chest CT scans showed greatest severity approximately 10 days after initial onset of symptoms. © RSNA, 2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges

2020-02-17

Chih‐Cheng Lai , Tzu-Ping Shih , Wen‐Chien Ko +2 more

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Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection

2020-02-20

Adam Bernheim , Xueyan Mei , Mingqian Huang +7 more

In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed … In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, "crazy-paving" pattern and the "reverse halo" sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).

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Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study

2020-02-25

Heshui Shi , Xiaoyu Han , Nanchuan Jiang +5 more

A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to … A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course.

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Correlation of Chest CT and RT-PCR Testing for Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases

2020-02-26

Tao Ai , Zhenlu Yang , Hongyan Hou +6 more

Background Chest CT is used in the diagnosis of coronavirus disease 2019 (COVID-19) and is an important complement to reverse-transcription polymerase chain reaction (RT-PCR) tests. Purpose To investigate the diagnostic … Background Chest CT is used in the diagnosis of coronavirus disease 2019 (COVID-19) and is an important complement to reverse-transcription polymerase chain reaction (RT-PCR) tests. Purpose To investigate the diagnostic value and consistency of chest CT as compared with RT-PCR assay in COVID-19. Materials and Methods This study included 1014 patients in Wuhan, China, who underwent both chest CT and RT-PCR tests between January 6 and February 6, 2020. With use of RT-PCR as the reference standard, the performance of chest CT in the diagnosis of COVID-19 was assessed. In addition, for patients with multiple RT-PCR assays, the dynamic conversion of RT-PCR results (negative to positive, positive to negative) was analyzed as compared with serial chest CT scans for those with a time interval between RT-PCR tests of 4 days or more. Results Of the 1014 patients, 601 of 1014 (59%) had positive RT-PCR results and 888 of 1014 (88%) had positive chest CT scans. The sensitivity of chest CT in suggesting COVID-19 was 97% (95% confidence interval: 95%, 98%; 580 of 601 patients) based on positive RT-PCR results. In the 413 patients with negative RT-PCR results, 308 of 413 (75%) had positive chest CT findings. Of those 308 patients, 48% (103 of 308) were considered as highly likely cases and 33% (103 of 308) as probable cases. At analysis of serial RT-PCR assays and CT scans, the mean interval between the initial negative to positive RT-PCR results was 5.1 days ± 1.5; the mean interval between initial positive to subsequent negative RT-PCR results was 6.9 days ± 2.3. Of the 1014 patients, 60% (34 of 57) to 93% (14 of 15) had initial positive CT scans consistent with COVID-19 before (or parallel to) the initial positive RT-PCR results. Twenty-four of 57 patients (42%) showed improvement on follow-up chest CT scans before the RT-PCR results turned negative. Conclusion Chest CT has a high sensitivity for diagnosis of coronavirus disease 2019 (COVID-19). Chest CT may be considered as a primary tool for the current COVID-19 detection in epidemic areas. © RSNA, 2020

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Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China

2020-02-20

Jinjin Zhang , Xiang Dong , Yiyuan Cao +5 more

Abstract Background Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status … Abstract Background Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status of patients infected with SARS‐CoV‐2. Methods Electronic medical records including demographics, clinical manifestation, comorbidities, laboratory data, and radiological materials of 140 hospitalized COVID‐19 patients, with confirmed result of SARS‐CoV‐2 viral infection, were extracted and analyzed. Results An approximately 1:1 ratio of male (50.7%) and female COVID‐19 patients was found, with an overall median age of 57.0 years. All patients were community‐acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%), and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self‐reported by several patients. Asthma or other allergic diseases were not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) patients and current smokers (1.4%) were rare. Bilateral ground‐glass or patchy opacity (89.6%) was the most common sign of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe ( r = .486, P < .001) and nonsevere ( r = .469, P < .001) patients after hospital admission. Significantly higher levels of D‐dimer, C‐reactive protein, and procalcitonin were associated with severe patients compared to nonsevere patients (all P < .001). Conclusion Detailed clinical investigation of 140 hospitalized COVID‐19 cases suggests eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma, and COPD are not risk factors for SARS‐CoV‐2 infection. Older age, high number of comorbidities, and more prominent laboratory abnormalities were associated with severe patients.

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Pathological findings of COVID-19 associated with acute respiratory distress syndrome

2020-02-18

Zhe Xu , Lei Shi , Yijin Wang +7 more

Since late December, 2019, an outbreak of a novel coronavirus disease (COVID-19; previously known as 2019-nCoV)1Wu F Zhao S Yu B et al.A new coronavirus associated with human respiratory disease … Since late December, 2019, an outbreak of a novel coronavirus disease (COVID-19; previously known as 2019-nCoV)1Wu F Zhao S Yu B et al.A new coronavirus associated with human respiratory disease in China.Nature. 2020; (published online Feb 3.)DOI:10.1038/s41586-020-2008-3Crossref Scopus (7724) Google Scholar, 2Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Summary Full Text Full Text PDF PubMed Scopus (33292) Google Scholar was reported in Wuhan, China,2Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Summary Full Text Full Text PDF PubMed Scopus (33292) Google Scholar which has subsequently affected 26 countries worldwide. In general, COVID-19 is an acute resolved disease but it can also be deadly, with a 2% case fatality rate. Severe disease onset might result in death due to massive alveolar damage and progressive respiratory failure.2Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Summary Full Text Full Text PDF PubMed Scopus (33292) Google Scholar, 3Chan JF Yuan S Kok KH et al.A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.Lancet. 2020; 395: 514-523Summary Full Text Full Text PDF PubMed Scopus (6268) Google Scholar As of Feb 15, about 66 580 cases have been confirmed and over 1524 deaths. However, no pathology has been reported due to barely accessible autopsy or biopsy.2Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Summary Full Text Full Text PDF PubMed Scopus (33292) Google Scholar, 3Chan JF Yuan S Kok KH et al.A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.Lancet. 2020; 395: 514-523Summary Full Text Full Text PDF PubMed Scopus (6268) Google Scholar Here, we investigated the pathological characteristics of a patient who died from severe infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by postmortem biopsies. This study is in accordance with regulations issued by the National Health Commission of China and the Helsinki Declaration. Our findings will facilitate understanding of the pathogenesis of COVID-19 and improve clinical strategies against the disease. A 50-year-old man was admitted to a fever clinic on Jan 21, 2020, with symptoms of fever, chills, cough, fatigue and shortness of breath. He reported a travel history to Wuhan Jan 8–12, and that he had initial symptoms of mild chills and dry cough on Jan 14 (day 1 of illness) but did not see a doctor and kept working until Jan 21 (figure 1). Chest x-ray showed multiple patchy shadows in both lungs (appendix p 2), and a throat swab sample was taken. On Jan 22 (day 9 of illness), the Beijing Centers for Disease Control (CDC) confirmed by reverse real-time PCR assay that the patient had COVID-19. He was immediately admitted to the isolation ward and received supplemental oxygen through a face mask. He was given interferon alfa-2b (5 million units twice daily, atomisation inhalation) and lopinavir plus ritonavir (500 mg twice daily, orally) as antiviral therapy, and moxifloxacin (0·4 g once daily, intravenously) to prevent secondary infection. Given the serious shortness of breath and hypoxaemia, methylprednisolone (80 mg twice daily, intravenously) was administered to attenuate lung inflammation. Laboratory tests results are listed in the appendix (p 4). After receiving medication, his body temperature reduced from 39·0 to 36·4 °C. However, his cough, dyspnoea, and fatigue did not improve. On day 12 of illness, after initial presentation, chest x-ray showed progressive infiltrate and diffuse gridding shadow in both lungs. He refused ventilator support in the intensive care unit repeatedly because he suffered from claustrophobia; therefore, he received high-flow nasal cannula (HFNC) oxygen therapy (60% concentration, flow rate 40 L/min). On day 13 of illness, the patient's symptoms had still not improved, but oxygen saturation remained above 95%. In the afternoon of day 14 of illness, his hypoxaemia and shortness of breath worsened. Despite receiving HFNC oxygen therapy (100% concentration, flow rate 40 L/min), oxygen saturation values decreased to 60%, and the patient had sudden cardiac arrest. He was immediately given invasive ventilation, chest compression, and adrenaline injection. Unfortunately, the rescue was not successful, and he died at 18:31 (Beijing time). Biopsy samples were taken from lung, liver, and heart tissue of the patient. Histological examination showed bilateral diffuse alveolar damage with cellular fibromyxoid exudates (figure 2A, B). The right lung showed evident desquamation of pneumocytes and hyaline membrane formation, indicating acute respiratory distress syndrome (ARDS; figure 2A). The left lung tissue displayed pulmonary oedema with hyaline membrane formation, suggestive of early-phase ARDS (figure 2B). Interstitial mononuclear inflammatory infiltrates, dominated by lymphocytes, were seen in both lungs. Multinucleated syncytial cells with atypical enlarged pneumocytes characterised by large nuclei, amphophilic granular cytoplasm, and prominent nucleoli were identified in the intra-alveolar spaces, showing viral cytopathic-like changes. No obvious intranuclear or intracytoplasmic viral inclusions were identified. The pathological features of COVID-19 greatly resemble those seen in SARS and Middle Eastern respiratory syndrome (MERS) coronavirus infection.4Ding Y Wang H Shen H et al.The clinical pathology of severe acute respiratory syndrome (SARS): a report from China.J Pathol. 2003; 200: 282-289Crossref PubMed Scopus (628) Google Scholar, 5Ng DL Al Hosani F Keating MK et al.Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in the United Arab Emirates, April 2014.Am J Pathol. 2016; 186: 652-658Summary Full Text Full Text PDF PubMed Scopus (311) Google Scholar In addition, the liver biopsy specimens of the patient with COVID-19 showed moderate microvesicular steatosis and mild lobular and portal activity (figure 2C), indicating the injury could have been caused by either SARS-CoV-2 infection or drug-induced liver injury. There were a few interstitial mononuclear inflammatory infiltrates, but no other substantial damage in the heart tissue (figure 2D). Peripheral blood was prepared for flow cytometric analysis. We found that the counts of peripheral CD4 and CD8 T cells were substantially reduced, while their status was hyperactivated, as evidenced by the high proportions of HLA-DR (CD4 3·47%) and CD38 (CD8 39·4%) double-positive fractions (appendix p 3). Moreover, there was an increased concentration of highly proinflammatory CCR6+ Th17 in CD4 T cells (appendix p 3). Additionally, CD8 T cells were found to harbour high concentrations of cytotoxic granules, in which 31·6% cells were perforin positive, 64·2% cells were granulysin positive, and 30·5% cells were granulysin and perforin double-positive (appendix p 3). Our results imply that overactivation of T cells, manifested by increase of Th17 and high cytotoxicity of CD8 T cells, accounts for, in part, the severe immune injury in this patient. X-ray images showed rapid progression of pneumonia and some differences between the left and right lung. In addition, the liver tissue showed moderate microvesicular steatosis and mild lobular activity, but there was no conclusive evidence to support SARS-CoV-2 infection or drug-induced liver injury as the cause. There were no obvious histological changes seen in heart tissue, suggesting that SARS-CoV-2 infection might not directly impair the heart. Although corticosteroid treatment is not routinely recommended to be used for SARS-CoV-2 pneumonia,1Wu F Zhao S Yu B et al.A new coronavirus associated with human respiratory disease in China.Nature. 2020; (published online Feb 3.)DOI:10.1038/s41586-020-2008-3Crossref Scopus (7724) Google Scholar according to our pathological findings of pulmonary oedema and hyaline membrane formation, timely and appropriate use of corticosteroids together with ventilator support should be considered for the severe patients to prevent ARDS development. Lymphopenia is a common feature in the patients with COVID-19 and might be a critical factor associated with disease severity and mortality.3Chan JF Yuan S Kok KH et al.A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.Lancet. 2020; 395: 514-523Summary Full Text Full Text PDF PubMed Scopus (6268) Google Scholar Our clinical and pathological findings in this severe case of COVID-19 can not only help to identify a cause of death, but also provide new insights into the pathogenesis of SARS-CoV-2-related pneumonia, which might help physicians to formulate a timely therapeutic strategy for similar severe patients and reduce mortality. This online publication has been corrected. The corrected version first appeared at thelancet.com/respiratory on February 25, 2020 This online publication has been corrected. The corrected version first appeared at thelancet.com/respiratory on February 25, 2020 Contributors F-SW and JZhao conceived the study. ZX and LS designed the study. F-SW and JZhao supervised the overall study. ZX and LS collected specimens. LH, PZ, and HL collected clinical data. SL collected pathological images. LZ and TG disposed of tissues and H&E staining. LS and YW analysed and interpreted the data. YT analysed the pathological data. CB and JD formulated the treatment regimen and analysed the x-ray images. JZhang, JS, PX, and CZ did the flow cytometric analysis. LS and YW made the tables and figures. LS and YW searched the literature. LS and YW wrote the manuscript. CZ, F-SW, and JZhao critically revised the manuscript. Declaration of interests We declare no competing interests. Download .pdf (1.17 MB) Help with pdf files Supplementary appendix Correction to Lancet Respir Med 2020; 8: 420–22Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; 8: 420–22—In this Case Report "by obtaining biopsy samples at autopsy" has been replaced with "by postmortem biopsies" in paragraph 1, "microvascular" has been replaced with "microvesicular" in two incidences in paragraph 5, and "(B) Frequency of Th17 (CD4+ CCR6+CCR4+) subset" has been changed to "(B) Frequency of Th17 (CD4+ CCR6+) subset" on page 3 of the appendix. Full-Text PDF

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Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China

2020-02-24

Zunyou Wu , Jennifer M. McGoogan

This Viewpoint summarizes key epidemiologic and clinical findings from all cases of coronavirus disease 2019 (COVID-19) reported through February 11, 2020, in mainland China, and case trends in response to … This Viewpoint summarizes key epidemiologic and clinical findings from all cases of coronavirus disease 2019 (COVID-19) reported through February 11, 2020, in mainland China, and case trends in response to government attempts to control and contain the infection.

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

2020-02-24

Xiaobo Yang , Yu Yuan , Jiqian Xu +7 more

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Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

2020-02-19

Ning Tang , Dengju Li , Xiong Wang +1 more

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Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies

2020-02-18

Jianjun Gao , Zhenxue Tian , Xu Yang

The coronavirus disease 2019 (COVID-19) virus is spreading rapidly, and scientists are endeavoring to discover drugs for its efficacious treatment in China. Chloroquine phosphate, an old drug for treatment of … The coronavirus disease 2019 (COVID-19) virus is spreading rapidly, and scientists are endeavoring to discover drugs for its efficacious treatment in China. Chloroquine phosphate, an old drug for treatment of malaria, is shown to have apparent efficacy and acceptable safety against COVID-19 associated pneumonia in multicenter clinical trials conducted in China. The drug is recommended to be included in the next version of the Guidelines for the Prevention, Diagnosis, and Treatment of Pneumonia Caused by COVID-19 issued by the National Health Commission of the People's Republic of China for treatment of COVID-19 infection in larger populations in the future.

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Clinical Characteristics of Coronavirus Disease 2019 in China

2020-02-28

Wei‐jie Guan , Zhengyi Ni , Yu Hu +7 more

BackgroundSince December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients.MethodsWe extracted … BackgroundSince December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients.MethodsWe extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death.ResultsThe median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission.ConclusionsDuring the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.) Quick Take Clinical Characteristics of Covid-19 2m 8s

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Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

2020-03-03

Qiurong Ruan , Kun Yang , Wenxia Wang +2 more

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In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

2020-03-06

Xueting Yao , Fei Ye , Miao Zhang +7 more

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in 2019 and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares … Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in 2019 and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late phase in critically ill patients with SARS-CoV-2. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. Methods The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2–infected Vero cells. Physiologically based pharmacokinetic (PBPK) models were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen while considering the drug’s safety profile. Results Hydroxychloroquine (EC50 = 0.72 μM) was found to be more potent than chloroquine (EC50 = 5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached 3 times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. Conclusions Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

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Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?

2020-03-12

Lei Fang , George Karakiulakis , Michael Roth

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Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China

2020-03-06

Chuan Qin , Luo‐Qi Zhou , Ziwei Hu +7 more

In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China.Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from 10 … In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China.Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from 10 January to 12 February 2020 were collected and analyzed. The data on laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between patients with severe and nonsevere infection.Of the 452 patients with COVID-19 recruited, 286 were diagnosed as having severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough, and myalgia. Severe cases tend to have lower lymphocyte counts, higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and were more impaired in severe cases. Both helper T (Th) cells and suppressor T cells in patients with COVID-19 were below normal levels, with lower levels of Th cells in the severe group. The percentage of naive Th cells increased and memory Th cells decreased in severe cases. Patients with COVID-19 also have lower levels of regulatory T cells, which are more obviously decreased in severe cases.The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.

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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

2020-03-01

Fei Zhou , Ting Yu , Ronghui Du +7 more

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COVID-19 and the cardiovascular system

2020-03-05

Ying‐Ying Zheng , Yi‐Tong Ma , Jinying Zhang +1 more

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the … Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.

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Features, Evaluation and Treatment Coronavirus (COVID-19)

2020-03-20

Marco Cascella , Michael Rajnik , Arturo Cuomo +2 more

According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health In the last twenty years, several viral epidemics such as … According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded Most recently, the Middle East respiratory syndrome (MERS-CoV) was first identified in Saudi Arabia in 2012 In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, Published literature can trace the beginning of symptomatic individuals back to the beginning of December As they were unable to identify the causative agent, these first cases were classified as pneumonia of unknown etiology The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program The etiology of this illness is now attributed to a novel virus belonging to the (CoV) family, COVID-19 On February 11, 2020, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a which is the acronym of coronavirus disease 2019 In the past twenty years, two additional epidemics have occurred SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases This new virus seems to be contagious and has quickly spread globally In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States Initially, the new virus was called 2019-nCoV Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is similar to the one that caused the SARS outbreak (SARS-CoVs) The CoVs have become the major pathogens of emerging respiratory disease outbreaks They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the very high level, on February 28, 2020 Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving World governments are at work to establish countermeasures to stem possible devastating effects Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing Many uncertainties remain with regard to both the virus-host interac ion and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system In the midst of the crisis, the authors have chosen to use the Statpearls platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated

World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19)

2020-02-26

Catrin Sohrabi , Zaid Alsafi , Niamh O’Neill +5 more

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Detection of SARS-CoV-2 in Different Types of Clinical Specimens

2020-03-11

Wen‐Ching Wang , Yanli Xu , Ruqin Gao +4 more

This study describes results of PCR and viral RNA testing for SARS-CoV-2 in bronchoalveolar fluid, sputum, feces, blood, and urine specimens from patients with COVID-19 infection in China to identify … This study describes results of PCR and viral RNA testing for SARS-CoV-2 in bronchoalveolar fluid, sputum, feces, blood, and urine specimens from patients with COVID-19 infection in China to identify possible means of non-respiratory transmission.

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A Review of Coronavirus Disease-2019 (COVID-19)

2020-03-13

Tanu Singhal

There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The … There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.

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Epidemiology of COVID-19 Among Children in China

2020-03-16

Yuanyuan Dong , Xi Mo , Yabin Hu +4 more

To identify the epidemiological characteristics and transmission patterns of pediatric patients with the 2019 novel coronavirus disease (COVID-19) in China.Nationwide case series of 2135 pediatric patients with COVID-19 reported to … To identify the epidemiological characteristics and transmission patterns of pediatric patients with the 2019 novel coronavirus disease (COVID-19) in China.Nationwide case series of 2135 pediatric patients with COVID-19 reported to the Chinese Center for Disease Control and Prevention from January 16, 2020, to February 8, 2020, were included. The epidemic curves were constructed by key dates of disease onset and case diagnosis. Onset-to-diagnosis curves were constructed by fitting a log-normal distribution to data on both onset and diagnosis dates.There were 728 (34.1%) laboratory-confirmed cases and 1407 (65.9%) suspected cases. The median age of all patients was 7 years (interquartile range: 2-13 years), and 1208 case patients (56.6%) were boys. More than 90% of all patients had asymptomatic, mild, or moderate cases. The median time from illness onset to diagnoses was 2 days (range: 0-42 days). There was a rapid increase of disease at the early stage of the epidemic, and then there was a gradual and steady decrease. The disease rapidly spread from Hubei province to surrounding provinces over time. More children were infected in Hubei province than any other province.Children of all ages appeared susceptible to COVID-19, and there was no significant sex difference. Although clinical manifestations of children's COVID-19 cases were generally less severe than those of adult patients, young children, particularly infants, were vulnerable to infection. The distribution of children's COVID-19 cases varied with time and space, and most of the cases were concentrated in Hubei province and surrounding areas. Furthermore, this study provides strong evidence of human-to-human transmission.

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RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

2020-03-20

Philippe Gautret , Jean‐Christophe Lagier , Philippe Parola +7 more

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Kidney disease is associated with in-hospital death of patients with COVID-19

2020-03-20

Yichun Cheng , Ran Luo , Kun Wang +7 more

In December 2019, a coronavirus 2019 (COVID-19) disease outbreak occurred in Wuhan, Hubei Province, China, and rapidly spread to other areas worldwide. Although diffuse alveolar damage and acute respiratory failure … In December 2019, a coronavirus 2019 (COVID-19) disease outbreak occurred in Wuhan, Hubei Province, China, and rapidly spread to other areas worldwide. Although diffuse alveolar damage and acute respiratory failure were the main features, the involvement of other organs needs to be explored. Since information on kidney disease in patients with COVID-19 is limited, we determined the prevalence of acute kidney injury (AKI) in patients with COVID-19. Further, we evaluated the association between markers of abnormal kidney function and death in patients with COVID-19. This was a prospective cohort study of 701 patients with COVID-19 admitted in a tertiary teaching hospital that also encompassed three affiliates following this major outbreak in Wuhan in 2020 of whom 113 (16.1%) died in hospital. Median age of the patients was 63 years (interquartile range, 50-71), including 367 men and 334 women. On admission, 43.9% of patients had proteinuria and 26.7% had hematuria. The prevalence of elevated serum creatinine, elevated blood urea nitrogen and estimated glomerular filtration under 60 ml/min/1.73m2 were 14.4, 13.1 and 13.1%, respectively. During the study period, AKI occurred in 5.1% patients. Kaplan-Meier analysis demonstrated that patients with kidney disease had a significantly higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated baseline serum creatinine (hazard ratio: 2.10, 95% confidence interval: 1.36-3.26), elevated baseline blood urea nitrogen (3.97, 2.57-6.14), AKI stage 1 (1.90, 0.76-4.76), stage 2 (3.51, 1.49-8.26), stage 3 (4.38, 2.31-8.31), proteinuria 1+ (1.80, 0.81-4.00), 2+∼3+ (4.84, 2.00-11.70), and hematuria 1+ (2.99, 1.39-6.42), 2+∼3+ (5.56,2.58- 12.01) were independent risk factors for in-hospital death after adjusting for age, sex, disease severity, comorbidity and leukocyte count. Thus, our findings show the prevalence of kidney disease on admission and the development of AKI during hospitalization in patients with COVID-19 is high and is associated with in-hospital mortality. Hence, clinicians should increase their awareness of kidney disease in patients with severe COVID-19.

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Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

2020-03-13

Chaomin Wu , Xiaohong Chen , Yanping Cai +7 more

<h3>Importance</h3> Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 … <h3>Importance</h3> Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. <h3>Objective</h3> To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. <h3>Exposures</h3> Confirmed COVID-19 pneumonia. <h3>Main Outcomes and Measures</h3> The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. <h3>Results</h3> Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). <h3>Conclusions and Relevance</h3> Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

2020-03-18

Bin Cao , Yeming Wang , Danning Wen +7 more

No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, … No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first.A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).

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Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China

2020-03-25

Shaobo Shi , Mu Qin , Bo Shen +7 more

<h3>Importance</h3> Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. <h3>Objective</h3> To … <h3>Importance</h3> Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. <h3>Objective</h3> To explore the association between cardiac injury and mortality in patients with COVID-19. <h3>Design, Setting, and Participants</h3> This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. <h3>Main Outcomes and Measures</h3> Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed. <h3>Results</h3> A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years;<i>P</i> < .001); had more comorbidities (eg, hypertension in 49 of 82 [59.8%] vs 78 of 334 [23.4%];<i>P</i> < .001); had higher leukocyte counts (median [interquartile range (IQR)], 9400 [6900-13 800] vs 5500 [4200-7400] cells/μL) and levels of C-reactive protein (median [IQR], 10.2 [6.4-17.0] vs 3.7 [1.0-7.3] mg/dL), procalcitonin (median [IQR], 0.27 [0.10-1.22] vs 0.06 [0.03-0.10] ng/mL), creatinine kinase–myocardial band (median [IQR], 3.2 [1.8-6.2] vs 0.9 [0.6-1.3] ng/mL), myohemoglobin (median [IQR], 128 [68-305] vs 39 [27-65] μg/L), high-sensitivity troponin I (median [IQR], 0.19 [0.08-1.12] vs <0.006 [<0.006-0.009] μg/L), N-terminal pro-B-type natriuretic peptide (median [IQR], 1689 [698-3327] vs 139 [51-335] pg/mL), aspartate aminotransferase (median [IQR], 40 [27-60] vs 29 [21-40] U/L), and creatinine (median [IQR], 1.15 [0.72-1.92] vs 0.64 [0.54-0.78] mg/dL); and had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings (53 of 82 patients [64.6%] vs 15 of 334 patients [4.5%]). Greater proportions of patients with cardiac injury required noninvasive mechanical ventilation (38 of 82 [46.3%] vs 13 of 334 [3.9%];<i>P</i> < .001) or invasive mechanical ventilation (18 of 82 [22.0%] vs 14 of 334 [4.2%];<i>P</i> < .001) than those without cardiac injury. Complications were more common in patients with cardiac injury than those without cardiac injury and included acute respiratory distress syndrome (48 of 82 [58.5%] vs 49 of 334 [14.7%];<i>P</i> < .001), acute kidney injury (7 of 82 [8.5%] vs 1 of 334 [0.3%];<i>P</i> < .001), electrolyte disturbances (13 of 82 [15.9%] vs 17 of 334 [5.1%];<i>P</i> = .003), hypoproteinemia (11 of 82 [13.4%] vs 16 of 334 [4.8%];<i>P</i> = .01), and coagulation disorders (6 of 82 [7.3%] vs 6 of 334 [1.8%];<i>P</i> = .02). Patients with cardiac injury had higher mortality than those without cardiac injury (42 of 82 [51.2%] vs 15 of 334 [4.5%];<i>P</i> < .001). In a Cox regression model, patients with vs those without cardiac injury were at a higher risk of death, both during the time from symptom onset (hazard ratio, 4.26 [95% CI, 1.92-9.49]) and from admission to end point (hazard ratio, 3.41 [95% CI, 1.62-7.16]). <h3>Conclusions and Relevance</h3> Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

2020-03-26

Tao Chen , Di Wu , Huilong Chen +7 more

Abstract Objective To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. Design Retrospective case series. Setting Tongji Hospital in Wuhan, China. Participants Among a cohort … Abstract Objective To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. Design Retrospective case series. Setting Tongji Hospital in Wuhan, China. Participants Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. Main outcome measures Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. Results The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. Conclusion Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

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Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis

2020-03-26

Wei-jie Guan , Wenhua Liang , Yi Zhao +7 more

Background The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. Objective To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. Methods … Background The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. Objective To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. Methods We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. Results The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424–5.048)), diabetes (1.59 (1.03–2.45)), hypertension (1.58 (1.07–2.32)) and malignancy (3.50 (1.60–7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16–2.77) among patients with at least one comorbidity and 2.59 (1.61–4.17) among patients with two or more comorbidities. Conclusion Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.

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Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)

2020-03-27

Tao Guo , Yongzhen Fan , Ming Chen +7 more

<h3>Importance</h3> Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal … <h3>Importance</h3> Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce. <h3>Objective</h3> To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19. <h3>Design, Setting, and Participants</h3> This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020. Analysis began February 25, 2020. <h3>Main Outcomes and Measures</h3> Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels. <h3>Results</h3> Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died. The mean (SD) age was 58.50 (14.66) years. Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels. The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs. Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]). Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530,<i>P</i> < .001) and N-terminal pro–brain natriuretic peptide (NT-proBNP) levels (β = 0.613,<i>P</i> < .001). Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (<i>P</i> = .001;<i>P</i> < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (<i>P</i> = .96;<i>P</i> = .16). During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels. The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (<i>P</i>= .13). <h3>Conclusions and Relevance</h3> Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable. Myocardial injury is associated with cardiac dysfunction and arrhythmias. Inflammation may be a potential mechanism for myocardial injury. Aggressive treatment may be considered for patients at high risk of myocardial injury.

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Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

2020-03-27

Ning Tang , Huan Bai , Xing Chen +3 more

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Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy

2020-04-06

Giacomo Grasselli , Alberto Zangrillo , Alberto Zanella +7 more

In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected … In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited.To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy.Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020.SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs.Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network.Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2 was greater than 50% in 89% of patients. The median Pao2/Fio2 was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median Fio2 was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, -10% [95% CI, -14% to 6%]; P = .006), and median Pao2/Fio2 was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, -8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower Pao2/Fio2 (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, -27 [95% CI, -42 to -12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age ≥64 years) had higher mortality than younger patients (n = 795; age ≤63 years) (36% vs 15%; difference, 21% [95% CI, 17%-26%]; P < .001).In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.

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The pathogenesis and treatment of the `Cytokine Storm' in COVID-19

2020-04-11

Qing Ye , Bili Wang , Jianhua Mao

Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows … Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.

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Compassionate Use of Remdesivir for Patients with Severe Covid-19

2020-04-10

Jonathan Grein , Norio Ohmagari , Daniel D. Shin +7 more

Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the … Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).

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Incidence of thrombotic complications in critically ill ICU patients with COVID-19

2020-04-10

Frederikus A. Klok , Marieke J.H.A. Kruip , Nardo J. M. van der Meer +7 more

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Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

2020-04-22

Safiya Richardson , Jamie S. Hirsch , Mangala Narasimhan +7 more

There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).To describe the clinical characteristics and outcomes of patients with COVID-19 … There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system.Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates.Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission.Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected.A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/min, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1).This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

Endothelial cell infection and endotheliitis in COVID-19

2020-04-21

Zsuzsanna Varga , Andreas J. Flammer , Peter Steiger +7 more

Cardiovascular complications are rapidly emerging as a key threat in coronavirus disease 2019 (COVID-19) in addition to respiratory disease. The mechanisms underlying the disproportionate effect of severe acute respiratory syndrome … Cardiovascular complications are rapidly emerging as a key threat in coronavirus disease 2019 (COVID-19) in addition to respiratory disease. The mechanisms underlying the disproportionate effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with cardiovascular comorbidities, however, remain incompletely understood.1Zhou F Yu T Du R et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Summary Full Text Full Text PDF PubMed Scopus (18730) Google Scholar, 2Horton R Offline: COVID-19—bewilderment and candour.Lancet. 2020; 3951178Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar SARS-CoV-2 infects the host using the angiotensin converting enzyme 2 (ACE2) receptor, which is expressed in several organs, including the lung, heart, kidney, and intestine. ACE2 receptors are also expressed by endothelial cells.3Ferrario CM Jessup J Chappell MC et al.Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2.Circulation. 2005; 111: 2605-2610Crossref PubMed Scopus (1278) Google Scholar Whether vascular derangements in COVID-19 are due to endothelial cell involvement by the virus is currently unknown. Intriguingly, SARS-CoV-2 can directly infect engineered human blood vessel organoids in vitro.4Monteil V KH Prado P Hagelkrüys A et al.Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2.Cell. 2020; (published online in press.)https://www.cell.com/pb-assets/products/coronavirus/CELL_CELL-D-20-00739.pdfDate accessed: April 17, 2020Summary Full Text Full Text PDF PubMed Scopus (1597) Google Scholar Here we demonstrate endothelial cell involvement across vascular beds of different organs in a series of patients with COVID-19 (further case details are provided in the appendix). Patient 1 was a male renal transplant recipient, aged 71 years, with coronary artery disease and arterial hypertension. The patient's condition deteriorated following COVID-19 diagnosis, and he required mechanical ventilation. Multisystem organ failure occurred, and the patient died on day 8. Post-mortem analysis of the transplanted kidney by electron microscopy revealed viral inclusion structures in endothelial cells (figure A, B). In histological analyses, we found an accumulation of inflammatory cells associated with endothelium, as well as apoptotic bodies, in the heart, the small bowel (figure C) and lung (figure D). An accumulation of mononuclear cells was found in the lung, and most small lung vessels appeared congested. Patient 2 was a woman, aged 58 years, with diabetes, arterial hypertension, and obesity. She developed progressive respiratory failure due to COVID-19 and subsequently developed multi-organ failure and needed renal replacement therapy. On day 16, mesenteric ischaemia prompted removal of necrotic small intestine. Circulatory failure occurred in the setting of right heart failure consequent to an ST-segment elevation myocardial infarction, and cardiac arrest resulted in death. Post-mortem histology revealed lymphocytic endotheliitis in lung, heart, kidney, and liver as well as liver cell necrosis. We found histological evidence of myocardial infarction but no sign of lymphocytic myocarditis. Histology of the small intestine showed endotheliitis (endothelialitis) of the submucosal vessels. Patient 3 was a man, aged 69 years, with hypertension who developed respiratory failure as a result of COVID-19 and required mechanical ventilation. Echocardiography showed reduced left ventricular ejection fraction. Circulatory collapse ensued with mesenteric ischaemia, and small intestine resection was performed, but the patient survived. Histology of the small intestine resection revealed prominent endotheliitis of the submucosal vessels and apoptotic bodies (figure C). We found evidence of direct viral infection of the endothelial cell and diffuse endothelial inflammation. Although the virus uses ACE2 receptor expressed by pneumocytes in the epithelial alveolar lining to infect the host, thereby causing lung injury, the ACE2 receptor is also widely expressed on endothelial cells, which traverse multiple organs.3Ferrario CM Jessup J Chappell MC et al.Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2.Circulation. 2005; 111: 2605-2610Crossref PubMed Scopus (1278) Google Scholar Recruitment of immune cells, either by direct viral infection of the endothelium or immune-mediated, can result in widespread endothelial dysfunction associated with apoptosis (figure D). The vascular endothelium is an active paracrine, endocrine, and autocrine organ that is indispensable for the regulation of vascular tone and the maintenance of vascular homoeostasis.5Flammer AJ Anderson T Celermajer DS et al.The assessment of endothelial function: from research into clinical practice.Circulation. 2012; 126: 753-767Crossref PubMed Scopus (910) Google Scholar Endothelial dysfunction is a principal determinant of microvascular dysfunction by shifting the vascular equilibrium towards more vasoconstriction with subsequent organ ischaemia, inflammation with associated tissue oedema, and a pro-coagulant state.6Bonetti PO Lerman LO Lerman A Endothelial dysfunction - a marker of atherosclerotic risk.Arterioscl Throm Vas. 2003; 23: 168-175Crossref PubMed Scopus (1923) Google Scholar Our findings show the presence of viral elements within endothelial cells and an accumulation of inflammatory cells, with evidence of endothelial and inflammatory cell death. These findings suggest that SARS-CoV-2 infection facilitates the induction of endotheliitis in several organs as a direct consequence of viral involvement (as noted with presence of viral bodies) and of the host inflammatory response. In addition, induction of apoptosis and pyroptosis might have an important role in endothelial cell injury in patients with COVID-19. COVID-19-endotheliitis could explain the systemic impaired microcirculatory function in different vascular beds and their clinical sequelae in patients with COVID-19. This hypothesis provides a rationale for therapies to stabilise the endothelium while tackling viral replication, particularly with anti-inflammatory anti-cytokine drugs, ACE inhibitors, and statins.7Anderson TJ Meredith IT Yeung AC Frei B Selwyn AP Ganz P The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion.N Engl J Med. 1995; 332: 488-493Crossref PubMed Scopus (1111) Google Scholar, 8Taddei S Virdis A Ghiadoni L Mattei P Salvetti A Effects of angiotensin converting enzyme inhibition on endothelium-dependent vasodilatation in essential hypertensive patients.J Hypertens. 1998; 16: 447-456Crossref PubMed Scopus (105) Google Scholar, 9Flammer AJ Sudano I Hermann F et al.Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis.Circulation. 2008; 117: 2262-2269Crossref PubMed Scopus (104) Google Scholar, 10Hurlimann D Forster A Noll G et al.Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis.Circulation. 2002; 106: 2184-2187Crossref PubMed Scopus (550) Google Scholar, 11Feldmann M Maini RN Woody JN et al.Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed.Lancet. 2020; (published online April 9.)https://doi.org/10.1016/S0140-6736(20)30858-8Summary Full Text Full Text PDF PubMed Scopus (442) Google Scholar This strategy could be particularly relevant for vulnerable patients with pre-existing endothelial dysfunction, which is associated with male sex, smoking, hypertension, diabetes, obesity, and established cardiovascular disease, all of which are associated with adverse outcomes in COVID-19. ZV and AJF contributed equally as first authors, and RAS, FR, and HM contributed equally as last authors. AJF reports fees from Alnylam, Amgen, AstraZeneca, Fresenius, Imedos Systems, Novartis, Pfizer, Roche, Vifor, and Zoll, unrelated to this Correspondence. MRM reports consulting relationships with Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, NupulseCV, FineHeart, Leviticus, Baim Institute for Clinical Research, Riovant, and Triple Gene, unrelated to this Correspondence. FR has been paid for the time spent as a committee member for clinical trials, advisory boards, other forms of consulting and lectures or presentations. These payments were made directly to the University of Zurich and no personal payments were received in relation to these trials or other activities. All other authors declare no competing interests. Download .pdf (1.83 MB) Help with pdf files Supplementary appendix Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort studyThe potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Full-Text PDF Electron microscopy of SARS-CoV-2: a challenging task – Authors' replyWe thank Cynthia Goldsmith and colleagues for their interest in our recent Correspondence.1 We described autopsy findings from patients who had died from COVID-19 and showed a systemic endotheliitis with evidence of loss of integrity of the endothelial monolayer.1 Full-Text PDF Electron microscopy of SARS-CoV-2: a challenging taskWe read with interest the Correspondence by Zsuzsanna Varga and colleagues1 on the possible infection of endothelial cells by SARS-CoV-2 using electron microscopic (EM) images as evidence. However, we believe the EM images in the Correspondence do not show coronavirus particles but instead show cross-sections of the rough endoplasmic reticulum (RER). These spherical structures are surrounded by dark dots, which might have been interpreted as spikes on coronavirus particles but are instead ribosomes. Full-Text PDF

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Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

2020-04-29

Yeming Wang , Dingyu Zhang , Guanhua Du +7 more

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High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study

2020-05-04

Julie Helms , Charles Tacquard , François Séverac +7 more

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Effective treatment of severe COVID-19 patients with tocilizumab

2020-04-29

Xiaoling Xu , Mingfeng Han , Tiantian Li +7 more

Significance In patients with coronavirus disease 2019, a large number of T lymphocytes and mononuclear macrophages are activated, producing cytokines such as interleukin-6 (IL-6), which bind to the IL-6 receptor … Significance In patients with coronavirus disease 2019, a large number of T lymphocytes and mononuclear macrophages are activated, producing cytokines such as interleukin-6 (IL-6), which bind to the IL-6 receptor on the target cells, causing the cytokine storm and severe inflammatory responses in lungs and other tissues and organs. Tocilizumab, as a recombinant humanized anti-human IL-6 receptor monoclonal antibody, can bind to the IL-6 receptor with high affinity, thus preventing IL-6 itself from binding to its receptor, rendering it incapable of immune damage to target cells, and alleviating the inflammatory responses.

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Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis

2020-03-12

Jing Yang , Ya Zheng , Xi Gou +7 more

BackgroundAn outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan, China; the epidemic is more widespread than initially estimated, with cases now confirmed in multiple countries.AimsThe aim of this meta-analysis … BackgroundAn outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan, China; the epidemic is more widespread than initially estimated, with cases now confirmed in multiple countries.AimsThe aim of this meta-analysis was to assess the prevalence of comorbidities in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients and the risk of underlying diseases in severe patients compared to non-severe patients.MethodsA literature search was conducted using the databases PubMed, EMBASE, and Web of Science through February 25, 2020. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random-effects models.ResultsSeven studies were included in the meta-analysis, including 1 576 infected patients. The results showed the most prevalent clinical symptom was fever (91.3%, 95% CI: 86–97%), followed by cough (67.7%, 95% CI: 59–76%), fatigue (51.0%, 95% CI: 34–68%) and dyspnea (30.4%, 95% CI: 21–40%). The most prevalent comorbidities were hypertension (21.1%, 95% CI: 13.0–27.2%) and diabetes (9.7%, 95% CI: 7.2–12.2%), followed by cardiovascular disease (8.4%, 95% CI: 3.8–13.8%) and respiratory system disease (1.5%, 95% CI: 0.9–2.1%). When compared between severe and non-severe patients, the pooled OR of hypertension, respiratory system disease, and cardiovascular disease were 2.36 (95% CI: 1.46–3.83), 2.46 (95% CI: 1.76–3.44) and 3.42 (95% CI: 1.88–6.22) respectively.ConclusionWe assessed the prevalence of comorbidities in the COVID-19 patients and found that underlying disease, including hypertension, respiratory system disease and cardiovascular disease, may be risk factors for severe patients compared with non-severe patients.

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Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study

2020-05-22

Annemarie B Docherty , Ewen M. Harrison , Christopher Green +7 more

Abstract Objective To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United Kingdom during the growth phase of the first wave of … Abstract Objective To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United Kingdom during the growth phase of the first wave of this outbreak who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study, and to explore risk factors associated with mortality in hospital. Design Prospective observational cohort study with rapid data gathering and near real time analysis. Setting 208 acute care hospitals in England, Wales, and Scotland between 6 February and 19 April 2020. A case report form developed by ISARIC and WHO was used to collect clinical data. A minimal follow-up time of two weeks (to 3 May 2020) allowed most patients to complete their hospital admission. Participants 20 133 hospital inpatients with covid-19. Main outcome measures Admission to critical care (high dependency unit or intensive care unit) and mortality in hospital. Results The median age of patients admitted to hospital with covid-19, or with a diagnosis of covid-19 made in hospital, was 73 years (interquartile range 58-82, range 0-104). More men were admitted than women (men 60%, n=12 068; women 40%, n=8065). The median duration of symptoms before admission was 4 days (interquartile range 1-8). The commonest comorbidities were chronic cardiac disease (31%, 5469/17 702), uncomplicated diabetes (21%, 3650/17 599), non-asthmatic chronic pulmonary disease (18%, 3128/17 634), and chronic kidney disease (16%, 2830/17 506); 23% (4161/18 525) had no reported major comorbidity. Overall, 41% (8199/20 133) of patients were discharged alive, 26% (5165/20 133) died, and 34% (6769/20 133) continued to receive care at the reporting date. 17% (3001/18 183) required admission to high dependency or intensive care units; of these, 28% (826/3001) were discharged alive, 32% (958/3001) died, and 41% (1217/3001) continued to receive care at the reporting date. Of those receiving mechanical ventilation, 17% (276/1658) were discharged alive, 37% (618/1658) died, and 46% (764/1658) remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital. Conclusions ISARIC WHO CCP-UK is a large prospective cohort study of patients in hospital with covid-19. The study continues to enrol at the time of this report. In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity. This study has shown the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks. Study registration ISRCTN66726260.

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Remdesivir for the Treatment of Covid-19 — Final Report

2020-05-22

John H. Beigel , Kay M Tomashek , Lori E. Dodd +7 more

BackgroundAlthough several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.MethodsWe conducted a double-blind, randomized, placebo-controlled … BackgroundAlthough several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.MethodsWe conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.ResultsA total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan–Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%).ConclusionsOur data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.) Quick Take Remdesivir for the Treatment of Covid-19 — Final Report 1m 45s

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Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

2020-05-21

Maximilian Ackermann , Stijn E. Verleden , Mark Kuehnel +7 more

BackgroundProgressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about … BackgroundProgressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19.MethodsWe examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro–computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression.ResultsIn patients who died from Covid-19–associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth — predominantly through a mechanism of intussusceptive angiogenesis — was 2.7 times as high as that in the lungs from patients with influenza (P<0.001).ConclusionsIn our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. (Funded by the National Institutes of Health and others.)

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Extrapulmonary manifestations of COVID-19

2020-07-01

Aakriti Gupta , Mahesh V. Madhavan , Kartik Sehgal +7 more

Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19)

2020-07-10

W. Joost Wiersinga , Andrew Rhodes , Allen C. Cheng +2 more

<h3>Importance</h3> The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia … <h3>Importance</h3> The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. <h3>Observations</h3> SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. <h3>Conclusions and Relevance</h3> As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

2020-07-13

Jérôme Hadjadj , Nader Yatim , Laura Barnabei +7 more

Interferons interfere with lung repair Interferons (IFNs) are central to antiviral immunity. Viral recognition elicits IFN production, which in turn triggers the transcription of IFN-stimulated genes (ISGs), which engage in … Interferons interfere with lung repair Interferons (IFNs) are central to antiviral immunity. Viral recognition elicits IFN production, which in turn triggers the transcription of IFN-stimulated genes (ISGs), which engage in various antiviral functions. Type I IFNs (IFN-α and IFN-β) are widely expressed and can result in immunopathology during viral infections. By contrast, type III IFN (IFN-λ) responses are primarily restricted to mucosal surfaces and are thought to confer antiviral protection without driving damaging proinflammatory responses. Accordingly, IFN-λ has been proposed as a therapeutic in coronavirus disease 2019 (COVID-19) and other such viral respiratory diseases (see the Perspective by Grajales-Reyes and Colonna). Broggi et al. report that COVID-19 patient morbidity correlates with the high expression of type I and III IFNs in the lung. Furthermore, IFN-λ secreted by dendritic cells in the lungs of mice exposed to synthetic viral RNA causes damage to the lung epithelium, which increases susceptibility to lethal bacterial superinfections. Similarly, using a mouse model of influenza infection, Major et al. found that IFN signaling (especially IFN-λ) hampers lung repair by inducing p53 and inhibiting epithelial proliferation and differentiation. Complicating this picture, Hadjadj et al. observed that peripheral blood immune cells from severe and critical COVID-19 patients have diminished type I IFN and enhanced proinflammatory interleukin-6– and tumor necrosis factor-α–fueled responses. This suggests that in contrast to local production, systemic production of IFNs may be beneficial. The results of this trio of studies suggest that the location, timing, and duration of IFN exposure are critical parameters underlying the success or failure of therapeutics for viral respiratory infections. Science , this issue p. 706 , p. 712 , p. 718 ; see also p. 626

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Dexamethasone in Hospitalized Patients with Covid-19

2020-07-17

Peter Horby , Wei Shen Lim , Jonathan Emberson +7 more

BackgroundCoronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.MethodsIn this controlled, open-label trial comparing … BackgroundCoronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.MethodsIn this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the final results of this assessment.ResultsA total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.92 to 1.55).ConclusionsIn patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.) Quick Take Dexamethasone and Covid-19 2m 20s

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New coronavirus infection (COVID-19) in an initially healthy teenager — focus on acute myocardial injury

2025-06-25

V. V. Sokolovskaya , А. А. Литвинова , A.V. Krikova +3 more | CHILDREN INFECTIONS

Objective: to demonstrate a clinical case of fulminant COVID-19 in a teenager without comorbid pathology. The article presents a clinical case of a fulminant course of a new coronavirus infection … Objective: to demonstrate a clinical case of fulminant COVID-19 in a teenager without comorbid pathology. The article presents a clinical case of a fulminant course of a new coronavirus infection in a 16-year-old teenager with the development of multiple organ failure (bilateral polysegmental pneumonia, grade 2 respiratory failure, cardiovascular and renal-hepatic insufficiency). The emphasis is placed on heart damage with the development of acute myocardial damage, which is confirmed by high levels of troponin I and pericarditis. Conclusion : the described clinical case demonstrates the development of multiple organ failure and death in an initially healthy child. The development of acute myocardial injury is shown.

Efficacy of convalescent plasma therapy in improving survival in non-immunized COVID-19 patients

2025-06-24

Tânia Portella Costa , Dayanne Mozaner Bordin , Mateus Nóbrega Aoki +1 more | Virology Journal

Convalescent plasma (CP), obtained from individuals who have recovered from COVID-19, has been widely explored as a potential therapeutic option, particularly in the absence of vaccines and monoclonal antibody treatments. … Convalescent plasma (CP), obtained from individuals who have recovered from COVID-19, has been widely explored as a potential therapeutic option, particularly in the absence of vaccines and monoclonal antibody treatments. This study aimed to evaluate the effectiveness of CP therapy in improving survival among non-immunized COVID-19 patients hospitalized in Brazil. This retrospective unicentric cohort study was conducted at a private hospital in Campo Largo, Paraná, Brazil, from July 2020 to February 2021. A total of 245 hospitalized COVID-19 patients were included, confirmed by RT-qPCR or antigen testing. Patients were divided into two groups: those receiving CP alongside standard treatment (n=100) and those receiving standard treatment alone (n=145). Survival outcomes were assessed using Kaplan-Meier analysis and Cox regression, while inflammatory responses were evaluated through C-reactive protein (CRP) measurements. Patients treated with CP had a significantly higher survival rate (91%) compared to the control group (82.8%) (P=0.0363). The survival benefit persisted throughout the follow-up period, with a 2.25-fold lower risk of death in the CP group after adjusting for age (P=0.0480). However, no significant differences in CRP levels were observed between groups at discharge, suggesting that CP's benefits may be mediated through immune modulation rather than direct anti-inflammatory effects. Our findings indicate that CP therapy significantly improves survival in non-immunized COVID-19 patients, reinforcing its potential role in settings with limited access to advanced treatments. Future studies should explore CP's mechanisms of action and its integration into broader therapeutic strategies.

The Dual Role of ACE2 in IBD: Balancing SARS-CoV-2 Susceptibility and Gut Homeostasis

2025-06-24

Laura Francesca Pisani , Guglielmo Albertini Petroni , Luca Pastorelli +1 more | Inflammatory Bowel Diseases

Ischemic modified albumin and thiol levels in Coronavirus disease 19: a systematic review and meta-analysis

2025-06-23

Asma Mousavi , Shayan Shojaei , Peyvand Parhizkar +3 more | Diagnostic and Prognostic Research

Thromboelastography in COVID-19 patients: An observational study in the South African context

2025-06-23

Bavinash Pillay , Sarah Alexandra van Blydenstein , Shahed Omar | African Journal of Laboratory Medicine

Background: Coronavirus disease 2019 (COVID-19) increases the risk of venous thromboembolism, requiring monitoring of low molecular weight heparin (LMWH) via a time-consuming, costly and often unavailable test – anti-factor Xa … Background: Coronavirus disease 2019 (COVID-19) increases the risk of venous thromboembolism, requiring monitoring of low molecular weight heparin (LMWH) via a time-consuming, costly and often unavailable test – anti-factor Xa (anti-Xa). An affordable, rapid point-of-care alternative, the thromboelastogram, is available, but performance comparisons to anti-Xa are lacking. Objective: This study evaluated the relationship between anti-Xa and thromboelastogram in patients with COVID-19 receiving LMWH. Methods: This was a retrospective study of patients with COVID-19 receiving LMWH at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, between November 2020 and January 2021. Blood samples tested with thromboelastogram and anti-Xa were drawn at three timepoints (one prior to and two after administration of LMWH). Thromboelastogram parameters comprised reaction time (R-time; onset of testing to the start of clot formation), kinetics time (K-time; start of clot formation until the clot reached 20 mm), and thromboelastogram coagulation index (overall coagulation status of whole blood). Results: Forty-two patients with COVID-19 (15 male and 27 female) met the study criteria. There was a statistically significant, low to moderate correlation (Spearman’s correlation coefficient [rs 0.43, p = 0.014]) between anti-Xa and thromboelastogram coagulation index. A statistically significant moderate correlation (rs 0.52, p = 0.002) between anti-Xa and R-time, and a statistically significant low correlation (rs 0.35, p = 0.049) between anti-Xa and K-time, were found. All correlations were 48 h post admission. Conclusion: Thromboelastogram coagulation index, R-times and K-times had a statistically significant association with anti-Xa levels in patients with COVID-19. Further research is required regarding their clinical utility. What this study adds: Thromboelastograms may represent a more cost-effective and accessible option to the conventional anti-Xa test in patients receiving LMWH. However, future research with larger sample sizes, varying disease profiles, and severity of illness is required.

Clinical features of novel coronavirus infection (omicron variant) in patients with end-stage kidney disease

2025-06-23

P. I. Miklush , К. В. Жданов , A. N. Belskykh +7 more | Bulletin of the Russian Military Medical Academy

BACKGROUND: Before the emergence of the omicron variant, novel coronavirus infection in patients with end-stage kidney disease was characterized by a severe course and poor prognosis. Since January 2022, the … BACKGROUND: Before the emergence of the omicron variant, novel coronavirus infection in patients with end-stage kidney disease was characterized by a severe course and poor prognosis. Since January 2022, the omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the most prevalent strain in Russia. This strain is associated with uncommon virus-induced lung injury and significantly lower hospitalization and mortality rates compared to previous variants. AIM: This study aimed to assess the course of the omicron variant of SARS-CoV-2 in patients with end-stage kidney disease. METHODS: The retrospective cohort study included 33 medical records of patients with end-stage kidney disease who had been treated for novel coronavirus infection at the Infectious Diseases Clinic of Kirov Military Medical Academy and Botkin Clinical Infectious Diseases Hospital between January 2022 and February 2024. Following a comprehensive analysis of the medical records, the patients were divided into two groups. Group 1 included 12 patients with novel coronavirus infection in the form of acute respiratory viral infection without lung involvement. Group 2 comprised 21 patients with virus-induced lung injury. RESULTS: The omicron variant of SARS-CoV-2 frequently caused lung injury, including acute respiratory failure, in patients with end-stage kidney disease. The early stages of inpatient treatment for this group of patients were characterized by fever (≥ 37.2°C), tachycardia (≥ 90 bpm), National Early Warning Score ≥ 4, and prolonged viral shedding (12 [10; 18] vs 9 [7,5; 9,5] days, p = 0.002). CONCLUSION: The high prevalence of comorbidities and frequent occurrence of virus-induced lung injury leading to acute respiratory failure underscore a unique cohort of patients with end-stage kidney disease requiring programmed hemodialysis and highlight the ongoing challenge of novel coronavirus infection, even during the spread of the omicron variant of SARS-CoV-2.

Plasma Proteomic Profiling Yields a High-Performance Biomarker Panel for Predicting a Poor Prognosis in Patients with COVID-19

2025-06-23

Z T Zhang , Huqin Yang , Leyi Gao +4 more | Journal of Proteome Research

Background The coronavirus disease 2019 (COVID-19) pandemic increased the demand for reliable tests to predict disease severity and mortality. Methods In training cohort, we obtained traditional clinical data and plasma … Background The coronavirus disease 2019 (COVID-19) pandemic increased the demand for reliable tests to predict disease severity and mortality. Methods In training cohort, we obtained traditional clinical data and plasma proteomics performed using the Olink proteomics platform from 52 fatal COVID-19 cases (COVID-19-F), 50 severe COVID-19 cases (COVID-19-S), 55 moderate/mild COVID-19 cases (COVID-19-M), and 54 healthy controls. Receiver operating characteristic (ROC) curves and logistic regression were applied to judge the accuracy of biomarkers to predict in-hospital mortality and build combined panel. An independent external cohort was used for validation. Results In total, 19 clinical parameters and 92 proteins were assessed. Traditional clinical indices did not show adequate predictive value of short-term mortality in severe COVID-19. In proteomics analysis, 75 proteins were differentially expressed among the four groups. Pathway analysis revealed an imbalance of inflammatory responses and excessive immunity in COVID-19-F. Subsequently, a novel plasma biomarker panel (including interleukin 8 and osteoprotegerin) was developed, with AUC values of 0.791 and 0.781 when comparing COVID-19-F to COVID-19-M or COVID-19-S, respectively. The predictive power of the panel was verified in an external cohort. Conclusions Our standardized assays yielded a prediction panel of mortality during hospitalization in patients with COVID-19.

Relationship Between Atherogenic Indices and Cardiovascular Thromboembolic Events in Patients with COVID-19 Pneumonia

2025-06-23

Hakan Kılcı , Adem Melekoğlu , G. Doğan +3 more | Hitit Medical Journal

Objective: COVID-19, caused by coronavirus SARS-CoV-2, is a pandemic viral respiratory infection in which venous and arterial thromboembolic events are often observed. This study aimed to investigate the relationship between … Objective: COVID-19, caused by coronavirus SARS-CoV-2, is a pandemic viral respiratory infection in which venous and arterial thromboembolic events are often observed. This study aimed to investigate the relationship between atherogenic indices and cardiovascular thromboembolic events in patients with COVID-19 pneumonia. Material and Method: In this retrospective study, a total of 805 inpatients (median age 63 [IQR: 52-74] years; 45.1% female) who were diagnosed with COVID-19 pneumonia between March 2020 and December 2020 were evaluated. Patients were divided into two groups based on cardiovascular thromboembolic events with cardiovascular thromboembolic events (n=96) and without-cardiovascular thromboembolic events (n=709). All clinical and demographic data and laboratory results were analyzed. Atherogenic Index of Plasma (AIP (log10 (triglyceride/ HDL)), Atherogenic Coefficient (AC (HDL/ non-HDL)), Risk Index of Castelli-I (CRI-I (Total cholesterol/ HDL)), and Risk Index of Castelli-II (CRI-II (LDL/ HDL)) were calculated. Results: Atherogenic Coefficient, CRI-I, and CRI-II values were significantly higher in the cardiovascular thromboembolic event group (p=0.001, p=0.001, p=0.007, respectively). AIP values were higher in the cardiovascular thromboembolic events group but were not statistically significant (p=0.051). In the cardiovascular thromboembolic events group, HDL values were found to be significantly lower (p=0.001), but CRP and D-dimer values were found to be significantly higher (p

Chronic heart failure and hypoalbuminemia are risk factors of poorer mRNA SARS-CoV-2 vaccine response in maintenance Hemodialysis patients (the COVaccinDia study)

2025-06-23

Pierre Laurent , Marianne Renou , N. El Esper +4 more | BMC Nephrology

Chronic kidney disease represents an immunocompromising condition and a cause of a lower vaccine efficacy, even in patients undergoing maintenance dialysis. Recent SARS-CoV-2 outbreaks have prompted clinicians to better understand … Chronic kidney disease represents an immunocompromising condition and a cause of a lower vaccine efficacy, even in patients undergoing maintenance dialysis. Recent SARS-CoV-2 outbreaks have prompted clinicians to better understand the underlying mechanisms and establish more suitable vaccination schedules. In a single-center, retrospective, observational study of patients undergoing maintenance dialysis in France, we studied the factors associated with the intensity of the humoral response to a SARS-CoV-2 vaccine in this population, including specific dialysis-related variables. After having received three doses of SARS-CoV-2 mRNA vaccine, a cohort of 80 patients was divided into low-responders (28 patients with an anti-SARS-CoV-2 antibody level of 50-1830 AU/mL) and responders (52 patients with an antibody level > 1830 AU/mL). We found that chronic heart failure (p < 0.00001), higher performance status (p = 0.004), hypoalbuminemia (p < 0.001), lymphopenia (p = 0.003), Rhesus status positivity (p = 0.02), and absence of response to a hepatitis B virus vaccine (p = 0.02) were associated with a poor response to a third dose of SARS-CoV-2 vaccine. In contrast, none of the dialysis-related variables were associated with the vaccine response. In multivariate logistic regression, chronic heart failure (p < 0.0001) and hypoalbuminemia (p = 0.0004) remained associated with a lower humoral response to SARS-CoV-2 vaccine. Our results showed that chronic heart failure and hypoalbuminemia were factors associated with a poor humoral response after three doses of SARS-CoV-2 vaccine. However, we found no association between specific dialysis-related variables and the anti-SARS-CoV-2 antibody titer.

Evolutionary dynamics of heparan sulfate utilization by SARS-CoV-2

2025-06-23

Shuhei Higuchi , Yafei Liu , Jun Shimizu +7 more | mBio

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants have acquired enhanced infectivity compared to earlier variants. To elucidate the underlying molecular mechanisms, we conducted CRISPR library screening to identify … Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants have acquired enhanced infectivity compared to earlier variants. To elucidate the underlying molecular mechanisms, we conducted CRISPR library screening to identify cell surface molecules that interact with the Omicron spike protein. Our findings revealed a significantly higher affinity between the Omicron spike and cell surface heparan sulfate compared to the wild-type spike. This increased binding affinity enables Omicron variants to infect cells expressing low levels of ACE2, which are minimally infected by the wild-type virus. Mutational analysis of heparan sulfate binding sites on the Omicron spike protein, coupled with electrostatic potential mapping, suggested that the accumulation of positively charged mutations has contributed to the enhanced heparan sulfate binding. Comparative analysis of heparan sulfate binding among Omicron subvariants-including BA.1, BA.2, BA.4, BA.5, XBB.1, and BA.2.86-revealed that most are likely to bind efficiently to heparan sulfate, but potential heparan sulfate binding sites of the spike protein have shifted from the early Omicron variants to more recent ones. Furthermore, we discovered that cell surface heparan sulfate proteoglycans are cleaved by TMPRSS2, a protease essential for wild-type SARS-CoV-2 infection. These findings suggest that SARS-CoV-2 is evolving to enhance its infectivity by optimizing its interaction with cell surface heparan sulfate.IMPORTANCEThe Omicron variant has evolved to become highly infectious by acquiring numerous mutations. Understanding the impact of these mutations can provide valuable insights into the drivers of viral evolution and aid in the development of improved viral surveillance and vaccines. Our study demonstrates that the Omicron variants contain mutations that enhance their ability to bind to heparan sulfate. Highly infectious human viruses often utilize heparan sulfate for infection, suggesting that heparan sulfate likely plays a crucial role in viral adaptation to human hosts. Furthermore, we found that cell surface heparan sulfate proteoglycans are sensitive to TMPRSS2, while most other cell surface proteins are resistant to TMPRSS2. Given that TMPRSS2 is known to enhance the infectivity of earlier severe acute respiratory syndrome coronavirus 2 variants but cleaves heparan sulfate proteoglycans, it is probable that the high heparan sulfate binding acquired by the Omicron variant contributes to its decreased infectivity against TMPRSS2-expressing cells compared to earlier variants.

COVID-19 management in patients with comorbid conditions

2025-06-23

Adekunle Sanyaolu , Chuku Okorie , Aleksandra Marinković +7 more | World Journal of Virology

The novel coronavirus disease 2019 (COVID-19) causes serious respiratory illness and related disorders. Vulnerable populations, including those with chronic obstructive pulmonary disease, heart disease, diabetes, chronic kidney disease, obesity, and … The novel coronavirus disease 2019 (COVID-19) causes serious respiratory illness and related disorders. Vulnerable populations, including those with chronic obstructive pulmonary disease, heart disease, diabetes, chronic kidney disease, obesity, and the elderly, face an increased risk of severe complications. As the pandemic evolves, various diagnostic techniques are available to detect severe acute respiratory distress syndrome (SARS-CoV-2), including clinical presentation, rapid antigen/antibody testing, molecular testing, supplemental laboratory analysis, and imaging. Based on peer-reviewed data, treatment options include convalescent plasma transfusion, corticosteroids, antivirals, and immunomodulatory medications. Convalescent plasma therapy, historically used in outbreaks like Middle East respiratory syndrome, Ebola, and SARS, is suggested by the World Health Organization for critically ill COVID-19 patients when vaccines or antiviral drugs are unavailable. Neutralizing antibodies in convalescent plasma help control viral load and improve patient outcomes, especially when administered early, though effectiveness varies. The United States Food and Drug Administration has authorized its emergency use for severe COVID-19 cases, but potential risks such as transfusion reactions and transfusion-related acute lung injury require further investigation to establish definitive efficacy. Antiviral agents like Remdesivir, an adenosine nucleotide analog, inhibit viral RNA polymerase and have shown efficacy in reducing COVID-19 severity, leading to its emergency use authorization for hospitalized patients. Other antivirals like ritonavir, lopinavir, and umifenovir disrupt viral replication and entry, but their effectiveness against SARS-CoV-2 remains under investigation. Dexamethasone, a corticosteroid, has been used in critically ill COVID-19 patients to reduce inflammation and prevent respiratory failure, as shown in the RECOVERY trial. Other immunosuppressants like ruxolitinib, baricitinib, and colchicine help modulate the immune response, reducing cytokine storms and inflammation-related complications. However, corticosteroids carry risks such as hyperglycemia, immunosuppression, and delayed viral clearance, requiring careful administration. Systematic reviews of clinical studies revealed that hydroxychloroquine with or without azithromycin did not decrease viral load nor reduce the severity of symptoms, but increased mortality among acutely hospitalized patients. There was no improvement in patients' clinical conditions after 15 days compared to standard treatment. The United States Food and Drug Administration has revoked the authorization for the use of hydroxychloroquine in COVID-19 patients due to the null benefit-risk balance. Monoclonal antibodies like itolizumab, gimsilumab, sarilumab, and tocilizumab are being studied for their ability to reduce the severe inflammatory response in COVID-19 patients, particularly cytokine release syndrome and acute respiratory distress syndrome. These antibodies target specific immune pathways to decrease pro-inflammatory cytokines, with some showing promising results in clinical trials, though their use remains under investigation. The Clustered Regularly Interspaced Short Palindromic Repeats/Cas13 family of enzymes, sequenced from many COVID-19-positive patients, can potentially inhibit SARS-CoV-2 replication, cleave the RNA genome, and aid in the amplification of the genome assay. Cas13 can also target emerging pathogens via an adeno-associated virus vector when delivered to the infected lungs. In addition to pharmacological agents, vaccines effectively prevent symptomatic infection, reduce hospitalizations, minimize mortality rates, and ultimately reduce the severity of the disease. This paper aims to explore the management of patients with underlying conditions who present with COVID-19 to lessen the burden on healthcare systems.

COVID-19 and a Tale of Three Drugs: To Repurpose, or Not to Repurpose–That Was the Question

2025-06-23

Chris R. Triggle , Ross MacDonald | Viruses

On 11 March 2020, the World Health Organisation (WHO) declared a global pandemic caused by the SARS-CoV-2 coronavirus that earlier in February 2020 the WHO had named COVID-19 (coronavirus disease … On 11 March 2020, the World Health Organisation (WHO) declared a global pandemic caused by the SARS-CoV-2 coronavirus that earlier in February 2020 the WHO had named COVID-19 (coronavirus disease 2019). There were neither drugs nor vaccines that were known to be effective against the virus, stimulating an urgent worldwide search for treatments. An evaluation of existing drugs by ‘repurposing’ was initiated followed by a transition to de novo drug discovery. Repurposing of an already approved drug may accelerate the introduction of that drug into clinical use by circumventing early, including preclinical studies otherwise essential for a de novo drug and reducing development costs. Early in the pandemic three drugs were identified as repurposing candidates for the treatment of COVID-19: (i) hydroxychloroquine, an anti-malarial also used to treat rheumatoid arthritis and lupus; (ii) ivermectin, an antiparasitic approved for both human and veterinary use; (iii) remdesivir, an anti-viral originally developed to treat hepatitis C. The scientific evidence, both for and against the efficacy of these three drugs as treatments for COVID-19, vied with public demand and politicization as unqualified opinions clashed with evidence-based medicine. To quote Hippocrates, “There are in fact two things, science and opinion; the former begets knowledge, the latter ignorance”.

Correction: Estimating the impact of non-pharmaceutical interventions on COVID mortality using reductions in influenza mortality as an effect indicator

2025-06-23

Robert D. Morris | Journal of Public Health Policy

Evaluation of the efficacy and safety of an interleukin-17 inhibitor in hospitalized COVID-19 patients

2025-06-21

З. М. Мержоева , Andrey I. Yaroshetskiy , Н. А. Царева +5 more | Consilium Medicum

Aim. To evaluate the clinical efficacy and safety of netakimab (an interleukin-17 inhibitor) in hospitalized patients with severe COVID-19. Materials and methods. A retrospective case-control study was conducted involving 171 … Aim. To evaluate the clinical efficacy and safety of netakimab (an interleukin-17 inhibitor) in hospitalized patients with severe COVID-19. Materials and methods. A retrospective case-control study was conducted involving 171 patients. The main group (n=83) received subcutaneous netakimab (120 mg) in addition to standard therapy (hydroxychloroquine, azithromycin, corticosteroids, anticoagulants). The control group (n=88) received standard treatment alone. Inclusion criteria included SpO2≤92%, body temperature over 38°C for 3 days or more, C-reactive protein (CRP) ≥40 mg/L, and lymphopenia/leukopenia. Outcomes analyzed were changes in temperature, SpO2/FiO2 ratio, NEWS2 (National Early Warning Score 2), CRP levels, need for invasive/non-invasive ventilation (IMV/NIV), intensive care unit transfer, and mortality. Results. By day 3 of therapy, the netakimab group showed statistically significant improvements in temperature (36.7°C vs. 36.9°C; p=0.01), SpO2/FiO2 ratio (272 vs. 266; p=0.03), NEWS2 (3 points vs. 5 points; p=0.05), and CRP reduction (29 mg/L vs. 57 mg/L; p=0.0001). However, no significant differences were observed in clinical outcomes (intensive care unit transfer, IMV/NIV need, mortality). Hospitalization duration was shorter in the main group (15 days vs. 16 days; p=0.02). Mild adverse events were reported in 57 patients in the main group and 55 in the control group. Conclusion. Netakimab use was associated with improved oxygenation, reduced inflammatory markers, and faster fever resolution but did not impact major clinical outcomes. These findings require validation in randomized prospective trials.

Commentary: Evaluation of post-COVID mortality risk in cases classified as severe acute respiratory syndrome in Brazil: a longitudinal study for medium and long term

2025-06-20

Júlio Croda | Frontiers in Medicine

Application of Antirheumatic Drugs During the Epidemic Period of COVID-19

2025-06-20

Meng‐Xin Tian , Fan Yang , Yanying Liu | Infectious Diseases in Clinical Practice

Abstract In response to the COVID-19 pandemic, many therapeutic techniques have been developed to effectively manage viral infections and mitigate the cytokine storm. Numerous scientific studies have shown the significance … Abstract In response to the COVID-19 pandemic, many therapeutic techniques have been developed to effectively manage viral infections and mitigate the cytokine storm. Numerous scientific studies have shown the significance of antirheumatic medications in the management of COVID-19. This article aims to examine the role of antirheumatic medications in modulating the immune system and inhibiting the heightened inflammatory response in the body. Additionally, the study will explore the current uses and corroborating evidence of antirheumatic medications in treating COVID-19, with a particular focus on addressing the future long COVID-19 period and epidemic outbreaks.

Severe Transaminitis in SARS-CoV-2 and EBV Coinfection: A Case Report

2025-06-19

Joseph H Kelly , Kenji Hamanaka , Abigail Polzin | Research Square (Research Square)

<title>Abstract</title> Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Epstein-Barr Virus (EBV) are each individually associated with mild hepatic injury and, rarely, with hyperbilirubinemia. SARS-CoV-2 and EBV coinfection is … <title>Abstract</title> Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Epstein-Barr Virus (EBV) are each individually associated with mild hepatic injury and, rarely, with hyperbilirubinemia. SARS-CoV-2 and EBV coinfection is not well documented, but mild hepatic injury has been demonstrated. This case highlights a rare case of severe transaminitis and hyperbilirubinemia from SARS-CoV-2 and EBV coinfection. Case presentation: A 25-year-old man, with no significant past medical history, acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Epstein-Barr virus (EBV) coinfection and developed severe transaminitis, moderate hyperbilirubinemia, and hepatosplenomegaly. The patient’s transaminitis returned to baseline over the course of weeks with no long-term sequelae. Conclusions: While SARS-CoV-2 and EBV are each independently associated with mild hepatic injury, this case highlights a rare presentation of severe liver injury, possibly due to synergistic viral effects.

From Disruption to Recovery: Strategic Education Policy for Post-Pandemic Brunei

2025-06-19

Suraya Hamid , Rosmawijah Jawawi , Sallimah M. Salleh +1 more | International Journal of Research and Innovation in Social Science

The COVID-19 pandemic has significantly disrupted education systems worldwide, including in Brunei Darussalam, where extended school closures have adversely impacted student learning, particularly among those from low socioeconomic backgrounds. In … The COVID-19 pandemic has significantly disrupted education systems worldwide, including in Brunei Darussalam, where extended school closures have adversely impacted student learning, particularly among those from low socioeconomic backgrounds. In response, the Ministry of Education prioritized the development of a sustainable and equitable learning recovery strategy. Guided by an integrated theoretical framework combining Educational Resilience Theory and Systems Theory in Education, this study investigates the extent of pandemic-induced learning loss and identifies strategic policy interventions. A qualitative approach was employed, incorporating document analysis, secondary survey data from 36,740 students across 147 public schools, and structured school-level observations. Analysis of the data identified two key contributing factors to the learning gap: human-related and organizational challenges. The study proposes four policy alternatives and recommends the integration of the Student Resource Management System (SRMS) and the Learning Accelerated Recovery Program (LARP) as strategic responses to mitigate learning disparities. This paper advocates for a resilient, inclusive, and future-ready education system aligned with Brunei’s long-term national goals.

The fibrin-derived peptide FX06 protects human pulmonary endothelial cells against the COVID-19-triggered cytokine storm

2025-06-19

Z G Wang , Д. А. Лебедев , Simeng Li +7 more | Frontiers in Immunology

Introduction Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major health emergency since its emergence in late 2019. Endothelial dysfunction is a … Introduction Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major health emergency since its emergence in late 2019. Endothelial dysfunction is a hallmark of COVID-19, leading to severe illness, i.e. coagulopathy, multi-organ failure. FX06, a fibrin-derived peptide naturally occurring in the human body, formerly known as Bβ 15-42 , is a promising therapeutic candidate for endothelial complications like capillary leakage in COVID-19 and other forms of acute respiratory disorders. The aim of this project is to investigate whether FX06 can attenuate COVID-19 cytokine-triggered inflammatory processes in vitro . Methods To mimic the inflammatory status of COVID-19, a human pulmonary microvascular endothelial cell line (ECs) – HULEC-5a, was treated with a cytokine cocktail comprised of ten different cytokines or chemokines at concentrations found in serum profiles of COVID-19 patients with severe illness, further referred to as the severe cytokine cocktail. ECs were treated with the severe cytokine cocktail for 24 h, in the absence or presence of FX06 for 2 h. Results The severe cytokine cocktail enhanced peripheral blood mononuclear cell (PBMC)-endothelial adhesion and monolayer transmigration. This deleterious effect was significantly reduced by FX06. FX06 was also shown to mitigate the cytotoxic activity of allogeneic CD8 + T cells, which increased upon cytokine treatment. FX06 restored continuous vascular endothelial (VE)-cadherin/CD144 distribution on the EC surface and reversed morphological changes mediated by the severe cytokine cocktail, such as the elongation of F-actin stress fibers. FX06 reduced capillary-like structure formation of the severe cytokine cocktail treated-ECs, indicating FX06 down-regulated the pro-inflammatory angiogenic activity caused by the severe cytokine cocktail. Additionally, FX06 might assist in maintaining the normal barrier function of ECs by altering the surface expression of Syndecan-1 (SDC1/CD138). Proteomics and phosphoproteomics analyses demonstrated that FX06 in the presence of the severe cytokine cocktail inactivated RhoGTPase, which was confirmed by western blotting that FX06 attenuated RhoA, a member of RhoGTPase, enhanced by the severe cytokine cocktail and down-regulated the expression of the phosphorylated downstream protein, ROCK1. Conclusion Overall, FX06 shows promising potential in normalizing ECs and reducing vascular leakage to protect the endothelium against the proinflammatory effect of COVID-19-triggered cytokines.

Body Mass Index and COVID-19: An Overview Among an Italian Multicentric Cohort of Healthcare Workers in the Pre- and Post-Vaccination Eras—ORCHESTRA Project

2025-06-19

Gianluca Spiteri , Lorena Torroni , Maria Grazia Lourdes Monaco +7 more | Vaccines

Background The prevalence of obesity is increasing all over the world, resulting in a global health emergency. The impact of obesity on the risk of SARS-CoV-2 infection and symptom severity, … Background The prevalence of obesity is increasing all over the world, resulting in a global health emergency. The impact of obesity on the risk of SARS-CoV-2 infection and symptom severity, especially among high-risk working populations such as health workers, deserves further studies. Methods A multicentric retrospective cohort study was conducted among health workers at four Italian University Hospitals belonging to the ORCHESTRA Project. Data were collected through an online survey, investigating sociodemographic and clinical data, until September 2022. Results The questionnaire was filled out by 5777 health workers. The median age was 46 years old (I-III quartile 20-72) and 75.5% were females. Data on BMI was available for 5470 participants. Overweight and obese subjects amounted to 23.4% and 9.8%, respectively. Naïve health workers were the majority (57.4%). Overweight and obese subjects were at a higher risk of infection only before vaccination with respect to normoweight subjects (RRR = 1.28 (IC 95% 1.01-1.62, p = 0.039) and 1.36 (1.00-1.86, p = 0.047), respectively). Major acute and post-acute COVID-19 symptoms were more common among obese subjects, as compared to those with a normal weight (35.2% vs. 23.5%, and 14.2% vs. 9.3%). BMI did not reduce antibody levels after vaccination. On the contrary, overweight and obese health workers had a significantly higher RGM after the third dose (1.12 and 1.48, respectively; normal weight as reference). Conclusions Overweight and obese subjects are at a higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 vaccination fosters a high antibody response even in these individuals. Vaccination against SARS-CoV-2 should be prioritized in subjects with a high BMI, especially in highly exposed workers, such as health workers.

Cytokines from Macrophages Activated by Spike S1 of SARS-CoV-2 Cause eNOS/Arginase Imbalance in Endothelial Cells

2025-06-19

Giulia Recchia Luciani , Rossana Visigalli , Valeria Dall’Asta +2 more | International Journal of Molecular Sciences

Multiple lines of evidence suggest that endothelial dysfunction is a key player in the pathogenesis of COVID-19, with cytokine storm as one of the main primary causes. Among the mechanisms … Multiple lines of evidence suggest that endothelial dysfunction is a key player in the pathogenesis of COVID-19, with cytokine storm as one of the main primary causes. Among the mechanisms underlying endothelial damage, clinical findings identify alterations in arginine metabolism, as patients with severe COVID-19 exhibit lower levels of nitric oxide synthase (eNOS) and upregulated arginase. In this study, we investigated, in human endothelial cells (HUVECs), the effect of conditioned medium from macrophages activated with SARS-CoV-2 Spike protein (CM_S1) on arginine metabolism. The results indicate that CM_S1 causes a marked decrease in eNOS and an increase in arginase, along with a greater intracellular arginine content and the induction of the CAT2 transporter. These effects are ascribable to the inflammatory mediators released by macrophages in CM_S1, mainly TNFα and IL-1β. Since infliximab, an antibody targeting TNFα, and baricitinib, an inhibitor of the JAK/STAT pathway, correct the observed imbalance between eNOS and arginase, our findings suggest the potential efficacy of a combined therapy to counteract endothelial dysfunction in COVID-19.

Importance and comparison of inflammatory biomarkers in COVID-19 patients follow-up in intensive care unit

2025-06-18

Mustafa Deniz , Esra Özdemir | Journal of Medicine and Palliative Care

Aims: This study aimed to determine the power of laboratory parameters and biomarkers in predicting the prognosis of patients admitted to the intensive care units (ICU) with COVID-19 in a … Aims: This study aimed to determine the power of laboratory parameters and biomarkers in predicting the prognosis of patients admitted to the intensive care units (ICU) with COVID-19 in a state hospital. Methods: In this retrospective study, the hospital automation system of all patients admitted to Bolu İzzet Baysal State Hospital’s ICUs because of COVID-19 between March 2020 and December 2021 were recorded and examined. Demographic data, blood tests, APACHE II score, and inflammatory biomarkers were also recorded. The results of patients who survived and did not survive were compared. Results: The study included 452 patients and the mortality was 72.6%. Exitus patients had higher APACHE II scores and age. The mortality rate was significantly higher in patients with neurological disorders. For patients who did not survive, blood leukocyte, procalcitonin, LDH, and creatinine levels were higher, whereas blood lymphocyte and thrombocyte levels were lower. Based on the ROC analyses, the lymphocyte count AUC was 0.624, APACHE II score AUC was 0.618, serum procalcitonin level AUC was 0.584, and platelet count was 0.560. Age, APACHE II score, neutrophil-to-lymphocyte ratio, and lymphocyte count were associated with mortality according to a univariate logistic regression analysis. Age (OR (95 CI%)1.02 (1.00-1.04, p=0.018)), APACHE II (OR (95 CI%)1.05 (1.01-1.09, p=0.018)), and neutrophil to lymphocyte ratio (OR (95 CI%) 1.02 (1.01-1.03, p=0.003)) were associated with mortality according to multivariate logistic regression Conclusion: For patients admitted to the ICU, laboratory parameters and inflammatory biomarkers can help in diagnosis, follow-up, and prognosis in COVID-19. We believe that combinations of hemogram parameters are effective in predicting clinical follow-up and prognosis.

Oral <scp>MIB</scp>‐626 (β Nicotinamide Mononucleotide) Safely Raises Blood Nicotinamide Adenine Dinucleotide Levels in Hospitalized Patients With <scp>COVID</scp>‐19 and Acute Kidney Injury: A Randomized Controlled Trial

2025-06-18

Karol M. Pencina , David E. Leaf , Rodrigo J. Valderrábano +7 more | FASEB BioAdvances

ABSTRACT Nicotinamide adenine dinucleotide (NAD + ) plays an important role in the innate immune response and is depleted during SARS‐CoV‐2 infection due to increased turnover. It is unknown whether … ABSTRACT Nicotinamide adenine dinucleotide (NAD + ) plays an important role in the innate immune response and is depleted during SARS‐CoV‐2 infection due to increased turnover. It is unknown whether treatment with NAD + precursors can safely raise NAD + levels in patients with COVID‐19. To determine whether MIB‐626 ( β‐ nicotinamide mononucleotide), an NAD + precursor, can safely increase blood NAD + levels and attenuate acute kidney injury (AKI) and inflammation in hospitalized patients with COVID‐19, 42 adults, ≥ 18 years, hospitalized with COVID‐19 and AKI, were randomized in a 3:2 ratio to MIB‐626 1.0‐g or placebo tablets twice daily for 14 days. Circulating NAD + and its metabolites, markers of AKI, inflammation, and disease severity, were assessed. MIB‐626 treatment significantly but gradually raised blood NAD + levels to a peak between 5 to 14 days (16.0 ± 6.9, 25.5 ± 12.6, and 42.6 ± 25.6 μg/mL at baseline, days 5 and 14) and raised plasma concentrations of NAD + metabolites 1‐methylnicotinamide, N‐methyl, 2‐pyridone, 4‐carboxamide rapidly to a peak by day 3. Changes in serum creatinine, cystatin‐C, and serum markers of AKI did not differ significantly between groups. Serum CRP, IL‐6, and TNFα and indices of disease severity also did not differ between groups. MIB‐626 treatment of patients with COVID‐19 and AKI safely and substantially raised blood NAD + and plasma concentrations of NAD + metabolites. Markers of AKI, inflammation, and disease severity did not differ between groups, likely due to the slow rise in NAD + levels. Future studies should assess whether a rapid increase in NAD + by parenteral administration can attenuate disease severity and AKI. Trial Registration: ClinicalTrials.gov Identifier: NCT05038488

Aspirin reduces the risk of type 2 diabetes associated with COVID-19

2025-06-18

Valentina Trimarco , Raffaele Izzo , Daniela Pacella +7 more | npj Metabolic Health and Disease

Effectiveness and safety of azvudine in the treatment of COVID-19 patients: a retrospective cohort study using propensity score matching

2025-06-18

Jing Zhang , Fang Wang , Ying Xie +3 more | Frontiers in Cellular and Infection Microbiology

Background Clinical trials have demonstrated the efficacy of azvudine in alleviating clinical symptoms among patients with coronavirus disease 2019 (COVID-19). However, evidence regarding its real-world effectiveness and safety profile remains … Background Clinical trials have demonstrated the efficacy of azvudine in alleviating clinical symptoms among patients with coronavirus disease 2019 (COVID-19). However, evidence regarding its real-world effectiveness and safety profile remains limited. Objective To evaluate the effectiveness and safety of azvudine in COVID-19 patients. Methods This retrospective cohort study included 192 COVID-19 patients hospitalized in Fengtai District, Beijing, from November 1 to December 31, 2022. Patients were divided into azvudine (n=118) and non-azvudine (n=74) groups. Propensity score matching (PSM) was applied to balance baseline characteristics (age, sex, vaccination status, etc.), yielding 48 matched pairs. Outcomes included time to SARS-CoV-2 RNA negativity, hospitalization duration, and symptom resolution (fever, cough). Adverse events were recorded. Results After PSM, 48 pairs of COVID-19 patients were identified. The azvudine group exhibited significantly shorter hospitalization than the non-azvudine group (median: 8 vs. 10 days, P ≤ 0.05). No significant differences were observed in time to RNA negativity (4.23 vs. 4.52 days, P &gt;0.05), fever duration (2 vs. 2 days, P &gt;0.05), or cough duration (4.5 vs. 5 days, P &gt;0.05). One case of mild gastrointestinal discomfort was reported in the azvudine group. Conclusion Azvudine significantly reduced hospitalization duration in mild-to-moderate COVID-19 patients with a favorable safety profile.

Benefit and risk associated with interleukin-6 receptor inhibitor administration during severe COVID-19: a retrospective multicentric study none

2025-06-17

Charlène Lefèvre , Thomas Funck‐Brentano , Marine Cachanado +7 more | Research Square (Research Square)

<title>Abstract</title> <bold>Purpose</bold> During severe and critical COVID-19, therapeutic options remain scarce. Among interventions, the use of interleukin-6 receptor inhibitor (IL-6Ri) is especially controversial due to persistent uncertainty about their efficacy … <title>Abstract</title> <bold>Purpose</bold> During severe and critical COVID-19, therapeutic options remain scarce. Among interventions, the use of interleukin-6 receptor inhibitor (IL-6Ri) is especially controversial due to persistent uncertainty about their efficacy and safety. <bold>Methods</bold> We conducted a multicentric retrospective French observational study. All severe or critical COVID-19 requiring hospital admission were included from march 1st 2020 to December 31th 2021. Our main aim was to compare the occurrence of secondary infections function of the administration of IL-6Ri. Digestive, hematological complications and survival were also analyzed. <bold>Results</bold> Among 2587 patients requiring hospital admission, 1603 had a severe COVID-19 and 984 a critical one requiring ICU admission. 224 received at least one dose of tocilizumab or sarilumab. Incidence of secondary infection was 29.5% in the IL-6Ri group <italic>vs.</italic> 19.5% without IL-6Ri (unadjusted OR: 1.73 [1.27;2.34]; p = 0.0004) in the whole population. This result remained consistent after adjustment, without multiple imputation (MI) (adjusted OR: 2.12 [1.51; 2.97]; p < 0.0001) and after MI (adjusted OR: 1.47 [1.25; 1.72]; p < 0.0001)). Incidence of hematological or digestive complication were similar between groups. Mortality of patients admitted in ward was higher in the IL-6Ri group (18.7% <italic>vs</italic> 10.5%, p = 0.0155). No difference in 28 days, ICU, hospital of 90 days mortality was noticed among ICU patients. <bold>Conclusion</bold> in this population, administration of IL-6Ri was associated with a higher risk of secondary infection in the whole population and with a higher mortality among patients who spent their whole stay in ward. <bold>Registration</bold> NCT05017441 (January 31st 2024)

Collaboration and Decision-Support Tools to Mitigate Nirmatrelvir/Ritonavir Drug Interactions

2025-06-17

Marsha L. Pike , Erica Fischer‐Cartlidge , S Hirn +5 more | Clinical Nurse Specialist

Purpose/Objectives Nirmatrelvir/ritonavir (Paxlovid) is used to treat mild to moderate COVID-19 for patients at high risk for disease progression. However, its use presents challenges due to drug-to-drug interactions that affect … Purpose/Objectives Nirmatrelvir/ritonavir (Paxlovid) is used to treat mild to moderate COVID-19 for patients at high risk for disease progression. However, its use presents challenges due to drug-to-drug interactions that affect its effectiveness and the safety of coadministered medications. In response, a nurse-initiated protocol and interprofessional prescribing guidance were developed at a large nonprofit academic medical center to expedite proactive treatment for at-risk, ambulatory patients with COVID-19. The guidance was based on a standardized risk score. Description of the Project Decision-support tools were developed collaboratively with the pharmacy team and built into the electronic health record to provide just-in-time directives for prescribers. Patients who would otherwise have been excluded were prescribed nirmatrelvir/ritonavir using evidence-based, drug-to-drug interaction management strategies coupled with patient education and supported by the team infrastructure. Outcome Between November 1, 2020, and February 1, 2023, 3802 patients at high risk for disease progression who had a documented drug-to-drug interaction with nirmatrelvir/ritonavir were evaluated for treatment. Of these patients, 2351 (61.8%) were treated. Conclusion Our management strategies efficiently and safely provided treatment to more than 60% of patients at high risk of disease progression who would otherwise have been excluded from receiving this medication option due to drug-to-drug interactions with nirmatrelvir/ritonavir.

Letter to the editor: “Heart failure and co-morbidities confer a negative prognosis in COVID-19 infection”

2025-06-17

Rachana Mehta , Ranjana Sah | International Journal of Cardiology

SARS-CoV-2 in Asthmatic Children: Same Consequences in Different Endotypes?

2025-06-16

Alice Bosco , Vassilios Fanos , Serena Bosone +3 more | Metabolites

During the early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, concerns arose regarding the susceptibility of asthmatic children, one of the most common chronic conditions in … During the early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, concerns arose regarding the susceptibility of asthmatic children, one of the most common chronic conditions in childhood and a major cause of hospitalization in pediatric settings. Unexpectedly, evidences showed milder clinical courses and fewer asthma exacerbations in these patients, even if cases of critical and fatal infection, often related to specific clinical features of the patient, are not negligible. In this regard, obesity is considered not only an important comorbidity in patients with difficult-to-treat asthma but also a risk factor for more severe forms of COVID-19. These observations are of even greater concern in the context of an increase in childhood obesity that began even before the SARS-CoV-2 pandemic and has continued also as a consequence of it. Given asthma's heterogeneity, especially in children, an endotype-based approach is crucial. This is possible through a detailed analysis of the complex metabolic pathways that correlate asthma, COVID-19 infection and obesity thanks to new high-through-put technologies, especially metabolomics, which with minimally invasive sampling, including on exhaled breath condensate (EBC), can provide precise and unbiased evidence in support of existing endotypes, making it possible to identify not only the most vulnerable individuals and thus risk stratification through specific biomarkers, but also new molecular and therapeutic targets. This review explores asthma endotypes by highlighting their shared immunometabolic pathways with COVID-19. Findings suggest that metabolomics could enable more accurate risk stratification and guide personalized interventions during viral pandemics, especially in the presence of relevant comorbidities such as obesity.

Comparative analysis of candidal carriage rates in long-term and short-term COVID-19 patients: An RT-PCR study

2025-06-16

Ramya Sekar , Kavitha Bottu , Protyusha GB +2 more | Journal of Oral Biology and Craniofacial Research

The Association between COVID-19 Infection and both rs34224237IL-6 and rs1800871 IL-10 Gene Polymorphisms

2025-06-16

Aso Faeq Salih | University of Thi-Qar Journal of Science

Investigate the polymorphism of the IL-6 and IL-10 genes in COVID-19 patients was the goal of this study. Fifty COVID-19 patients and 50 samples as control used in this study … Investigate the polymorphism of the IL-6 and IL-10 genes in COVID-19 patients was the goal of this study. Fifty COVID-19 patients and 50 samples as control used in this study on 7/12/2023. The results recorded that a significantly relation (P= 0.03) of rs34224237 (AAAAAAAAA SNP) was detected in the studied samples (COVID-19) and control, that variation of A nucleotide in position 22726806. While, the results of this study showed a high significantly relationship (P= 0.0007) of rs1800871 (A>G) in position 206773289. In conclusion, This study showed the polymorphism of IL-10 (rs1800871, A>G SNP) was a highly significantly associated with COVID-19 infection, which could be employed as a diagnostic marker for COVID-19 infections.

COVID-19 yoğun bakımda takip edilen ARDS hastalarında iki farklı deksametazon dozunun hiperinflamasyon üzerine etkinliğinin retrospektif olarak değerlendirilmesi

2025-06-16

Merve Yaman , Murat Emre Tokur , Canan Balcı | Türk yoğun bakım derneği dergisi/Türk yoğun bakım dergisi

Giriş ve Amaç: Yoğun bakımda COVID-19 ile takip edilen ARDS hastalarında kullanılan iki farklı deksametazon tedavi protokolünün klinik ve laboratuvar sonuçlarını retrospektif olarak karşılaştırmak. Yöntem ve Gereçler: Pandemi Yoğun Bakım … Giriş ve Amaç: Yoğun bakımda COVID-19 ile takip edilen ARDS hastalarında kullanılan iki farklı deksametazon tedavi protokolünün klinik ve laboratuvar sonuçlarını retrospektif olarak karşılaştırmak. Yöntem ve Gereçler: Pandemi Yoğun Bakım Üniteleri’nde deksametazon tedavisi başlanmış hastalar iki gruba ayrıldı. Grup 1: 6 mg/gün deksametazon tedavisi alanlar (n=41), Grup 2: 0-5 gün 20 mg/gün ve 6-10 gün 10 mg/gün deksametazon tedavisi alanlar (n=39). 0. günden 10. güne gruplar arası klinik sonuçlar ve laboratuvar değerlerin değişimleri karşılaştırıldı. Bulgular: 20 mg deksametazon verilen hastalarda 0. gün APACHE II skorları anlamlı düzeyde yüksek tespit edildi (p: 0,039). Hastaların yoğun bakımdaki on günlük deksametazon tedavisi sonrasında 0. ve 10. gün parametre değişimleri incelendiğinde; 20 mg grubunda prokalsitonin ve D-Dimer değerlerinin istatistiksel olarak anlamlı bir artış gösterdiği belirlendi (sırasıyla p: 0.038 ve p: 0.025). Son olarak deksametazon tedavisinin mortalite üzerindeki etkisi incelendi ve gruplar arasında fark saptanmadı. Tartışma ve Sonuç: COVID-19 yoğun bakım ünitelerindeki ARDS hastalarında, deksametazon tedavisiyle ilgili literatürde mortalite karşılaştırmaları yapılmıştır. Bizlerse çalışmamızda farklı olarak mortaliteyle birlikte laboratuvar parametreleri açısından karşılaştırma yaptık. Sonuç olarak; deksametazon tedavisinin klinik ve laboratuvar parametreleri iyileştirdiği fakat fayda/zarar oranı ve yan etkileri açısından bakıldığında; viral solunum yolu enfeksiyonlarında oksijen tedavisi ihtiyacı olan olgularda 6 mg dozunun, hiperinflamasyonun ön planda olduğu şiddetli olgularda ise 20 mg dozunun güvenle kullanılabileceğini düşünmekteyiz.

Riesgo de eventos cardiovasculares tras COVID-19 e infecciones respiratorias: un estudio de base poblacional

2025-06-15

| Revista Médica del Uruguay

Diferencias en las características clínicas y el manejo de los pacientes diagnosticados de COVID-19 en Atención Primaria en 2020 en función de la edad

2025-06-15

Ana Martínez González , Sergio Calleja Argudo , Miguel Ángel Nieves Sanchís +2 more | Revista Clínica de Medicina de Familia

Objetivos: conocer las manifestaciones clínicas y el manejo de la COVID-19 en la población infantil y juvenil frente a la población adulta que fueron diagnosticados en Atención Primaria (AP) en … Objetivos: conocer las manifestaciones clínicas y el manejo de la COVID-19 en la población infantil y juvenil frente a la población adulta que fueron diagnosticados en Atención Primaria (AP) en 2020. Métodos: serie de casos: 853 pacientes diagnosticados de COVID-19 en 2020, bien por criterios clínicos o con apoyo de exploraciones complementarias, y seguidos por pediatras y médicas/médicos de familia, seleccionados por muestreo sistemático a partir del listado de pacientes con dicho diagnóstico. Mediciones principales. Variable dependiente: ingreso en hospital o fallecimiento por COVID-19. Variables independientes: edad, sexo, entorno sociofamiliar, datos clínicos y número de consultas. El análisis estadístico fue realizado con SPSS 25.0: estadística descriptiva, comparación de proporciones (X2) y medianas (U de Mann-Whitney). Resultados: el rango de edad fue 0-92 años, con mediana de 45 y rango intercuartílico (RI): 27-58; el 13,1% eran menores de 18 años; el 52,8% eran mujeres. Solo la rinorrea era significativamente (p = 0,007) más frecuente en < 18 años (37,3% versus 23,3%). No existían diferencias estadísticamente significativas en cuanto a la presentación de fiebre, alteración de conciencia, hemoptisis, vómitos y diarrea. El resto de síntomas eran significativamente más habituales en pacientes ≥ 18 años. La mediana de consultas era 3, con una significativa (p < 0,0001) mayor dispersión para ≥ 18 años (RI: 2-6 versus 2-4). Los ≥ 18 años precisaron ingreso hospitalario con significativa (p = 0,05) mayor frecuencia (14,3% versus 4,1%) en menores. Ninguno de estos ingresó en una unidad de cuidados intensivos (UCI). Conclusiones: la gran mayoría de pacientes presentó un cuadro clínico leve. Las complicaciones que precisaron asistencia hospitalaria, en comparación con pacientes en edad infantil (< 18 años), fueron más frecuentes en los de más edad. Palabras clave: COVID-19, signos y síntomas, Atención Primaria de Salud, edad.

Changes in Physiological Blood Constants in Comorbid Patients after COVID-19

2025-06-15

A. Tursunbaeva , T. Zhumabaeva | Bulletin of Science and Practice

Clinical and laboratory parameters of hospital outpatient cards of patients with concomitant chronic diseases (comorbid patients) in 4 age groups from 30‒41, 41‒50, 51‒60, 61 and above years discharged from … Clinical and laboratory parameters of hospital outpatient cards of patients with concomitant chronic diseases (comorbid patients) in 4 age groups from 30‒41, 41‒50, 51‒60, 61 and above years discharged from the city infectious diseases hospital in Osh were assessed and analyzed. In the examined comorbid patients, the physiological constants of the blood changed depending on the age and concomitant diseases of the patient before infection with SOVID-19. The aim of the study was to investigate the impact of various combinations of comorbidities in patients before SARS-CoV-2 infection on the severity and outcomes of the new coronavirus infection. The object of the study was the biochemical blood parameters of 86 hospital outpatient cards of patients with concomitant chronic diseases (comorbid patients) aged 30‒61 years discharged from the city infectious diseases hospital in Oshduring the SARS-CoV-2 viral infection of 2021 from the districts of Osh region, Batken region and Osh city of the Kyrgyz Republic. The results showed that the severity of the infection in patients depended on their chronic diseases: hypertension (HTN), diabetes mellitus (DM), obesity (OJ), chronic exacerbation of pulmonary disease (CEPD), rheumatoid arthritis (RA), coronary heart disease (CHD), cardiovascular failure (CVF), iron deficiency anemia (IDA). The effect of various combinations of comorbidities in patients before SARS-CoV-2 infection on the severity and outcomes of the new coronavirus infection was studied. The paper analyzes the impact of various combinations of concomitant diseases in patients before SARS-CoV-2 infection on the severity and outcomes of the new coronavirus infection. Clinical and laboratory indicators demonstrate the dynamics of decreased saturation in comorbid patients in the age category of 50 and above. It was shown that in the incubation period, from day 1 to day 14, and in the early phase of the disease (COVID-19), the number of leukocytes and lymphocytes in the peripheral blood was normal or slightly reduced. Platelet measurements showed that many patients had indicators within the normal range (from 57‒67%), only in age groups 1 and 4, thrombocytopenia was observed from 20‒22%, in groups 1, 3, 4, thrombocytosis from 29‒33%.

Cycle Threshold Value as A Death Predictor of COVID-19 Patients

2025-06-15

Desi Oktariana , Mgs. Irsan Saleh , Syahri Banun +7 more | INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY

For several years, COVID-19 has been a major problem in human health and also caused a global socio-economic crisis. However, the impact of viral load on patient mortality has not … For several years, COVID-19 has been a major problem in human health and also caused a global socio-economic crisis. However, the impact of viral load on patient mortality has not been thoroughly investigated. This study analyzes the association between CT value and the mortality of COVID-19 patients in inpatients at Mohammad Hoesin Hospital. This study used observational analysis with a longitudinal retrospective design. This study had 280 subjects. Fifty-four of the 280 patients died (19.3%) 33% had a CT <22.93; 16.7% had a CT 22.93-29.93; 31.5% had a CT 29.94-34.9, 18.5% had a CT >35 with p-value >0.05 for patient mortality. Analysis of age, comorbidities, and clinical severity of patient mortality showed a p-value <0.05. Meanwhile, gender analysis of patient mortality showed a p-value >0.05. These results indicate that the CT value cannot predict patient mortality. Patients with older age, comorbidities, and admission with severe clinical severity have a higher risk of death.

The Intersection of SARS-CoV-2 and Diabetes

2025-06-14

Jake Nichols , Amber M. Smith , Colleen B. Jonsson | Microorganisms

The interplay between comorbidities and viral infections is a critical factor that influences disease severity and outcomes. Diabetes Mellitus (DM) is one such comorbidity that significantly elevates the risk of … The interplay between comorbidities and viral infections is a critical factor that influences disease severity and outcomes. Diabetes Mellitus (DM) is one such comorbidity that significantly elevates the risk of severe viral infection from coronaviruses, namely, SARS-CoV-2. DM is characterized by either a lack of insulin production (type 1 diabetes) or insulin resistance (type 2 diabetes), both of which contribute to a state of hyperglycemia, or high blood sugar. Hyperglycemia significantly promotes chronic inflammation, metabolic dysfunction, and immune dysregulation, which put diabetics at an elevated risk of critical health outcomes. Additionally, diabetes is hypothesized to amplify viral titers during infection by promoting the expression of the viral entry receptor ACE2 and providing a favorable cellular energy environment for viral replication. This review focuses on explaining the mechanisms that link diabetics with more severe COVID-19 disease and exploring some of the mechanisms that contribute to the phenomenon where COVID-19 can promote new-onset diabetes. By highlighting the interconnections between diabetes and COVID-19, this review aims to emphasize the implications that the SARS-CoV-2 outbreak has had on metabolic health.

2052-LB: Holding the Line—Hemoglobin A1c and Rates of Laboratory Testing Did Not Change during the Pandemic at a Student-Run Free Clinic

2025-06-13

Qi Yu , Ed Chao , N. Rodríguez +1 more | Diabetes

Introduction and Objective: While free clinics crucially aid underserved individuals, few studies have focused on diabetes care in these settings during the COVID-19 pandemic. The accelerated adoption of telehealth introduced … Introduction and Objective: While free clinics crucially aid underserved individuals, few studies have focused on diabetes care in these settings during the COVID-19 pandemic. The accelerated adoption of telehealth introduced new benefits and challenges. We examined whether clinical outcomes — including hemoglobin A1c (HbA1c) — and the rate of undergoing laboratory testing differed before and during the pandemic, in University of California, San Diego Student-Run Free Clinic Project (UCSD SRFCP) patients living with diabetes. Methods: We reviewed electronic medical records for 207 UCSD SRFCP patients living with diabetes during the two years before (3/2018-3/2020), and 196 patients in the initial two years of (3/2020-3/2022) the COVID-19 pandemic. Clinical outcome measures included laboratory values, such as HbA1c, and blood pressure. Process performance was defined as the percentage of patients who obtained these measures. The Independent Samples t-test and Fisher’s Exact test compared both measures for each time frame. Results: There was no statistically significant change for most of the measures, including: HbA1c (8.4% for both periods, P=0.84), and LDL (92 mg/dL vs. 91 mg/dL, P=0.83). In the pandemic group, triglycerides decreased (249 mg/dL vs. 190 mg/dL, P=0.0066), and HDL for females increased (46 mg/dL vs. 50 mg/dL, P=0.0302). The percentage of patients obtaining HbA1c was similar (100% vs. 98%). Those receiving blood pressure measurements declined from 99% to 80%. Conclusion: In contrast to other studies, we found no difference in most outcomes, such as HbA1c, and the rate that patients obtained laboratory studies before and during the first two years of the COVID-19 pandemic. Two laboratory parameters improved. Further investigations could contribute to efforts to better support underserved patients living with diabetes. Disclosure J. Yu: None. E.C. Chao: Stock/Shareholder; Doximity, Viatris Inc., Pfizer Inc. N. Rodriguez: None. M. Johnson: None.

Longitudinal effects of Johnson & Johnson COVID-19 vaccination on metabolic biomarkers in type 2 diabetes mellitus in Ethiopia

2025-06-13

Chala Kenenisa Edae , Abdisa Tufa Bedada , Maria Degef Teklemariam +2 more | World Journal of Diabetes

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has disproportionately impacted individuals with type 2 diabetes mellitus (T2DM), increasing their risk of severe illness and mortality. Vaccination has been a crucial … BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has disproportionately impacted individuals with type 2 diabetes mellitus (T2DM), increasing their risk of severe illness and mortality. Vaccination has been a crucial intervention in mitigating these risks. However, the metabolic effects of COVID-19 vaccination, particularly the Johnson & Johnson (J&J) vaccine, in diabetic populations remain inadequately explored. This study investigated the longitudinal effects of the J&J vaccine on lipid and eicosanoid biomarkers to assess its metabolic safety and potential cardiovascular benefits. AIM To evaluate the long-term impact of the J&J COVID-19 vaccine on lipid and eicosanoid biomarkers in Ethiopian patients with T2DM. METHODS This prospective cohort study was conducted at Adama Hospital Medical College (Oromia, Ethiopia) from May 2023 to June 2024. A total of 224 T2DM patients (57 vaccinated, 167 unvaccinated) were monitored for 1 year. Biomarkers including triglycerides (TGs), high-density lipoprotein (HDL), total cholesterol (TC), prostaglandins (PGs), and thromboxanes (TXs) were measured at baseline and at 3 months, 6 months, 9 months, and 1 year post-vaccination. Statistical analyses included Generalized Estimating Equations to assess longitudinal biomarker changes. RESULTS TG and PG levels remained stable across all time points. HDL levels showed a temporary decline at 3 months (mean difference [MD] = -4.33; P < 0.001) and 6 months (MD = -2.62; P < 0.001) but recovered by 9 months (MD = 2.09; P = 0.001) and 1 year (MD = 2.38; P < 0.001). TC exhibited a significant decrease at 3 months (MD = -16.44, P = 0.001) before stabilizing. TX levels showed a consistent decline across all follow-ups (e.g., 1 year: MD = -0.08; P = 0.036), suggesting a reduced thrombotic risk. Correlation analysis indicated significant interrelations among biomarkers, emphasizing their roles in metabolic and inflammatory pathways. CONCLUSION The J&J COVID-19 vaccine exhibited metabolic safety in patients with T2DM, with transient HDL and TC reductions that later stabilized and a sustained TX decline, suggesting potential cardiovascular benefits. Further studies are needed to explore long-term immunometabolic effects on high-risk populations.

CORRELATION BETWEEN C-REACTIVE PROTEIN (CRP) LEVELS AND CHEST CT SEVERITY SCORES IN COVID-19 PATIENTS: A RETROSPECTIVE STUDY

2025-06-13

R Bharathi , Vidhya Prasanth , Saravanan Vaithiyalingam | Journal of Population Therapeutics and Clinical Pharmacology