Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The 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. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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

Background The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide However, little is known about the causes of death and the virus's pathologic features Objective To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests Design Prospective cohort study Setting Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19 Patients The first 12 consecutive COVID-19-positive deaths Measurements Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed Clinical data and medical course were evaluated Results Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2) Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively) Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart Limitation Limited sample size Conclusion The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it Primary funding source University Medical Center Hamburg-Eppendorf

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study.

Immunology of COVID-19: Current State of the Science.

Little is known of the pathologic changes that lead to death in patients with COVID-19. This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19.

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19.

BACKGROUND: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. RESULTS: We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. CONCLUSIONS: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2028836

Efficacy of Tocilizumab in Patients Hospitalized with Covid-19.

With the dramatic increase of confirmed cases of coronavirus disease (COVID-19) and the increasing death toll in China, timely and effective management of severely and critically ill patients appears to be particularly important. Previous studies on COVID-19 mainly described the general features of patients (1). However, little attention has been paid to clinical characteristics and outcomes of intensive care patients, data on whom are scarce but are of paramount importance to reduce mortality. Some of the results of these studies have been previously reported in the form of an abstract (2).

Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19.

Addition of adjuvant corticosteroid therapy to standard antiviral treatment of patients with coronavirus disease (COVID-19) is common in clinical practice. However, evidence is scarce regarding the efficacy of adjuvant corticosteroids in patients who are critically ill. We retrospectively evaluated the effects of adjuvant corticosteroid treatment on the outcome of 244 critically ill patients with COVID-19, using a risk stratification model that adjusts for potential differences between the steroid group (n=151) and the non-steroid group (n=93). We observed that adjuvant corticosteroid therapy was independent from 28-day mortality, either in multivariate logistic regression of the entire cohort after adjustment for major mortality-associated variables (age, SpO2/FiO2, and lymphocyte count) and individual propensity score (adjusted OR: 1.05; 95% CI: −1.92-2.01), or in propensity score-matched (1:1 without replacement) case-control analysis (62 patients in 31 pairs; log-rank test P=0.17). Additionally, subgroup analyses of 147 (60%) patients who had dyspnea and 87 (36%) patients who had ARDS revealed corticosteroid treatment was not associated with clinical outcome (both, P>0.3). However, increased corticosteroids dosage was significantly associated with elevated mortality risk after adjustment for administration duration (P=0.003); every ten-milligram increase in hydrocortisone-equivalent dosage was associated with additional 4% mortality risk (adjusted HR: 1.04, 95% CI: 1.01-1.07). Our findings indicated that limited effect of corticosteroid therapy could pose to overall survival and prudent dose within effective limits may be recommended for critically ill patients under certain circumstances.

/pdf/adjuvant-corticosteroid-therapy-for-critically-ill-patients-141o3i62y0.pdf

Adjuvant corticosteroid therapy for critically ill patients with COVID-19

Chen H. et al. Simplified Immune-dysregulation Index: A novel marker predicts 28-day mortality of intensive care patients with COVID-19. Intensive Care Medicine (2020); DOI: 10.1007/s00134-020-06114-2 Simplified Immune-dysregulation Index: A novel marker predicts 28-day mortality of intensive care patients with COVID-19 Hui Chen1, Jun Wang1, Nan Su1, Xiebing Bao2, Yongsheng Li3#, Jun Jin1# 1Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215000, Jiangsu, China 2National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University,Suzhou, China 3Department of Intensive Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, Hubei, China

/pdf/simplified-immune-dysregulation-index-a-novel-marker-48wa2ixhf5.pdf

Simplified immune-dysregulation index: a novel marker predicts 28-day mortality of intensive care patients with COVID-19.

Acute respiratory distress syndrome (ARDS) is an acute and diffuse inflammatory lung injury in a short time, one of the common severe manifestations of the respiratory system that endangers human life and health. As an innate immune cell, macrophages play a key role in the inflammatory response. For a long time, the role of pulmonary macrophages in ARDS has tended to revolve around the polarization of M1/M2. However, with the development of single-cell RNA sequencing, fate mapping, metabolomics, and other new technologies, a deeper understanding of the development process, classification, and function of macrophages in the lung are acquired. Here, we discuss the function of pulmonary macrophages in ARDS from the two dimensions of anatomical location and cell origin and describe the effects of cell metabolism and intercellular interaction on the function of macrophages. Besides, we explore the treatments for targeting macrophages, such as enhancing macrophage phagocytosis, regulating macrophage recruitment, and macrophage death. Considering the differences in responsiveness of different research groups to these treatments and the tremendous dynamic changes in the gene expression of monocyte/macrophage, we discussed the possibility of characterizing the gene expression of monocyte/macrophage as the biomarkers. We hope that this review will provide new insight into pulmonary macrophage function and therapeutic targets of ARDS. 

/pdf/the-role-of-lung-macrophages-in-acute-respiratory-distress-23sn64ay.pdf

The role of lung macrophages in acute respiratory distress syndrome

Background Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the causative agent of coronavirus disease 2019 (COVID-19). Lung lesions are considered to be the main damage caused by SARSCoV-2 infection. In addition, liver injury has also been reported to occur during the course of the disease in severe cases. However, the effect of antiviral treatment on liver injury in critically ill patients is not yet clear. Methods We retrospectively evaluated the effect of antiviral treatment and antiviral drug arbidol on liver injury in COVID-19 critically ill patients. Baseline characteristics were collected from patients who were admitted to intensive care units of Tongji Hospital in Wuhan, China, and confounders were balanced by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses. Results Both the PSM (OR=2.77; 95% CI: 1.03, 7.48; P=0.045) and the IPTW-adjusted (OR=2.33; 95% CI: 1.02, 5.34; P=0.047) results showed that COVID-19 critically ill patients receiving antiviral treatment had a significantly higher risk of liver injury. However, arbidol treatment did not have a significant effect on liver injury (IPTW: OR=2.11; 95% CI: 0.79, 5.67; P=0.14). Conclusions Our results show that although arbidol treatment does not seem to be significantly associated with liver injury complications, the overall use of antiviral drugs increases the risk of liver injury for critically ill patients with COVID-19. Antiviral drugs are widely used to treat COVID-19, but we recommend that for critically ill patients, antiviral treatment should be used with caution considering both effectiveness and potential adverse effects.

/pdf/liver-injury-after-antiviral-treatment-of-critically-ill-555cvur5e9.pdf

Yongsheng Li

Papers

Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19.

Adjuvant corticosteroid therapy for critically ill patients with COVID-19

Simplified immune-dysregulation index: a novel marker predicts 28-day mortality of intensive care patients with COVID-19.

The role of lung macrophages in acute respiratory distress syndrome

Liver injury after antiviral treatment of critically ill patients with COVID-19: a single-centered retrospective cohort study.