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

/pdf/clinical-characteristics-and-day-90-outcomes-of-4244-6bpmow2brz.pdf

Clinical characteristics and day-90 outcomes of 4244 ctritically ill adults with COVID-19: a prospective cohort study

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency that continues to strain healthcare systems. Emerging research describes a plethora of patient factors-including demographic, clinical, immunologic, hematological, biochemical, and radiographic findings-that may be of utility to clinicians to predict COVID-19 severity and mortality. We present a synthesis of the current literature pertaining to factors predictive of COVID-19 clinical course and outcomes. Findings associated with increased disease severity and/or mortality include age > 55 years, multiple pre-existing comorbidities, hypoxia, specific computed tomography findings indicative of extensive lung involvement, diverse laboratory test abnormalities, and biomarkers of end-organ dysfunction. Hypothesis-driven research is critical to identify the key evidence-based prognostic factors that will inform the design of intervention studies to improve the outcomes of patients with COVID-19 and to appropriately allocate scarce resources.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/rmv.2146

Predictors of COVID-19 severity: A literature review.

Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA and a sustained interferon (IFN) response, all of which are recapitulated and required for pathology in the SARS-CoV-2-infected MISTRG6-hACE2 humanized mouse model of COVID-19, which has a human immune system1-20. Blocking either viral replication with remdesivir21-23 or the downstream IFN-stimulated cascade with anti-IFNAR2 antibodies in vivo in the chronic stages of disease attenuates the overactive immune inflammatory response, especially inflammatory macrophages. Here we show that SARS-CoV-2 infection and replication in lung-resident human macrophages is a critical driver of disease. In response to infection mediated by CD16 and ACE2 receptors, human macrophages activate inflammasomes, release interleukin 1 (IL-1) and IL-18, and undergo pyroptosis, thereby contributing to the hyperinflammatory state of the lungs. Inflammasome activation and the accompanying inflammatory response are necessary for lung inflammation, as inhibition of the NLRP3 inflammasome pathway reverses chronic lung pathology. Notably, this blockade of inflammasome activation leads to the release of infectious virus by the infected macrophages. Thus, inflammasomes oppose host infection by SARS-CoV-2 through the production of inflammatory cytokines and suicide by pyroptosis to prevent a productive viral cycle. 

https://www.nature.com/articles/s41586-022-04802-1.pdf

Inflammasome activation in infected macrophages drives COVID-19 pathology

Lymphopenia during the COVID-19 infection: What it shows and what can be learned.

Objectives: An outbreak of coronavirus disease (COVID-19) in 2019 in Wuhan, China, has spread quickly worldwide. However, the risk factors associated with COVID-19-related mortality remain controversial. Methods: A total of 245 adult patients with laboratory-confirmed COVID-19 from two centers were analyzed. Chi-square, Fisher's exact, and the Mann-Whitney U-tests were used to compare the clinical characteristics between the survivors and non-survivors. To explore the risk factors associated with in-hospital death, univariable and multivariable cox regression analyses were used. Results: Of the 245 patients included in this study, 23 (9.4%) died in the hospital. The multivariate regression analysis showed increased odds of in-hospital deaths associated with age, D-dimer levels >1,000 ng/L, platelet count <125, and higher serum creatinine levels. Conclusions: We identified risk factors that show significant association with mortality in adult COVID-19 patients, and our findings provide valuable references for clinicians to identify high-risk patients with COVID-19 at an early stage.

/pdf/analysis-of-the-risk-factors-for-mortality-in-adult-covid-19-47fdolw4as.pdf

Analysis of the Risk Factors for Mortality in Adult COVID-19 Patients in Wuhan: A Multicenter Study

Background: A novel type of coronavirus (SARS-CoV-2) with unclear origin first appeared in Wuhan in December, 2019, showing human-to-human transmission Adoptin

Confusion and Thinking on the Diagnosis and Treatment of Patients with Negative RT-PCR Results for SARS-CoV-2

Lymphocyte subset (CD4+, CD8+) counts reflect the severity of infection and predict the clinical outcomes in patients with COVID-19.

Background: Coronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients. Methods: Patient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality. Results: Logistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19. Conclusion: Elevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19.

Prognostic Potential of Liver Enzymes in Patients With COVID-19 at the Leishenshan Hospital in Wuhan

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Analysis of the Risk Factors for Mortality in Adult COVID-19 Patients in Wuhan: A Multicenter Study

Confusion and Thinking on the Diagnosis and Treatment of Patients with Negative RT-PCR Results for SARS-CoV-2

Lymphocyte subset (CD4+, CD8+) counts reflect the severity of infection and predict the clinical outcomes in patients with COVID-19.

Prognostic Potential of Liver Enzymes in Patients With COVID-19 at the Leishenshan Hospital in Wuhan