ABSTRACT
Background: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has gradually become a global public health crisis. Some patients who have recovered from COVID-19 subsequently tested positive again for SARS-CoV-2 after discharge (retesting-positive, RTP). However, the underlying mechanism is unknown.Methods: Here, 30 RTP patients, 20 convalescent patients, and 20 healthy controls were enrolled for analysis of the immunological characteristics of their peripheral blood mononuclear cells (PBMCs). Furthermore, we sought to comprehensively characterize the transcriptional changes in the three groups by transcriptome sequencing.Findings: It was found that the absolute numbers of CD4+ T cells, CD8+ T cells, and NK cells were not decreased remarkably, while the expression of activation markers on these cells was significantly decreased in RTP patients. Furthermore, the percentage of granzyme B-producing T cells was also decreased in RTP patients compared with that in convalescent patients. Moreover, the high expression of inhibitor of differentiation-1 (ID1) and the low expression of IFITM10 may be associated with the insufficient activation of immune cells and RTP occurrence.Interpretation: Our findings provide insights into the impaired immune function and pathogenesis of RTP occurrence in COVID-19, which may contribute to the development of immunotherapy for RTP patients.Funding Statement: This work was supported by China National Center for Biotechnology Development (2020YFC0843800 and 2020YFC0846800), Ministry of Science and Technology of China (2020TFC0844100), and China Postdoctoral Science Foundation (2020T130112ZX).Declaration of Interests: The authors declare no potential conflict of interest.Ethics Approval Statement: The studies were approved by the Ethics Committee of the First Affiliated Hospital of the University of Science & Technology of China (2020-XG(H)-005) and Peking University First Hospital (2020-Research-112) for Emerging Infectious Diseases. Experiments were conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki, the Principles of Good Clinical Practice, and the guidelines of China’s regulatory requirements.
Subject(s)
Coronavirus Infections , Communicable Diseases, Emerging , COVID-19ABSTRACT
BACKGROUND The worldwide COVID-19 pandemic develops rapidly. There is a pressing need to find an effective therapy. METHODS We have assembled a cohort consisting 504 hospitalized COVID-19. Information of patients characteristics and antiviral medication use during hospital stay is collected. The study objective is to evaluate the treatment efficacy of selected antiviral medications on mortality and lesion absorption based on chest CT scan. RESULTS The overall mortality rate was 15.67% in the cohort. Older age, lower SpO2 level, bigger lesion, early admission data, and the presence of pre-existing conditions were associated with higher mortality. After adjusting for sex, pre-existing condition, age, SpO2, lesion size, admission data, hospital, and anti-viral medications use, Arbidol and Oseltamivir use is associated with a reduction in mortality. The OR is 0.183 (95% CI, 0.075 to 0.446; p<0.001) for Arbidol and 0.220 (95% CI, 0.069 to 0.707; p=0.011) for Oseltamivir. Compared with patients taking neither Arbidol nor Oseltamivir, the OR is 0.253 (95% CI, 0.064 to 1.001; p=0.050) for patients taking Oseltamivir only; 0.190 (95% CI, 0.076 to 0.473; p<0.001) for patients taking Arbidol only; and 0.030 (95% CI, 0.003 to 0.310; p=0.003) for patients taking both, after adjusting for patients characteristics and Lopinavir/Ritonavir use. Similarly, Arbidol is also associated with faster lesion absorption after adjusting for patients characteristics as well as Oseltamivir and Lopinavir/Ritonavir use. CONCLUSIONS Arbidol is able to substantially associated with a reduction in mortality among hospitalized COVID-19 patients. The combination of Arbidol and Oselmativir may further associated with a reduction in mortality. There is no proven treatment benefit of Lopinavir/Ritonavir.
Subject(s)
COVID-19ABSTRACT
Background Wuhan, China was the epicenter of the 2019 coronavirus outbreak. As a designated hospital, Wuhan Pulmonary Hospital has received over 700 COVID-19 patients. With the COVID-19 becoming a pandemic all over the world, we aim to share our epidemiological and clinical findings with the global community. Methods In this retrospective cohort study, we studied 340 confirmed COVID-19 patients from Wuhan Pulmonary Hospital, including 310 discharged cases and 30 death cases. We analyzed their demographic, epidemiological, clinical and laboratory data and implemented our findings into an interactive, free access web application. Findings Baseline T lymphocyte Subsets differed significantly between the discharged cases and the death cases in two-sample t-tests: Total T cells (p < 2.2e-16), Helper T cells (p < 2.2e-16), Suppressor T cells (p = 1.8-14), and TH/TS (Helper/Suppressor ratio, p = 0.0066). Multivariate logistic regression model with death or discharge as the outcome resulted in the following significant predictors: age (OR 1.05, p 0.04), underlying disease status (OR 3.42, p 0.02), Helper T cells on the log scale (OR 0.22, p 0.00), and TH/TS on the log scale (OR 4.80, p 0.00). The McFadden pseudo R-squared for the logistic regression model is 0.35, suggesting the model has a fair predictive power. Interpretation While age and underlying diseases are known risk factors for poor prognosis, patients with a less damaged immune system at the time of hospitalization had higher chance of recovery. Close monitoring of the T lymphocyte subsets might provide valuable information of the patients condition change during the treatment process. Our web visualization application can be used as a supplementary tool for the evaluation.
Subject(s)
COVID-19 , DeathABSTRACT
Summary Background: To date, large amounts of epidemiological and case study data have been available for the Coronavirus Disease 2019 (COVID-19), which suggested that the mortality was related to not just respiratory complications. Here, we specifically analyzed kidney functions in COVID-19 patients and their relations to mortality. Methods: In this multi-centered, retrospective, observational study, we included 193 adult patients with laboratory-confirmed COVID-19 from 2 hospitals in Wuhan, 1 hospital in Huangshi (Hubei province, 83 km from Wuhan) and 1 hospital in Chongqing (754 km from Wuhan). Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected, including data regarding to kidney functions. Data were compared among three groups: non-severe COVID-19 patients (128), severe COVID-19 patients (65) and a control group of other pneumonia (28). For the data from computed tomographic (CT) scans, we also included a control group of healthy subjects (110 cases, without abnormalities in the lung and without kidney diseases). The primary outcome was a common presence of kidney dysfunctions in COVID-19 patients and the occurrence of acute kidney injury (AKI) in a fraction of COVID-19 patients. Secondary outcomes included a survival analysis of COVID-19 patients in conditions of AKI or comorbid chronic illnesses. Findings: We included 193 COVID-19 patients (128 non-severe, 65 severe (including 32 non-survivors), between January 6th and February 21th,2020; the final date of follow-up was March 4th, 2020) and 28 patients of other pneumonia (15 of viral pneumonia, 13 of mycoplasma pneumonia) before the COVID-19 outbreak. On hospital admission, a remarkable fraction of patients had signs of kidney dysfunctions, including 59% with proteinuria, 44% with hematuria, 14% with increased levels of blood urea nitrogen, and 10% with increased levels of serum creatinine, although mild but worse than that in cases with other pneumonia. While these kidney dysfunctions might not be readily diagnosed as AKI at admission, over the progress during hospitalization they could be gradually worsened and diagnosed as AKI. A univariate Cox regression analysis showed that proteinuria, hematuria, and elevated levels of blood urea nitrogen, serum creatinine, uric acid as well as D-dimer were significantly associated with the death of COVID-19 patients respectively. Importantly, the Cox regression analysis also suggested that COVID-19 patients that developed AKI had a ~5.3-times mortality risk of those without AKI, much higher than that of comorbid chronic illnesses (~1.5 times risk of those without comorbid chronic illnesses). Interpretation: To prevent fatality in such conditions, we suggested a high degree of caution in monitoring the kidney functions of severe COVID-19 patients regardless of the past disease history. In addition, upon day-by-day monitoring, clinicians should consider any potential interventions to protect kidney functions at the early stage of the disease and renal replacement therapies in severely ill patients, particularly for those with strong inflammatory reactions or a cytokine storm. Funding: None.