ABSTRACT
Background: Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. Methods: Rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified published and unpublished RCTs by September 14, 2020 (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, PubMed, Cochrane COVID-19 registry). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine/chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status. Results: Sixty-two trials were potentially eligible. We included 16 unpublished trials (1596 patients) and 10 publications/preprints (6317 patients). The combined summary OR on all-cause mortality for hydroxychloroquine was 1.08 (95%CI: 0.99, 1.18; I-square=0%; 24 trials; 7659 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-square=0%; 4 trials; 307 patients). We identified no subgroup effects. Conclusions: We found no benefit of hydroxychloroquine or chloroquine on the survival of COVID-19 patients. For hydroxychloroquine, the confidence interval is compatible with increased mortality (OR 1.18) or negligibly reduced mortality (OR 0.99). Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.
Subject(s)
COVID-19ABSTRACT
In order to elucidate novel aspects of the host response to SARS-CoV-2 we performed RNA sequencing on peripheral blood samples across 77 timepoints from 46 subjects with COVID-19 and compared them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a conserved transcriptomic response in peripheral blood that is heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, that persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95). The transcriptome in peripheral blood reveals unique aspects of the immune response in COVID-19 and provides for novel biomarker-based approaches to diagnosis.
Subject(s)
COVID-19 , Blood Coagulation Disorders, Inherited , Pneumonia, BacterialABSTRACT
Background: Understanding the epidemiology of SARS-CoV-2 is essential for public health control efforts. Social, demographic, and political characteristics at the US county level might be associated with the trajectories of SARS-CoV-2 case incidence. Objective: To understand how underlying social, demographic, and political characteristics at the US county level might be associated with the trajectories of SARS-CoV-2 case incidence. Design: Retrospective analysis of the trajectory of reported SARS-CoV-2 case counts at the US county level during June 1, 2020 - June 30,2020 and social, demographic, and political characteristics of the county. Setting: United States. Participants: Reported SARS-CoV-2 cases. Exposures: Metropolitan designation, Social Deprivation Index (SDI), 2016 Republican Presidential Candidate Victory. Main Outcomes and Measures: SARS-CoV-2 case incidence. Results: 1023/3142 US counties were included in the analysis. 678 (66.3%) had increasing SARS-CoV-2 case counts between June 1 - June 30, 2020. In univariate analysis, counties with increasing case counts had a significantly higher SDI (median 48, IQR 24 - 72) than counties with non-increasing case counts (median 40, IQR 19 - 66; p=0.009). In the multivariable model, metropolitan areas of 250,000 - 1 million population, higher percentage of Black residents and a 10-point or greater Republican victory were independently associated with increasing case counts. Limitations: The data examines county-level voting patterns and does not account for individual voting behavior, subjecting this work to the potential for ecologic fallacy. Conclusion: Increasing case counts of SARS-CoV-2 in the US are likely driven by a combination of social disadvantage, social networks, and behavioral factors. Addressing social disadvantage and differential belief systems that may correspond with political alignment will be essential for pandemic control.