ABSTRACT
COVID-19 outbreak has caused over 3 million deaths worldwide. Understanding disease pathology and the factors that drive severe and fatal clinical outcomes is of special relevance. Studying the role of the respiratory microbiota in COVID-19 is particularly important since it’s known that the respiratory microbiota interacts with the host immune system, contributing to clinical outcomes in chronic and acute respiratory diseases. Here, we characterized the microbiota in the respiratory tract of patients with mild, severe, or fatal COVID-19, and compared with healthy controls and patients with non-COVID-19-pneumonia. We comparatively studied the microbial composition, diversity, and microbiota structure across study groups and correlated the results with clinical data. We found differences in diversity and abundance of bacteria between groups, higher levels of dysbiosis in the respiratory microbiota of COVID-19 patients (regardless of severity level), differences in diversity structure among mild, severe, and fatal COVID-19, and the presence of specific bacteria that correlated with clinical variables associated with increased mortality risk. Our data suggest that host-related and environmental factors could be affecting the respiratory microbiota before SARS-CoV-2 infection, potentially compromising the immunological response of the host against disease and promoting secondary bacterial infections. For instance, the high levels of dysbiosis coupled with low microbial structural complexity in the respiratory microbiota of COVID-19 patients, possibly resulted from antibiotic uptake and comorbidities, could have consequences for the host and microbial community level. Altogether, our findings identify the respiratory microbiota as a potential factor associated with COVID-19 severity.
Subject(s)
COVID-19 , Bacterial InfectionsABSTRACT
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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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 We systematically identified published and unpublished RCTs by September 14, 2020 (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, PubMed, Cochrane COVID-19 registry).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.