SARS-CoV-2 viral replication persists in the human lung for several weeks after onset of symptomatic severe COVID-19 and is associated with attenuated pulmonary immunity and variant-specific clinical sequalae (preprint)

The immunopathogenesis of severe COVID-19 is incompletely understood. In contradistinction to the upper respiratory tract where replicating (culturable) SARS-CoV-2 is recoverable approximately ~ 4 to 8 days after symptom onset, there is paucity of data about the frequency or duration of replicating virus in the lower respiratory tract (the human lung). We undertook lung tissue sampling (needle biopsy), within ~2 hours of death, in 42 mechanically ventilated decedents during the Beta and Delta waves. Lung biopsy cores underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, immunohistochemistry and cell-based flow cytometry of deconstructed tissue. 38% (16/42) of patients had culturable virus in the lung (persisting for up to 4 weeks after symptom onset). This, hitherto, undescribed bio-phenotype of lung-specific persisting viral replication was associated with an enhanced pulmonary pro-inflammatory response and variant-specific increased rates of bacterial bronchopneumonia and accelerated death. These findings question existing paradigms and suggest that in a subset of patients, concurrent, rather than sequential active viral replication continues to drive a heightened pro-inflammatory response. Our findings have potential implications for the design of therapeutic interventional strategies and clinical management of severe COVID-19 disease.

An African, Multi-Centre Evaluation of Patient Care and Clinical Outcomes for Patients with COVID-19 Infection Admitted to High-Care or Intensive Care Units (preprint)

Background: There is little data on critically ill COVID-19 patients in under-resourced environments, and none from Africa. The objectives of this study were to determine resources, patient comorbidities and critical care interventions associated with mortality in critically ill COVID-19 African patients. Methods: African multicentre, prospective observational cohort study of adult patients referred to intensive care or high-care units with suspected or known COVID-19 infection. Patient follow up was until hospital discharge, censored at 30 days. The study recruited from March to September 2020. Findings: 1243 patients from 38 hospitals in six countries participated. The hospitals had a median of 2 (interquartile range (IQR) 1-4) intensivists, with a nurse to patient ratio of 1:2 (IQR 1:3 to 1:1). Pulse oximetry was available to all patients in 29/35 (82·9%) sites, and 21/35 (60%) of sites could provide dialysis or proning. The 30-day mortality following critical care admission was 54·7% (95% confidence interval (CI) 51·9-57·6). Factors independently associated with mortality were an increasing age (odds ratio (OR) 1·04, 95% CI 1·02-1·05, p<0·001), a quick SOFA score of 3 (OR 3·61, 95% CI 1·41-9·24, p=0·01), increasing respiratory support defined as the need for continuous positive airway pressure (OR 5·86, 95% CI 1·47-23·35, p=0·01), invasive mechanical ventilation (OR 16·42, 95% CI 4·52-59·65, p<0·001), three organ systems requiring support at admission (OR 5·52, 95% CI 1·13-27·01, p=0·04), cardiorespiratory arrest within 24 hours prior to admission (OR 4·43, 95% CI 1·01-19·54, p=0·05) and vasopressor requirements (OR 2·73, 95% CI 1·71-4·36, p<0·001). Human immunodeficiency virus was not associated with mortality (OR 1·84, 95% CI 0·99-3·40, p=0·05). Interpretation: Mortality in critically ill COVID-19 African patients is higher than any other region, with an excess mortality of 18 and 29 deaths per 100 patients compared to other regions. Mortality is associated with limited critical care resources and severity of organ dysfunction at admission.Trial Registration: This study was registered on ClinicalTrials.gov (NCT04367207).Funding Statement: African Covid-19 Critical Care Outcomes Study (ACCCOS) was partially supported by a grant from the Critical Care Society of Southern Africa.Declaration of Interests: We have no competing interests to declare.Ethics Approval Statement: The primary ethics approval was from the Human Research Ethics Committee of the University of Cape Town (HREC 213/2020)