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.

SARS-CoV-2 RNA levels in Scotland's wastewater (preprint)

Nationwide, wastewater-based monitoring was newly established in Scotland to track the levels of SARS-CoV-2 viral RNA shed into the sewage network, during the COVID-19 pandemic. We present a curated, reference data set produced by this national programme, from May 2020 to February 2022. Viral levels were analysed by RT-qPCR assays of the N1 gene, on RNA extracted from wastewater sampled at 122 locations. Locations were sampled up to four times per week, typically once or twice per week, and in response to local needs. We report sampling site locations with geographical coordinates, the total population in the catchment for each site, and the information necessary for data normalisation, such as the incoming wastewater flow values and ammonia concentration, when these were available. The methodology for viral quantification and data analysis is briefly described, with links to detailed protocols online. These wastewater data are contributing to estimates of disease prevalence and the viral reproduction number (R) in Scotland and in the UK.

Elements of Effective Online Instruction in Law (preprint)

The Covid pandemic has had a significant impact on law school pedagogy, although how much that impact will remain and be a benefit post-pandemic remains to be seen. This article argues that we should leverage what we learned and use it to redesign our courses for a future world of hybrid teaching, so as not to lose what we gained by returning to in-person teaching as if nothing happened to us or our students. It offers suggestions about how to go about doing that—how to capture the benefits of what has been learned about online teaching in the 2020–21 Academic Year, and apply it to our teaching going forward. Among those suggestions is to redesign our courses from back to front, starting with articulating our learning outcomes and then developing modules designed to meet those outcomes, with formative assessment for each module as the semester progresses. It also suggests maximizing the precious in-person time we will regain post-pandemic by intentionally moving some of our content online, and deliberately choosing how to deliver that online content best. Doing these things deliberately will contribute to making us more effective teachers, and help our students become more effective learners—in law school, and in their future lives as practitioners.

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)