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.

Effectiveness of early-treatment interventions on self-reported long COVID: A multi-arm, multi-stage adaptive platform control trial (preprint)

Approximately 20% of people infected with COVID-19 develop at least one persistent condition potentially attributable to their SARS-CoV-2 infection. We sought to determine the effectiveness of early COVID-19 treatment interventions on long COVID symptoms. We conducted a multi-arm multi-stage adaptive platform trial at 12 public health clinics in Brazil between June 2020 and July 2022. Participants were followed for 60. Patients received one of six interventions (doxazosin, fluvoxamine, fluvoxamine in combination with inhaled budesonide, interferon-lambda, ivermectin, or metformin) or matching placebo. The primary outcome was persistence of COVID-19 symptoms at 60 days after randomization. We analyzed data from 5,700 participants across study cohorts. Overall, approximately 22% of patients reported at least one ongoing symptom 60 days after randomization, regardless of the early treatment they received. At day 60, we did not find any statistical benefit of any intervention on recovery, cure fractions, or PROMIS scores (mental and physical).

Canada’s Response to International Travel During COVID-19 Pandemic – A Media Analysis (preprint)

Background The media play a critical role in informing the public about the pandemic. International travel is a highly contested subject in the media during the COVID-19 pandemic at both the international and national levels. We examined Canadian media reporting on international travel restrictions during the pandemic, how these restrictions aligned with the IHR (2005), and how the narrative around international travel evolved for the pandemic.MethodsWe analysed Canada’s top three national newspapers by circulation, namely – The Globe and Mail, The National Post and The Toronto Star, published between Jan 1, 2020 - May 31, 2020. Our search yielded a total of 378 articles across the three newspapers. Upon removing duplicates and screening the remaining articles, we included a total of 62 articles for the analysis. We conducted a qualitative media content analysis by using the inductive coding approach.ResultsThree major themes were identified within the articles. These included: 1) The role of scientific and expert evidence in implementing travel restrictions; 2) Federal legislation, regulations and enforcement of international travel measures; and 3) Compliance with WHO guidelines in travel restriction policy- and decision-making. The federal government relied on scientific evidence for implementing international travel restrictions. The federal government fully exercised its powers under the Quarantine Act to enforce travel regulations and comply with the IHR (2005). The government embraced rules-based international order by following WHO recommendations on international travel, contributing to delaying border closure and travel restrictions until mid-March.Conclusion The media focussed significantly on international travel related issues during the early phase of pandemic. The dominant media narrative remained the need for earlier travel restrictions against international travel.