SARS-CoV-2 viral replication persists in the human lung for several weeks after symptom onset

Abstract

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.

Comment on: “Dexamethasone treatment for COVID-19 is related to increased mortality in hematologic malignancy patients: results from the EPICOVIDEHA registry”

“…6 There is persistent viral replication in the lungs, which is associated with accelerated death and secondary bacterial infection. 7 The dosage and duration of dexamethasone use were not described in detail in this study. High doses and long courses of glucocorticoid therapy may be associated with an increased risk of death.…”