Organ-specific genome diversity of replication-competent SARS-CoV-2

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not always confined to the respiratory system, as it impacts people on a broad clinical spectrum from asymptomatic to severe systemic manifestations resulting in death. Further, accumulation of intra-host single nucleotide variants during prolonged SARS-CoV-2 infection may lead to emergence of variants of concern (VOCs). Still, information on virus infectivity and intra-host evolution across organs is sparse. We report a detailed virological analysis of thirteen postmortem coronavirus disease 2019 (COVID-19) cases that provides proof of viremia and presence of replication-competent SARS-CoV-2 in extrapulmonary organs of immunocompromised patients, including heart, kidney, liver, and spleen (NCT04366882). In parallel, we identify organ-specific SARS-CoV-2 genome diversity and mutations of concern N501Y, T1027I, and Y453F, while the patient had died long before reported emergence of VOCs. These mutations appear in multiple organs and replicate in Vero E6 cells, highlighting their infectivity. Finally, we show two stages of fatal disease evolution based on disease duration and viral loads in lungs and plasma. Our results provide insights about the pathogenesis and intra-host evolution of SARS-CoV-2 and show that COVID-19 treatment and hygiene measures need to be tailored to specific needs of immunocompromised patients, even when respiratory symptoms cease.

Considerable escape of SARS-CoV-2 Omicron to antibody neutralization

“…The swab was provided and sequenced by the laboratory of Virology of Hopital Européen Georges Pompidou (Assistance Publique -Hopitaux de Paris). The Omicron-positive sample was cultured on Vero E6 cells as previously described 42 Viral growth was confirmed by RT-qPCR 3 days post-infection (p.i.). At day 6 p.i., a cytopathic effect (CPE) was detected and a full-length sequencing of the virus was performed.…”

High Incidence of SARS-CoV-2 Variant of Concern Breakthrough Infections Despite Residual Humoral and Cellular Immunity Induced by BNT162b2 Vaccination in Healthcare Workers: A Long-Term Follow-Up Study in Belgium

“…The libraries were sequenced on a MinION using R9.4.1 flow cells (Oxford Nanopore Technologies, Oxford, UK) and MinKnow software (v21.02.1 for Windows, Oxford Nanopore technologies, Oxford, UK) The resulting fast5 reads were base called and demultiplexed using Guppy (v5.0.16 for Windows, Oxford Nanopore technologies, Oxford, UK) in super accuracy mode. Genome assembly was performed using the ARTIC bioinformatics pipeline v1.1.3, which entails adapter trimming and mapping to the reference strain Wuhan-Hu-1 (MN908947), as previously described [37].…”

Immune response in COVID-19: what is next?

“…Consistently, defective GC formation is associated with CD4 + T cell depletion in the lymph nodes of severe COVID-19 patients [ 109 ]. This defect and delay to develop antibodies against spike protein may contribute to viral dissemination and longer persistence of SARS-CoV-2 in patients [ 110 ]. Moreover, premature T cell depletion due to apoptosis was associated with a lower B-cell response in individuals infected with filovirus [ 111 ] or retrovirus [ 112 , 113 ].…”