Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 226, Issue 9, Pages 1588-1592Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiac134
Keywords
SARS-CoV-2; breakthrough infection; gastrointestinal tract; nonhuman primates; suboptimal prophylaxis
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Funding
- National Institute of Allergy and Infectious Disease [HHSN272201700033I]
- National Institutes of Health Office of Research Infrastructure Programs, Office of the Director [OD011104]
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Breakthrough gastrointestinal COVID-19 was observed in a rhesus macaque undergoing low-dose monoclonal antibody prophylaxis, indicating intrahost virus evolution within the gut.
Breakthrough gastrointestinal COVID-19 was observed after experimental SARS-CoV-2 upper mucosal infection in a rhesus macaque undergoing low-dose monoclonal antibody prophylaxis. High levels of viral RNA were detected in intestinal sites contrasting with minimal viral replication in upper respiratory mucosa. Sequencing of virus recovered from tissue in 3 gastrointestinal sites and rectal swab revealed loss of furin cleavage site deletions present in the inoculating virus stock and 2 amino acid changes in spike that were detected in 2 colon sites but not elsewhere, suggesting compartmentalized replication and intestinal viral evolution. This suggests suboptimal antiviral therapies promote viral sequestration in these anatomies. Breakthrough COVID-19 was observed after experimental SARS-CoV-2 infection in a rhesus macaque undergoing low-dose monoclonal antibody prophylaxis that resulted in unique intrahost evolution of the virus within the gut of the infected animal.
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