Breakthrough gastrointestinal COVID 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 three gastrointestinal sites and rectal swab revealed loss of furin cleavage site deletions present in the inoculating virus stock and two amino acid changes in spike that were detected in two colon sites but not elsewhere, suggesting compartmentalized replication and intestinal viral evolution. This suggests suboptimal antiviral therapies promote viral sequestration in these anatomies.
Breakthrough gastrointestinal COVID and intra-host evolution consequent to combination monoclonal antibody prophylaxis