Abstract
Because of the recognized systemic nature of SARS-CoV-2 infection, a non-invasive and unbiased method is needed to clarify its spatiotemporal dynamics in vivo after transmission. We recently developed a probe based on the anti-SARS-CoV-2 spike antibody CR3022 to study SARS-CoV-2 pathogenesis in vivo. Herein, we describe its use in immunoPET to investigate SARS-CoV-2 infection of rhesus macaques. Using PET/CT imaging of macaques at different times post-SARS-CoV-2 inoculation, we demonstrate that the 64Cu-labelled CR3022-F(ab’)2 probe targeting the spike protein of SARS-CoV-2 can be used to study the dynamics of infection within the respiratory tract and uncover novel sites of infection. Differences in lung pathology between infection with the WA1 isolate and the delta variant were readily observed using immunoPET and corroborated CT lung pathology. The ability of the probe to illuminate lung- associated pathology demonstrates its specificity and function to detect infection in PET scan. The 64Cu-CR3022-probe also demonstrated dynamic changes occurring between 1- and 2-weeks post-infection. Remarkably, a robust signal was seen in the male genital tract (MGT) of all three animals studied. Infection of the MGT was validated by immunofluorescence imaging of infected cells in the testicular and penile tissue and severe pathology was observed in the testes of one animal at 2-weeks post-infection. The results presented here underscore the utility of using immunoPET to study the dynamics of SARS-CoV-2 infection to understand its pathogenicity and discover new anatomical sites of viral replication. We provide direct evidence for SARS-CoV-2 infection of the MGT in rhesus macaques revealing the possible pathologic outcomes of viral replication at these sites.
Competing Interest Statement
The authors have declared no competing interest.
