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bioRxiv · 10.1101/2022.02.25.481974

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

Madden, P. J.·Thomas, Y.·Blair, R. V.·Samer, S.·Doyle, M.·Midkiff, C. C.·Becker, M. E.·Arif, M. S.·McRaven, M. D.·Simons, L. M.·Carias, A. M.·Martinelli, E.·Lorenzo-Redondo, R.·Hultquist, J. F.·Villinger, F. J.·Veazey, R. S.·Hope, T. J.
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Abstract

The systemic nature of SARS-CoV-2 infection is highly recognized, but poorly characterized. A non-invasive and unbiased method is needed to clarify whole body spatiotemporal dynamics of SARS-CoV-2 infection 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 three rhesus macaques. Using PET/CT imaging of macaques at different times post-SARS-CoV-2 inoculation, we track the 64Cu-labelled CR3022-F(ab)2 probe targeting the spike protein of SARS-CoV-2 to study the dynamics of infection within the respiratory tract and uncover novel sites of infection. Using this method, we uncovered differences in lung pathology between infection with the WA1 isolate and the delta variant, which were readily corroborated through computed tomography scans. 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. Graphic AbstractPET/CT detected SARS-CoV-2 infection of 4 different tissues in the male genital tract illuminates the cause of COVID-19 clinical sequalae of male sexual health and fertility O_FIG O_LINKSMALLFIG WIDTH=189 HEIGHT=200 SRC="FIGDIR/small/481974v2_ufig1.gif" ALT="Figure 1"> View larger version (74K): org.highwire.dtl.DTLVardef@188c53aorg.highwire.dtl.DTLVardef@4c639forg.highwire.dtl.DTLVardef@120799forg.highwire.dtl.DTLVardef@110edb1_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Diagram shows schematic illustration of the male genital tract of the rhesus macaque. Virus icon shows sites of SARS-CoV-2 PET signal. Text highlighting the clinical sequalae associated with each sight of infection is shown in text adjacent to each infection site. C_FIG

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Madden, P. J., Thomas, Y., Blair, R. V., Samer, S., Doyle, M., Midkiff, C. C., Becker, M. E., Arif, M. S., McRaven, M. D., Simons, L. M., Carias, A. M., Martinelli, E., Lorenzo-Redondo, R., Hultquist, J. F., Villinger, F. J., Veazey, R. S., Hope, T. J.. 2022-02-28. An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques. https://doi.org/10.1101/2022.02.25.481974

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