The Impact of SIV-Induced Immunodeficiency on Clinical Manifestation, Immune Response, and Viral Dynamics in SARS-CoV-2 Coinfection

Melton, A.; Rowe, L. A.; Penney, T.; Krzykwa, C.; Goff, K.; Scheuermann, S. E.; Melton, H. J.; Williams, K.; Golden, N.; Moore Green, K.; Smith, B.; Russell-Lodrigue, K.; Dufour, J. P.; Doyle-Meyers, L. A.; Schiro, F.; Aye, P. P.; Lifson, J. D.; Beddingfield, B. J.; Blair, R. V.; Bohm, R. P.; Kolls, J. K.; Rappaport, J.; Hoxie, J. A.; Maness, N. J.

doi:10.1101/2023.11.15.567132

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bioRxiv · 10.1101/2023.11.15.567132

The Impact of SIV-Induced Immunodeficiency on Clinical Manifestation, Immune Response, and Viral Dynamics in SARS-CoV-2 Coinfection

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Abstract

Persistent and uncontrolled SARS-CoV-2 replication in immunocompromised individuals has been observed and may be a contributing source of novel viral variants that continue to drive the pandemic. Importantly, the effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. Here we conducted a pilot study wherein two pigtail macaques (PTM) chronically infected with SIVmac239 were exposed to SARS-CoV-2 and monitored for six weeks for clinical disease, viral replication, and viral evolution, and compared to our previously published cohort of SIV-naive PTM infected with SARS-CoV-2. At the time of SARS-CoV-2 infection, one PTM had minimal to no detectable CD4+ T cells in gut, blood, or bronchoalveolar lavage (BAL), while the other PTM harbored a small population of CD4+ T cells in all compartments. Clinical signs were not observed in either PTM; however, the more immunocompromised PTM exhibited a progressive increase in pulmonary infiltrating monocytes throughout SARS-CoV-2 infection. Single-cell RNA sequencing (scRNAseq) of the infiltrating monocytes revealed a less activated/inert phenotype. Neither SIV-infected PTM mounted detectable anti-SARS-CoV-2 T cell responses in blood or BAL, nor anti-SARS-CoV-2 neutralizing antibodies. Interestingly, despite the diminished cellular and humoral immune responses, SARS-CoV-2 viral kinetics and evolution were indistinguishable from SIV-naive PTM in all sampled mucosal sites (nasal, oral, and rectal), with clearance of virus by 3-4 weeks post infection. SIV-induced immunodeficiency significantly impacted immune responses to SARS-CoV-2 but did not alter disease progression, viral kinetics or evolution in the PTM model. SIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants.

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Melton, A., Rowe, L. A., Penney, T., Krzykwa, C., Goff, K., Scheuermann, S. E., Melton, H. J., Williams, K., Golden, N., Moore Green, K., Smith, B., Russell-Lodrigue, K., Dufour, J. P., Doyle-Meyers, L. A., Schiro, F., Aye, P. P., Lifson, J. D., Beddingfield, B. J., Blair, R. V., Bohm, R. P., Kolls, J. K., Rappaport, J., Hoxie, J. A., Maness, N. J.. 2023-11-16. The Impact of SIV-Induced Immunodeficiency on Clinical Manifestation, Immune Response, and Viral Dynamics in SARS-CoV-2 Coinfection. https://doi.org/10.1101/2023.11.15.567132

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