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Front Immunol . SIV/SARS-CoV-2 coinfection in rhesus macaques impacts viral shedding, host immunity, the microbiome, and viral evolution

tetano

Editor, Senior Moderator
Front Immunol


. 2025 May 20:16:1587688.
doi: 10.3389/fimmu.2025.1587688. eCollection 2025. SIV/SARS-CoV-2 coinfection in rhesus macaques impacts viral shedding, host immunity, the microbiome, and viral evolution

Megan N Fredericks[SUP] 1 2 [/SUP], Zohar Kolodner[SUP] 1 2 [/SUP], Adam Waalkes[SUP] 3 [/SUP], Kaitlin Sawatzki[SUP] 4 [/SUP], Linhui Hao[SUP] 4 [/SUP], Dustin R Long[SUP] 5 [/SUP], Kelsi Penewit[SUP] 3 [/SUP], Cecily C Midkiff[SUP] 6 [/SUP], Carter J McCormick[SUP] 3 [/SUP], Semira Beraki[SUP] 1 2 [/SUP], Paul T Edlefsen[SUP] 7 [/SUP], Jeana Barrow[SUP] 2 [/SUP], Alexander L Greninger[SUP] 4 [/SUP], Michael Gale[SUP] 2 4 8 [/SUP], Robert V Blair[SUP] 5 [/SUP], Stephen J Salipante[SUP] 3 [/SUP], Deborah H Fuller[SUP] 1 2 [/SUP], Megan A O'Connor[SUP] 1 2 3 [/SUP]



Affiliations
Abstract

People living with HIV (PLWH) have an increased risk of severe COVID-19, including prolonged viral shedding and emergence of mutations. To investigate the simian immunodeficiency virus (SIV) macaque model for HIV/SARS-CoV-2 coinfection, seven SIV+ rhesus macaques were co-infected with SARS-CoV-2. COVID-19 in all macaques was mild. SARS-CoV-2 replication persisted in the upper, but not the lower respiratory tract for 14 days post-infection. Animals showed impaired generation of anti-SARS-CoV-2 antibodies and T-cells. Animals also displayed transient changes in microbial communities in the upper airway and gastrointestinal tract. Evidence of SARS-CoV-2 evolution was observed in the upper respiratory tract. This study demonstrates that SIV/SARS-CoV-2 coinfection in rhesus macaques recapitulates aspects of COVID-19 in PLWH. We show that SIV impairs anti-SARS-CoV-2 immunity, potentially leading to prolonged viral shedding, altered pathogenesis, and viral evolution. This highlights the importance of HIV status in COVID-19 and supports the use of this model for HIV/SARS-CoV-2 coinfection.

Keywords: AIDS; COVID-19; HIV; immunocompromised; immunodeficiency; nonhuman primate.

 
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