ORIGINAL RESEARCH article

Front. Immunol.

Sec. Viral Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1587688

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

Provisionally accepted
Megan FredericksMegan Fredericks1,2Zohar KolodnerZohar Kolodner1,2Adam WaalkesAdam Waalkes1Kaitlin SawatzkiKaitlin Sawatzki1Linhui HaoLinhui Hao1Dustin R LongDustin R Long1Kelsi PenewitKelsi Penewit1Cecily C MidkiffCecily C Midkiff3Carter J McCormickCarter J McCormick1Semira BerakiSemira Beraki1,2Paul T EdlefsenPaul T Edlefsen4Jeana BarrowJeana Barrow2Alexander L GreningerAlexander L Greninger1Michael GaleMichael Gale1,2,5Robert V BlairRobert V Blair3Stephen J SalipanteStephen J Salipante1Deborah FullerDeborah Fuller1,2Megan A O'ConnorMegan A O'Connor1*
  • 1University of Washington, Seattle, United States
  • 2Washington National Primate Research Center, University of Washington, Seattle, Washington, United States
  • 3Tulane National Primate Research Center, School of Medicine, Tulane University, Covington, Kentucky, United States
  • 4Fred Hutchinson Cancer Center, Seattle, Washington, United States
  • 5University of Minnesota Twin Cities, St. Paul, Minnesota, United States

The final, formatted version of the article will be published soon.

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

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- 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: HIV, immunocompromised, COVID-19, nonhuman primate, aids, immunodeficiency

Received: 04 Mar 2025; Accepted: 15 Apr 2025.

Copyright: © 2025 Fredericks, Kolodner, Waalkes, Sawatzki, Hao, Long, Penewit, Midkiff, McCormick, Beraki, Edlefsen, Barrow, Greninger, Gale, Blair, Salipante, Fuller and O'Connor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Megan A O'Connor, University of Washington, Seattle, United States

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material