AUTHOR=Fredericks Megan N. , Kolodner Zohar , Waalkes Adam , Sawatzki Kaitlin , Hao Linhui , Long Dustin R. , Penewit Kelsi , Midkiff Cecily C. , McCormick Carter J. , Beraki Semira , Edlefsen Paul T. , Barrow Jeana , Greninger Alexander L. , Gale Michael , Blair Robert V. , Salipante Stephen J. , Fuller Deborah H. , O’Connor Megan A. 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1587688

DOI=10.3389/fimmu.2025.1587688

ISSN=1664-3224

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.