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

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

PMC · DOI: 10.21203/rs.3.rs-6033850/v1 · Research Square · 2025-03-26

## TL;DR

This study shows that SIV/SARS-CoV-2 co-infection in macaques mimics aspects of HIV/Covid-19 co-infection in humans, including immune impairment and viral evolution.

## Contribution

The study introduces a novel non-human primate model for HIV/SARS-CoV-2 co-infection and reveals immune and viral dynamics.

## Key findings

- SARS-CoV-2 replication persisted in the upper respiratory tract for 14 days.
- SIV impaired anti-SARS-CoV-2 antibody and T-cell responses.
- SARS-CoV-2 evolution was observed in the upper respiratory tract.

## 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 co-infection, 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 co-infection 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 co-infection.

## Linked entities

- **Diseases:** SARS-CoV-2 (MONDO:0100096), COVID-19 (MONDO:0100096)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** -infection (MESH:D007239), COVID-19 (MESH:D000086382)
- **Species:** Simian immunodeficiency virus (no rank) [taxon 11723], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus 1 (no rank) [taxon 11676], Macaca mulatta (rhesus macaque, species) [taxon 9544]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11975012/full.md

## References

70 references — full list in the complete paper: https://tomesphere.com/paper/PMC11975012/full.md

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Source: https://tomesphere.com/paper/PMC11975012