338 – High-Fat and -Sugar Diet but Not SIV Coinfection Enhances SARS-CoV-2 Shedding in Infected Macaques

Background

Numerous risk factors for severe SARS-CoV-2 infection have been identified, including diabetes, obesity, and cardiovascular disease. These conditions often co-occur and may be influenced by diet. We sought to investigate the impact of diet directly on SARS-CoV-2 infection, as well as the understudied area of SARS-CoV-2 and HIV co-infection, which we modeled with SIV infection in macaques.

Methods

Three control pigtail macaques (PTM, 1F & 2M) were infected with 1×10⁶ TCID₅₀ Delta strain SARS-CoV-2 and monitored following infection until euthanasia and necropsy (Nx) on day 30. Six additional PTM (3M, 3F) were fed a high fat and sugar chow (HFD) for 63 days prior to SARS-CoV-2 infection, then followed until euthanasia and Nx on days 30-32 SARS-CoV-2. A final six PTM (4M, 2F) were fed the HFD prior to SIV infection (IV SIV_agm), then infected with SARS-CoV-2 on day 35 of SIV and monitored until euthanasia and Nx on days 30-32 of SARS-CoV-2. 

Results

Macaques fed the HFD experienced significant shifts in stool bacteria Beta diversity from pre- to post-HFD time points before infection (Adonis testing, unweighted UniFrac distances). All three groups demonstrated significant shifts in Beta diversity from prior to SARS-CoV-2 infection and SARS-CoV-2 time points, though this did not remain significant for control animals with weighted UniFrac distances. HFD fed, SIV+ animals expressed significantly more MX1 transcript in Nx colon tissue and bronchioalveolar lavage (BAL) cells at day 28 of SARS-CoV-2 than HFD fed, SIV- animals, suggesting an enhanced inflammatory response with SIV infection. Three other immune-related transcripts were also significantly elevated in BAL cells of HFD, SIV+ animals vs. HFD, SIV-, while 72 immune-related transcripts were significantly elevated in BAL cells from HFD, SIV- animals vs. controls. SARS-CoV-2 RNA, including subgenomic RNA indicating viral replication, was shed at considerably higher levels and for longer durations in HFD fed, SIV- animals than controls in both the stool and nose swabs, while shedding was not markedly different in HFD fed SIV+ vs. SIV- animals.

Conclusions

Dietary change alone resulted in distinct alterations to the gut microbiome and SARS-CoV-2 shedding from the gastrointestinal as well as respiratory tracts, while SARS-CoV-2 shedding was not significantly altered by SIV co-infection. However, immune responses to SARS-CoV-2 appear distinct in SIV+ and SIV- animals, with a potentially heightened inflammatory state in SIV+ macaques.