Background
Diabetes, obesity, cardiopulmonary diseases, and HIV infection all increase the risk for severe COVID-19. Diet can contribute to the development of co-morbidities such as obesity and diabetes but has been less well studied for its direct impact on SARS-CoV-2 infection. We have investigated the impact of a high fat and sugar chow (Western diet, WD) along with SIV co-infection on Delta strain SARS-CoV-2 infection in pigtailed macaques (PTMs).
Methods
Control group (n=3, 2M, 1F) PTMs were sampled pre- and post-SARS-CoV-2 infection until euthanasia and necropsy (Nx) at day 30 post-infection. A second group of PTMs (n=6, 3M, 3F) initiated the WD 63 days before SARS-CoV-2 infection and was maintained on the WD until Nx 30-32 days post-infection. Sampling was performed prior to WD feeding, pre-infection with WD, and post-infection with WD. SIV co-infected PTMs (n=6, 4M, 2F) were also sampled prior to and during WD feeding, which was maintained until Nx following SARS-CoV-2 infection. SIV infection (IV) was 35 days before SARS-CoV-2 infection.
Results
WD significantly altered the beta diversity of the gut bacterial microbiome, and shedding of SARS-CoV-2 subgenomic RNA (indicating viral replication) was prolonged in stool and nasal swabs (NS). Immune responses to SARS-CoV-2 infection were significantly reduced: peripheral lymphocytes increased on day 8 SARS-CoV-2 in controls and WD-fed PTMs, but were significantly lower in WD animals. Additionally, IL6 was significantly reduced at peak in WD animals relative to controls. Lung pathology was modestly increased from controls. SIV co-infection prolonged shedding of SARS-CoV-2 subgenomic RNA in NS, and significantly enhanced lung pathology. SIV-infected PTMs demonstrated significant elevations in several inflammatory markers, including IL6, CXCL11 (ITAC), and CXCL9 (MIG). MX1 expression in colon tissue and lymph nodes was also significantly increased with SIV co-infection.
Conclusions
Both WD and SIV co-infection enhanced SARS-CoV-2 pathogenesis in PTMs, with prolonged SARS-CoV-2 RNA shedding suggesting poorer viral control in both conditions, and with increased pathology in both conditions. However, the mechanisms of heightened disease appear distinct, with suppressed immune responses in WD-fed animals and a heighted inflammatory state in SIV co-infection. These findings improve our understanding of the unique impacts of co-morbidities or environmental conditions (diet) on COVID-19 severity and suggest distinct therapies for reducing disease.