Gastrointestinal symptoms and viral RNA (vRNA) in stool have been described in human SARS-CoV-2 infections. However, intestinal pathology and related inflammation have not been extensively described in humans or animal models. Here we investigate the effect of SARS-CoV-2 infection on the gut mucosa and inflammation in rhesus macaques (RM) and humans.
Fourteen adult RM were infected with US/WA-1/2020 SARS-CoV-2 instilled intranasally and intratracheally. Animal clinical features (mass, temperature, etc.) and samples (nasal swabs, throat swabs, blood, stool, etc.) were collected at baseline and up to day 10 post-infection at necropsy. RNA was extracted from swab and stool samples and vRNA measured by qRT-PCR. Plasma samples were assessed for inflammatory biomarkers by ELISA. Tissues collected at necropsy were fixed and evaluated for microbial translocation through immunohistochemical (IHC) staining of bacterial products; H&E staining was also performed. Tissues were additionally collected from uninfected RM and processed in the same manner. Human plasma samples from individuals with moderate COVID-19 were collected at early infection and recovery time points and assessed for inflammatory biomarkers.
SARS-CoV-2 infection of RM did not induce fever nor weight loss over five percent. vRNA was detected in all animals in nasal and throat swabs. vRNA, including subgenomic RNA indicative of viral replication, was also detected in stool samples. Scores for translocating bacteria in colon sections stained by IHC for bacterial products were higher for SARS-CoV-2 infected RM than uninfected controls. Additionally, follicles made up a higher percentage of total mesenteric lymph node area in SARS-CoV-2 infected animals than control RM. Furthermore, soluble CD14 in plasma increased significantly from baseline to day 10 of SARS-CoV-2 infection (p=0.0006) and decreased significantly in humans from early infection to recovery time points (p=0.0295).
Thus, adult RM experienced mild to moderate SARS-CoV-2 infections yet demonstrated evidence of microbial translocation. Humans similarly demonstrated evidence of microbial translocation that decreased upon recovery from COVID-19. These data suggest gut pathology in SARS-CoV-2 infection may be contributing to systemic inflammation in COVID-19.