A diminished immune response underlies age-related SARS-CoV-2 pathologies

Pathobiology and dysbiosis of the respiratory and intestinal microbiota in 14 months old Golden Syrian hamsters infected with SARS-CoV-2

“…In this old-age GSH model utilized within this study, SARS2 infection led to weight loss starting at 2 dpc and high vRNA loads in the NT, trachea, lungs, and heart at 3 and 6 dpc. This is consistent with previous studies using aged GSH at 7-9 months showing peak weight loss at 6 to 7 dpc [12][13][14]. SARS2 and FLUAV-SARS2 GSHs had similar vRNA loads for respiratory and non-respiratory tissues except for significantly increased vRNA loads in the heart at 3 dpc and the NTs at 6 dpc in GSHs exposed to SARS2 only.…”

“…have been associated with increased inflammation by stimulating epithelial cells to produce IL-6, IL-8, and CCL20, which can then prompt recruitment of neutrophils and mucosal Th17 immune responses [39]. A recent study showed increased TGFβ, IL-17, and neutrophil recruitment within the respiratory tract of SARS2 infected aged GSH (40+ weeks) compared to young GSH (6-8 weeks) [14]. Similarly, moderate to large numbers of neutrophils, notably at 6 dpc, were also observed within this study by histopathology in both SARS2 groups.…”

“…Similarly, moderate to large numbers of neutrophils, notably at 6 dpc, were also observed within this study by histopathology in both SARS2 groups. Elevated levels of neutrophils within the lung are a hallmark of COVID-19 and has been hypothesized to contribute to the severe disease pathology observed in aged individuals [14,40,41]. Increased serum levels of IL-6 and IL-8 have also been associated with disease severity in COVID-19 adult patients and enrichment of CCL20 has been observed in mechanically ventilated patients with COVID-19 [42][43][44].…”

“…Golden Syrian hamsters (GSH) are naturally susceptible to SARS2 replication in the respiratory tract, inducing severe lung pathology [4,5]. Generally, GSH at 5-8 weeks of age have been used in experimental studies [6][7][8][9][10][11]; however, multiple groups reported that 8-10-month-old GSHs (equivalent to ~40-50 human years) develop more severe disease by exhibiting increased weight loss and slower lung recovery post-infection, emulating more severe disease presentation in older individuals [12][13][14]. The vulnerability of enhanced illness in the elderly population has been hypothesized to encompass a combination of immunopathology from exacerbated immune response and immunosenescence [2].…”

Pathobiology and dysbiosis of the respiratory and intestinal microbiota in 14 months old Golden Syrian hamsters infected with SARS-CoV-2

“…Golden Syrian hamsters (GSH) are naturally susceptible to SARS2 replication in the respiratory tract, inducing severe lung pathology [4,5]. Generally, GSH at 5-8 weeks of age have been used in experimental studies [6][7][8][9][10][11]; however, multiple groups reported that 8-10-month-old GSHs develop more severe disease by exhibiting increased weight loss and slower lung recovery post-infection, emulating more severe disease presentation in older individuals [12][13][14]. The vulnerability of enhanced illness in the elderly population has been hypothesized to encompass a combination of immunopathology from exacerbated immune response and immunosenescence [2].…”