SARS-CoV-2 infection augments species- and age-specific predispositions in cotton rats

Abstract

Heterogeneity of COVID-19 manifestations in human population is vast, for reasons unknown. Cotton rats are a clinically relevant small animal model of human respiratory viral infections. Here, we demonstrate for the first time that SARS-CoV-2 infection in cotton rats affects multiple organs and systems, targeting species- and age-specific biological processes. Infection of S. fulviventer, which developed a neutralizing antibody response and were more susceptible to SARS-CoV-2 replication in the upper respiratory tract, was accompanied by hyperplasia of lacrimal drainage-associated lymphoid tissue (LDALT), a first known report of mucosa-associated lymphoid tissue activation at the portal of SARS-CoV-2 entry. Although less permissive to viral replication, S. hispidus showed hyperplasia of bone marrow in the facial bones and increased pulmonary thrombosis in aged males. Augmentation of these features by SARS-CoV-2 infection suggests a virus-induced breach in regulatory mechanisms which could be devastating for people of all ages with underlying conditions and in particular for elderly with a multitude of ongoing disorders.

The Impact of COVID-19 on People Living with HIV-1 and HIV-1-Associated Neurological Complications

“…They usually experience physical and cognitive impairments, chronic immune activation and multimorbidity even without COVID-19 at ages younger than HIV-1 negative people [ 125 , 126 , 127 , 128 , 129 ]. Thus, aging and age-associated comorbidity make PLWH succumb to SARS-CoV-2 infection and COVID-19 severity [ 130 ]. Since COVID-19 also causes neurological syndromes, SARS-CoV-2 may imply a cumulative effect on preexisting HAND or may lead to the development of HAND.…”

“…Several cohort studies on PLWH have demonstrated that PLWH are among the high-risk group for contracting SARS-CoV-2 infection [16,[178][179][180]. PLWH are more likely to be infected with SARS-CoV-2 due to immunocompromised status owing to HIV-1 infection-induced dysregulated immune response/immune suppression and underlying comorbidities [130,181]. Moreover, there was complex immune dysregulation observed with higher levels of IFNα/β and T-cell activation in coinfected people than in healthy controls [182,183].…”