The immunological aftermath of SARS-CoV-2: How prior infection impacts subsequent pulmonary injury

Abstract

Abstract Following pulmonary insults there are persistent alterations in the lung that influence responsiveness to subsequent injury. Over 600 million individuals have survived SARS-CoV-2 (SCV2) infection. Thus, the impact of SCV2 on the ability of the newly remodeled lung to handle various pulmonary challenges is of significant interest and therapeutic importance. Using the K18-hACE2 mouse model, we found that SCV2 resulted in an expanded pool of recruited alveolar macrophages along with persistent lymphocytic perivascular cuffs up to 90 days post-infection in the absence of detectable viral antigen. SCV2 resolved lungs had only modest changes following an OVA-specific allergic response compared to mock infected controls. In contrast, despite no differences in bacterial burdens, SCV2 experienced lungs had significantly less inflammation following infection with Bordetella pertussis compared to mock controls. However, this was not consistent for all bacterial driven inflammatory responses. Specifically, we observed an exacerbation of LPS derived inflammation in mice that had recovered from SCV2. The balance of inflammatory responses in these models was associated with specific changes in lipid mediators (LMs). Together, our data reveal the impact of SCV2 infection on the ability of the lung to optimally respond to a variety of inflammation provoking stimuli and underscore the potential role of LMs in the trained innate immune response.