Germinal center-induced immunity is correlated with protection against SARS-CoV-2 reinfection but not lung damage.

Germinal centers (GCs) elicit protective humoral immunity through a combination of antibody-secreting cells and memory B cells, following pathogen invasion or vaccination. However, the possibility of a GC response inducing protective immunity against reinfection following SARS-CoV-2 infection remains unknown. Here, we found that GC activity was consistent with the seroconversion observed in recovered macaques and humans. Rechallenge with a different clade of virus resulted in a significant reduction in replicating virus titers in respiratory tracts in macaques with a high GC activity. However, diffuse alveolar damage and increased fibrotic tissue were observed in the lungs of reinfected macaques. Our study highlights the importance of GCs developed during natural SARS-CoV-2 infection in managing viral loads in the subsequent infections. However, their ability to alleviate lung damage remains to be determined. These results may improve our understanding of SARS-CoV-2-induced immune responses, resulting in better COVID-19 diagnosis, treatment, and vaccine development.