SARS-CoV-2 and COVID-19 immunopathogenesis have several pathways. Therapies that prevent viral infection and regulate defective immune responses may stop numerous diseases. When developing and testing COVID-19 vaccines, consider immune dysfunction and disease severity. More research is needed on the host immune response to SARS-CoV-2, especially healthy versus dysfunctional consequences. These help detect immunological correlates of protection and illness severity for patient triage.