Innate and adaptive immune responses to SARS-CoV-2 in humans: relevance to acquired immunity and vaccine responses

The factors responsible for the spectrum of coronavirus 19 (COVID-19) disease severity and the genesis and nature of protective immunity against COVID-19 remain elusive. Multiple studies have investigated the immune responses to COVID-19 in various populations, including those without evidence of COVID-19 infection. Information regarding innate and adaptive immune responses to the novel severe respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved rapidly. Data are accumulating defining disease phenotypes that aid in rational and informed development of new therapeutic approaches for the treatment of patients infected with SARS-CoV-2 and the development of novel vaccines. In this paper, data on important innate immune responses are summarized, including cytokines, specifically interleukin (IL)-6 and complement, and potential treatments are explored. Adaptive immune responses and derivative therapeutics such as monoclonal antibodies directed at spike proteins are also examined. Finally, data on real-time assessments of adaptive immune responses are explored, which include CD4⁺ /CD8⁺ T cells, natural killer (NK) T cells, memory B cells and T follicular cells with specificities for COVID-19 peptides in infected and normal individuals. Data of two novel vaccines have been released, both showing > 95% efficacy in preventing SARS-CoV-2 infection. Analysis of humoral and cellular responses to the vaccines will determine the robustness and durability of protection. In addition, long-term assessment of SARS-CoV-2 memory B and T cell-mediated immune responses in patients recovering from an infection or those with cross-reactive immunological memory will help to define risk for future SARS-CoV infections. Finally, patients recovering from SARS-CoV-2 infection may experience prolonged immune activation probably due to T cell exhaustion. This will be an important new frontier for study.