Mild COVID-19 presentations in unexposed individuals favour development of long-lived immune responses to SARS-CoV-2

Abstract Background Coronavirus disease 2019 (COVID-19), originally reported in Wuhan, China in December 2019 rapidly spread throughout the world resulting in a global pandemic from March 2020. Caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the clinical spectrum ranges from asymptomatic to severe and fatal disease. Most patients experience uncomplicated disease, with a wide range of clinical presentations including, headache, fever, cough, dyspnea, sore throat, fatigue, asnomia, myalgia, abdominal pain, diarrhea and nausea. It is well documented that immune responses to SARS-CoV-2 contribute to both immune protection and pathogenesis. Although much useful research has focussed on immune responses predisposing to severe COVID-19, much less is known on whether diverse uncomplicated disease presentations influence the quality and/or magnitude of the immune response to the virus. Methods To address this knowledge gap, we pursued a systems immunology approach integrating high dimensional mass cytometry and cytokine responses after SARS-CoV-2 re-stimulation of peripheral blood mononuclear cells (PBMC) from a retrospective study conducted in Australia in 2020. Results Cell populations identified by mass cytometry significantly expanding in response to spike-protein in vitro stimulation segregated the cohort in patients having ≥ 4 or ≤ 3 symptoms. Cell populations featured by patients with no more than 3 symptoms included CCR7 + T H2 cells, T H2 -polarised T FH cells, along with IgM + classical memory B cells and CXCR3 low , CD10 low classical monocytes. Notably, these responses persisted for 6 months post-exposure, in the absence of new infections. Conclusions Together, our results suggest that in previously COVID-19 naïve individuals, mild COVID-19 presentations might support the development of long-lasting immunity to SARS-CoV-2, able to contribute to protection during re-infection.