Functional SARS-CoV-2-specific immune memory persists after mild COVID-19

Pepper, Marion; Rodda, Lauren; Netland, Jason; Shehata, Laila; Pruner, Kurt; Morawski, Peter; Thouvenel, Chris; Takahara, Kennidy; Eggenberger, Julie; Hemann, Emily; Waterman, Hayley; Fahning, Mitchell; Chen, Yu; Rathe, Jennifer; Stokes, Caleb; Wrenn, Samuel; Fiala, Brooke; Carter, Lauren; Hamerman, Jessica; King, Neil; Gale, Michael; Campbell, Daniel; Rawlings, David

The recently emerged SARS-CoV-2 virus is currently causing a global pandemic and cases continue to rise. The majority of infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it is unknown whether this can induce persistent immune memory that might contribute to herd immunity. Thus, we performed a longitudinal assessment of individuals recovered from mildly symptomatic COVID-19 to determine if they develop and sustain immunological memory against the virus. We found that recovered individuals developed SARS-CoV-2-specific IgG antibody and neutralizing plasma, as well as virus-specific memory B and T cells that not only persisted, but in some cases increased numerically over three months following symptom onset. Furthermore, the SARS-CoV-2-specific memory lymphocytes exhibited characteristics associated with potent antiviral immunity: memory T cells secreted IFN-γ and expanded upon antigen re-encounter, while memory B cells expressed receptors capable of neutralizing virus when expressed as antibodies. These findings demonstrate that mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks associated with antiviral protective immunity.