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

Abstract

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.

SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike

“…Titers against both the spike and N protein persisted even 2+ months after symptom onset ( Fig. 1c), indicating the antibody response against these two antigens is stable amongst subjects with symptomatic infection, a finding consistent with other reports 6,7 . We did not observe a statistical difference in antibody titers against the spike and N protein by individual subjects in either the acute or convalescent subject cohorts ( Fig.…”

Cross-reactive memory T cells and herd immunity to SARS-CoV-2

“…A recent COVID-19 study observed approximately 3 SARS-CoV-2-exposed (not PCR-confirmed) potentially asymptomatic cases with T cell responses in the absence of seroconversion 10 . Although there has been extensive discussion in the public arena, and in public health circles, of whether a large population of seronegative previously SARS-CoV-2-infected people exists, if one excludes the issue of poor-quality serological kits, the preponderance of data supports the conclusion that the vast majority of SARS-CoV-2-infected individuals do seroconvert, at least for a duration of months 4,14,[37][38][39][40][41] . Quantitatively, these estimates range from 99% in a New York City study of 624 PCR-confirmed cases to 91.1% in an Icelandic study of 1,797 patients 37,40 .…”

Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration

“…On the basis of these findings, we focused on correlates of clinical outcomes in convalescent plasma donors that could be inferred through cell-based assays. Recent studies have correlated B cell responses in some individuals with immunity and protection (4). B cells participate in the antiviral immune response by first rapidly releasing germline or neargermline antibodies from plasmablasts, via an extrafollicular pathway.…”