Robust human cellular immune responses to the pandemic coronavirus provides comfort of prolonged immunity post- infection and vaccination

 

Highlights

• 1.
  Acute phase SARS-CoV-2-specific T cells display an activated cytotoxic phenotype
• 2.
  Broad and polyfunctional SARS-CoV-2-specific T cell responses in convalescent phase
• 3.
  Detection of SARS-CoV-2-specific T cell responses also in seronegative individuals

From the discussion to the 2020 Sekine Cell paper  

Of particular note, we detected similar memory T cell responses directed against the internal (nucleocapsid) and surface proteins (membrane and/or spike) in some individuals lacking detectable circulating antibodies specific for SARS-CoV-2. Indeed, about twice as many healthy individuals who donated blood during the pandemic generated memory T cell responses in the absence of detectable circulating antibody responses, implying that seroprevalence as an indicator may underestimate the extent of population-level immunity against SARS-CoV-2. 

Our study was cross-sectional in nature and limited in terms of clinical follow-up and overall donor numbers in each outcome-defined group. It therefore remains to be determined if robust memory T cell responses in the absence of detectable circulating antibodies can protect against severe forms of COVID-19. This scenario has nonetheless been inferred from previous studies of MERS and SARS-CoV-1 (Channappanavar et al., 2014; Li et al., 2008; Zhao et al., 2017; Zhao et al., 2016), both of which have been shown to induce potent memory T cell responses that persist while antibody responses wane (Alshukairi et al., 2016; Shin et al., 2019; Tang et al., 2011). Notably, waning antibodies, as distinguished in SARS-CoV-2 infection (Ibarrondo et al., 2020; Long et al., 2020), is a natural phenomenon following coronavirus infections (Callow et al., 1990). The fact that memory B cells (Juno et al., 2020) and robust T cell memory is formed after SARS-CoV-2 infection, suggests that potent adaptive immunity is maintained to provide protection against severe re-infection. In line with these observations, none of the convalescent individuals in this study, including those with previous mild disease, have experienced further episodes of COVID-19.  

Of note, we detected cross-reactive T cell responses against spike or membrane in 28% of the unexposed healthy blood donors, consistent with a high degree of pre-existing immune responses potentially induced by other coronaviruses (Braun et al., 2020; Grifoni et al., 2020; Le Bert et al., 2020). 

Please cite this article as: 

Sekine, T., Perez-Potti, A., Rivera-Ballesteros, O., Strålin, K., Gorin, J.-B., Olsson, A., Llewellyn-Lacey, S., Kamal, H., Bogdanovic, G., Muschiol, S., Wullimann, D.J., Kammann, T., Emgård, J., Parrot, T., Folkesson, E., Karolinska COVID-19 Study Group, Rooyackers, O., Eriksson, L.I., Henter, J.-I., Sönnerborg, A., Allander, T., Albert, J., Nielsen, M., Klingström, J., Gredmark-Russ, S., Björkström, N.K., Sandberg, J.K., Price, D.A., Ljunggren, H.-G., Aleman, S., Buggert, M., 

Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19, Cell (2020), doi: https://doi.org/10.1016/j.cell.2020.08.017.