Innate and adaptive immunity to SARS-CoV-2 and predisposing factors

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has affected all countries worldwide. Although some symptoms are relatively mild, others are still associated with severe and even fatal clinical outcomes. Innate and adaptive immunity are important for the control of SARS-CoV-2 infections, whereas a comprehensive characterization of the innate and adaptive immune response to COVID-19 is still lacking and the mechanisms underlying immune pathogenesis and host predisposing factors are still a matter of scientific debate. Here, the specific functions and kinetics of innate and adaptive immunity involved in SARS-CoV-2 recognition and resultant pathogenesis are discussed, as well as their immune memory for vaccinations, viral-mediated immune evasion, and the current and future immunotherapeutic agents. We also highlight host factors that contribute to infection, which may deepen the understanding of viral pathogenesis and help identify targeted therapies that attenuate severe disease and infection.

Contrasting Effects of SARS-CoV-2 Vaccination vs. Infection on Antibody and TCR Repertoires

“…Solid lines indicate regression fits; shaded areas indicate 95% confidence intervals. Dotted black line at ∼10 3 indicates manufacturer’s cutoff for positive vs. negative. Note strong negative trend with age in vaccinees (blue) but not infectees (salmon).…”

“…19–21 The 68 TRBs they identified were found in 40% of COVID-19 repertoires vs. 17% of pre-pandemic controls. This suggests significant enrichment even as the majority of individuals with COVID-19 lacked these sequences and a significant minority of controls (1 in 6) had them despite these control samples having been collected before the pandemic (which has been observed in other contexts, 22 perhaps indicating cross-reactivity with previously circulating coronaviruses, which are very common in human populations 3 ).…”

“…Moreover, most studies investigated only BCRs or only TCRs, but not both in the same cohort, despite the importance of both antibody and T-cell responses in SARS-CoV-2 infection. 2,3 To our knowledge only two previous COVID-19 studies 4,5 have sequenced TCR from lllδ T cells, a little-studied subset that may be important in mucosal antimicrobial immunity. 6,7 How SARS-CoV-2 virus or vaccine exposure affects different B– and T-cell subsets (IgM+ vs. non-IgM+ B-cells, CD4+ vs. CD8+ T cells) has also been insufficiently explored.…”

“…6,7 How SARS-CoV-2 virus or vaccine exposure affects different B– and T-cell subsets (IgM+ vs. non-IgM+ B-cells, CD4+ vs. CD8+ T cells) has also been insufficiently explored. 2,3…”

Longitudinal transcriptional changes reveal genes from the natural killer cell-mediated cytotoxicity pathway as critical players underlying COVID-19 progression

“…Convalescent patients report prolonged COVID-19 symptoms beyond the time course for typical cold and flu events, which highlights the possibility of long-term tissue damage generated by this virus (Ladds et al, 2020; Nalbandian et al, 2021; Ryan et al, 2022; Subramanian et al, 2022). Similarly as other respiratory viruses, it is known that SARS-CoV-2 triggers an immune response involving the recruitment, activation, and differentiation of innate and adaptive immune cells (Newton, Cardani, & Braciale, 2016; Shen et al, 2023; Wauters et al, 2021). For mildly-ill patients, these coordinated immunological efforts resolve infection but for unknown reasons the virus evades these responses in severely-ill patients to produce life-threatening COVID-19 (Park, 2020; Rashid et al, 2022; Sun, Xie, Bu, Zhong, & Zeng, 2022; Thorne et al, 2022).…”