Humoral and T cell responses to SARS-CoV-2 reveal insights into immunity during the early pandemic period in Pakistan

BMC Infect Dis. 2023 Dec 1;23(1):846. doi: 10.1186/s12879-023-08829-1.

Abstract

Background: Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP).

Methods: HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell - IFN-γ activation was assessed by ELISpot.

Results: Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike.

Conclusions: Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population.

Keywords: IgG; Interferon-gamma; Receptor binding domain; SARS-CoV-2; Spike; T cells.

MeSH terms

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19* / epidemiology
  • Enzyme-Linked Immunospot Assay
  • Humans
  • Immunity, Humoral
  • Immunoglobulin G
  • Pakistan / epidemiology
  • Pandemics
  • SARS-CoV-2*
  • Seroepidemiologic Studies
  • Spike Glycoprotein, Coronavirus
  • T-Lymphocytes

Substances

  • Spike Glycoprotein, Coronavirus
  • Immunoglobulin G
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • spike protein, SARS-CoV-2