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

Kiran Iqbal Masood, Shama Qaiser, Syed Hani Abidi, Erum Khan, Syed Faisal Mahmood, Areeba Hussain, Zara Ghous, Khekahsan Imtiaz, Natasha Ali, Muhammad Hasan, Haris Ali Memon, Maliha Yameen, Shiza Ali, Sadaf Baloch, Gulzar Lakhani, Paula M. Alves, Najeeha Talat Iqbal, Kumail Ahmed, Junaid Iqbal, Zulfiqar A. BhuttaRabia Hussain, Martin Rottenberg, J. Pedro Simas, Marc Veldhoen, Kulsoom Ghias, Zahra Hasan

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number846
JournalBMC Infectious Diseases
Issue number1
Publication statusPublished - Dec 2023


  • IgG
  • Interferon-gamma
  • Receptor binding domain
  • SARS-CoV-2
  • Spike
  • T cells


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