Dynamics of IgG Antibody Responses to SARS-CoV-2 Reveals Insight into Immunity During the Early Pandemic Period in Pakistan

Background: COVID-19 related disease morbidity and mortality has varied worldwide. We investigated antibody and T cell responses to SARS-CoV-2 in COVID-19 cases and exposed but healthy individuals further compared with pre-pandemic controls in a high infectious disease burden setting. Methods: IgG antibodies against Spike and Spike Receptor Binding Domain (RBD) were determined by ELISA in a Health Care cohort (HC; n=304), COVID-19 cases (n=163) and Pre-Pandemic Controls (PPC; n=114). Neutralizing antibody assays and T cell ELISpot assays were also conducted. Findings: IgG anti Spike proteins and RBD were present in all three groups albeit at varying levels. The highest rate of positivity was observed in COVID-19 cases (87.7% to Spike; 53.9% to RBD); followed by HC (35% to Spike; 21.3% to RBD) and PPC (12.2% to Spike; 10.50% to RBD). Antibody positivity in HC rose from 4.5% in October 2020 to 61% in January 2021. Levels of IgG antibodies to Spike and RBD strongly correlated in COVID-19 and HC but not in PPC. IgG to RBD was associated with neutralizing activity against SARS-CoV-2. Spike reactive T cells were identified in COVID-19 patients (6/18), HC (2/7) and but only one PPC (1/6). Interpretation: IgG to Spike and RBD in pre-pandemic sera is likely associated with cross-protection induced by other pathogens. The increasing percentage of IgG antibody positivity in HCC over the pandemic period may be due to expansion of cross-reactive B cells as observed in PPC, due either to exposure or asymptomatic subclinical infection with SARS-CoV-2. Neutralizing activity of RBD IgG antibodies and reactive T cells to Spike in PPC suggests the presence of memory B and T cells to cross-reactive epitopes that can expand quickly, jumpstarting protection against SARS-CoV-2.Funding Information: This work was supported by the Provost’s Academic Priorities Fund, Aga Khan University. Funding support was also received through Swedish Research Council project SRL 4-182/2019. We acknowledge the support for recombinant protein provided by IBET, NOVA University, Portugal. MV was supported by the European Union H2020 ERA project (No 667824 – EXCELLtoINNOV).Conflict of Interests: The authors have no competing interests to declare.Ethical Approval: This study was approved by the Ethical Review Committee of The Aga Khan University (projects #2020-5152-11688 and 2020-3687-10181).