Evidence of rapid rise in population immunity from SARS-CoV-2 subclinical infections through pre-vaccination serial serosurveys in Pakistan

Background Understanding factors associated with protective immunity against emerging viral infections is crucial for global health. Pakistan reported its first COVID-19 case on 26 February 2020, but experienced relatively low COVID-19-related morbidity and mortality between 2020 and 2022. The underlying reasons for this remain unclear, and our research aims to shed light on this crucial issue. Methods We conducted a serial population-based serosurvey over 16 months (rounds 1-4, July 2020 to November 2021) across households in urban (Karachi) and rural (Matiari) Sindh, sampling 1100 households and 3900 individuals. We measured antibodies in sera and tested a subset of respiratory samples for COVID-19 using polymerase chain reaction (PCR) and antigen tests, also measuring haemoglobin (Hb), C-reactive protein (CRP), vitamin D, and zinc in round 1. Results Participants showed 23% (95% confidence interval (CI) = 21.9-24.5) antibody seroprevalence in round 1, increasing across rounds 2-4 to 29% (95% CI = 27.4-30.6), 49% (95% CI = 47.2-50.9), and 79% (95% CI = 77.4-80.8), respectively. Urban residents had 2.6 times (95% CI = 1.9-3.6) higher odds of seropositivity than rural residents. Seropositivity did not differ between genders. Individuals aged 20-49 years had 7.5 (95% CI = 4.6-12.4) times higher odds of seropositivity compared to children aged 0-4 years. Most participants had no symptoms associated with COVID-19, with no reported mortality. Vitamin D deficiency was linked to seroprevalence. COVID-19 was confirmed in 1.8% of individuals tested via RT-PCR and antigen tests. Conclusions The data suggests a steady increase in humoral immunity in Pakistan, likely due to increased transmission and associated asymptomatic disease. Overall, this reflects the longitudinal trend of protection against severe acute respiratory syndrome coronavirus 2, leading to the relatively low morbidity and mortality observed in the population.