Temporal Mapping of SARS-CoV-2 Variants During the Pandemic Reveals Similar Genomic Divergence in Unvaccinated and Vaccinated Cohorts, and in Both Adults and Children

Background: About 1.6 million COVID-19 cases have been reported from Pakistan across 6 pandemic waves associated with different SARS-CoV-2 variants. Vaccinations were introduced in 2021 however there is paucity of information regarding the effect of vaccinations in the context of SARS-CoV-2 viral transmission. We investigated the association of vaccinations with circulating SARS-CoV-2 variants by studying the phylogenetic diversity of strains infecting vaccinated and unvaccinated cases in Pakistan. Methods We analyzed the diversity of SARS-CoV-2 strains in children (< 18 years) tested at Aga Khan University Hospital during the period. We downloaded SARS-CoV-2 genome data from GISAID for samples collected May 2021-October 2022. SARS-CoV-2 variants were analyzed as per age, sex and vaccination status. Phylogenetic diversity was determined using the Augur pipeline and visualized using the Auspice platform. Results Of the 569 samples analyzed, 54.1% samples were collected in 2021, 47.1% were from females, and 71% were from individuals aged below 18 years. Variants identified include Wildtype (3.87%), Alpha (2.11%), Beta (1.76%), Delta (45.17%), and Omicron (45.87%). The dominant variant in 2021 was Delta, mainly the B.1.167.2 lineage, while Omicron dominated in 2022 with BA.5.2 being the most common lineage. Overall, 29.3% of the cohort was vaccinated. Of note, there was no difference in preponderance of variants between vaccinated and unvaccinated groups. There was no difference in SARS-CoV-2 variant distribution among age groups. Genomic divergence between those < 18 years and >18 years was similar. Facility-based analysis on pediatrics aged < 18 years showed Delta and Omicron to have been dominant in 2021 and 2022 respectively. PCR-based comparison of viral load revealed a significant variability (p=0.0002) among the SARS-CoV-2 variants. Amongst children, Omicron had the highest viral load. Conclusions Our study reveals that SARS-CoV-2 infections were caused by similar strains in both vaccinated and unvaccinated cohorts, as well as between younger and older age groups. This provides important insights into a population where high rates of subclinical transmission were observed and explains the low rates of COVID-19 morbidity and mortality observed.