Genomic Epidemiology of SARS-CoV-2 variants in unvaccinated children found to be similar to that of adults with COVID-19 vaccinations

<ns3:p>Background Pakistan experienced six COVID-19 waves with varying SARS-CoV-2 variants. Vaccination campaigns began in 2021, in an age-stratified manner starting with the older-aged individuals, yet the relationship between vaccination status and variant transmission remains unclear. We investigated SARS-CoV-2 phylogenetic diversity in relation to age and vaccination status, with a focus on children. Methods We analyzed 569 SARS-CoV-2 genome sequences collected across Pakistan from May 2021 to October 2022. Metadata including age, sex, and vaccination status were retrieved from GISAID. Additional data such as viral load was available for a set of 143 pediatric samples (&lt; 18 years) sequenced at Aga Khan University Hospital (AKUH), Karachi, and was analyzed separately to gain further insights. Phylogenetic analyses were conducted using the Augur pipeline and visualized via Auspice. Viral loads were inferred from Ct values of SARS-CoV-2 PCR diagnostic assays. Results Among the 569 genomes, Delta (45.2%) dominated in 2021 and Omicron (45.9%) in 2022. Of these, 71% were from individuals &lt;18 years; 29.3% were vaccinated. Variant distribution showed no significant difference between vaccinated and unvaccinated individuals (p=0.75), nor between age groups (&lt;18 vs ≥18 years; p=0.60). Pediatric samples from AKUH Karachi mirrored national trends, with Delta predominating in 2021 and Omicron in 2022. Omicron variants were associated with higher viral loads (p&lt;0.001). Conclusions SARS-CoV-2 variant distribution and genomic divergence were comparable across vaccination status and age groups. In a population with high subclinical transmission and delayed pediatric vaccination, our findings highlight the stability of variant spread irrespective of host immunity status, suggesting the role of widespread prior exposure in shaping transmission dynamics.</ns3:p>