Molecular Epidemiology of SARS-CoV-2 in Healthcare Workers and Identification of Viral Genomic Correlates of Transmissibility and Vaccine Break Through Infection: A Retrospective Observational Study From a Cancer Hospital in Eastern India

Background: Despite COVID vaccination with COVISHIELD vaccine (ChAdOx1 ncov-19) large number of healthcare workers (HCWs) was getting infected in wave-2 of the pandemic in a cancer hospital in eastern part of India. Methods: Retrospective observational study of HCWs. Whole genome sequencing of SARS CoV-2 using Illumina NovaSeq was done. Mutations from both waves were compared to identify genomic correlates of transmissibility and vaccine breakthrough infections. Findings: Vaccine breakthrough infections were seen in 127 HCWs out of 1,806 fully vaccinated staff (7.03%). Median number of HCWs infected per day in wave-1 was 0.92 versus 3.25 in wave-2. Majority of wave-1 samples belonged to B.1 and B.1.1 lineage. Variant of concern- Delta variant (90%), and variant of interest- Kappa variant (10%), was seen in only wave-2 samples. Total mutation observed in wave-2 samples (median = 44) was 1.8 times than wave-1 sample (median=24). Same trend was observed in coding mutation count. Spike protein in wave-2 samples contain 13 non-synonymous mutation as compared to 8 seen in wave-1 samples. E484Q- vaccine escape mutant was detected in five samples of wave-2; T478K – highly infectious mutation was seen in 31 samples of wave-2. We identified a novelcoding disruptive in-frame deletion (c.467_472delAGTTCA, p.Glu156_Arg158delinsGly) in the Spike protein. This mutation was seen only in wave-2 (78%, n=39) samples. The mutation overlaps the spike protein NTD domain and is present in the supersite b-hairpin. Interpretation: We noted that vaccine breakthrough infections (although mostly mild) were not uncommon and occurred despite two doses of COVISHIELD vaccine. The potential causes of vaccine breakthrough infections, and the most optimal schedule for HCWs need to be investigated. Funding Information: Study was funded by the institutional research fund of Tata Medical Center, Kolkata, India. Declaration of Interests: None to declare. Ethics Approval Statement: The TMC-IRB approved the study on 10th October 2020. The memo number was 2020/Govt/33/IRB46.