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

Indian J Med Microbiol. 2023 Jan-Feb:41:104-110. doi: 10.1016/j.ijmmb.2022.09.010. Epub 2022 Oct 13.

Abstract

Purpose: Despite COVID vaccination with ChAdOx1 ncov-19 (COVISHIELD®) (ChAdOx1 ncov-19) a large number of healthcare workers (HCWs) were getting infected in wave-2 of the pandemic in a cancer hospital of India. It was important therefore to determine the genotypes responsible for vaccine breakthrough infections.

Methods & objectives: 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.

Results: Vaccine breakthrough infections were seen in 127 HCWs out of 1806 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). Spike protein in wave-2 samples had 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.

Conclusion: The circulating virus strains in wave-2 infections demonstrated a greater degree of infectivity. There was a significant change in the genotypes observed in wave-1 and wave-2 infections along with almost twice the number of mutations. We noted that vaccine breakthrough infections (although mostly mild).

Keywords: Delta variant; SARS CoV-2; Vaccine breakthrough infections; Variant of concern; Whole genome sequencing.

Publication types

  • Observational Study

MeSH terms

  • Breakthrough Infections
  • COVID-19*
  • Cancer Care Facilities
  • ChAdOx1 nCoV-19
  • Communicable Diseases*
  • Genomics
  • Health Personnel
  • Humans
  • India
  • Molecular Epidemiology
  • Neoplasms*
  • Postoperative Complications
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus

Substances

  • ChAdOx1 nCoV-19
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants