Clinicogenomic analysis of breakthrough infections by SARS CoV2 variants after ChAdOx1 nCoV- 19 vaccination in healthcare workers

Kale, P.; Gupta, E.; Bihari, C.; Patel, N.; Rooge, S.; Pandey, A.; Bajpai, M.; Khillan, V.; Chattopadhyay, P. C.; Devi, P.; Maurya, R.; Jha, N.; Mehta, P.; Kumar, M.; Sharma, P.; Saifi, S.; S, A.; Alam, S.; Uppili, B.; Faruq, M.; Agrawal, A.; Pandey, R.; Sarin, S. K.

Background: India saw a massive surge and emergence of SARS CoV2 variants. We elucidated clinical and humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19 vaccine in healthcare workers (HCWs). Methods: The study was conducted on 1858 HCWs receiving two doses of ChAdOx1 nCoV- 19 vaccine. Serial blood samples were collected to measure SARS CoV2 IgG and neutralizing antibodies. 46 RT-PCR positive samples from VBT infections were subjected to whole genome sequencing (WGS). Results: Infection was confirmed in 219 (11.79%) HCWs of which 21.46% (47/219) were non-vaccinated, significantly more (p <0.001) than 9.52% (156/1639) vaccinated group. VBT infections were significantly higher in doctors and nurses compared to other hospital staff (p <0.001). Unvaccinated individuals had 1.57 times higher risk of infection compared to partially vaccinated (p 0.02) and 2.49 times than fully vaccinated (<0.001). Partially vaccinated were at higher risk of infection than fully vaccinated (RR 1.58,p 0.01). There were 3 (1.36%) severe cases and 1 death in unvaccinated group compared to none in the vaccinated. Non-response after 14 days of second dose was seen in 6.5% (3/46) and low antibody levels (1-4.62 S/CO) in 8.69% (4/46). Delta variant (B.1.617.2) was dominant (69.5%) and reinfection was documented in 4 (0.06%) HCWs. Conclusions: Nearly one in ten vaccinated HCWs can get infected, more so with only single dose (13.65%) than two doses (8.62%). Fully vaccinated are better protected with higher humoral immune response. Genomic analysis revealed an alarming rise of Delta variant (B.1.617.2) in VBT infections.