Clinical Characterization and Genomic Analysis of Samples from COVID-19 Breakthrough Infections during the Second Wave among the Various States of India

Gupta, Nivedita; Kaur, Harmanmeet; Yadav, Pragya Dhruv; Mukhopadhyay, Labanya; Sahay, Rima R.; Kumar, Abhinendra; Nyayanit, Dimpal A.; Shete, Anita M.; Patil, Savita; Majumdar, Triparna; Rana, Salaj; Gupta, Swati; Narayan, Jitendra; Vijay, Neetu; Barde, Pradip; Nataraj, Gita; B., Amrutha Kumari; Kumari, Manasa P.; Biswas, Debasis; Iravane, Jyoti; Raut, Sharmila; Dutta, Shanta; Devi, Sulochana; Barua, Purnima; Gupta, Piyali; Borkakoty, Biswa; Kalita, Deepjyoti; Dhingra, Kanwardeep; Fomda, Bashir; Joshi, Yash; Goyal, Kapil; John, Reena; Munivenkatappa , Ashok; Dhodapkar, Rahul; Pandit, Priyanka; Devi, Sarada; Dudhmal, Manisha; Kinariwala, Deepa; Khandelwal, Neeta; Tiwari, Yogendra Kumar; Khatri, Prabhat Kiran; Gupta, Anjli; Khatri, Himanshu; Malhotra, Bharti; Nagasundaram, Mythily; Dar, Lalit; Sheikh, Nazira; Shastri, Jayanthi; Aggarwal, Neeraj; Abraham, Priya

From March to June 2021, India experienced a deadly second wave of COVID-19, with an increased number of post-vaccination breakthrough infections reported across the country. To understand the possible reason for these breakthroughs, we collected 677 clinical samples (throat swab/nasal swabs) of individuals from 17 states/Union Territories of the country who had received two doses (n = 592) and one dose (n = 85) of vaccines and tested positive for COVID-19. These cases were telephonically interviewed and clinical data were analyzed. A total of 511 SARS-CoV-2 genomes were recovered with genome coverage of higher than 98% from both groups. Analysis of both groups determined that 86.69% (n = 443) of them belonged to the Delta variant, along with Alpha, Kappa, Delta AY.1, and Delta AY.2. The Delta variant clustered into four distinct sub-lineages. Sub-lineage I had mutations in ORF1ab A1306S, P2046L, P2287S, V2930L, T3255I, T3446A, G5063S, P5401L, and A6319V, and in N G215C; Sub-lineage II had mutations in ORF1ab P309L, A3209V, V3718A, G5063S, P5401L, and ORF7a L116F; Sub-lineage III had mutations in ORF1ab A3209V, V3718A, T3750I, G5063S, and P5401L and in spike A222V; Sub-lineage IV had mutations in ORF1ab P309L, D2980N, and F3138S and spike K77T. This study indicates that majority of the breakthrough COVID-19 clinical cases were infected with the Delta variant, and only 9.8% cases required hospitalization, while fatality was observed in only 0.4% cases. This clearly suggests that the vaccination does provide reduction in hospital admission and mortality.