key: cord-1054948-0krk54z5 authors: Ghosh, A.; Walia, S.; Rattan, R.; Kanampalliwar, A.; Jha, A.; Aggarwal, S.; Fatma, S.; Das, N.; Chayani, N.; Prasad, P.; Raghav, S. K.; Parida, A. title: Genomic profiles of Covishield and Covaxin breakthrough SARS-CoV-2 strains from Odisha, India date: 2021-08-20 journal: nan DOI: 10.1101/2021.08.16.21261912 sha: 4400623048e032e69c320ff69086ef91d3affe04 doc_id: 1054948 cord_uid: 0krk54z5 Vaccine breakthrough infections pose a vast challenge in the eradication of the COVID pandemic situation. Emerging SARS-CoV-2 variants of concern infecting the immunized individuals indicate an ongoing battle between host immunity and natural selection of the pathogen. Our report sheds light on the prominent SARS-CoV-2 variations observed in the isolates from AZD1222/Covishield and BBV152/Covaxin vaccinated subjects. India has experienced 426,290 cumulative fatalities due to COVID-19 as of August 06, 2021 (https://covid19.who.int/table). Subsequent waves of SARS-CoV-2 infection with rapid resurgence in transmission and mortality deployed potential vaccine candidates to generate an effective immune response against SARS-CoV-2. In India, five COVID-vaccines are authorized for emergency use, out of which the adenovirusvector based vaccine from Oxford University and AstraZeneca UK marketed as Covishield, and the indigenous inactivated virus vaccine Covaxin by Bharat Biotech are majorly deployed through government and private healthcare centers. Both the vaccines pose tolerable safety outcomes and enhanced immune responses [1, 2] . The emergence of novel variants of concern (VOC), novel spike (S) protein mutations leading to higher infectivity rate and vaccine escape . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) [4] . In this study, we summarize 36 COVID vaccine breakthrough cases, which were SARS-CoV-2 RT-PCR positive despite evidence of an antibody response following vaccination. Data for this study were included from individuals who had been Amplicon based dual indexed paired-end libraries for viral genome sequencing were prepared by COVIDSeq kit and sequenced using NextSeq-550 platform (Illumina). After demultiplexing, non-Host (Human) extracted reads using Kraken2 taxonomic classifier [5] , were aligned using BWA against the Wuhan-Hu-1 (NC_045512.2) reference genome. Primer regions from the aligned sequences were trimmed using iVar followed by removal of duplicate reads. Single . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 20, 2021. ; https://doi.org/10.1101/2021.08.16.21261912 doi: medRxiv preprint 4 nucleotide variants and short INDELs were called using GATK4 Haplotypecaller using ploidy 1 followed by removal of low-quality variants (Quality by depth, QD < 5) by GATK VariantFiltration. Consensus sequences generated using BCFTOOL consensus and regions having no aligned reads were hard-masked. Clade and lineage of the viral genomes were determined using Nextclade (https://clades.nextstrain.org/) and PANGOLIN (pangoLEARN version 2021-07-28) respectively [6] . Rooted (root: NC_045512.2) phylogenetic tree of 549 sequences (522 other sequences collected in same timeframe from Odisha) was constructed using method described in [7] . All the calculations and statistical tests were performed using base R functions. As a part of the regular COVID-19 genomic surveillance, we identified and sequenced 36 vaccine breakthrough infection cases. The study group consisted of 12 females, 24 males with age ranging from 23 to 65 years (median = 38.50, sd = 13.58) (Supplementary table 1 When we looked for high frequency variants (present in > 20% of samples) in these two vaccination groups, COVAXIN cases contained an overall higher number of variants (n=42) in comparison to the COVISHILD group (n=28) (Figure 1 A, 1B) . Although two of the cases were Interestingly, most of the breakthrough cases shared presence of S:L452R, S:T478K in receptor binding domain (RBD) along with S:D614G and S:P681R near S1-S2 furin cleavage site. All these spike variants have been proposed to be associated with increased infectivity through different mechanisms ( Figure 1D) [9]. In the study group, 7 out of 36 patients reported comorbidities i.e., diabetes, blood pressure, rest 26 patients did not report any complications, disease history is unknown for three cases. Out of 36 patients only 1 patient was hospitalized with comorbidities, 23 recovered in home isolation, for 8 individuals the treatment status is unknown. Except for three unknown cases, the rest of the patients didn't report any prior history of SARS-CoV-2 infection at the time of sample collection. In this study we found that SARS-CoV-2 variant of concern Delta (B.1.617.2) is overrepresented in the vaccine break-through cases, which could be due to its higher prevalence as well during . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 20, 2021. ; https://doi.org/10.1101/2021.08.16.21261912 doi: medRxiv preprint that period. Recent studies suggested that the effectiveness of BNT162b2 (Pfizer) and ChAdOx1 (AstraZeneca) has been reduced in comparison to Alpha (B.1.1.7) variant. Also the same has been observed in neutralizing capability of sera from fully vaccinated individuals [4, 10] . One other in vitro study suggested that S:L452R and S:E484Q present in RDB domain of . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 20, 2021. ILS provided an intramural grant to perform the study. The authors declare no conflict of interest. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 20, 2021. ; https://doi.org/10.1101/2021.08.16.21261912 doi: medRxiv preprint Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization Improved metagenomic analysis with Kraken 2 Assignment of epidemiological lineages in an emerging pandemic using the pangolin tool. Virus Evol Analysis of Indian SARS-CoV-2 Genomes Reveals is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 20, 2021.