Motivation From an isolated epidemic, COVID-19 has now emerged as a global pandemic. The availability of genomes in the public domain following the epidemic provides a unique opportunity to understand the evolution and spread of the SARS-CoV-2 virus across the globe. Results We performed whole-genome sequencing of 303 Indian isolates, and analyzed them in the context of publicly available data from India. We describe a distinct phylogenetic cluster (Clade I/A3i) of SARS-CoV-2 genomes from India, which encompasses 22% of all genomes deposited in the public domain from India. Globally approximately 2% of genomes, which till date could not be mapped to any distinct known cluster fall in this clade. Conclusions The cluster is characterized by a core set of 4 genetic variants and has a nucleotide substitution rate of 1.1 x 10 -3 variants per site per year, lower than the prevalent A2a cluster. Epidemiological assessments suggest that the common ancestor emerged at the end of January 2020 and possibly resulted in an outbreak followed by countrywide spread. To the best of our knowledge, this is the first comprehensive study characterizing this cluster of SARS-CoV-2 in India.
From an isolated epidemic, COVID-19 has now emerged as a global pandemic. The availability of genomes in the public domain following the epidemic provides a unique opportunity to understand the evolution and spread of the SARS-CoV-2 virus across the globe. The availability of whole genomes from multiple states in India prompted us to analyse the phylogenetic clusters of genomes in India. We performed whole-genome sequencing for 64 genomes making a total of 361 genomes from India, followed by phylogenetic clustering, substitution analysis, and dating of the different phylogenetic clusters of viral genomes. We describe a distinct phylogenetic cluster (Clade I / A3i) of SARS-CoV-2 genomes from India, which encompasses 41% of all genomes sequenced and deposited in the public domain from multiple states in India. Globally 3.5% of genomes, which till date could not be mapped to any distinct known cluster fall in this newly defined clade. The cluster is characterized by a core set of shared genetic variants -C6312A (T2016K), C13730T (A88V/A97V), C23929T, and C28311T (P13L). Further, the cluster is also characterized by a nucleotide substitution rate of 1.4 x 10 -3 variants per site per year, lower than the prevalent A2a cluster, and predominantly driven by variants in the E and N genes and relative sparing of the S gene. Epidemiological assessments suggest that the common ancestor emerged in the month of February 2020 and possibly resulted in an outbreak followed by countrywide spread, as evidenced by the low divergence of the genomes from across the country. To the best of our knowledge, this is the first comprehensive study characterizing the distinct and predominant cluster of SARS-CoV-2 in India.
Dear Editor,COVID-19 has an extremely variable prognosis, ranging from asymptomatic and mildly affected individuals to severe disease and death. We have investigated the transcriptional changes in 36 COVID-19 positive Indian patients hospitalized during the first surge (Figure 1A, Table S1, and Supplementary Methods) against 5 COVID-19 negative samples. RNA was isolated from naso/oropharyngeal swabs for paired end sequencing using the Illumina Nova-seq 6000. We identified 251 upregulated (220 protein coding) and 9068 downregulated (3252 protein coding) differentially expressed genes (DEGs) (adjusted p-value < 0.05 and absolute log2 fold change > 1) (Figure 1B, Tables S2 and S3). Seven patients were critical and required intensive care unit (ICU) intervention, while 23 were discharged from COVID-19 ward (W), although no significant differences could be seen in their transcriptional profiles (Figure 1C). The overall transcriptional reduction, irrespective of disease severity (Figure 1C), is well correlated with the phenomenon of fading host cell functionality and prominent viral protein synthesis, and may be associated with interference in host cellular processes and responses. 1 The results indicate a diverse transcriptomic profile in response to SARS-CoV-2, in line with the variable prognosis seen in many COVID-19 patients. However, we find robust activation of the innate immune response concomitant with a reduction in the gene expression profiles associated with cardiac, muscular, and neurological processes, as well as peripheral neurosensory markers.Immune response genes were highly upregulated (Figure 2A and Table S4), with prominent clusters of genes associated with multiple viral infections (Figure 2B and Table S5) marking the activation of infection clearance pathways. Meta-analysis of published datasets identified a signature of 19 upregulated genes (Table S6), linking Type I interferon (IFN) signaling, host defense, and innate immune responses in SARS-CoV-2 infection (Fig-This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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