Studies on host-pathogen interaction have identified human ACE2 as a host cell receptor responsible for mediating infection by coronavirus (COVID-19). Subsequent studies have shown striking difference of allele frequency among Europeans and Asians for a polymorphism rs2285666, present in ACE2. It has been revealed that the alternate allele (TT-plus strand or AA-minus strand) of rs2285666 elevate the expression level of this gene upto 50%, hence may play a significant role in SARS-CoV-2 susceptibility. Therefore, we have first looked the phylogenetic structure of rs2285666 derived haplotypes in worldwide populations and compared the spatial frequency of this particular allele with respect to the COVID-19 infection as well as case-fatality rate in India. For the first time, we ascertained a significant positive correlation for alternate allele (T or A) of rs2285666, with the lower infection as well as case-fatality rate among Indian populations. We trust that this information will be useful to understand the role of ACE2 in COVID-19 susceptibility.

It was shown that the human Angiotensin-converting enzyme 2 (ACE2) is the receptor of recent coronavirus SARS-CoV-2, and variation in this gene may affect the susceptibility of a population. Therefore, we have analysed the sequence data of ACE2 among 393 samples worldwide, focusing on South Asia. Genetically, South Asians are more related to West Eurasian populations rather than to East Eurasians. In the present analyses of ACE2, we observed that the majority of South Asian haplotypes are closer to East Eurasians rather than to West Eurasians. The phylogenetic analysis suggested that the South Asian haplotypes shared with East Eurasians involved two unique event polymorphisms (rs4646120 and rs2285666). In contrast with the European/American populations, both of the SNPs have largely similar frequencies for East Eurasians and South Asians, Therefore, it is likely that among the South Asians, host susceptibility to the novel coronavirus SARS-CoV-2 will be more similar to that of East Eurasians rather than to that of Europeans.

SARS-CoV-2, the causative agent for COVID-19, an ongoing pandemic, engages the ACE2 receptor to enter the host cell through S protein priming by a serine protease, TMPRSS2 . Variation in the TMPRSS2 gene may account for the disparity in disease susceptibility between populations. Therefore, in the present study, we have used next-generation sequencing (NGS) data of world populations from 393 individuals and analyzed the TMPRSS2 gene using a haplotype-based approach with a major focus on South Asia to study its phylogenetic structure and their haplotype sharing among various populations worldwide. Our analysis of phylogenetic relatedness showed a closer affinity of South Asians with the West Eurasian populations therefore, host disease susceptibility and severity particularly in the context of TMPRSS2 will be more akin to West Eurasian instead of East Eurasian. This is in contrast to our prior study on the ACE2 gene which shows South Asian haplotypes have a strong affinity towards West Eurasians. Thus ACE2 and TMPRSS2 have an antagonistic genetic relatedness among South Asians. Considering the significance of the TMPRSS2 gene in the SARS-CoV-2 pathogenicity, COVID-19 infection and intensity trends could be directly associated with increased expression therefore, we have also tested the SNPs frequencies of this gene among various Indian state populations with respect to the case fatality rate (CFR). Interestingly, we found a significant positive association between the rs2070788 SNP (G Allele) and the CFR among Indian populations. Further our cis eQTL analysis of rs2070788 shows that the GG genotype of the rs2070788 tends to have a significantly higher expression of TMPRSS2 gene in the lung compared to the AG and AA genotypes thus validating the previous observation and therefore it might play a vital part in determining differential disease vulnerability. We trust that this information will be useful in understanding the role of the TMPRSS2 variant in COVID-19 susceptibility and using it as a biomarker may help to predict populations at risk.

Infection born by Coronavirus SARS-CoV-2 has swept the world within a time of a few months. It has created a devastating effect on humanity with social and economic depressions. Europe and America were the hardest hit continents. India has also lost several lives, making the country fourth most deadly worldwide. However, the infection and death rate per million and the case fatality ratio in India were substantially lower than many of the developed nations. Several factors have been proposed including the genetics. One of the important facts is that a large chunk of Indian population is asymptomatic to the SARS-CoV-2 infection. Thus, the real infection in India is much higher than the reported number of cases. Therefore, the majority of people are already immune in the country. To understand the dynamics of real infection as well as level of immunity against SARS-CoV-2, we have performed antibody testing (serosurveillance) in the urban region of fourteen Indian districts encompassing six states. In our survey, the seroprevalence frequency varied between 0.01-0.48, suggesting high variability of viral transmission among states. We also found out that the cases reported by the Government were several fold lower than the real infection. This discrepancy is majorly driven by a higher number of asymptomatic cases. Overall, we suggest that with the high level of immunity developed against SARS-CoV-2 in the majority of the districts, it is less likely to have a second wave in India.

With the growing evidence on the variable human susceptibility against COVID-19, it is evident that some genetic loci modulate the severity of the infection. Recent studies have identified several loci associated with greater severity. More recently, a study has identified a 50 kb genomic segment introgressed from Neanderthal adding a risk for COVID-19, and this genomic segment is present among 16% and 50% people of European and South Asian descent, respectively. Our studies on ACE2 identified a haplotype present among 20% and 60% of European and South Asian populations, respectively, which appears to be responsible for the low case fatality rate among South Asian populations. This result was also consistent with the real-time infection rate and case fatality rate among various states of India. We readdressed this issue using both of the contrasting datasets and compared them with the real-time infection rates and case fatality rate in India. We found that the polymorphism present in the 50 kb introgressed genomic segment (rs10490770) did not show any significant correlation with the infection and case fatality rate in India.

The COVID-19 pandemic resulted in multiple waves of infection worldwide. The large variations in case fatality rate among different geographical regions suggest that the human susceptibility against this virus varies substantially. Several studies from different parts of the world showed a significant association of ABO blood group and COVID-19 susceptibility. It was demonstrated that individuals with blood group O are at the lower risk of coronavirus infection. To establish the association of ABO blood group in SARS-CoV-2 susceptibility, we for the first time analysed SARS-CoV-2 neutralising antibodies among 509 individuals, collected from three major districts of Eastern Uttar Pradesh region of India. Interestingly, we found neutralising antibodies in a significantly higher percentage of people with blood group AB (0.36) followed by B (0.31), A (0.22) and lowest in people with blood group O (0.11). We further estimated that people with blood group AB are at comparatively higher risk of infection than other blood groups. Thus, among the asymptomatic SARS-CoV-2 recovered people blood group AB has highest, whilst individuals with blood group O has lowest risk of infection.

The archipelago of Lakshadweep is considered as a stopover to the maritime route since ancient time. It is not very clear when the human first occupied these islands, however in the long history of the islands, the local legends suggest that Lakshadweep has been ruled by different kingdoms. To have a better understanding of peopling of Lakshadweep, we have analysed 557 individuals from eight major islands for mitochondrial DNA and 166 individuals for Y chromosome markers. We found a strong founder effect for both paternal and maternal lineages. Moreover, we report a close genetic link of Lakshadweep islanders with the Maldives, Sri Lanka and India. Most of the Lakshadweep islands share the haplogroups specific to South Asia and West Eurasia, except Minicoy Island that also shares haplogroups of East Eurasia. The paternal and maternal ancestries of the majority of island populations suggest their arrival from distinct sources. We found that the maternal ancestry was closer to South Indian populations, whereas the paternal ancestry was overwhelmed with the haplogroups, more common in the Maldives and North of India. In conclusion, our first genetic data suggest that the majority of human ancestry in Lakshadweep is largely derived from South Asia with minor influences from East and West Eurasia.

The COVID-19 pandemic has resulted several waves of infection in many countries worldwide. The large variations in case fatality ratio among different geographical regions suggests that the human susceptibility against this virus varies substantially. Several studies from different parts of the world showed a significant association of ABO blood group and COVID-19 susceptibility. It was shown that individuals with blood group O are at the lower risk of coronavirus infection. To establish the association of ABO blood group in SARS-CoV-2 susceptibility, we for the first time analysed SARS-CoV-2 neutralising antibodies as well as blood groups among 509 random individuals from three major districts of Eastern Uttar Pradesh region of India. . Interestingly, we found neutralising antibodies in significantly higher percentage of people with blood group AB (0.36) followed by B (0.31), A (0.22) and lowest in people with blood group O (0.11). This indicates that people with blood group AB are at comparatively higher risk of infection than other blood groups. Further, in line to previous reports we too observed that people with blood group O have significantly decreased risk of SARS-CoV-2 infection. Thus, among the asymptomatic SARS-CoV-2 infected individuals with blood group AB has highest, whilst blood group O has lowest risk of infection.