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      Clinical profile of patients infected with suspected SARS-CoV-2 Omicron variant of concern, Tamil Nadu, India, December 2021-January 2022

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          Abstract

          Background & objectives:

          COVID-19 cases have been rising rapidly in countries where the SARS-CoV-2 variant of concern (VOC), Omicron (B.1.1.529) has been reported. We conducted a study to describe the epidemiological and clinical characteristics and outcomes of COVID-19 patients with ‘S’ gene target failure (SGTF, suspected Omicron). Furthermore, their clinical outcomes with COVID-19 patients with non-SGTF (non-Omicron) were also compared.

          Methods:

          This study was conducted in Tamil Nadu, India, between December 14, 2021 and January 7, 2022 among patients who underwent reverse transcription-PCR testing for SARS-CoV-2 in four laboratories with facilities for S gene screening. Consecutively selected COVID-19 patients with SGTF were telephonically contacted, seven and 14 days respectively after their date of positive result to collect information on the socio-demographic characteristics, previous history of COVID-19, vaccination status and clinical course of illness along with treatment details. To compare their outcomes with non-SGTF patients, one randomly suspected non-Omicron case for every two suspected Omicron cases from the line-list were selected, matching for the date of sample collection and the testing laboratory.

          Results:

          A total of 1175 SGTF COVID-19 patients were enrolled for this study. Almost 6 per cent (n=72) reported a history of previous infection. 141 (13.5%) suspected Omicron cases were non-vaccinated, while 148 (14.2%) and 703 (67.4%) had received valid one and two doses of COVID-19 vaccines, respectively. Predominant symptoms reported included fever (n=508, 43.2%), body pain (n=275, 23.4%), running nose (n=261, 22.2%) and cough (n=249, 21.2%). Five (0.4%) of the 1175 suspected Omicron cases required oxygen supplementation as compared to ten (1.6%) of the 634 suspected non-Omicron cases. No deaths were reported among omicron suspects, whereas there were four deaths among suspected non-Omicron cases.

          Interpretation & conclusions:

          Majority of the suspected Omicron cases had a mild course of illness. The overall severity of these cases was less compared to the suspected non-Omicron cases.

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          Most cited references4

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          Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

          The SARS-CoV-2 Omicron BA.1 variant emerged in 2021 1 and has multiple mutations in its spike protein 2 . Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.
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            SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo

            The emergence of SARS-CoV-2 variants of concern with progressively increased transmissibility between humans is a threat to global public health. The Omicron variant of SARS-CoV-2 also evades immunity from natural infection or vaccines1, but it is unclear whether its exceptional transmissibility is due to immune evasion or intrinsic virological properties. Here we compared the replication competence and cellular tropism of the wild-type virus and the D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) variants in ex vivo explant cultures of human bronchi and lungs. We also evaluated the dependence on TMPRSS2 and cathepsins for infection. We show that Omicron replicates faster than all other SARS-CoV-2 variants studied in the bronchi but less efficiently in the lung parenchyma. All variants of concern have similar cellular tropism compared to the wild type. Omicron is more dependent on cathepsins than the other variants of concern tested, suggesting that the Omicron variant enters cells through a different route compared with the other variants. The lower replication competence of Omicron in the human lungs may explain the reduced severity of Omicron that is now being reported in epidemiological studies, although determinants of severity are multifactorial. These findings provide important biological correlates to previous epidemiological observations.
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              Seroprevalence of IgG antibodies against SARS-CoV-2 among the general population and healthcare workers in India, June–July 2021: A population-based cross-sectional study

              Background India began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March–June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs). Methods and findings We did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6–9 years, 5,798 (20%) were aged 10–17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age ( p < 0.001) and was not different in rural and urban areas ( p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey. Conclusions Nearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June–July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions. Manoj Murhekar and co-workers report on the seroprevalence of anti-SARS-CoV-2 antibodies in India. Why was this study done? Earlier nationwide COVID-19 serosurveys conducted in India indicated an increase in seroprevalence from 0.73% (95% CI 0.34% to 1.13%) in May–June 2020 to 6.6% (95% CI 5.8% to 7.4%) in September–October 2020 and 24.1% (95% CI 23.0% to 25.3%) in December 2020–January 2021. India began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India witnessed a severe second wave of COVID-19 in March–June 2021. What did the researchers do and find? The fourth nationwide serosurvey indicated that about two-thirds of India’s population aged ≥6 years had antibodies against SARS-CoV-2 by June–July 2021. Seroprevalence increased with age, but was not different in urban slum, urban non-slum, and rural areas. Seroprevalence was significantly higher among individuals who had received 2 doses of COVID-19 vaccine compared to unvaccinated individuals. About 85% of healthcare workers working in district-level health facilities had antibodies against SARS-CoV-2. What do these findings mean? The substantial seroprevalence of anti-SARS-CoV-2 antibodies in the Indian population should provide some measure of protection against future waves of COVID-19 in the country. About one-third of the population in India did not have detectable antibodies against SARS-CoV-2 by June–July 2021. It is therefore necessary to accelerate the coverage of COVID-19 vaccination among adults.
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                Author and article information

                Journal
                Indian J Med Res
                Indian J Med Res
                IJMR
                Indian J Med Res
                The Indian Journal of Medical Research
                Wolters Kluwer - Medknow (India )
                0971-5916
                0975-9174
                January 2022
                January 2022
                : 155
                : 1
                : 165-170
                Affiliations
                [1 ] School of Public Health, ICMR-National Institute of Epidemiology, Chennai, Tamil Nadu, India
                [2 ] Department of Epidemiology & Biostatistics, ICMR-National Institute of Epidemiology, Chennai, Tamil Nadu, India
                [3 ] Department of Health & Family Welfare, Directorate of Public Health & Preventive Medicine, Government of Tamil Nadu, Chennai, Tamil Nadu, India
                [4 ] Department of Community Medicine, Madras Medical College, Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India
                Author notes
                For correspondence: Dr Manoj V. Murhekar, Department of Epidemiology & Biostatistics, ICMR National Institute of Epidemiology, Chennai 600 077, Tamil Nadu, India e-mail: mmurhekar@ 123456gmail.com
                [#]

                Equal contribution

                Article
                IJMR-155-165
                10.4103/ijmr.ijmr_312_22
                9552397
                35417991
                b3d9d936-4c78-4283-8a4c-ad78baf68727
                Copyright: © 2022 Indian Journal of Medical Research

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 04 February 2022
                Categories
                Original Article

                Medicine
                b.1.1.529,covid-19,epidemiology,omicron,sars-cov-2,severity,variant of concern
                Medicine
                b.1.1.529, covid-19, epidemiology, omicron, sars-cov-2, severity, variant of concern

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