Seroprevalence of SARS-CoV-2-specific anti-spike IgM, IgG, and anti-nucleocapsid IgG antibodies during the second wave of the pandemic: A population-based cross-sectional survey across Kashmir, India.

Background: Within Kashmir, which is one of the topographically distinct areas in the Himalayan belt of India, a total of 2,236 cumulative deaths occurred by the end of the second wave. We aimed to conduct this population-based study in the age group of 7 years and above to estimate the seropositivity and its attributes in Kashmir valley. Methods: We conducted a community-based household-level cross-sectional study, with a multistage, population-stratified, probability-proportionate-to-size, cluster sampling method to select 400 participants from each of the 10 districts of Kashmir. We also selected a quota of healthcare workers, police personnel, and antenatal women from each of the districts. Households were selected from each cluster and all family members with age 7 years or more were invited to participate. Information was collected through a standardized questionnaire and entered into Epicollect 5 software. Trained healthcare personnel were assigned for collecting venous blood samples from each of the participants which were transferred and processed for immunological testing. Testing was done for the presence of SARS-CoV-2-specific anti-spike IgM, IgG antibodies, and anti-nucleocapsid IgG antibodies. Weighted seropositivity was estimated along with the adjustment done for the sensitivity and specificity of the test used. Findings: The data were collected from a total of 4,229 participants from the general population within the 10 districts of Kashmir. Our results showed that 84.84% (95% CI 84.51-85.18%) of the participants were seropositive in the weighted imputed data among the general population. In multiple logistic regression, the variables significantly affecting the seroprevalence were the age group 45-59 years (odds ratio of 0.73; 95% CI 0.67-0.78), self-reported history of comorbidity (odds ratio of 1.47; 95% CI 1.33-1.61), and positive vaccination history (odds ratio of 0.85; 95% CI 0.79-0.90) for anti-nucleocapsid IgG antibodies. The entire assessed variables showed a significant role during multiple logistic regression analysis for affecting IgM anti-spike antibodies with an odds ratio of 1.45 (95% CI 1.32-1.57) for age more than 60 years, 1.21 (95% CI 1.15-1.27) for the female gender, 0.87 (95% CI 0.82-0.92) for urban residents, 0.86 (95% CI 0.76-0.92) for self-reported comorbidity, and an odds ratio of 1.16 (95% CI 1.08-1.24) for a positive history of vaccination. The estimated infection fatality ratio was 0.033% (95% CI: 0.034-0.032%) between 22 May and 31 July 2021 against the seropositivity for IgM antibodies. Interpretation: During the second wave of the SARS-CoV-2 pandemic, 84.84% (95% CI 84.51-85.18%) of participants from this population-based cross-sectional sample were seropositive against SARS-CoV-2. Despite a comparatively lower number of cases reported and lower vaccination coverage in the region, our study found such high seropositivity across all age groups, which indicates the higher number of subclinical and less severe unnoticed caseload in the community.

The burden of SARS-CoV-2 among healthcare workers across 16 hospitals of Kashmir, India-A seroepidemiological study.

SARS-CoV-2 pandemic has greatly affected healthcare workers because of the high risk of getting infected. The present cross-sectional study measured SARS-CoV-2 antibody in healthcare workers of Kashmir, India. METHODS: Serological testing to detect antibodies against nucleocapsid protein of SARS-CoV-2 was performed in 2003 healthcare workers who voluntarily participated in the study. RESULTS: We report relatively high seropositivity of 26.8% (95% CI 24.8-28.8) for SARS-CoV-2in healthcare workers, nine months after the first case was detected in Kashmir. Most of the healthcare workers (71.7%) attributed infection to the workplace environment. Among healthcare workers who neither reported any prior symptom nor were they ever tested for infection by nasopharyngeal swab test, 25.5% were seropositive. CONCLUSION: We advocate interval testing by nasopharyngeal swab test of all healthcare workers regardless of symptoms to limit the transmission of infection within healthcare settings.

Seroprevalence of SARS-CoV-2-specific IgG antibodies in Kashmir, India, 7 months after the first reported local COVID-19 case: results of a population-based seroprevalence survey from October to November 2020.

OBJECTIVES: We designed a population-based survey in Kashmir to estimate the seroprevalence of SARS-CoV-2-specific IgG antibodies in the general population aged 18 years and above. SETTING: The survey was conducted among 110 villages and urban wards across 10 districts in Kashmir from 17 October 2020 to 4 November 2020. PARTICIPANTS: Individuals aged 18 years and above were eligible to be included in the survey. Serum samples were tested for the presence of SARS-CoV-2-specific IgG antibodies using the Abbott SARS-CoV-2 IgG assay. PRIMARY AND SECONDARY OUTCOME MEASURES: We labelled assay results equal to or above the cut-off index value of 1.4 as positive for SARS-CoV-2-specific IgG antibodies. Seroprevalence estimates were adjusted for the sampling design and assay characteristics. RESULTS: Out of 6397 eligible individuals enumerated, 6315 (98.7%) agreed to participate. The final analysis was done on 6230 participants. Seroprevalence adjusted for the sampling design and assay characteristics was 36.7% (95% CI 34.3% to 39.2%). Seroprevalence was higher among the older population. Among seropositive individuals, 10.2% (247/2415) reported a history of COVID-19-like symptoms. Out of 474 symptomatic individuals, 233 (49.2%) reported having been tested. We estimated an infection fatality rate of 0.034%. CONCLUSIONS: During the first 7 months of the COVID-19 epidemic in Kashmir Valley, approximately 37% of individuals were infected. The reported number of COVID-19 cases was only a small fraction of the estimated number of infections. A more efficient surveillance system with strengthened reporting of COVID-19 cases and deaths is warranted.

SARS-CoV-2 Seroprevalence Among Healthcare Workers by Workplace Exposure Risk in Kashmir, India.

BACKGROUND: SARS-CoV-2 infection (COVID-19) poses a tremendous challenge to healthcare systems across the globe. Serologic testing for SARS-CoV-2 infection in healthcare workers (HCWs) may quantify the rate of clinically significant exposure in an institutional setting and identify those HCWs who are at greatest risk. METHODS: We conducted a survey and SARS-CoV-2 serologic testing among a convenience sample of HCWs from 79 non-COVID and 3 dedicated COVID hospitals in District Srinagar of Kashmir, India. In addition to testing for the presence of SARS-CoV-2-specific immunoglobulin G (IgG), we collected information on demographics, occupational group, influenza-like illness (ILI) symptoms, nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) testing status, history of close unprotected contacts, and quarantine/travel history. RESULTS: Of 7,346 eligible HCWs, 2,915 (39.7%) participated in the study. The overall prevalence of SARS-CoV-2-specific IgG antibodies was 2.5% (95% CI, 2.0%-3.1%), while HCWs who had ever worked at a dedicated COVID-19 hospital had a substantially lower seroprevalence of 0.6% (95% CI, 0.2%-1.9%). Higher seroprevalence rates were observed among HCWs who reported a recent ILI (12.2%), a positive RT-PCR (27.6%), a history of being put under quarantine (4.9%), and a history of close unprotected contact with a person with COVID-19 (4.4%). Healthcare workers who ever worked at a dedicated COVID-19 hospital had a lower multivariate-adjusted risk of seropositivity (odds ratio, 0.21; 95% CI, 0.06-0.66). CONCLUSIONS: Our investigation suggests that infection-control practices, including a compliance-maximizing buddy system, are valuable and effective in preventing infection within a high-risk clinical setting. Universal masking, mandatory testing of patients, and residential dormitories for HCWs at COVID-19-dedicated hospitals is an effective multifaceted approach to infection control. Moreover, given that many infections among HCWs are community-acquired, it is likely that the vigilant practices in these hospitals will have spillover effects, creating ingrained behaviors that will continue outside the hospital setting.

Seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar, northern India - A cross-sectional study.

BACKGROUND: Prevalence of IgG antibodies against SARS-CoV-2 infection provides essential information for deciding disease prevention and mitigation measures. We estimate the seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar. METHODS: 2906 persons >18 years of age selected from hospital visitors across District Srinagar participated in the study. We tested samples for the presence of SARS-CoV-2 specific IgG antibodies using a chemiluminescent microparticle immunoassay-based serologic test. RESULTS: Age- and gender-standardized seroprevalence was 3.6% (95% CI 2.9% to 4.3%). Age 30-69 years, a recent history of symptoms of an influenza-like-illness, and a history of being placed under quarantine were significantly related to higher odds of the presence of SARS-CoV-2 specific IgG antibodies. The estimated number of SARS-CoV-2 infections during the two weeks preceding the study, adjusted for test performance, was 32602 with an estimated (median) infection-to-known-case ratio of 46 (95% CI 36 to 57). CONCLUSIONS: The seroprevalence of SARS-CoV-2 specific IgG antibodies is low in the District. A large proportion of the population is still susceptible to the infection. A sizeable number of infections remain undetected, and a substantial proportion of people with symptoms compatible with COVID-19 are not tested.

A novel G26A variation in 5' half of TGIF1 gene associates with high myopia in ethnic Kashmiri population from India.

This study aims to look at novel variations in TGIF1 gene and explores their potential association with high myopia in an ethnic population from Kashmir (India). Genomic DNA was genotyped for polymorphic variations, and allele frequencies were tested for the Hardy-Weinberg disequilibrium in 240 ethnic Kashmiri cases with high myopia with a spherical equivalent of >-6 diopters (D) and compared with emmetropic controls with spherical equivalent within -0.5D in one or both eyes represented by a sample size of 228. In this study, we found a novel sequence variation G26A (GAT to AAT) in 5' half of TGIF1 gene (p. aspartic acid >asparagine) at a frequency of 62% (148/240, P ≤ 0.0001). Variation appears to associate with high myopia significantly (P ≤ 0.001) as it happens to be present only in high myopia affected individuals. Further, it shows statistical significance for its association with gender and the degree of myopia (P ≤ 0.05). In addition, in silico predictions show that variation likely has an impact on the structure and functional properties of the protein. The assessment of the I-TASSER protein structure showed higher energy for a wild-type protein (-5820.186 kJ/mol) as compared to mutant protein (-6595.593 kJ/mol).

Promoter Hypermethylation and Its Impact on Expression of MGMT Gene in the GIT Malignant Patients of Kashmiri Origin.

Epigenetic alterations, in addition to multiple gene abnormalities, are involved in the genesis and progression of human cancers. Gastrointestinal tract (GIT) cancer is a major medical and economic burden worldwide. Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumor suppressor genes. Although a number of cancer-associated genes have been found to be hypermethylated in GIT cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. O6-methyguanine DNA methyltransferase (MGMT) is a DNA-repair gene that removes mutagenic and cytotoxic adducts from the O6 position of guanine induced by alkylating agents. MGMT promoter hypermethylation and reduced expression have been found in some primary human carcinomas. We studied DNA methylation of CpG islands of the MGMT gene and its relation with MGMT protein expression in human GIT carcinomas. A total of 210 GIT tumor samples and 90 adjacent normal tissues were analyzed for MGMT promoter methylation by methylation-specific polymerase chain reaction after bisulfite modification of DNA and same samples were analyzed for MGMT protein expression by Western blotting. The methylation frequencies of MGMT gene promoter were 41.4%, 34.2%, and 44.2% in stomach, esophageal, and colorectal cancer cases while as 16.6, 13.3, and 13.3 in respective controls. MGMT protein was found downregulated in controls of all GIT. The results suggest that methylation at CpG islands of MGMT may be responsible for the downregulation of MGMT protein expression in GIT cancers.

Diminished expression of MGMT & RASSF1A genes in gastric cancer in ethnic population of Kashmir.

BACKGROUND: Cancer initiation and progression are accompanied by profound changes in DNA. DNA methylation that was the first epigenetic alterations identified in cancer. DNA hypermethylation at promoter sites is closely associated with down regulation of protein and as major participant in the development and progression of series of human tumors. Therefore we hypothesized that promoter hypermethylation of RASSF1A & MGMT gene could influence susceptibility to gastric cancer (GC) as well, and we conducted this study to test the hypothesis in Kashmiri population. METHODS: A hospital based case-control study; including 200 GC cases and 200 matched controls from patients who went surgical resection. Promoter hypermethylation was determined by Methylation Specific Polymerase chain reaction. The expression of MGMT & RASSF1A protein was examined by Western blotting technique. RESULTS: Frequency of promoter region hypermethylation of MGMT gene were 46.5% in cases and 5.5% in controls (P<0.05) while as in case of RASSF1A frequency was 44% in cases and 4.5% in controls (P<0.05). Further, frequency of hypermethylation of both genes was found predominant in males, aged and advanced pathological stage subjects. Loss of MGMT expression was found in 46.5% cases (P<0.05) while as loss of RASSF1A expression was found in 40.5% cases (P<0.05). In both genes a positive correlation was observed between promoter CpG island hypermethylation and down regulation of respective proteins. CONCLUSIONS: These findings indicate that promoter hypermethylation at CpG island may be responsible for reduction of expression at protein level which may be an initial event in carcinogenesis and the progression of GC.

Comparison of hematological parameters in untreated and treated subclinical hypothyroidism and primary hypothyroidism patients.

BACKGROUNDS: Thyroid hormones play an important physiological role in human metabolism. Erythrocyte abnormalities are frequently associated with thyroid disorder. However, they are rarely investigated and related to the subclinical and primary hypothyroidism in Kashmiri Patients. In this study an attempt was made to study hematological parameters in untreated and treated subclinical hypothyroidism and primary hypothyroidism patients. METHODS: This retrospective study included 600 subjects, among which were untreated subclinical hypothyroid (n=110), treated subclinical hypothyroid (n=110), untreated primary hypothyroid (n=100), treated primary hypothyroid (n=100) and euthyroid (n=180). This study was carried out at Department of Biochemistry, Government Medical College Srinagar. The hematological parameters and thyroid profile of the subjects were assessed by the Sysmex (Italy) and ECLIA (Germany) 2010 automatic analyzer. Mean, standard deviation (SD), analysis of variance (Two-way ANOVA), and multiple comparisons were used to report our results, with p<0.05 or p<0.01 considered as statistically significant. RESULTS: In this study group we compared the hematological parameters in these groups, untreated subclinical hypothyroid, treated subclinical hypothyroid, untreated primary hypothyroid, treated primary hypothyroid and euthyroid. We found that hematological parameters like Hb, RBC, MCV, HCT, RDW,RBC% were significantly increased in untreated subclinical hypothyroidism and untreated primary hypothyroidsm, with the p value being less than 0.05 whereas, in treated SCH & Pr. Hypothyroid, results were insignificant. The results reported in these groups as mean±SD, were statistically tested by ANOVA and multiple comparison tests. In untreated subclinical hypothyroid the values were: Hb (10.83±1.33 g/dl), RBC (4.21±0.66 10(6)/µl), MCV (84.56±6.84 fL), HCT (38.5±2.2%), RDW (17.91±2.37 fL), RBC% (84.36±13.2%) and in untreated primary hypothyroid, Hb (10.73±0.86 g/dl), RBC (4.63±0.51 10(6)/µl), MCV (83.34±6.92 fL), HCT (38.6±2.6%), RDW (14.93±5.47 fL), RBC% (92.63±10.30%) suggesting that these patients were at risk of anemia and other erythrocyte abnormalities. MCV is an inexpensive approach to study the types of anemia and explore related information like production, destruction, loss and morphological changes of RBC'S. CONCLUSION: The thyroid dysfunction is frequently associated with anemia in subclinical hypothyroidism and primary hypothyroidism. Subclinical hypothyroidism (SCH) is associated with serious complications. Substantial numbers of patients with the risk of SCH could be getting converted into primary hypothyroidism. Such conditions should be identified and corrected. On the other hand, their presence could move to a thyroid dysfunction, allowing its early management.