Indian J Med Res, Official publication of Indian Council of Medical Research,India

Despite the continued vaccination efforts, there had been a surge in breakthrough infections, and the emergence of the B.1.1.529 omicron variant of SARS-CoV-2 in India. There is a paucity of information globally on the role of newer XBB variants in community transmission. Here, we investigated the mutational patterns among hospitalised patients infected with the XBB omicron sub-variant, and checked if there was any association between the rise in the number of COVID-19 cases and the observed novel mutations in Tamil Nadu, India. Nasopharyngeal and oropharyngeal swabs, collected from symptomatic and asymptomatic COVID-19 patients were subjected to real-time PCR followed by Next Generation Sequencing (NGS) to rule out the ambiguity of mutations in viruses isolated from the patients (n = 98). Using the phylogenetic association, the mutational patterns were used to corroborate clinico-demographic characteristics and disease severity among the patients. Overall, we identified 43 mutations in the S gene across 98 sequences, of which two were novel mutations (A27S and T747I) that have not been reported previously with XBB sub-variants in the available literature. Additionally, the XBB sequences from our cohort had more mutations than omicron B.1.1.529. The phylogenetic analysis comprising six major branches clearly showed convergent evolution of XBB. Our data suggests that age, and underlying conditions (e.g., diabetes, hypertension, and cardiovascular disease) or secondary complications confers increased susceptibility to infection rather than vaccination status or prior exposure. Many vaccinated individuals showed evidence of a breakthrough infection, with XBB.3 being the predominant variant identified in the study population. Our study indicates that the XBB variant is highly evasive from available vaccines and may be more transmissible, and potentially could emerge as the ‘next’ predominant variant, which likely could overwhelm the existing variants of SARS-CoV-2 omicron variants. National Health Mission (India), 10.13039/100004441 SIDA 10.13039/100020422 SARC , VINNMER (Sweden), 10.13039/100016958 ORIP / 10.13039/100000002 NIH (USA).

Healthcare workers (HCWs) are at high risk of tuberculosis (TB) infection due to their continued occupational exposure to patients with active TB disease. The prevalence of latent TB infections (LTBI) among the HCWs of primary healthcare centers (PHCs) has seldom been investigated. PHCs provide effective and preventive medical care largely for the rural population. Comparatively, the HCWs of PHCs are likely to have an increased risk of occupational exposure and reactivation of LTBI. A cross-sectional study (March–April 2024) was carried out to assess the prevalence of LTBI among the HCWs of 64 PHCs across Thiruvallur district, India. Blood samples (n = 392) were analyzed using a commercial QuantiFERON-TB Gold Plus assay. A comprehensive hematological, biochemical, and immunological workup was performed, including cell count, blood glucose determination, liver/renal function tests, and serum ferritin concentration estimation, which were subsequently correlated with LTBI status using multivariate logistic regression analysis. The study revealed an LTBI prevalence of 25.3% (n = 99) among HCWs of PHCs. The red cell distribution width (RDW) was significantly associated (p = 0.002) with LTBI positivity among the different parameters analyzed. Factors such as individuals’ age (p = 0.029), underlying comorbid conditions (30.3%; p = 0.035), and longer employment duration (28%; p = 0.034) were significantly associated with IGRA positivity. Further, IGRA positivity was significantly associated with decreased RDW standard deviation (RDW-SD). This phenomenon was observed especially among females, the obese, and participants with the ‘O’ blood group. Although the exact prevalence of LTBI in the general population is not known, it is estimated to range from 20-48%. The study reported the prevalence of LTBI among HCWs of PHCs (25.3%) and factors associated with IGRA positivity including age, underlying comorbid conditions, and years of employment. Our findings will aid in developing and establishing an appropriate framework for TB screening and clinical testing guidance for HCWs.

Background: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. Methods: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. Results: The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. Conclusion: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.