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Introduction: Biomarkers of prognostic and predictive relevance are needed for the practical management of COVID-19. Objective: The authors aimed to assess a battery of inflammatory cytokines in patients with SARS-CoV-2 to determine the cytokines of prognostic and predictive relevance in COVID-19. Methods: In a cohort of 100 patients with SARS-CoV-2 (RT-PCR confirmed), hospitalised in Shri Maharaja Hari Singh Hospital associated to Government Medical College Srinagar, India, the level of a battery of cytokines, IL-6, IL-8, IL-10, IL-1α, vascular endothelial growth factor (VEGF), TNF-α, and ferritin were estimated by ELISA on a multimode microplate reader. Results: The deranged levels of these cytokines were mostly found in patients >60 years of age, with cough and pneumonia as the most common symptoms. A significant association was found between IL-6 and IL-8, disease severity (p=0.002; p=0.007), and poor disease outcome (p=0.040; p=0.009), respectively. A significant association was also found between decreased levels of VEGF and poor disease outcome (p=0.020). Further receiver operating characteristic analysis, univariant and multivariant (after adjusting for age, gender, and other inflammatory markers), revealed increased IL-10 (area under the curve [AUC]: 0.72) and IL-6 (AUC: 0.70) as independent markers of both disease severity (p=0.02; p=0.01) and disease outcome (P=0.03; p=0.02), respectively, and decreased VEGF (AUC: 0.69) as an independent marker of disease outcome (p=0.03). A significant association between cough and IL-8 (p=0.01) and IL-10 levels (p=0.03), and of diabetes and raised ferritin levels (p=0.01), with very high ferritin levels (>1500 ng/mL), was found in those who are likely to develop hyperinflammatory phenotype. Conclusion: The authors conclude that ‘IL-6, IL10, VEGF, and IL-8’ are the signature inflammatory cytokine panel/profile in COVID-19, particularly in patients from Kashmir. Increased IL-10 and IL-6 levels proved to be equally significant independent prognosticators of COVID-19 severity and outcome, and decreased VEGF levels were independent predictors of poor disease outcome in patients with SARS-CoV-2. Testing of the signature inflammatory cytokine panel is, therefore, recommended for optimal clinical decision-making in patients with COVID-19 from Kashmir, India.

Background: The complete blood count (CBC) profile has been found extremely useful in monitoring the growth of SARS-CoV-2 infection; however, predictive CBC parameters that could be used in the management of the disease may vary in different populations. Methods: This study comparatively analyzed the CBC profile of SARS-CoV-2 patients (N = 75; confirmed positive by real-time polymerase chain reaction [PCR]) and healthy individuals (confirmed negative by real-time PCR) from Kashmir (north India). Results: Compared with healthy individuals, most of the CBC parameters (hemoglobin levels [13.43 vs 10.9 g/dL; P = 0.0001], lymphocytes [16.04% vs 30.8%; P = 0.00001], monocytes [5.53% vs 7.53%; P = 0.009], and platelet count [150 vs 186 ×103 µL; P = 0.037]) were significantly low in SARS-CoV-2 infected patients, while neutrophilia was more common in infected patients (76.77% vs 59.26%). Among derived parameters, the neutrophil-to-lymphocyte ratio (NLR; 7.31 vs 2.04; P = 0.001) and derived NLR (d-NLR; 4.43 vs 1.5; P = 0.0002) were significantly high in SARS-CoV-2 patients. Further correlation analysis revealed a significant association of neutrophilia with the severity of the disease in SARS-CoV-2 infected patients. Moreover, receiver operating characteristic (ROC) analysis of derived CBC parameters (NLR, d-NLR, and platelet‐to-lymphocyte ratio [PLR] with disease severity and disease outcome) revealed d-NLR as better predictive marker of disease severity (area under the curve [AUC] = 0.658) and disease outcome (AUC = 0.766) compared to PLR with disease severity (AUC = 0.645) and disease outcome (AUC = 0.693). Conclusion: We therefore conclude, of the CBC parameters neutrophilia as the marker of disease severity and among derived parameters, d-NLR as an early predictive biomarker of both disease severity and poor disease outcome in SARS-CoV-2 patients.

Background: Recurrent miscarriage (RM) represents the spontaneous termination of two or more successive pregnancies. TNFα is a proinflammatory cytokine that is often considered harmful for embryonic development when expressed beyond normal levels. Aim: The study was conducted to assess the association between TNFα-308 polymorphism and RM pathogenesis. Methods: Samples of blood were obtained from patients and controls through venipuncture. The levels of TNFα in serum were measured by ELISA. TNFα gene promoter-associated single-nucleotide polymorphism was investigated with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques with precise primers and the restriction endonuclease, NcoI. Results: Serum TNFα levels in patients were considerably high (p 0.9999) models, respectively. Further, the TNFα-308G/A genotype frequencies were in concord with HWE both in the controls (χ2 = 3.235; p = 0.1985) and the patients (χ2 = 0.0117; p = 0.9942). Conclusion: The serum TNFα levels were significantly higher in the patients than the controls. The genotyping analysis also demonstrated that TNFα-308G/A SNP significantly increases the overall risk of RM, suggesting that the SNP modulates the TNFα gene expression and thereby increases serum TNFα levels that adversely affect the pregnancy outcome.

Purpose: There has been growing evidence that inflammatory markers play a role in the development as well as severity of Type 2 diabetes mellitus (T2DM). This study has been designed to decipher the involvement of C-Reactive Protein (CRP), Tumor Necrosis Factor (TNFα), Interleukin-6 (IL-6) and Interleukin-10 (IL-10) in the etiopathogenesis of T2DM. Basic procedures: A total of 480 T2DM cases and 540 healthy controls were recruited for the study. Blood samples were collected from each study subject to measure the serum levels of CRP, TNFα, IL-6 and IL-10. Main findings: We found that serum levels of CRP in mg/dl (4.2 ± 0.9), TNFα in pg/ml (34.5 ± 8.8), IL-6 in pg/ml (19.2 ± 7.2) in T2DM patients were significantly high as compared to control participants (CRP; 1.4 ± 0.6, TNFα; 12.7 ± 3.4, IL-6; 3.1 ± 1.4; P < 0.0001). The serum levels of IL-10 in pg/ml were lower in T2DM cases compared to controls (4.35 ± 1.2 vs. 9.6 ± 1.2). In addition, we observed a significant association of CRP levels with insulin resistance, obesity and dyslipidemia. Increased TNFα levels were strongly associated with female gender, Poor glycemic control and strong family history of diabetes. Poor glycemic control was significantly associated with elevated IL-6 levels. Moreover, significantly reduced IL-10 levels were found in T2DM patients with sedentary lifestyle; low educational and rural background. Conclusions: This study showed a strong relationship between TNFα, IL-6, CRP, IL-10 and T2DM patients of Kashmiri ethnicity, treated at SMHS Hospital. Thus, supporting other studies and showing that cytokines may be good markers for T2DM development.

BackgroundWithin 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.MethodsWe 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.FindingsThe 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.InterpretationDuring 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.

Introduction: The surge in novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease-2019 (COVID-19) has overwhelmed the health system. To help health-care workers and policy makers prioritize treatment and to decrease the burden on health systems caused by COVID-19, clinical severity along with various clinico-biochemical parameters was evaluated by designing a cross-sectional study comprising 236 SARS-CoV-2-infected individuals from Kashmir Valley, India. Methods: Briefly, real-time polymerase chain reaction (RT-PCR) was used for the confirmation of SARS-CoV-2 infection. The principles of spectrophotometry and chemiluminescent microparticle immunoassay (CMIA) were employed to estimate the levels of glucose, TSH, and 25-hydroxy vitamin D levels in serum of infected patients. Results: A total of 236 patients infected with SARS-CoV-2 were taken for this cross-sectional study. Patients with COVID-19 had a male predominance (72.9 vs. 27.1%) and a higher prevalence of 25-hydroxy vitamin D deficiency (72.0 vs. 28.0%) with a mean 25-hydroxy vitamin D levels of 24.0 ± 13.9 in ng/mL. We observed a varied clinical spectrum of SARS-CoV-2 infection with 36.4%, 23.7%, and 29.7% patients having mild, moderate, and severe disease, respectively. We observed that severity of SARS-CoV-2 infection was significantly associated with older age group, hypertension, low TSH levels, and 25-hydroxy vitamin D deficiency. Conclusion: We conclude that not only old age but also hypertension and low levels of TSH and 25-hydroxy vitamin D levels could significantly lead to clinical severity of SARS-CoV-2 infection.

Lung cancer is the dominant emerging factor in cancer-related mortality around the globe. Therapeutic interventions for lung cancer are not up to par, mainly due to reoccurrence/relapse, chemoresistance, and late diagnosis. People are currently interested in miRNAs, which are small double-stranded (20–24 ribonucleotides) structures that regulate molecular targets (tumor suppressors, oncogenes) involved in tumorigeneses such as cell proliferation, apoptosis, metastasis, and angiogenesis via post-transcriptional regulation of mRNA. Many studies suggest the emerging role of miRNAs in lung cancer diagnostics, prognostics, and therapeutics. Therefore, it is necessary to intensely explore the miRNOME expression of lung tumors and the development of anti-cancer strategies. The current review focuses on the therapeutic, diagnostic, and prognostic potential of numerous miRNAs in lung cancer.