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Background and Aims: COVID‐19 vaccinations have reduced morbidity and mortality from the disease. Antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) have been associated with immune protection. Seroprevalence studies revealed high immunoglobulin G (IgG) antibody levels to SARS‐CoV‐2 in the Pakistani population before vaccinations. We investigated the effect of BBIBP‐CorV vaccination on circulating IgG antibodies and interferon (IFN)‐γ from T cells measured in a cohort of healthy individuals, with respect to age, gender, and history of COVID‐19. Methods: The study was conducted between April and October 2021. BBIBP‐CorV vaccinated participants were followed up to 24 weeks. Antibodies to SARS‐CoV‐2 Spike protein and its receptor‐binding domain (RBD) were measured. IFNγ secreted by whole blood stimulation of Spike protein and extended genome antigens was determined. Results: Study participants with a history of prior COVID‐19 displayed a higher magnitude of IgG antibodies to Spike and RBD. IgG seropositivity was greater in those with prior COVID‐19, aged 50 years or younger and in females. At 24 weeks after vaccination, 37.4% of participants showed IFN‐γ responses to SARS‐CoV‐2 antigens. T cell IFN‐γ release was higher in those with prior COVID‐19 and those aged 50 years or less. Highest IFN‐γ release was observed to extended genome antigens in individuals both with and without prior COVID‐19. Conclusion: We found that IgG seropositivity to both Spike and RBD was affected by prior COVID‐19, age and gender. Importantly, seropositive responses persisted up to 24 weeks after vaccination. Persistence of vaccine induced IgG antibodies may be linked to the high seroprevalence observed earlier in unvaccinated individuals. Increased T cell reactivity to Spike and extended genome antigens reflects cellular activation induced by BBIBP‐CorV. COVID‐19 vaccination may have longer lasting immune responses in populations with a higher seroprevalence. These data inform on vaccination booster policies for high‐risk groups. Key points: Baseline seropositivity high in population in those without prior COVID‐19—no antibody waning after vaccination may be due to cross‐reactivity or continued transmission ‐inactivated vaccination induced T cell response to antigens other than Spike providing additional immunogenicity ‐COVID‐19 vaccination may have longer lasting immune responses in populations with a higher seroprevalence—these data inform on vaccination booster policies [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) outcomes are worsened by type II diabetes mellitus (DM). Protective immunity against Mycobacterium tuberculosis (MTB) is driven by cytokines. Latent TB (LTBi) is common but its effect on the diabetic host is not well understood. We investigated mycobacterial antigen‐stimulated responses in peripheral blood mononuclear cell (PBMC) isolated from healthy endemic controls (EC), those with LTBi, DM groups with and without LTBi, as compared with TB patients. Cytokines were measured using a Luminex‐based assay. Gene expression was determined by RT‐PCR. In DM‐LTBi cases, PPD‐stimulated proinflammatory cytokines; IFN‐γ, IL‐6, IL‐2, TNF‐α and GM‐CSF and anti‐inflammatory cytokines, IL‐5 and IL‐13 were raised as compared with EC. DM‐LTBi PPD‐stimulated IFN‐γ, IL‐6 and TNF‐α mRNA titres were found raised in DM‐LTBi, whilst suppressor of cytokine signalling (SOCS)‐3 expression was lowered. Within DM cases, stratification based on HbA1c levels revealed raised IFN‐γ but lowered IL‐6 gene expression in those with controlled levels as compared with uncontrolled glycaemic levels. Further, SOCS1 expression levels were found higher in DM cases with controlled glycaemia when compared with EC. Overall, we show that diabetics with LTBi manifest raised levels of inflammatory and anti‐inflammatory cytokines concomitant with reduced SOCS3 mRNA expression. Reduced glycaemic control results in further inflammatory dysregulation impacting conversing impacting IFN‐γ and IL‐6 activation. These results suggest that dysregulated immune activation in diabetes is exacerbated by LTBi, lack of glycaemic control may further compromise immunity against MTB infection. [ABSTRACT FROM AUTHOR]

Objectives: To assess the diagnostic accuracy of different cut-off values of pleural fluid adenosine deaminase levels as a diagnostic method for tuberculous pleural effusion., Methods: The prospective study was conducted from 2014 to 2016 at the Aga Khan University Hospital, Karachi, and comprised pleural fluid samples of adult patients with and without tuberculosis which were tested for adenosine deaminase levels, and divided into tuberculosis group A and non-tuberculosis group B. Sensitivity, specificity, negative predictive value and positive predictive value were calculated using different cut-offs. Data was analysed using IBM SPSS (Statistical Package for Social Sciences) version 21.0 (IBM Corp., Armonk, NY)., Results: Of 155 patients, 46(29.7%) had tuberculosis; 30(65.2%) males and 16(34.8%) females. Those who did not have tuberculosis were 109(70.3%); 69(63.3%) males and 40(36.7%) females. The adenosine deaminase levels were elevated in group A compared to group B (p<0.001). The cut-off of 30U/L showed the highest sensitivity (71.7%) and negative predictive value (87.4%), and a specificity of 82.6%. The cut-off of 50U/L showed the highest specificity (89.9%) with sensitivity 52.2%, and the cut-off of 40U/L showed the highest positive predictive value of 68.9% with sensitivity 67.4% and specificity 87.2%., Conclusions: Pleural fluid adenosine deaminase testing for diagnosing tuberculosis pleuritis revealed highest sensitivity and moderate specificity for cut-off value of 30U/L.