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Abstract Hypervitaminosis D leads to toxic effects, including hypercalcemia, which can cause severe damage to various organs. Fetuin-A, a glycoprotein with anti-inflammatory properties, may protect tissues from such damage. This study explores the role of Fetuin-A in mitigating hypervitaminosis D-induced damage in renal, hepatic, and cardiac tissues. The objectives of this study were to: (1) Assess the extent of tissue damage from high-dose vitamin D in a murine model by examining the histopathological changes in liver, kidney and heart. (2) Investigate Fetuin-A's protective effect against this damage. Thirty-six albino rats were divided into four groups: (1) control, (2) vitamin D toxicity, (3) Fetuin-A + vitamin D, and (4) Fetuin-A only. Vitamin D was administered subcutaneously at 250 μg/20 g/day for 3 days. Fetuin-A was given at 100 μl/20 g, starting 7 days before vitamin D treatment. Histopathological analysis of liver, kidney, and heart tissues was performed using H&E and Alizarin Red staining and findings were analysed statistically. Vitamin D toxicity caused significant tissue damage, including apoptosis, inflammation, and calcification in the liver, kidneys, and heart. Pre-treatment with Fetuin-A reduced calcification and inflammation, preserving tissue architecture. Fetuin-A-only rats showed no damage or calcification. Fetuin-A provided statistically significant protection against vitamin D-induced damage, reducing oxidative stress and calcification in affected organs. These findings suggest Fetuin-A could be a potential therapeutic agent for hypervitaminosis D.

Abstract Background Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP). Methods HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell – IFN-γ activation was assessed by ELISpot. Results Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike. Conclusions Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population.

Abstract 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.

Introduction: Depression and anxiety among tuberculosis (TB) patients can adversely affect TB treatment adherence and completion. Aim: We studied whether integrating mental health services into existing TB treatment programs would reduce symptoms of depression and anxiety and improve treatment completion among patients with drug-susceptible TB. Methods: Integrated practice units (IPUs) for TB and mental health were established within six existing TB treatment facilities in Karachi, Pakistan. Patients were screened for depression and anxiety and, if symptomatic, offered a mental health intervention consisting of at least four counseling sessions. We measured changes in reported levels of depression and anxiety symptoms from baseline following completion of counseling sessions, and rates of TB treatment completion. Results: Between February 2017 and June 2018, 3500 TB patients were screened for depression and anxiety. 1057 (30.2%) symptomatic patients received a baseline adherence session. 1012 enrolled for a mental health intervention received at least 1 counseling session. 522 (51.5%) reported no symptoms after four to six sessions. Symptomatic patients who completed at least four counseling sessions had higher rates of TB treatment completion than those who did not (92.9% vs 75.1%; p < 0.0001). Conclusion: Mental health interventions integrated within TB programs can help reduce symptoms of depression and anxiety and improve TB treatment completion.