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Background: Curcumin, quercetin, and vitamin D3 (cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit promising anti-inflammatory, immunomodulatory, broad-spectrum antiviral, and antioxidant activities. Objective: The present study aimed to investigate the possible therapeutic benefits of a single oral formulation containing supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 (COVID-19) in a pilot open-label, randomized controlled trial conducted at Mayo Hospital, King Edward Medical University, Lahore, Pakistan. Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed, mild to moderate symptomatic COVID-19 outpatients were randomized to receive either the standard of care (SOC) ( n = 25) (control arm) or a daily oral co-supplementation of 168 mg curcumin, 260 mg quercetin, and 9 µg (360 IU) of cholecalciferol, as two oral soft capsules b.i.d. as an add-on to the SOC ( n = 25) (CQC arm) for 14 days. The SOC includes paracetamol with or without antibiotic (azithromycin). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test, acute symptoms, and biochemistry including C-reactive protein (CRP), D-dimer, lactate dehydrogenase, ferritin, and complete blood count were evaluated at baseline and follow-up day seven. Results: Patients who received the CQC adjuvant therapy showed expedited negativization of the SARS-CoV-2 RT-PCR test, i.e., 15 (60.0%) vs. five (20.0%) of the control arm, p = 0.009. COVID-19- associated acute symptoms were rapidly resolved in the CQC arm, i.e., 15 (60.0%) vs. 10 (40.0%) of the control arm, p = 0.154. Patients in the CQC arm experienced a greater fall in serum CRP levels, i.e., from (median (IQR) 34.0 (21.0, 45.0) to 11.0 (5.0, 16.0) mg/dl as compared to the control arm, i.e., from 36.0 (28.0, 47.0) to 22.0 (15.0, 25.0) mg/dl, p = 0.006. The adjuvant therapy of co-supplementation of CQC was safe and well-tolerated by all 25 patients and no treatment-emergent effects, complications, side effects, or serious adverse events were reported. Conclusion: The co-supplementation of CQC may possibly have a therapeutic role in the early stage of COVID-19 infection including speedy negativization of the SARS-CoV-2 RT-PCR test, resolution of acute symptoms, and modulation of the hyperinflammatory response. In combination with routine care, the adjuvant co-supplementation of CQC may possibly help in the speedy recovery from early-stage mild to moderate symptoms of COVID-19. Further research is warranted. Clinical Trial Registration: Clinicaltrials.gov , identifier NCT05130671

Dengue fever, caused by the dengue virus (DENV), poses a significant global health threat, with a dramatic increase in cases driven by climate change, urbanization, and mosquito resistance. In Pakistan, a country with a population of 240 million, the world’s fifth largest, dengue has emerged as an escalating public health crisis, with seasonal outbreaks severely straining the healthcare system. Despite decades of vector control efforts, there has not been much success, necessitating the introduction of dengue vaccination to boost population immunity. Recent advancements in vaccine development demonstrate promising efficacy and safety profiles, even in dengue-naive individuals. Implementing a dengue vaccination program in Pakistan could significantly reduce the disease burden, lower healthcare costs, and prevent future outbreaks. Integrating vaccination with existing public health initiatives can achieve high coverage and improve overall public health outcomes.

Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection. Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19. Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical University, Lahore, PK. Patients were randomized to receive either standard of care (SC) plus an oral quercetin supplement (500 mg Quercetin Phytosome®, 1st week, TDS: 2nd week, BDS) ( n = 50, quercetin group) or SC alone ( n = 50, control group). Results: After one week of treatment, patients in the quercetin group showed a speedy recovery from COVID-19 as compared to the control group, i.e., 34 patients (vs. 12 in the control group) tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ( p = 0.0004), and 26 patients (vs. 12 in the control group) had their COVID-19-associated acute symptoms resolved ( p = 0.0051). Patients in the quercetin group also showed a significant fall in the serum lactate dehydrogenase (LDH) mean values i.e., from 406.56 ± 183.92 to 257.74 ± 110.73 U/L, p = 0.0001. Quercetin was well-tolerated by all the 50 patients, and no side effects were reported. Conclusion: Our results, suggest the possible therapeutic role of quercetin in early-stage COVID-19, including speedy clearance of SARS-CoV-2, early resolution of the acute symptoms and modulation of the host’s hyperinflammatory response. Clinical Trial Registration: clinicaltrials.gov , identifier NCT04861298

Anatomical and physiological considerations indicate that the oral cavity is a primary source of the lung microbiota community, and recent studies have shown that the microbiota in the lungs contributes to immunological homeostasis, potentially altering the organ’s susceptibility to viral infection, including SARS-CoV-2. It has been proposed that, in the case of viral infection, lung Gram-negative bacteria could promote the cytokine cascade with a better performance than a microbiota mainly constituted by Gram-positive bacteria. Recent observations also suggest that Prevotella-rich oral microbiotas would dominate the oral cavity of SARS-CoV-2-infected patients. In comparison, Streptococcus-rich microbiotas would dominate the oral cavity of healthy people. To verify if the modulation of the oral microbiota could have an impact on the current coronavirus disease, we administered for 14 days a well-recognized and oral-colonizing probiotic (S. salivarius K12) to hospitalized COVID-19 patients. The preliminary results of our randomized and controlled trial seem to prove the potential role of this oral strain in improving the course of the main markers of pathology, as well as its ability to apparently reduce the death rate from COVID-19. Although in a preliminary and only circumstantial way, our results seem to confirm the hypothesis of a direct involvement of the oral microbiota in the construction of a lung microbiota whose taxonomic structure could modulate the inflammatory processes generated at the pulmonary and systemic level by a viral infection.

Rhino-orbital-cerebral mucormycosis (ROCM), a rare but fatal fungal infection, has recently emerged as a serious complication after corticosteroids therapy in COVID-19 patients, predominantly in diabetic and immunocompromised patients. The World Health Organization (WHO) COVID-19 current guidelines recommend corticosteroids administration in hospitalized COVID-19 patients requiring supplementary oxygen or mechanical ventilation. Herein, we report a case series of seven patients with COVID-19; three mild, three moderate, and one severe, from Lahore, Pakistan; all were using corticosteroids for managing their early mild symptoms of COVID-19 at home for around 2–3 weeks without a physician’s advise, presented, and admitted with ROCM to Mayo hospital, Lahore, from March to June 2021. Out of the seven patients, five patients had uncontrolled diabetes mellitus (DM) as comorbidity. Eye pain, facial swelling and pain, nasal blockage, and black coloration around eyes, on palate, and oral mucosa were the presenting complaints at the time of admission. All the patients had radiographic imaging, including computed tomography (CT), paranasal sinuses (PNS), or brain magnetic resonance imaging (MRI) carried out at the hospital, which confirmed mucosal thickening and adjacent sinus bony erosions with intracranial extension. All the patients were treated with local debridement of the infected necrotic tissue along with intravenous liposomal Amphotericin B and Posaconazole or Amphotericin B depending on the case. Due to timely management, in six out of seven patients, prognosis was good due to early diagnosis and treatment, while one patient with severe COVID-19 illness deteriorated and died. The misuse of corticosteroids for managing early mild symptoms of COVID-19 in diabetic and other immunocompromised patients can lead to fatal ROCM, which can further increase their risk of developing severe COVID-19 and mortality. It is stressed that only physician’s recommended therapeutic advice should be followed for managing early mild symptoms of COVID-19 in self-isolation and avoid the unnecessary use of corticosteroids. This case series also emphasizes that COVID-19 diabetic patients treated with corticosteroids need more vigilant monitoring and high suspicion of early diagnosis and treatment of invasive fungal infection. Early diagnosis and management can reduce morbidity and mortality.

Background & objective Diabetic kidney disease (DKD) is a major global burden, especially in Asia. This study aimed to evaluate the efficacy and safety of finerenone in diabetic kidney disease, comparing outcomes between Asian and non-Asian populations through a systematic review and meta-analysis. Methods A systematic search was conducted across PubMed, Cochrane Library, ClinicalTrials.gov, Google Scholar, and the Undermind AI platform from inception through March 2025. Studies included randomized controlled trials (RCTs) and subgroup analyses that evaluated finerenone in DKD patients. Primary outcomes included a reduction in the urinary albumin-to-creatinine ratio (UACR) and a decline in the estimated glomerular filtration rate (eGFR) of ≥40%. Secondary outcomes included cardiovascular events, mortality due to kidney failure, hyperkalemia (serum potassium >5.0 mmol/L), treatment discontinuation, hospitalization, and adverse event–related mortality. Risk ratios (RRs) and mean differences (MDs) were pooled using a random-effects model, and subgroup analyses were performed by ethnicity. Results Five eligible studies, comprising 8,763 participants, were included in this analysis. Finerenone significantly reduced UACR compared with placebo (MD = −0.38, 95% CI −0.42 to −0.35; p < 0.001), with consistent effects across Asian and non-Asian populations (subgroup p = 0.28). It also significantly reduced the risk of eGFR decline ≥40% (MD = −0.24 [−0.40, −0.09]; p = 0.002), with a greater benefit in the Asian subgroup (subgroup p = 0.03). Cardiovascular event risk was also reduced (RR = 0.85 [0.77–0.95]; p = 0.004), while mortality due to kidney failure showed a non-significant reduction (RR = 0.83 [0.64–1.07]; p = 0.15). Hyperkalemia risk was higher with finerenone (RR = 1.73, 95% CI 1.39–2.14), whereas adverse event–related mortality was lower (RR = 0.65, 95% CI 0.46–0.91). Conclusion Finerenone provides robust renoprotective and cardioprotective effects in DKD, with broadly consistent efficacy across Asian and non-Asian populations. A greater renal benefit was observed in Asians for eGFR decline ≥40%, though this requires cautious interpretation. Hyperkalemia risk was increased but largely manageable. These findings support integration into DKD therapy and highlight the need for ethnically inclusive, long-term, real-world trials. Clinical trial number Not applicable.

Dengue is a mosquito-borne flaviviral serious febrile illness, most common in the tropical and subtropical regions including Pakistan. Vitamin D is a strong immunomodulator affecting both the innate and adaptive immune responses and plays a pivotal role in pathogen-defense mechanisms. There has been considerable interest in the possible role of vitamin D in dengue viral (DENV) infection. In the present prospective cross-sectional study, we assessed a possible association between serum vitamin D deficiency (VDD) and susceptibility towards severe dengue fever (DF) illness. Serum vitamin D levels were measured at the time of hospitalization in 97 patients diagnosed with dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) at Mayo Hospital, King Edward Medical University, Lahore, PK, from 16 November 2021 to 15 January 2022. In terms of disease severity, 37 (38.1%) patients were DF, 52 (53.6%) were DHF grade 1 and 2, and 8 (8.2%) were DSS. The results revealed that most patients (75 (77.3%)) were vitamin-D-deficient (i.e., serum level < 20 ng/mL), including 27 (73.0%) in DF, 41 (78.8%) in DHF grade 1 and 2, and 7 (87.5%) in DSS. The degree of VDD was somewhat higher in DSS patients as compared to DF and DHF grade 1 and 2 patients. Overall, serum vitamin D levels ranged from 4.2 to 109.7 ng/mL, and the median (IQR) was in the VDD range, i.e., 12.2 (9.1, 17.8) ng/mL. Our results suggest that there may be a possible association between VDD and susceptibility towards severe dengue illness. Hence, maintaining sufficient vitamin D levels in the body either through diet or supplementation may help provide adequate immune protection against severe dengue fever illness. Further research is warranted.

Background: Berberine is a poorly absorbed natural alkaloid widely used as nutraceutical to counteract diarrhoea and to lower cholesterol and hyperglycaemia. It has also been reported to reduce signs and symptoms of polycystic ovary syndrome (PCOS). Objective: To explore, through a multi-centric, randomized, controlled and prospective study, the possible role played by a form berberine that is more easily absorbed (Berberine Phytosome ® , BP) in 130 Pakistani women with a diagnosis of PCOS and fertility problems due to menstrual and ovary abnormalities. Results: Ninety days of supplementation with BP, administered at 550 mg x2/ die , determined (i) resumption of regular menstruation in about 70% of women ( versus 16% in the control group; p < 0.0001), (ii) normalization of the ovaries anatomy in more than 60% of women ( versus 13% in the control group; p < 0.0001), (iii) acne improvement in 50% of women ( versus 16% in the control group; p = 0.0409) and (iv) hirsutism reduction in 14% of women ( versus 0% in the control group; p = 0.0152). The metabolic and the hormonal profiles of the women in the two groups did not significantly differentiate at the end of the study. BP was well-tolerated and no specific side-effects were registered. Respectively after one, two and 8 years of trying, three women supplemented with BP became and are currently pregnant. Conclusion: Our study showed the positive effects of BP supplementation in women with PCOS and confirmed the high safety profile of this nutraceutical. Clinical Trial Registration: https://clinicaltrials.gov/ , identifier NCT05480670

Background Dengue fever caused by dengue virus is a tropical disease and is among the deadliest vector-borne diseases. The humid and hot summers of Pakistan support the probation of the vectors responsible for the transmission of viral and other parasitic diseases. Methodology A retrospective study, from 2012- 2019, of dengue infected individuals from the Punjab province of Pakistan was carried out to analyze epidemiology, clinical and laboratory findings of subjects with dengue virus infection. Data was derived from National Institute of Health (NIH) followed by Dengue control program of Pakistan, covering the incidence rate in 36 districts of Punjab and Islamabad Capital Territory (ICT) respectively. Patients data including the presence of dengue specific antigen or/and antibodies such as NS1 and IgG/IgM were observed. The study also included the analysis of demographic data, geographic data, and the month-wise distribution of dengue cases to examine seasonal trends. Results We analyzed 25,682 dengue infected individuals. The statistical analysis revealed a significant association between genders in which male population was more affected by dengue than females. It was also noted that the middle age group was the most affected age group while the highest number of cases were reported in October. Rawalpindi and Lahore were the most affected cities in Punjab province while Islamabad represented the highest number of cases during the recent outbreak in 2019. The IgM and IgG antibodies were highly prevalent among the infected patients. Conclusion Dengue is endemic in Pakistan, circulating throughout the year. Highest number of cases were observed in the month of October, September and November respectively. Association between climate change and vector-borne diseases need to be investigated in Pakistan as they significantly influence the timing and intensity of dengue and other disease outbreaks. Further exploration of hematological parameters is required to better diagnose and treat the disease. For the effective control of dengue outbreaks, awareness campaigns on sewage management and vector control along with social factors are strongly recommended for better control and eradication of the disease.