Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19-Results From a Pilot Open-Label, Randomized Controlled Trial

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 NCT0513067

Vitamin D deficiency (VDD) and susceptibility towards severe Dengue fever:a prospective cross-sectional study of hospitalized Dengue fever patients from Lahore, Pakistan

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 &lt; 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.</p

Clinical Effects of <i>Streptococcus salivarius</i> K12 in Hospitalized COVID-19 Patients: Results of a Preliminary Study

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

Use of National Institute for Health and Care Excellence head injury guidelines among patients with delayed presentation after head trauma can lead to missed traumatic brain injury: A 5-year institutional review

Introduction: In 2014, traumatic brain injury (TBI) caused 3 million ER visits, hospitalizations, and deaths in the US. The National Institute for Health and Care Excellence (NICE) guidelines, initially generated using data from patients presenting within 24 h of head trauma, are used to determine the need for head computed tomography (CT) scan in patients after 24 h. The authors wanted to determine the proportion of CT scans for head trauma performed at our center in late presenters (\u3e24 h after head trauma), the incidence of intracranial pathology in early (24 h) versus late (\u3e24 h) presenters, and the sensitivity of the NICE guidelines for TBI in these two subpopulations. Methods: A retrospective chart review was conducted at a tertiary care center in Karachi. All people (\u3e16) who had a head CT for head trauma from 2010 to 2015 were included. Age, sex, primary diagnosis, comorbid disorders, mechanism-of-injury, duration (in hours) from head trauma to presentation, site, and extent of injury (injury severity scale), hospital stay, number and details of surgical procedures, CT scan findings, other injuries, and mortality were recorded. Means were compared using the Independent Sample t-test, while categorical variables were compared using χ2. Multivariate logistic regression analyses were used to identify TBI predictors. Results: The authors found 2009 eligible patients; seven were excluded due to incomplete medical records. The final statistical analysis comprised 2002 head trauma patients. Overall, 52% of early and late presenters had severe injuries, and 2.3% died. 32.2% of patients with head trauma had CT after 24 h. Early presenters were 46.7% traumatized, while late presenters were 63%. The NICE guidelines were 93% sensitive for early presenters and 83% for late presenters with traumatic intracranial injury. Conclusion: Patients coming to the emergency department after 24 h of head trauma are a large proportion of the overall head trauma population. The NICE guidelines for late-presenting head injuries are less sensitive and may overlook intracranial injuries if imaging is not performed

Alleviation of Cadmium Stress in Wheat through the Combined Application of Boron and Biochar via Regulating Morpho-Physiological and Antioxidant Defense Mechanisms

Cadmium (Cd) contamination in soil adversely affects crop productivity, grain quality, and human health. Applications of boron (B) and biochar are known to impart tolerance to crops against abiotic stresses. A pot experiment was performed to assess the effects of the sole and combined application of B and biochar on growth, physiological and antioxidant defense mechanisms, yield, and grain quality of wheat under Cd toxicity-induced stress. The treatments included control (0 mg kg&minus;1 and 0 g kg&minus;1), only Cd (15 mg kg&minus;1), only B (5 g kg&minus;1), only biochar (50 g kg&minus;1), B plus biochar, Cd plus B, Cd plus biochar, and Cd plus B plus biochar, which were applied at the time of sowing and were arranged using completely randomized design (CRD) with five replications. The individual Cd toxicity (15 mg kg&minus;1) significantly reduced chl a, chl b, and chl a+b, as well as primary metabolites (soluble protein, amino acids, total soluble sugar, and phenolic contents), while it increased the activities of enzymatic antioxidants like superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) in the leaves of wheat. In addition, Cd stress (15 mg kg&minus;1) increased lipid peroxidation in the form of malondialdehyde (MDA), and it enhanced the hydrogen peroxide (H2O2) content, electrolyte leakage (EL), and proline contents in the leaves. Furthermore, Cd (15 mg kg&minus;1) contamination reduced the grain yield and yield-related attributes relative to respective no-Cd treatments. Soil-applied B and biochar improved wheat grain yield by triggering the activities of enzymatic antioxidants. Individual or combined B and biochar applications improved proline contents and reduced H2O2 and MDA contents in plants. The combined application of B and biochar enhanced soluble sugars and total phenolic as compared to the control and Cd-contaminated plants. In conclusion, the combined application of B and biochar was found to be the best soil amendment strategy to improve the yield of wheat under Cd-contaminated soil

Alleviation of Cadmium Stress in Wheat through the Combined Application of Boron and Biochar via Regulating Morpho-Physiological and Antioxidant Defense Mechanisms

Cadmium (Cd) contamination in soil adversely affects crop productivity, grain quality, and human health. Applications of boron (B) and biochar are known to impart tolerance to crops against abiotic stresses. A pot experiment was performed to assess the effects of the sole and combined application of B and biochar on growth, physiological and antioxidant defense mechanisms, yield, and grain quality of wheat under Cd toxicity-induced stress. The treatments included control (0 mg kg−1 and 0 g kg−1), only Cd (15 mg kg−1), only B (5 g kg−1), only biochar (50 g kg−1), B plus biochar, Cd plus B, Cd plus biochar, and Cd plus B plus biochar, which were applied at the time of sowing and were arranged using completely randomized design (CRD) with five replications. The individual Cd toxicity (15 mg kg−1) significantly reduced chl a, chl b, and chl a+b, as well as primary metabolites (soluble protein, amino acids, total soluble sugar, and phenolic contents), while it increased the activities of enzymatic antioxidants like superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) in the leaves of wheat. In addition, Cd stress (15 mg kg−1) increased lipid peroxidation in the form of malondialdehyde (MDA), and it enhanced the hydrogen peroxide (H2O2) content, electrolyte leakage (EL), and proline contents in the leaves. Furthermore, Cd (15 mg kg−1) contamination reduced the grain yield and yield-related attributes relative to respective no-Cd treatments. Soil-applied B and biochar improved wheat grain yield by triggering the activities of enzymatic antioxidants. Individual or combined B and biochar applications improved proline contents and reduced H2O2 and MDA contents in plants. The combined application of B and biochar enhanced soluble sugars and total phenolic as compared to the control and Cd-contaminated plants. In conclusion, the combined application of B and biochar was found to be the best soil amendment strategy to improve the yield of wheat under Cd-contaminated soil