The effect of vitamin D and magnesium supplementation on clinical symptoms, and serum inflammatory and oxidative stress markers in patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial (preprint)

Objectives: This study aims to evaluate the effect of vitamin D and magnesium supplementation on clinical symptoms and serum inflammatory and oxidative stress markers in patients with COVID-19. Trial design: This study is a 4-arm randomized, double-blind, placebo-controlled clinical trial with a factorial design and the intervention period is 3 weeks. Participants: This study is conducted on COVID-19 patients admitted to the Shahid Mohammadi hospital in Bandar Abbas, Iran who be eligible for inclusion in the study. Patients are included only if they meet all of the following criteria: 1) aged from 18 to 65 years old, 2) confirmation of COVID-19 by RT-PCR test, 3) completing informed consent, 4) passing less than 48 hours since the patient's hospitalization, 5) no skin or gastrointestinal allergies due to taking multivitamin supplements, vitamin D, and magnesium, 6) having more than 30 breaths per minute and less than 93% oxygen saturation in room air and sea level. Patients are excluded if they have any of the following conditions: 1) pregnancy or lactation, 2) take a daily multivitamin or take a vitamin D or magnesium supplement in the last month, 3) participating in other clinical trials, 4) renal failure or dialysis, severe liver disease or cirrhosis, 5) known diagnosis of hypercalcemia, 6) discharging from the hospital less than 24 hours after the start of the intervention, 7) history of kidney stones in the last year, 8) transfer the patient to the ICU, 9) baseline vitamin D levels above 80 ng/ml, 9) baseline magnesium levels above 2.6 mg/dl. Intervention and comparator: Participants will be randomly allocated to one of the four following groups: A) Vitamin D (two 50,000 IU capsules at the beginning of the study, two 50,000 IU capsules on the 4th day, one 50,000 IU capsule on the 11th day, and one 50,000 IU capsule on the 17th day) and magnesium supplement (300 mg/day). B) Vitamin D capsule and magnesium placebo. C) Magnesium supplement and vitamin D placebo. D) Vitamin D placebo and magnesium placebo. Main outcomes: Clinical symptoms (fever, dry cough, shortness of breath, headache, myalgia, oxygen saturation, and mortality) and laboratory markers (CRP, MDA, TAC, WBC, neutrophils count, lymphocytes count, ratio of neutrophils to lymphocytes, levels of 25 hydroxyvitamin D and magnesium) Randomization: A computer-generated block randomization list is used for randomization. Blinding (masking): Investigators and patients are blinded to group allocation and treatment. A double-blind design is achieved using matched placebos. Numbers to be randomized (sample size): A total of 104 eligible patients are randomized into four groups of 26 subjects (1:1:1:1 allocation ratio). Discussion With the rapid prevalence of COVID-19 in recent years, more attention has been paid to effective dietary supplementation to improve clinical symptoms and biochemical parameters in these patients. To our knowledge, this is the first study to evaluate the effects of vitamin D supplementation in combination with magnesium or alone with respect to this infectious disease. The findings of the current RCT will provide evidence regarding the effectiveness of dietary supplementation strategies to improve COVID-19 outcomes. Trial Status: Ethical approval of the first version of the study protocol was obtained from the medical ethics committee of Hormozgan University of Medical Sciences, Bandar Abbas, Iran on May 30th, 2021 (IR.HUMS.REC.1400.085). Currently, the recruitment phase is ongoing since August 23th, 2021 and is anticipated to be complete by the end of August 2022. Trial registration: The study protocol was registered in the Iranian Registry of Clinical Trials (https://www.irct.ir; IRCT20210702051763N1) on August 14th, 2021. https://www.irct.ir/trial/57413 Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

The Efficacy of Famotidine in improvement of outcomes in Hospitalized COVID-19 Patients: A phase III randomised clinical trial (preprint)

IntroductionAs the first randomized clinical trial, this study evaluated the effect of Famotidine on the improvement of outcomes of hospitalized patients with COVID-19.MethodThis phase III randomized clinical trial was designed with two parallel arms, placebo-controlled, single-blind, and concealed allocation, and recruited 20 patients. Oral Famotidine 160 mg four times a day was given to patients until the discharge day or for a maximum of 14 days. Patients’ temperature, respiration rate, oxygen saturation, lung infiltration, lactate dehydrogenase (LDH) level and complete blood count (CBC) were measured at the baseline (before the intervention) and on day 14 after the intervention or on discharge day. Length of stay in the hospital and length of stay in the ICU were also measured as secondary outcomes of the study.ResultsThe results showed a significant decrease in LDH (P = 0.01), mean WBC (P = 0.04) and length of stay (P = 0.04) of patients with COVID-19 in the group treated with Famotidine compared to the control group. There was also a significant increase in oxygen saturation (P = 0.01) in the group treated with Famotidine compared to the control group. Cough improvement was also higher in the oral Famotidine group compared to the control group (P = 0.02).ConclusionThis was the first clinical trial on the effect of Famotidine on the improvement of hospitalized COVID-19 patients, which indicated that high-dose Famotidine improves patients’ clinical signs and reduces the severity of the disease and duration of hospitalization.

Predicting COVID-19 Preventive Behaviors based on Protection Motivation Theory in Hormozgan, Iran (preprint)

Background: The present research aimed to predict the preventive behaviors of COVID-19 in the light of the Protection Motivation Theory (PMT). Methods: The present cross-sectional research was conducted in 2 months (March 2020-April 2020) in Hormozgan Province of Iran. The research population comprised all residents above 15 years of age. They received an online questionnaire survey in two parts, demographic information along with PMT constructs. To analyze the data, independent t-test and one-way anova test, Multiple linear regression and the statistical technique of path analysis and structural equation modeling was used. All statistical calculations and hypothesis testing were performed using spss21 and Amos21 software and a significant level of hypothesis testing was considered to be 0.05Results: A total number of 2,032 subjects participated in this research, the mean age of whom was 34.84±9.8 (R=15-98). The majority of participants were between 31 - 40 years old, female (60.4%), married (72%), urban residents (87.3%), holding a Bachelor’s degree or higher (58.8%) and employed (58.8%). Statistically significant positive correlation coefficients were estimated between preventive behaviors of COVID-19 and perceived vulnerability (r=0.192, p<0.001), perceived severity (r=0.092, p<0.001), response efficacy (r=0.398, p<0.001) ,self efficacy (r=0.497, p<0.001) and protection motivation (r=0.595, p<0.001). Statistically significant negative correlations were found between behavior and maladaptive behavior rewards (r=-0.243, p<0.001) and perceived costs (r=-0.121, p<0.001). Conclusions: The present findings showed that maladaptive behavior reward and fear predicted protective behaviors negatively; response efficacy and self-efficacy predicted protective behaviors positively. The effect of self-efficacy was the strongest among all. The information provided in this research can contribute to policy-making in the country.

Predicting COVID-19 Preventive Behaviors based on Protection Motivation Theory in Hormozgan, Iran. (preprint)

Background: The present research aimed to predict the preventive behaviors of COVID-19 in the light of the Protection Motivation Theory (PMT).Methods: The present cross-sectional research was conducted in 2 months (March 2020-April 2020) in Hormozgan Province of Iran. The research population comprised all residents above 15 years of age. They received an online questionnaire survey in two parts, demographic information along with PMT constructs. To analyze the data, independent t-test and one-way anova test, Multiple linear regression and the statistical technique of path analysis and structural equation modeling was used. All statistical calculations and hypothesis testing were performed using spss21 and Amos21 software and a significant level of hypothesis testing was considered to be 0.05Results: A total number of 2,032 subjects participated in this research, the mean age of whom was 34.84±9.8 (R=15-98). The majority of participants were between 31 - 40 years old, female (60.4%), married (72%), urban residents (87.3%), holding a Bachelor’s degree or higher (58.8%) and employed (58.8%). Statistically significant positive correlation coefficients were estimated between preventive behaviors of COVID-19 and perceived vulnerability (r=0.192, p<0.001), perceived severity (r=0.092, p<0.001), response efficacy (r=0.398, p<0.001) ,self efficacy (r=0.497, p<0.001) and protection motivation (r=0.595, p<0.001). Statistically significant negative correlations were found between behavior and maladaptive behavior rewards (r=-0.243, p<0.001) and perceived costs (r=-0.121, p<0.001).Conclusions: The present findings showed that maladaptive behavior reward and fear predicted protective behaviors negatively; response efficacy and self-efficacy predicted protective behaviors positively. The effect of self-efficacy was the strongest among all. The information provided in this research can contribute to policy-making in the country.