Objective The goal of this randomized placebo-controlled clinical trial was to investigate the therapeutic efficacy of oral 25-hydroxyvitamin D 3 [25(OH)D 3 ] in improving vitamin D status in vitamin D deficient/insufficient patients infected with the SARS-CoV-2 (COVID-19) virus. Methods This is a multicenter randomized double blinded randomized placebo-controlled clinical trial. Participants were recruited from three hospitals that are affiliated to [Institution Blinded for Review], and [Institution Blinded for Review]. Results A total 106 hospitalized patients who had a circulating concentration of 25(OH)D <30 ng/ml were enrolled in this study. Within 30 and 60 days 79.4% (26 out of 34) and 100% (24 out of 24) of the patients who received 25(OH)D 3 became sufficient whereas ≤12.5% the patients in the placebo group became sufficient during 2 months follow-up. We observed an overall lower trend for hospitalization, ICU duration, needing ventilator assistance and mortality in the 25(OH)D3 group compared with placebo group but they weren’t statistically significant. Treatment with oral 25(OH)D 3 was associated with a significant increase in the lymphocyte percentage and decrease in the ratio of neutrophils to lymphocytes (NLR) in the patients. The lower NLR was significant associated with reduced ICU admission days and mortality. Conclusion Our analysis indicated that oral 25-hydroxyvitamin D 3 was able to correct vitamin D deficiency/insufficiency in COVID-19 patients that resulted in improved immune function by increasing blood lymphocyte percentage. RCTs with a larger sample size and with higher dose of 25(OH)D3 maybe needed to confirm the potential effect of 25(OH)D3 on reducing clinical outcomes in COVID-19 patients. Ethics and Dissemination The study protocol was approved by the Ethics Committee of [Institution Blinded for Review]. (Approval Number: IR.TUMS.VCR.REC.1399.061). Dissemination plans include academic publications, conference presentations and social media. Trial registration The protocol was registered with the Iranian Registry of Clinical Trials (IRCT) on April 11, 2020 [Number Blinded for Review]. and U.S. National Institutes of Health [Number Blinded for Review] on May 11, 2020.

Acute respiratory distress syndrome (ARDS) is commonly found in critically ill patients with coronavirus disease 2019 (COVID-19). As a non-pharmacological treatment of complementary and alternative medicine (CAM), cupping has been clinically used for respiratory symptoms. We sequentially identified a series of patients with COVID-19 with ARDS who were admitted to the intensive care unit (ICU). Warm cupping of the posterior thorax was performed for seven days. We collected longitudinal severity scores on cough, breathlessness, chest tightness, type of oxygen therapy, and oxygen saturation (SpO 2 ). We hereby report the changes in the severity scores in a series of eight patients who received 21 sessions of cupping in addition to conventional treatments. All patients reported improvement in symptom scores that was matched by an increase in SpO 2 by as much as 3.16%. All patients were discharged and did not require the use of a mechanical ventilator. The results suggest that combining cupping with conventional treatment may provide a good prognosis for patients with COVID-19 with ARDS.

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