Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S).

BACKGROUND: efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. OBJECTIVE: effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. METHODS: participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. OUTCOMES: primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. RESULTS: in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10-16) and 13 (12-18) ng/ml (P = 0.06) at baseline; and 60 (55-65) ng/ml and 4 (1-7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2-5) versus 5 (95% CI, 3-7), P = 0.01, intergroup difference - 2 (95% CI, -4 to -0.01); r = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P = 0.046)] was observed with vitamin D. CONCLUSIONS: single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov  id: NCT04952857 registered dated 7 July 2021. What is already known on this topic-vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds-high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy-vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced.

Association of Maternal Hyperuricemia with Post-Spinal Hypotension in Pre-Eclamptic Parturients Undergoing Emergency Cesarean Delivery: a Prospective Observational Study.

Pre-eclampsia is commonly associated with higher serum uric acid levels, which is known to increase vascular tone. A previous retrospective study established a positive correlation between raised serum uric acid levels and reduced incidence of post-spinal hypotension. However, until date, this correlation has not been prospectively evaluated in exclusively pre-eclamptic women. Pre-eclamptic parturients undergoing emergency cesarean delivery under subarachnoid block were included. Sample for measuring serum uric acid level was obtained prior to shifting patients for cesarean delivery. Following spinal anesthesia, we recorded episodes of hypotension (fall of mean arterial pressure more than 20% from baseline values), use of vasopressors, and intraoperative blood loss. Our primary objective was to study the association between maternal hyperuricemia and incidence of post-spinal hypotension. Our secondary objectives included amount of vasopressors administered to maintain targeted mean arterial pressure before delivery of the baby, intraoperative blood loss, and immediate neonatal outcome. A total of 95% parturients had hyperuricemia, with mean serum uric acid level being 6.94 ± 0.9 mg/dl. Incidence of post-spinal hypotension was significantly lower in women who had hyperuricemia as compared with those with normal serum uric acid levels (21% vs 75%; p = 0.015). Mean serum uric acid levels were significantly high (p = 0.001) in patients not requiring any vasopressors (7.2 ± 1.2 mg/dl) than in those requiring moderate (5.70 ± 0.79 mg/dl) to high dose (5.75 ± 0.77 mg/dl) of vasopressors. There is a high incidence of hyperuricemia in pre-eclamptic parturients. In these patients, elevated serum uric acid levels is associated with lower incidence of post-spinal hypotension and reduced need of vasopressors to maintain maternal blood pressure within a normal range.