The severity of COVID-19 upon hospital admission is associated with plasma omega-3 fatty acids.

Fatty acids are precursors of inflammatory oxylipins. In the context of COVID-19, an excessive production of pro-inflammatory cytokines is associated with disease severity. The objective was to investigate whether the baseline omega 3/omega 6 fatty acids ratio and the oxylipins were associated with inflammation and oxidative stress in unvaccinated patients with COVID-19, classified according to the severity of the disease during hospitalization. This Prospective population-based cohort study included 180 hospitalized patients with COVID-19. The patients were classified into five groups according to the severity of their disease. Group 1 was the least severe and Group 5 was the most severe. Three specific types of fatty acids-eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA)-as well as their enzymatic and non-enzymatic oxylipins were determined using chromatography coupled mass spectrometry. There was no difference in the ratio of omega-3 to omega-6 fatty acids between the groups (p = 0.276). However, the EPA/AA ratio was lower in Group 4 compared to Group 1 (p = 0.015). This finding was associated with an increase in both C-Reactive Protein (p < 0.001) and Interleukin-6 (p = 0.002). Furthermore, the concentration of F2-Isoprostanes was higher in Group 4 than in Group 1 (p = 0.009), while no significant changes were observed for other oxylipins among groups. Multivariate analysis did not present any standard of biomarkers, suggesting the high complexity of factors involved in the disease severity. Our hypothesis was confirmed in terms of EPA/AA ratio. A higher EPA/AA ratio upon hospital admission was found to be associated with lower concentration of C-Reactive Protein and Interleukin-6, leading to a better prognosis of hospitalized SARS-CoV-2 patients. Importantly, this beneficial outcome was achieved without any form of supplementation. The trial also provides important information that can be further applied to reduce the severity of infections associated with an uncontrolled synthesis of pro-inflammatory cytokines.Trial registration: https://clinicaltrials.gov/study/NCT04449718 -01/06/2020. ClinicalTrials.gov Identifier: NCT04449718.

Bone erosions associated with systemic bone loss on HR-pQCT in women with longstanding polyarticular juvenile idiopathic arthritis.

OBJECTIVES: To analyze longstanding polyarticular juvenile idiopathic arthritis (pJIA) for possible associations between localized bone damage (erosions), and systemic bone loss. Besides, to compare the systemic bone mass of pJIA with healthy controls. METHODS: Thirty-four pJIA women and 99 healthy controls (HC) were included. Radius and tibia of all subjects were scanned by HR-pQCT. Volumetric bone mineral density (vBMD), bone microarchitecture, and -finite element parameters were analyzed. Patients underwent HR-pQCT of 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the dominant hand, for bone erosions quantification. RESULTS: The mean age of patients was 31.5 ± 7.4yrs with a mean disease duration of 21.7 ± 9.2yrs. Bone erosions were detectable in 79% of patients. The number of bone erosions was positively correlated with cortical porosity (Ct.Po) at tibia (r = 0.575, p = 0.001), and radius (r = 0.423, p = 0.018); and negatively correlated with cortical vBMD at tibia (r=-0.420, p = 0.015). In a logistic regression analysis, adjusted for anti-CCP, the presence of bone erosions was independently associated with Ct.Po at radius (p = 0.018) and cortical vBMD at tibia (p = 0.020). Moreover, cortical and trabecular vBMD, trabecular number, and µ-finite element parameters were decreased in patients compared to HC (p < 0.05). CONCLUSION: Bone erosions in longstanding pJIA women were associated with decreased cortical bone parameters, and these patients showed systemic bone impairment at peripheral sites compared with healthy controls.

Persistent or new symptoms 1 year after a single high dose of vitamin D3 in patients with moderate to severe COVID-19.

Purpose: The aim of this study was to investigate the reported persistent or new symptoms 1 year after a single dose of 200,000 IU of vitamin D3 and hospitalization in patients with moderate to severe COVID-19. Methods: This is a post-hoc, exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial from two hospitals in São Paulo, Brazil, registered in ClinicalTrials.gov, NCT04449718. Discharged patients were followed for up to 1 year and evaluated by telephone interviews at 6 and 12 months. The primary and secondary outcomes were previously published. These post-hoc exploratory secondary outcomes are the persistent or new symptoms and quality of life (QoL) at the post-viral stage of COVID-19. Generalized estimating equations (GEE) for repeated measures with Bonferroni's adjustment were used for testing outcomes. Results: Between 2 June and 27 August 2020, we randomized 240 patients of which 144 were included in this study [the vitamin D3 (n = 71) or placebo (n = 73) group]. The mean (SD) age was 54.3 (13.1) years, and body mass index (BMI) was 32.4 (6.5) kg/m2. Fever demonstrated a significant main effect of time (P < 0.001) with a reduction from baseline to 6 (52-0) and 12 months (52-0). No significant differences between groups were observed for fever, cough, fatigue, fever, myalgia, joint pain, runny nose, nasal congestion, sore throat, hypertension, diabetes, cardiovascular disease, rheumatic disease, asthma, chronic obstructive pulmonary, chronic kidney disease, QoL, and new or persistent symptoms up to 1-year of follow-up. Conclusion: The findings do not support the use of 200,000 IU of vitamin D3 compared to placebo for the management of persistence or new symptoms, and QoL reported by moderate to severe patients after hospitalization for COVID-19.

Frailty in the context of COVID-19 pandemic: A life-threatening condition.

The pandemic outbreak of coronavirus disease 2019 (COVID-19) has caused emerging challenges for healthcare systems regarding the assistance to the older adult population which, added to the increased life expectancy, may be exposing frail older adults to an increased risk of unfavorable health outcomes. Frailty has a pathogenesis of multifactorial etiology and is defined as a condition characterized by progressive decline in physiological function, weakness, decreased strength, and reduced resilience to stressors, leading to vulnerability and an increased risk of fractures, falls, institutionalization, and death. In the context of COVID-19, frail older adults accounted for approximately 51% of hospitalized patients with confirmed cases and elevated risk of mortality in-hospital. In addition, frailty may be associated with recent "excess mortality" reported by the World Health Organization (WHO) in terms of the full death toll associated directly (due to the disease) or indirectly (due to the pandemic's impact on health systems and society) to COVID-19. Therefore, this mini review aimed to provide a summarized discussion from meta-analyses data regarding the impact of frailty in community-dwelling older adults hospitalized with COVID-19 on short-term mortality risk.

Prognostic Nutritional Index and Oxygen Therapy Requirement Associated With Longer Hospital Length of Stay in Patients With Moderate to Severe COVID-19: Multicenter Prospective Cohort Analyses.

Purpose: To evaluate whether the prognostic nutritional index (PNI) is related to the oxygen therapy requirement at hospital admission and to ascertain the prognostic effect of the PNI and the oxygen therapy requirement as predictors of hospital length of stay in patients with moderate to severe coronavirus disease 2019 (COVID-19). Methods: This is a post-hoc analysis in hospitalized patients with moderate to severe COVID-19. The participants were categorized: (1) non-oxygen therapy (moderate COVID-19 not requiring oxygen therapy); (2) nasal cannula therapy (severe COVID-19 requiring nasal cannula oxygen therapy); and (3) high-flow therapy (severe COVID-19 requiring high-flow oxygen therapy). PNI was calculated for each patient according to the following equation: serum albumin [g/dL] × 10 + total lymphocyte count [per mm3] × 0.005. The participants were categorized into malnutrition (PNI <40), mild malnutrition (PNI 40-45), and non-malnutrition (PNI > 45). Results: According to PNI, malnutrition was more prevalent in the high-flow therapy group (94.9%; P < 0.001) with significantly lower PNI compared to both groups even after adjusting for the center and C-reactive protein. Patients in the high-flow therapy group [9 days (95% CI 7.2, 10.7), P < 0.001] and malnutrition status [7 days (95% CI 6.6, 7.4), P = 0.016] showed a significant longer hospital length of stay compared to their counterparts. The multivariable Cox proportional hazard models showed significant associations between both oxygen therapy requirement and PNI categories and hospital discharge. Conclusion: In addition to oxygen therapy requirement, low PNI was associated with longer hospital length of stay. Our findings suggest that PNI could be useful in the assessment of nutritional status related to the prognosis of patients with moderate to severe COVID-19.

Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.

BACKGROUND: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES: We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1ß, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1ß (MIP-1ß), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS: The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS: The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.

Effect of a Single High-Dose Vitamin D3 on the Length of Hospital Stay of Severely 25-Hydroxyvitamin D-Deficient Patients with COVID-19.

OBJECTIVES: In this ancillary analysis of a multicenter, double-blinded, randomized, placebo-controlled trial, we investigated the effect of a single high dose of vitamin D3 on the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19. METHODS: The primary outcome was length of hospital stay, defined as the total number of days that patients remained hospitalized from the date of randomization until the date of hospital discharge. Secondary outcomes included serum levels of 25-hydroxyvitamin D, mortality during hospitalization, number of patients admitted to the intensive care unit, and number of patients who required mechanical ventilation. ClinicalTrials.gov: NCT04449718. RESULTS: Thirty-two patients were included in the study. The mean (SD) age was 58.5 (15.6) years, body mass index was 30.8 (8.6) kg/m2, and 25-hydroxyvitamin D level was 7.8 (1.6) ng/mL. No significant difference was observed in the median interquartile range of length of hospital stay between the vitamin D3 group (6.0 [4.0-18.0] days) versus placebo (9.5 [6.3-15.5] days) (log-rank p=0.74; hazard ratio, 1.13 [95% confidence interval (CI), 0.53-2.40]; p=0.76). Vitamin D3 significantly increased serum 25-hydroxyvitamin D levels in the vitamin D3 group compared with that in the placebo group (between-group difference, 23.9 ng/mL [95% CI, 17.7-30.1]; p<0.001). CONCLUSIONS: A dose of 200.000 IU of vitamin D3 did not significantly reduce the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19.

Supplement-based nutritional strategies to tackle frailty: A multifactorial, double-blind, randomized placebo-controlled trial.

BACKGROUND: Sarcopenia plays a central role in the development of frailty syndrome. Nutrition and exercise are cornerstone strategies to mitigate the transition to frailty; however, there is a paucity of evidence for which dietary and exercise strategies are effective. OBJECTIVE: This large, multifactorial trial investigated the efficacy of different dietary strategies to enhance the adaptations to resistance training in pre-frail and frail elderly. METHODS: This was a single-site 16-week, double-blind, randomized, placebo-controlled trial conducted at the Clinical Hospital, School of Medicine - University of São Paulo, Sao Paulo, Brazil. Four integrated, sub-investigations were conducted to compare: 1) leucine vs. placebo; 2) whey vs. soy vs. placebo; 3) creatine vs. whey vs. creatine plus whey vs. placebo; 4) women vs. men in response to whey. Sub-investigations 1 to 3 were conducted in women, only. Two-hundred participants (154 women/46 men, mean age 72 ± 6 years) underwent a twice-a-week, resistance training program. The main outcomes were muscle function (assessed by dynamic and isometric strength and functional tests) and lean mass (assessed by DXA). Muscle cross-sectional area, health-related quality of life, bone and fat mass, and biochemical markers were also assessed. RESULTS: We observed that leucine supplementation was ineffective to improve muscle mass and function. Supplementation with whey and soy failed to enhance resistance-training effects. Similarly, supplementation with neither whey nor creatine potentiated the adaptations to resistance training. Finally, no sex-based differences were found in response to whey supplementation. Resistance exercise per se increased muscle mass and function in all sub-investigations. There were no adverse effects. CONCLUSION: Neither protein (whey and soy), leucine, nor creatine supplementation enhanced resistance training-induced adaptations in pre-frail and frail elderly, regardless of sex. These findings do not support the notion that some widely used supplement-based interventions can add to the already potent effects of resistance exercise to counteract frailty-related muscle wasting and dynapenia. CLINICAL TRIAL REGISTRY: NCT01890382; https://clinicaltrials.gov/ct2/show/NCT01890382. DATA SHARING: Data described in the manuscript will be made available upon request pending application.

No independent associations between physical activity and clinical outcomes among hospitalized patients with moderate to severe COVID-19.

BACKGROUND: Regular physical activity (PA) has been postulated to improve, or at least maintain, immunity across the life span. However, the link between physical (in)activity and coronavirus disease 2019 (COVID-19) remains to be established. This small-scale prospective cohort study is nested within a randomized controlled trial aimed to investigate the possible associations between PA levels and clinical outcomes among hospitalized patients with moderate to severe COVID-19. METHODS: Hospitalized patients with COVID-19 (mean age: 54.9 years) were recruited from the Clinical Hospital of the School of Medicine of the University of Sao Paulo (a quaternary referral teaching hospital) and from Ibirapuera Field Hospital, both located in Sao Paulo, Brazil. PA level was assessed using the Baecke Questionnaire of Habitual Physical Activity. The primary outcome was hospital length of stay. The secondary outcomes were mortality, admission to the intensive care unit (ICU), and mechanical ventilation requirement. RESULTS: The median hospital length of stay was 7.0 ± 4.0 days, median ± IQR; 3.3% of patients died, 13.8% were admitted to the ICU, and 8.6% required mechanical ventilation. Adjusted linear regression models showed that PA indices were not associated with hospital length of stay (work index: ß = -0.57 (95% confidence interval (95%CI): -1.80 to 0.65), p = 0.355; sport index: ß = 0.43 (95%CI: -0.94 to 1.80), p = 0.536; leisure-time index: ß = 1.18 (95%CI: -0.22 to 2.59), p = 0.099; and total activity index: ß = 0.20 (95%CI: -0.48 to 0.87), p = 0.563). None of the PA indices were associated with mortality, admission to the ICU, or mechanical ventilation requirement (all p > 0.050). CONCLUSION: Among hospitalized patients with COVID-19, PA did not independently associate with hospital length of stay or any other clinically relevant outcomes. These findings should be interpreted as meaning that, among already hospitalized patients with more severe forms of COVID-19, being active is a potential protective factor likely outweighed by a cluster of comorbidities (e.g., type 2 diabetes, hypertension, weight excess) and older age, suggesting that the benefit of PA against the worsening of COVID-19 may vary across stages of the disease.

Influence of vitamin D status on hospital length of stay and prognosis in hospitalized patients with moderate to severe COVID-19: a multicenter prospective cohort study.

BACKGROUND: Vitamin D acts as a mediator in the immune system regulating antiviral mechanisms and inflammatory processes. Vitamin D insufficiency has been suggested as a potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although its impact on the prognosis of hospitalized patients with coronavirus disease 2019 (COVID-19) remains unclear. OBJECTIVE: This multicenter prospective cohort study was designed to investigate whether serum 25-hydroxyvitamin D [25(OH)D] concentration is associated with hospital length of stay and prognosis in hospitalized patients with COVID-19. METHODS: Patients with moderate to severe COVID-19 (n = 220) were recruited from 2 hospitals in Sao Paulo, Brazil. Serum 25(OH)D concentrations were categorized as follows: <10 ng/mL, 10 to <20 ng/mL, 20 to <30 ng/mL, and ≥30 ng/mL, and <10 ng/mL and ≥10 ng/mL. The primary outcome was hospital length of stay and the secondary outcomes were the rate of patients who required invasive mechanical ventilation and mortality. RESULTS: There were no significant differences in hospital length of stay when the 4 25(OH)D categories were compared (P = 0.120). Patients exhibiting 25(OH)D <10 ng/mL showed a trend (P = 0.057) for longer hospital length of stay compared with those with 25(OH)D ≥10 ng/mL [9.0 d (95% CI: 6.4, 11.6 d) vs. 7.0 d (95% CI: 6.6, 7.4 d)]. The multivariable Cox proportional hazard models showed no significant associations between 25(OH)D and primary or secondary outcomes. CONCLUSIONS: Among hospitalized patients with moderate to severe COVID-19, those with severe 25(OH)D deficiency (<10 ng/mL) exhibited a trend for longer hospital length of stay compared with patients with higher 25(OH)D concentrations. This association was not significant in the multivariable Cox regression model. Prospective studies should test whether correcting severe 25(OH)D deficiency could improve the prognosis of patients with COVID-19.

High-Protein Plant-Based Diet Versus a Protein-Matched Omnivorous Diet to Support Resistance Training Adaptations: A Comparison Between Habitual Vegans and Omnivores.

BACKGROUND: Acute protein turnover studies suggest lower anabolic response after ingestion of plant vs. animal proteins. However, the effects of an exclusively plant-based protein diet on resistance training-induced adaptations are under investigation. OBJECTIVE: To investigate the effects of dietary protein source [exclusively plant-based vs. mixed diet] on changes in muscle mass and strength in healthy young men undertaking resistance training. METHODS: Nineteen young men who were habitual vegans (VEG 26 ± 5 years; 72.7 ± 7.1 kg, 22.9 ± 2.3 kg/m2) and nineteen young men who were omnivores (OMN 26 ± 4 years; 73.3 ± 7.8 kg, 23.6 ± 2.3 kg/m2) undertook a 12-week, twice weekly, supervised resistance training program. Habitual protein intake was assessed at baseline and adjusted to 1.6 g kg-1 day-1 via supplemental protein (soy for VEG or whey for OMN). Dietary intake was monitored every four weeks during the intervention. Leg lean mass, whole muscle, and muscle fiber cross-sectional area (CSA), as well as leg-press 1RM were assessed before (PRE) and after the intervention (POST). RESULTS: Both groups showed significant (all p < 0.05) PRE-to-POST increases in leg lean mass (VEG: 1.2 ± 1.0 kg; OMN: 1.2 ± 0.8 kg), rectus femoris CSA (VEG: 1.0 ± 0.6 cm2; OMN: 0.9 ± 0.5 cm2), vastus lateralis CSA (VEG: 2.2 ± 1.1 cm2; OMN: 2.8 ± 1.0 cm2), vastus lateralis muscle fiber type I (VEG: 741 ± 323 µm2; OMN: 677 ± 617 µm2) and type II CSA (VEG: 921 ± 458 µm2; OMN: 844 ± 638 µm2), and leg-press 1RM (VEG: 97 ± 38 kg; OMN: 117 ± 35 kg), with no between-group differences for any of the variables (all p > 0.05). CONCLUSION: A high-protein (~ 1.6 g kg-1 day-1), exclusively plant-based diet (plant-based whole foods + soy protein isolate supplementation) is not different than a protein-matched mixed diet (mixed whole foods + whey protein supplementation) in supporting muscle strength and mass accrual, suggesting that protein source does not affect resistance training-induced adaptations in untrained young men consuming adequate amounts of protein. CLINICAL TRIAL REGISTRATION: NCT03907059. April 8, 2019. Retrospectively registered.

Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.

Importance: The efficacy of vitamin D3 supplementation in coronavirus disease 2019 (COVID-19) remains unclear. Objective: To investigate the effect of a single high dose of vitamin D3 on hospital length of stay in patients with COVID-19. Design, Setting, and Participants: This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020. Interventions: Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D3 (n = 120) or placebo (n = 120). Main Outcomes and Measures: The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. Results: Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention. Conclusions and Relevance: Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04449718.

Effect of a single high-dose vitamin d3 on the length of hospital stay of severely 25-hydroxyvitamin d-deficient patients with COVID-19

OBJECTIVES: In this ancillary analysis of a multicenter, double-blinded, randomized, placebo-controlled trial, we investigated the effect of a single high dose of vitamin D3 on the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19. METHODS: The primary outcome was length of hospital stay, defined as the total number of days that patients remained hospitalized from the date of randomization until the date of hospital discharge. Secondary outcomes included serum levels of 25-hydroxyvitamin D, mortality during hospitalization, number of patients admitted to the intensive care unit, and number of patients who required mechanical ventilation. ClinicalTrials.gov: NCT04449718. RESULTS: Thirty-two patients were included in the study. The mean (SD) age was 58.5 (15.6) years, body mass index was 30.8 (8.6) kg/m2, and 25-hydroxyvitamin D level was 7.8 (1.6) ng/mL. No significant difference was observed in the median interquartile range of length of hospital stay between the vitamin D3 group (6.0 [4.0-18.0] days) versus placebo (9.5 [6.3-15.5] days) (log-rank p=0.74; hazard ratio, 1.13 [95% confidence interval (CI), 0.53-2.40]; p=0.76). Vitamin D3 significantly increased serum 25-hydroxyvitamin D levels in the vitamin D3 group compared with that in the placebo group (between-group difference, 23.9 ng/mL [95% CI, 17.7-30.1]; p<0.001). CONCLUSIONS: A dose of 200.000 IU of vitamin D3 did not significantly reduce the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19.