IMPORTANCEThe efficacy of vitamin D 3 supplementation in coronavirus disease 2019 remains unclear.OBJECTIVE To investigate the effect of a single high dose of vitamin D 3 on hospital length of stay in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThis 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 D 3 (n = 120) or placebo (n = 120). MAIN OUTCOMES AND MEASURESThe 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. RESULTSOf 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 D 3 (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 D 3 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 D 3 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 D 3 , compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D 3 for treatment of moderate to severe COVID-19.

ImportancePatients with COVID-19 may exhibit 25-hydroxyvitamin D deficiency, but the beneficial effects of vitamin D3 supplementation in this disease remain to be proven by randomized controlled trials.ObjectiveTo investigate the efficacy and safety of vitamin D3 supplementation in patients with severe COVID-19.Design, Setting, and ParticipantsThis is a multicenter, double-blind, randomized, placebo-controlled trial conducted in two centers (a quaternary hospital and a field hospital) in Sao Paulo, Brazil. The trial included 240 hospitalized patients with severe COVID-19. The study was conducted from June 2, 2020 to October 7, 2020.InterventionsPatients were randomly allocated (1:1 ratio) to receive either a single oral dose of 200,000 IU of vitamin D3 or placebo.Main Outcomes and MeasuresThe primary outcome was hospital length of stay, defined as hospital discharge from the date of randomization or death. Secondary outcomes were mortality, admission to ICU, mechanical ventilation requirement, and serum levels of 25-hydroxyvitamin D, creatinine, calcium, C-reactive protein, and D-dimer.ResultsOf 240 randomized patients (mean age, 56 years; 56% men), 232 (96.7%) were included in the primary analysis. Log-rank test showed that hospital length of stay was comparable between the vitamin D3 supplementation and placebo groups (7.0 days [95% CI, 6.1 to 7.9] and 7.0 days [95% CI, 6.2 to 7.8 days]; hazard ratio, 1.12 [95% CI, 0.9 to 1.5]; P = .379; respectively). The rate of mortality (7.0% vs 5.1%; P = .590), admission to ICU (15.8% vs 21.2%; P = .314), and mechanical ventilation requirement (7.0% vs 14.4%; P = .090) did not significantly differ between groups. Vitamin D3 supplementation significantly increased serum 25-hydroxyvitamin D levels compared to placebo (difference, 24.0 ng/mL [95% CI, 21.0% to 26.9%]; P = .001). No adverse events were observed.Conclusions and RelevanceAmong hospitalized patients with severe COVID-19, vitamin D3 supplementation was safe and increased 25-hydroxyvitamin D levels, but did not reduce hospital length of stay or any other relevant outcomes vs placebo. This trial does not support the use of vitamin D3 supplementation as an adjuvant treatment of patients with COVID-19.Key pointsQuestionCan vitamin D3 supplementation reduce hospital length of stay in hospitalized patients with severe COVID-19?FindingsIn this double-blind, randomized, placebo-controlled trial involving 240 hospitalized patients with severe COVID-19, a single dose of 200,000 IU of vitamin D3 supplementation was safe and effective in increasing 25-hydroxyvitamin D levels, but did not significantly reduce hospital length of stay (hazard ratio, 1.12) or any other clinically-relevant outcomes compared with placebo.MeaningVitamin D3 supplementation does not confer therapeutic benefits among hospitalized patients with severe COVID-19.

Background The modulating effect of vitamin D on cytokine levels in severe coronavirus disease 2019 (COVID-19) remains unknown. Objectives 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 registered in ClinicalTrials.gov, NCT04449718. Patients with moderate to severe COVID-19 were recruited from two hospitals in Sao Paulo, Brazil. Of 240 randomized patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200 000 IU of vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, that has been published in our previous study. The prespecified secondary outcomes were serum levels of interleukin-1β, interleukin-6, interleukin-10, tumor necrosis factor alpha (TNF-α) and 25-hydroxyvitamin D. The post-hoc exploratory secondary outcomes were interleukin-4, interleukin-12p70, interleukin-17A, interferon gamma (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-8, interferon-inducible protein-10 (IP-10), macrophage inflammatory protein-1 beta (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), growth factor vascular endothelial (VEGF), and leukocytes count. Generalized estimating equations (GEE) for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. Results The study included 200 patients with a mean (SD) age 55.5 (14.3) years and body mass index (BMI) 32.2 (7.1) kg/m2, of which 109 (54.5%) were male. GM-CSF levels showed a significant group by time interaction effect (P = 0.04), although between-group difference at post-intervention 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 of vitamin D3, compared to placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. Clinical Trial Registration: ClinicalTrials.gov, NCT04449718.

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: &lt;10 ng/mL, 10 to &lt;20 ng/mL, 20 to &lt;30 ng/mL, and ≥30 ng/mL, and &lt;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 &lt;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 (&lt;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.

Diogo Souza Domiciano , Rosa Maria Rodrigues Pereira

BACKGROUNDImmunosuppressed patients are at high risk for opportunistic infections. We report a case of a 40-year old man with MALT lymphoma and systemic lupus erythematosus (SLE)-like nephritis, with a history of several infectious complications, who presented with a chronic left hand flexor tenosynovitis, diagnosed as atypical mycobacteriosis.

BACKGROUNDFaced with muscle weakness, a rheumatologist is often called to assess autoimmune diseases. It is imperative to keep in mind there is a wide range of differential diagnoses, such as neurological, metabolic and infectious diseases.

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