Calcifediol treatment and COVID-19-related outcomes
X Nogues, D Ovejero, J M Quesada-Gomez, R Bouillon, D Arenas, J Pascual, J Villar-Garcia, A Rial, C Gimenez-Argente, M L Cos, J Rodriguez-Morera, I Campodarve, R Guerri-Fernandez, M Pineda-Moncusí, PhD Natalia Garcia-Giralt
Background COVID-19 is a major health problem because of acute respiratory distress syndrome, saturation of intensive care units (ICU) and mortality.
Methods Our study aims to elucidate the effect of calcifediol [25(OH)D 3 ] treatment on ICU admission and mortality, in patients admitted to COVID-19 wards of Hospital del Mar, Barcelona, Spain. A total of 930 participants were included. Participants (n=551) were randomly assigned to calcifediol treatment (532 ug on day one and 266 ug on day 3, 7, 15, and 30) at the time of hospital admission or as controls (n=379). Findings ICU assistance was required by 110 (11.8%) participants. Out of 551 patients treated with calcifediol at admission, 30 (5.4%) required ICU, compared to 80 out of 379 controls (21.1%; p<0.0001). Logistic regression of calcifediol treatment on ICU admission, adjusted by age, gender, linearized 25(OH)D levels at baseline, and comorbidities showed that treated patients had a reduced risk to require ICU (RR 0.18 [95% CI 0.11;0.29]). Baseline 25(OH)D levels inversely correlated with the risk of ICU admission (RR 0.53 [95% CI 0.35;0.80]). Overall mortality was 10%. In the Intention-to-treat analysis, 36 (6.5%) out of 551 patients treated with calcifediol at admission died compared to 57 patients (15%) out of 379 controls (p=0.001). Adjusted results showed a reduced mortality for more of 60%. Higher baseline 25(OH)D levels were significantly associated with decreased mortality (RR 0.40 [95% CI 0.24;0.67]). Age and obesity were also predictors of mortality.
Interpretation In patients hospitalized with COVID-19, calcifediol treatment at the time of hospitalization significantly reduced ICU admission and mortality.
Implications of all the available evidence Vitamin D deficiency is common and even more so in COVID-19 patients compared to the general population. Rapid correction of such deficiency by calcifediol is easy, cheap, and appears as highly effective to control disease severity and avoid fatal outcomes in the setting of SARS-CoV-2 infection.
References
Adorini, Penna, Dendritic cell tolerogenicity: a key mechanism in immunomodulation by vitamin D receptor agonists, Hum Immunol
Amrein, Scherkl, Hoffmann, OH)D deficiency 2.0: an update on the current status worldwide, Eur J Clin Nutr
Baktash, Hosack, Patel, Vitamin D status and outcomes for hospitalised older patients with COVID-19, Postgrad Med J
Beigel, Tomashek, Dodd, Remdesivir for the Treatment of Covid-19 -Final Report, N Engl J Med
Boban, Novel coronavirus disease (COVID-19) update on epidemiology, pathogenicity, clinical course and treatments, Int J Clin Pract
Bouillon, Marcocci, Carmeliet, Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions, Endocr Rev
Carpagnano, Lecce, Quaranta, Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19, J Endocrinol Invest
Castillo, Costa, Barrios, Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study, J Steroid Biochem Mol Biol
Channappanavar, Perlman, Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Semin Immunopathol
Group, Horby, Lim, Dexamethasone in Hospitalized Patients with Covid-19 -Preliminary Report, N Engl J Med
Guan, Ni, Hu, Clinical Characteristics of Coronavirus Disease 2019 in China, N Engl J Med
Hastie, Pell, Sattar, Vitamin D and COVID-19 infection and mortality in UK Biobank, Eur J Nutr
Helming, Bose, Ehrchen, 1alpha,25-Dihydroxyvitamin D3 is a potent suppressor of interferon gamma-mediated macrophage activation, Blood
Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin Exp Res
Jordan, Adab, Cheng, Covid-19: risk factors for severe disease and death, BMJ
Kalil, Patterson, Mehta, Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19, N Engl J Med
Maghbooli, Sahraian, Ebrahimi, Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection, PLoS One
Martineau, Jolliffe, Hooper, Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ
Meltzer, Best, Zhang, Vokes, Arora et al., Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results, JAMA Netw Open
Nair, Venkatesh, Center, Vitamin D deficiency and supplementation in critical illness-the known knowns and known unknowns, Crit Care
Nirula, Shen, Skovronsky, Neutralizing Antibody LY-CoV555 for Outpatient Covid-19. Reply, N Engl J Med
Panagiotou, Tee, Ihsan, Original publication: Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID-19 are associated with greater disease severity, Clin Endocrinol (Oxf)
Pizzini, Aichner, Sahanic, Impact of Vitamin D Deficiency on COVID-19-A Prospective Analysis from the CovILD Registry, Nutrients
Quesada-Gomez, Bouillon, Is calcifediol better than cholecalciferol for vitamin D supplementation?, Osteoporos Int
Radujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger, Vitamin D Deficiency and Outcome of COVID-19 Patients, Nutrients
Russo, Pitter, Da Re, Tonon, Avossa et al., Epidemiology and public health response in early phase of COVID-19 pandemic, Veneto Region, Italy, 21 February to, Euro Surveill
Xu, Shi, Wang, Pathological findings of COVID-19 associated with acute respiratory distress syndrome, Lancet Respir Med
Ye, Tang, Liao, Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study, J Am Coll Nutr