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Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19

Mazziotti et al., J Endocrinol. Invest., doi:10.1007/s40618-021-01535-2

Mar 2021

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Vitamin D for COVID-19

8th treatment shown to reduce risk in October 2020

^*, now known with p < 0.00000000001 from 120 studies, recognized in 8 countries.

Lower risk for mortality, ICU admission, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,000+ studies for 60+ treatments. c19early.org

Retrospective 348 hospitalized patients in Italy showing vitamin D deficiency associated with acute hypoxemic respiratory failure. Vitamin D supplementation during hospitalization was not significantly associated with mortality or ventilation.

Cholecalciferol was used in this study. Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 65% [41‑79%] lower risk vs. 39% [26‑49%] lower risk. Cholecalciferol requires two hydroxylation steps to become activated - first in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol, paricalcitol, and alfacalcidol are active vitamin D analogs that do not require conversion. This allows them to have more rapid onset of action compared to cholecalciferol. The time delay for cholecalciferol to increase serum calcifediol levels can be 2-3 days, and the delay for converting calcifediol to active calcitriol can be up to 7 days.

This is the 25th of 120 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 248 sextillion).

29 studies are RCTs, which show efficacy with p=0.0000024.

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risk of death, 19.0% lower, OR 0.81, p = 0.49, treatment 116, control 232, supplementation, RR approximated with OR.

risk of mechanical ventilation, 67.0% higher, OR 1.67, p = 0.08, treatment 116, control 232, supplementation, RR approximated with OR.

risk of death, 2.4% lower, RR 0.98, p = 0.91, high D levels 187, low D levels 161, inverted to make RR<1 favor high D levels, odds ratio converted to relative risk, >12ng/mL, control prevalance approximated with overall prevalence, outcome based on serum levels.

risk of acute hypoxemic respiratory failure, 37.0% lower, RR 0.63, p = 0.006, high D levels 72 of 187 (38.5%), low D levels 97 of 161 (60.2%), NNT 4.6, inverted to make RR<1 favor high D levels, odds ratio converted to relative risk, >12ng/mL, outcome based on serum levels.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Mazziotti et al., 5 Mar 2021, retrospective, Italy, peer-reviewed, 11 authors, dosage varies.

This Paper Vitamin D All

Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19

G Mazziotti, E Lavezzi, A Brunetti, M Mirani, G Favacchio, A Pizzocaro, M T Sandri, A Di Pasquale, A Voza, M Ciccarelli, A G Lania

Journal of Endocrinological Investigation, doi:10.1007/s40618-021-01535-2

Purpose Hypovitaminosis D has emerged as potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population with variable effects on the outcome of the coronavirus disease-19 . The aim of this retrospective single-center study was to investigate the impact of hypovitaminosis D and secondary hyperparathyroidism on respiratory outcomes of COVID-19. Methods Three-hundred-forty-eight consecutive patients hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano, Milan (Italy) were evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum 25hydroxy-vitamin D [25(OH)D], parathyroid hormone (PTH) and inflammatory parameters at study entry and need of ventilation during the hospital stay. Results In the entire population, vitamin D deficiency (i.e., 25(OH)D values < 12 ng/mL) was significantly associated with acute hypoxemic respiratory failure at the study entry [adjusted odds ratio (OR) 2.48, 95% confidence interval 1.29-4.74; P = 0.006], independently of age and sex of subjects, serum calcium and inflammatory parameters. In patients evaluated for serum PTH (97 cases), secondary hyperparathyroidism combined with vitamin D deficiency was significantly associated with acute hypoxemic respiratory failure at study entry (P = 0.001) and need of ventilation during the hospital stay (P = 0.031). Conclusion This study provides evidence that vitamin D deficiency, when associated with secondary hyperparathyroidism, may negatively impact the clinical outcome of SARS-CoV-2-related pneumonia.

Supplementary Information The online version contains supplementary material available at https ://doi.org/10.1007/s4061 8-021-01535 -2. Compliance with ethical standards Conflict of interest All the authors do not have conflict of interest that is relevant to the subject matter or materials included in this work. Ethics approval All the procedures performed in the study were in accordance with the ethical standards of the Ethics Committee of IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all the individual partecipants included in the study. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Late treatment
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