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Survival implications vs. complications: unraveling the impact of vitamin D adjunctive use in critically ill patients with COVID-19—A multicenter cohort study

Al Sulaiman et al., Frontiers in Medicine, doi:10.3389/fmed.2023.1237903

Aug 2023

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Vitamin D for COVID-19

8th treatment shown to reduce risk in October 2020

^*, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.

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

No treatment is 100% effective. Protocols combine treatments. ^* >10% efficacy, ≥3 studies.

4,900+ studies for 102 treatments. c19early.org

Retrospective 1,435 ICU patients in Saudi Arabia, showing no significant difference in mortality, and longer mechanical ventilation with treatment. Vitamin D patients had higher Q1, median, and Q3 SOFA scores after propensity score matching. 98% of patients were treated with cholecalciferol.

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: 69% [47‑82%] lower risk vs. 39% [27‑49%] 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 115th of 122 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 587 sextillion).

30 studies are RCTs, which show efficacy with p=0.0000032.

This study is excluded in the after exclusion results of meta analysis: very late stage study using cholecalciferol instead of calcifediol or calcitriol.

Important missing comments or errors? Let us know.

risk of death, 22.0% higher, HR 1.22, p = 0.25, treatment 72 of 144 (50.0%), control 62 of 144 (43.1%).

risk of mechanical ventilation, 27.0% higher, OR 1.27, p = 0.046, treatment 144, control 144, RR approximated with OR.

risk of ICU admission, 17.0% higher, OR 1.17, p = 0.07, treatment 144, control 144, RR approximated with OR.

risk of hospitalization, no change, OR 1.00, p = 1.00, treatment 144, control 144, RR approximated with OR.

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

Al Sulaiman et al., 14 Aug 2023, retrospective, Saudi Arabia, peer-reviewed, 25 authors, study period March 2020 - July 2021, dosage not specified.

This Paper Vitamin D All

{ 'indexed': {'date-parts': [[2023, 8, 26]], 'date-time': '2023-08-26T08:16:04Z', 'timestamp': 1693037764963}, 'reference-count': 53, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2023, 8, 24]], 'date-time': '2023-08-24T00:00:00Z', 'timestamp': 1692835200000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': 'BackgroundDespite insufficient evidence, vitamin D ' 'has been used as adjunctive therapy in critically ill patients with COVID-19. This study ' 'evaluates the effectiveness and safety of vitamin D as an adjunctive therapy in critically ' 'ill COVID-19 patients.MethodsA ' 'multicenter retrospective cohort study that included all adult COVID-19 patients admitted to ' 'the intensive care units (ICUs) between March 2020 and July 2021. Patients were categorized ' 'into two groups based on their vitamin D use throughout their ICU stay (control vs. vitamin ' 'D). The primary endpoint was in-hospital mortality. Secondary outcomes were the length of ' 'stay (LOS), mechanical ventilation (MV) duration, and ICU-acquired complications. Propensity ' 'score (PS) matching (1:1) was used based on the predefined criteria. Multivariable logistic, ' 'Cox proportional hazards, and negative binomial regression analyses were employed as ' 'appropriate.ResultsA total of ' '1,435 patients were included in the study. Vitamin D was initiated in 177 patients (12.3%), ' 'whereas 1,258 patients did not receive it. A total of 288 patients were matched (1:1) using ' 'PS. The in-hospital mortality showed no difference between patients who received vitamin D ' 'and the control group (HR 1.22, 95% CI 0.87–1.71; p = 0.26). ' 'However, MV duration and ICU LOS were longer in the vitamin D group (beta coefficient 0.24 ' '(95% CI 0.00–0.47), p = 0.05 and beta coefficient 0.16 (95% CI ' '−0.01 to 0.33), p = 0.07, respectively). As an exploratory ' 'outcome, patients who received vitamin D were more likely to develop major bleeding than ' 'those who did not [OR 3.48 (95% CI 1.10, 10.94), p = ' '0.03].ConclusionThe use of ' 'vitamin D as adjunctive therapy in COVID-19 critically ill patients was not associated with ' 'survival benefits but was linked with longer MV duration, ICU LOS, and higher odds of major ' 'bleeding.', 'DOI': '10.3389/fmed.2023.1237903', 'type': 'journal-article', 'created': {'date-parts': [[2023, 8, 25]], 'date-time': '2023-08-25T03:02:12Z', 'timestamp': 1692932532000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Survival implications vs. complications: unraveling the impact of vitamin D adjunctive use in ' 'critically ill patients with COVID-19—A multicenter cohort study', 'prefix': '10.3389', 'volume': '10', 'author': [ {'given': 'Khalid', 'family': 'Al Sulaiman', 'sequence': 'first', 'affiliation': []}, {'given': 'Ghazwa B.', 'family': 'Korayem', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ohoud', 'family': 'Aljuhani', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ali F.', 'family': 'Altebainawi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mohammad S.', 'family': 'Shawaqfeh', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sumaiah J.', 'family': 'Alarfaj', 'sequence': 'additional', 'affiliation': []}, {'given': 'Reham A.', 'family': 'Alharbi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mawaddah M.', 'family': 'Ageeli', 'sequence': 'additional', 'affiliation': []}, {'given': 'Abdulrahman', 'family': 'Alissa', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ramesh', 'family': 'Vishwakarma', 'sequence': 'additional', 'affiliation': []}, {'given': 'Alnada', 'family': 'Ibrahim', 'sequence': 'additional', 'affiliation': []}, {'given': 'Abeer A.', 'family': 'Alenazi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Suliman', 'family': 'Alghnam', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nadiyah', 'family': 'Alshehri', 'sequence': 'additional', 'affiliation': []}, {'given': 'Maqbulah M.', 'family': 'Alshammari', 'sequence': 'additional', 'affiliation': []}, {'given': 'Alaa', 'family': 'Alhubaishi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mohammed', 'family': 'Aldhaeefi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Faisal F.', 'family': 'Alamri', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yadullah', 'family': 'Syed', 'sequence': 'additional', 'affiliation': []}, {'given': 'Raymond', 'family': 'Khan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mai', 'family': 'Alalawi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Khalaf A.', 'family': 'Alanazi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Faisal S.', 'family': 'Alresayes', 'sequence': 'additional', 'affiliation': []}, {'given': 'Khalid J.', 'family': 'Albarqi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ghassan', 'family': 'Al Ghamdi', 'sequence': 'additional', 'affiliation': []}], 'member': '1965', 'published-online': {'date-parts': [[2023, 8, 24]]}, 'reference': [ { 'key': 'B1', 'doi-asserted-by': 'publisher', 'first-page': '217', 'DOI': '10.1097/JCMA.0000000000000270', 'article-title': 'The outbreak of COVID-19: an overview', 'volume': '83', 'author': 'Wu', 'year': '2020', 'journal-title': 'J Chinese Med Assoc.'}, { 'key': 'B2', 'doi-asserted-by': 'publisher', 'first-page': '93', 'DOI': '10.7326/M20-6448', 'volume': '174', 'year': '2021', 'journal-title': 'Annal Int Med'}, { 'key': 'B3', 'doi-asserted-by': 'publisher', 'first-page': '953', 'DOI': '10.2174/1389557515666150519110830', 'article-title': 'Vitamin-D in the immune system: genomic and non-genomic actions', 'volume': '15', 'author': 'Trochoutsou', 'year': '2015', 'journal-title': 'Mini-Rev Med Chem'}, { 'key': 'B4', 'doi-asserted-by': 'publisher', 'first-page': '1129', 'DOI': '10.1017/S0950268806007175', 'article-title': 'Epidemic influenza and vitamin D', 'volume': '134', 'author': 'Cannell', 'year': '2006', 'journal-title': 'Epidemiol Infect.'}, { 'key': 'B5', 'doi-asserted-by': 'publisher', 'first-page': '276', 'DOI': '10.1186/s13054-018-2185-8', 'article-title': 'Vitamin D deficiency and supplementation in critical illness - 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'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 8, 25]], 'date-time': '2023-08-25T03:02:17Z', 'timestamp': 1692932537000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fmed.2023.1237903/full'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 8, 24]]}, 'references-count': 53, 'alternative-id': ['10.3389/fmed.2023.1237903'], 'URL': 'http://dx.doi.org/10.3389/fmed.2023.1237903', 'relation': {}, 'ISSN': ['2296-858X'], 'subject': ['General Medicine'], 'container-title-short': 'Front. Med.', 'published': {'date-parts': [[2023, 8, 24]]}}

Late treatment
is less effective

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

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