Association between vitamin D deficiency and clinical outcome in patients with COVID-19 in the post-Omicron phase

Chen et al., Frontiers in Nutrition, doi:10.3389/fnut.2025.1583276, Jun 2025

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Vitamin D for COVID-19

8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 126 studies, recognized in 18 countries.

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

No treatment is 100% effective. Protocols combine treatments.

5,900+ studies for 172 treatments. c19early.org

TriNetX PSM retrospective showing that vitamin D deficiency was significantly associated with increased 30-day mortality and adverse outcomes in COVID-19 patients, although the magnitude of this association decreased in the post-Omicron phase compared to pre-Omicron.

This is the 220th of 222 COVID-19 sufficiency studies for vitamin D, which collectively show higher levels reduce risk with p<0.0000000001 (1 in 742,551,930,931 vigintillion).

Important missing comments or errors? Let us know.

risk of death, 61.3% lower, RR 0.39, p = 0.007, high D levels 45,276, low D levels 45,276, both periods combined.

risk of death, 72.8% lower, OR 0.27, p < 0.001, high D levels 22,638, low D levels 22,638, inverted to make OR<1 favor high D levels, pre-Omicron, propensity score matching, RR approximated with OR.

risk of death, 45.1% lower, OR 0.55, p < 0.001, high D levels 22,638, low D levels 22,638, inverted to make OR<1 favor high D levels, post-Omicron, propensity score matching, RR approximated with OR.

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

Chen et al., 18 Jun 2025, retrospective, multiple countries, peer-reviewed, mean age 51.3, 6 authors, study period June 2022 - December 2023. Contact: ed102605@gmail.com.

This Paper Vitamin D All

Association between vitamin D deficiency and clinical outcome in patients with COVID-in the post-Omicron phase

Georgia Damoraki, Marcos Edgar Herkenhoff, Santa Catarina, Kuo-Chuan Hung, I-Wen Chen, Ting-Sian Yu, Yi-Chen Lai, Chih-Ping Yang, Chia-Hung Yu

Background: Vitamin D deficiency (VDD) has been associated with adverse outcomes in COVID-patients during the early pandemic phases, but whether this association persists in the post-Omicron era remains uncertain. This study aimed to investigate the evolving relationship between VDD and COVIDoutcomes across pandemic phases using a large healthcare database. Methods: We conducted a retrospective cohort study using the TriNetX Analytics Network, analyzing propensity-matched cohorts comprising , pairs from the post-Omicron phase (June -December ) and , pairs from the pre-Omicron phase (January -December ). VDD was defined as a serum -hydroxyvitamin D level < ng/ml, with vitamin D-sufficient patients (≥ ng/ml) serving as controls. The primary outcome was -day all-cause mortality, with secondary outcomes including acute kidney injury, respiratory failure, pneumonia, sepsis, and ICU admission. Results: The -day mortality in VDD vs. vitamin D-sufficient patients decreased from . % vs. . % [odds ratio (OR), . ; % CI, . -. ; p < . ] in the pre-Omicron phase to . % vs. . % (OR, . ; % CI, . -. ; p < . ) in the post-Omicron phase. Similar risk attenuation was observed across all secondary outcomes, including acute kidney injury (OR, . ; % CI, . -. vs. OR, . ; % CI, . -. ; both p < . ), respiratory failure (OR, . ; % CI, . -. vs. OR, . ; % CI, . -. ; both p < . ), and pneumonia (OR, . ; % CI, . -. vs. OR, . ; % CI, . -. ; p < . and p = . , respectively). Risk factor analysis identified several significant mortality predictors among patients with VDD in the post-Omicron phase, including malnutrition (OR, . ; % CI, . -. ; p < . ), liver disease (OR, . ; % CI, . -. ; p < . ), and neoplasms (OR, . ; % CI, . -. ; p < . ). Conclusion: VDD continues to be associated with adverse COVID-outcomes in the post-Omicron phase, albeit with a reduced magnitude. These findings support the importance of vitamin D screening in high-risk COVIDpatients, while emphasizing the need for adaptive risk assessment strategies that incorporate both established and emerging risk factors in the current pandemic landscape.

Ethics statement The studies involving humans were approved by Institutional Review Board of the Chi Mei Medical Center. The studies were conducted in accordance with the local legislation and institutional requirements. The Ethics Committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants' legal guardians/next of kin because this retrospective study utilized data from the TriNetX Analytics Network, which provides only deidentified patient counts and statistical summaries without direct interaction with individuals or interventions. Author contributions Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Generative AI statement The author(s) declare that no Gen AI was used in the creation of this manuscript. Publisher's note All claims expressed in article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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DOI record: { "DOI": "10.3389/fnut.2025.1583276", "ISSN": [ "2296-861X" ], "URL": "http://dx.doi.org/10.3389/fnut.2025.1583276", "abstract": "BackgroundVitamin D deficiency (VDD) has been associated with adverse outcomes in COVID-19 patients during the early pandemic phases, but whether this association persists in the post-Omicron era remains uncertain. This study aimed to investigate the evolving relationship between VDD and COVID-19 outcomes across pandemic phases using a large healthcare database.MethodsWe conducted a retrospective cohort study using the TriNetX Analytics Network, analyzing propensity-matched cohorts comprising 24,236 pairs from the post-Omicron phase (June 2022–December 2023) and 22,638 pairs from the pre-Omicron phase (January 2020–December 2021). VDD was defined as a serum 25-hydroxyvitamin D level &lt; 20 ng/ml, with vitamin D-sufficient patients (≥30 ng/ml) serving as controls. The primary outcome was 30-day all-cause mortality, with secondary outcomes including acute kidney injury, respiratory failure, pneumonia, sepsis, and ICU admission.ResultsThe 30-day mortality in VDD vs. vitamin D-sufficient patients decreased from 1.43% vs. 0.39% [odds ratio (OR), 3.67; 95% CI, 2.90–4.64; p &lt; 0.001] in the pre-Omicron phase to 0.89% vs. 0.49% (OR, 1.82; 95% CI, 1.46–2.28; p &lt; 0.001) in the post-Omicron phase. Similar risk attenuation was observed across all secondary outcomes, including acute kidney injury (OR, 2.11; 95% CI, 1.92–2.31 vs. OR, 1.41; 95% CI, 1.29–1.54; both p &lt; 0.001), respiratory failure (OR, 1.66; 95% CI, 1.44–1.92 vs. OR, 1.34; 95% CI, 1.16–1.54; both p &lt; 0.001), and pneumonia (OR, 1.34; 95% CI, 1.16–1.55 vs. OR, 1.23; 95% CI, 1.07–1.42; p &lt; 0.001 and p = 0.004, respectively). Risk factor analysis identified several significant mortality predictors among patients with VDD in the post-Omicron phase, including malnutrition (OR, 4.34; 95% CI, 3.18–5.92; p &lt; 0.001), liver disease (OR, 3.08; 95% CI, 2.23–4.25; p &lt; 0.001), and neoplasms (OR, 2.63; 95% CI, 2.01–3.45; p &lt; 0.001).ConclusionVDD continues to be associated with adverse COVID-19 outcomes in the post-Omicron phase, albeit with a reduced magnitude. These findings support the importance of vitamin D screening in high-risk COVID-19 patients, while emphasizing the need for adaptive risk assessment strategies that incorporate both established and emerging risk factors in the current pandemic landscape.", "alternative-id": [ "10.3389/fnut.2025.1583276" ], "author": [ { "affiliation": [], "family": "Chen", "given": "I-Wen", "sequence": "first" }, { "affiliation": [], "family": "Yu", "given": "Ting-Sian", "sequence": "additional" }, { "affiliation": [], "family": "Lai", "given": "Yi-Chen", "sequence": "additional" }, { "affiliation": [], "family": "Yang", "given": "Chih-Ping", "sequence": "additional" }, { "affiliation": [], "family": "Yu", "given": "Chia-Hung", "sequence": "additional" }, { "affiliation": [], "family": "Hung", "given": "Kuo-Chuan", "sequence": "additional" } ], "container-title": "Frontiers in Nutrition", "container-title-short": "Front. 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