Vitamin K & D Deficiencies Are Independently Associated With COVID-19 Disease Severity
Ankita P Desai, Sahera Dirajlal-Fargo, Jared C Durieux, Heather Tribout, Danielle Labbato, MD Grace A Mccomsey
Open Forum Infectious Diseases, doi:10.1093/ofid/ofab408
Background. We investigated the association of vitamin K and vitamin D with coronavirus disease 2019 (COVID-19) outcomes. Methods. Levels of inactive vitamin K-dependent dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP; marker of vitamin K status) and 25-hydroxyvitamin D (25(OH)D; vitamin D status) were measured in plasma samples from participants with confirmed acute COVID-19 and were age-and sex-matched to healthy controls. Unadjusted odds ratios and adjusted odds ratios (AORs) with 95% CIs were computed using cumulative logistic regression. Results. One hundred fifty subjects were included, 100 COVID-19+ and 50 controls. The median age (interquartile range) was 55 (48-63) years, and 50% were females. Thirty-four percent had mild COVID-19 disease, 51% moderate disease, and 15% severe. Dp-ucMGP levels were higher (ie, worse K status) in COVID-19+ vs controls (776.5 ng/mL vs 549.8 ng/mL; P < .0001) with similar 25(OH)D between groups (25.8 vs 21.9 ng/mL; P = .09). Participants who were vitamin D deficient (<20 ng/mL) had the worse vitamin K status (dp-ucMGP >780 ng/mL) and experienced the most severe COVID-19 outcomes. In adjusted models, every 1-unit increase in the log2 dp-ucMGP nearly doubled the odds of acute critical disease or death (AOR, 1.84; 95% CI, 1.01-3.45), and every 1-unit decrease in the natural log 25(OH)D was associated with >3 times the likelihood of severe COVID-19 disease (AOR, 0.29; 95% CI, 0.11-0.67). Conclusions. Early in acute COVID-19, both vitamin K and vitamin D deficiency were independently associated with worse COVID-19 disease severity, suggesting a potential synergistic interplay between these 2 vitamins in COVID-19.
Supplementary Data Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
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'abstract': '<jats:p>Background: Our aim was to investigate the impact of therapeutics with antiviral '
'activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on mortality of '
'older adults affected by coronavirus disease 2019 (COVID-19), taking into consideration the '
'time interval from symptoms onset to drugs administration. Methods: Data from 143 COVID-19 '
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'Emergency Department (Milan, Italy) and treated with Lopinavir/ritonavir (LPV/r) or '
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'analyzed. Statistical analysis was performed by using a logistic regression model and '
'survival analysis to assess the role of different predictors of in-hospital mortality, '
'including an early (<6 days from symptoms onset) vs. late treatment onset, signs and '
'symptoms at COVID-19 presentation, type of antiviral treatment (LPV/r or DVR/c) and patients’ '
'age (65–80 vs. >80 years old). Results: Multivariate analysis showed that an older age '
'(OR: 2.54) and dyspnea as presenting symptom (OR: 2.01) were associated with higher mortality '
'rate, whereas cough as presenting symptom (OR: 0.53) and a timely drug administration (OR: '
'0.44) were associated with lower mortality. Survival analysis demonstrated that the timing of '
'drug administration had an impact on mortality in 65–80 years-old patients (p = 0.02), '
'whereas no difference was seen in those >80 years-old. This impact was more evident in '
'patients with dyspnea as primary symptom of COVID-19, in whom mortality decreased from 57.1% '
'to 38.3% due to timely drug administration (OR: 0.5; p = 0.04). Conclusions: There was a '
'significant association between the use of a combined antiviral regimen and HCQ and lower '
'mortality, when timely-administered, in COVID-19 patients aged 65–80 years. Our findings '
'support timely treatment onset as a key component in the treatment of COVID-19.</jats:p>',
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