The Association of Low Vitamin K Status with Mortality in a Cohort of 138 Hospitalized Patients with COVID-19
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Abstract
It has recently been hypothesized that vitamin K could play a role in COVID-19. We aimed to test the hypotheses that low vitamin K status is a common characteristic of patients hospitalized with COVID-19 compared to population controls and that low vitamin K status predicts mortality in COVID-19 patients. In a cohort of 138 COVID-19 patients and 138 population controls, we measured plasma dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP), which reflects the functional vitamin K status in peripheral tissue. Forty-three patients died within 90 days from admission. In patients, levels of dp-ucMGP differed significantly between survivors (mean 877; 95% CI: 778; 995) and non-survivors (mean 1445; 95% CI: 1148; 1820). Furthermore, levels of dp-ucMGP (pmol/L) were considerably higher in patients (mean 1022; 95% CI: 912; 1151) compared to controls (mean 509; 95% CI: 485; 540). Cox regression survival analysis showed that increasing levels of dp-ucMGP (reflecting low vitamin K status) were associated with higher mortality risk (sex- and age-adjusted hazard ratio per doubling of dp-ucMGP was 1.49, 95% CI: 1.03; 2.24). The association attenuated and became statistically insignificant after adjustment for co-morbidities (sex, age, CVD, diabetes, BMI, and eGFR adjusted hazard ratio per doubling of dp-ucMGP was 1.22, 95% CI: 0.82; 1.80). In conclusion, we found that low vitamin K status was associated with mortality in patients with COVID-19 in sex- and age-adjusted analyses, but not in analyses additionally adjusted for co-morbidities. Randomized clinical trials would be needed to clarify a potential role, if any, of vitamin K in the course of COVID-19.
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SciScore for 10.1101/2020.12.21.20248613: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Measurements of dp-ucMGP in stored plasma samples from the biobank were approved by the Ethical Committee of the Capital Region of Denmark (record no. H-20047597). 2.2. Randomization A total of 4497 randomly selected persons living in 11 municipalities in the Western part of Copenhagen, covering part of the catchment area of Amager Hvidovre Hospital, were invited to a health examination and 1251 (28%) participated. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to …
SciScore for 10.1101/2020.12.21.20248613: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Measurements of dp-ucMGP in stored plasma samples from the biobank were approved by the Ethical Committee of the Capital Region of Denmark (record no. H-20047597). 2.2. Randomization A total of 4497 randomly selected persons living in 11 municipalities in the Western part of Copenhagen, covering part of the catchment area of Amager Hvidovre Hospital, were invited to a health examination and 1251 (28%) participated. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:There are several limitations of the present study. Firstly, the observational study design does not allow us to draw definite conclusions regarding causality. Randomized trials are needed to document potential beneficial effects of vitamin K supplementation on the course of COVID-19 disease. Second, we did not have data on Vitamin D status such as blood levels of 25-OH Vitamin D. This is a limitation because it has been hypothesized that Vitamin D and K could interact in COVID-19 disease.9 Third, assessment of lung damage such as CT-scans would have added valuable information on the tissue-specific effects of Vitamin K deficiency during COVID-19. Finally, a long-term follow-up of persistent symptoms among survivors of COVID-19 would have been of great interest to investigate, since any measure that prevents short-term outcomes may also have an influence on long-term outcomes such as persistence of symptoms. In conclusion, in the present study we confirmed that Vitamin K status is markedly lower in hospitalized COVID-19 patients compared to population controls and that low Vitamin K status predicts mortality in patients with COVID-19. Whether Vitamin K supplementation in COVID-19 patients can change the course of disease and prevent death or long-term consequences of COVID-19 remains to be tested in randomized clinical trials.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.12.21.20248613: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Measurements of dp-ucMGP in stored plasma samples from the biobank were approved by the Ethical Committee of the Capital Region of Denmark (record no. H-20047597). 2.2. Randomization A total of 4497 randomly selected persons living in 11 municipalities in the Western part of Copenhagen, covering part of the catchment area of Amager Hvidovre Hospital, were invited to a health examination and 1251 (28%) participated. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to …
SciScore for 10.1101/2020.12.21.20248613: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Measurements of dp-ucMGP in stored plasma samples from the biobank were approved by the Ethical Committee of the Capital Region of Denmark (record no. H-20047597). 2.2. Randomization A total of 4497 randomly selected persons living in 11 municipalities in the Western part of Copenhagen, covering part of the catchment area of Amager Hvidovre Hospital, were invited to a health examination and 1251 (28%) participated. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
There are several limitations of the present study. Firstly, the observational study design does not allow us to draw definite conclusions regarding causality. Randomized trials are needed to document potential beneficial effects of vitamin K supplementation on the course of COVID-19 disease. Second, we did not have data on Vitamin D status such as blood levels of 25-OH Vitamin D. This is a limitation because it has been hypothesized that Vitamin D and K could interact in COVID-19 disease.9 Third, assessment of lung damage such as CT-scans would have added valuable information on the tissue-specific effects of Vitamin K deficiency during COVID-19. Finally, a long-term follow-up of persistent symptoms among survivors of COVID-19 would have been of great interest to investigate, since any measure that prevents short-term outcomes may also have an influence on long-term outcomes such as persistence of symptoms. In conclusion, in the present study we confirmed that Vitamin K status is markedly lower in hospitalized COVID-19 patients compared to population controls and that low Vitamin K status predicts mortality in patients with COVID-19. Whether Vitamin K supplementation in COVID-19 patients can change the course of disease and prevent death or long-term consequences of COVID19 remains to be tested in randomized clinical trials.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
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