Article
Version 1
Preserved in Portico This version is not peer-reviewed
Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19
Version 1
: Received: 24 April 2020 / Approved: 25 April 2020 / Online: 25 April 2020 (03:13:45 CEST)
Version 2 : Received: 29 May 2020 / Approved: 29 May 2020 / Online: 29 May 2020 (04:16:20 CEST)
Version 2 : Received: 29 May 2020 / Approved: 29 May 2020 / Online: 29 May 2020 (04:16:20 CEST)
A peer-reviewed article of this Preprint also exists.
Abstract
Introduction: Coronavirus 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2. The majority of patients have at most mild symptoms, however, a significant proportion develops respiratory failure. COVID-19 may also progress beyond the lungs. Coagulopathy and thromboembolism are prevalent in severe COVID-19 and relate to decreased survival. Coagulation is an intricate balance between clot promoting and dissolving processes in which vitamin K plays a well-known role. We hypothesized that vitamin K status is reduced in patients with severe COVID-19. Methods: Vitamin K status was assessed by measuring desphospho-uncarboxylated matrix Gla protein (dp-ucMGP; inversely related to vitamin K status) and the rate of elastin degradation by measuring desmosine. We included 123 patients who were admitted with COVID-19 and 184 controls. Results: Dp-ucMGP levels were significantly elevated in COVID-19 patients (1,673Å}1,584 pmol/L) compared to controls (536±291 pmol/L; p<0.0005). Dp-ucMGP levels were significantly higher in COVID-19 patients with unfavorable outcome compared to those with less severe disease. Furthermore, dp-ucMGP and desmosine levels were significantly associated (r=0.65; p<0.0005). Conclusions: Vitamin K status was reduced in patients with COVID-19 and related to poor prognosis. Also, low vitamin K status seems to be associated with accelerated elastin degradation. An intervention trial is now needed to assess whether vitamin K administration improves outcome in patients with COVID-19.
Keywords
COVID-19; vitamin K; vitamin K antagonists; SARS-CoV-2; matrix Gla protein; desmosine; protein C; protein S
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Commenter: Edward Lynam
The commenter has declared there is no conflict of interests.
If Vitamin K2-MK7 could protect a high portion of the population from spread, it could represent a means of controlling the pandemic. If this can be demonstrated, someone should get the Nobel Prize.
Commenter:
Commenter's Conflict of Interests: RJ discloses application of a patent for vitamin K status as a prognostic and therapeutic biomarker in COVID-19.
Commenter: Rosa Fasching
The commenter has declared there is no conflict of interests.
Commenter:
Commenter's Conflict of Interests: RJ discloses application of a patent for vitamin K status as a prognostic and therapeutic biomarker in COVID-19.
We think that the most likely reasons for the extreme extrahepatic vitamin K deficiency that we found in severe Covid-19 patients are:
1. enhanced vitamin K utilization in the lungs to activate MGP for the protection of partially degraded elastic fibers
2. poor vitamin K consumption
3. calcified and/or partially degraded pulmonary elastic fibers at baseline, which have increased vulnerability to SARS-CoV-2-induced proteolytic activity, which will upregulate MGP synthezis and need for vitamin K to activate this additional MGP.
Commenter: Gordon Shotwell
The commenter has declared there is no conflict of interests.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613455/
https://github.com/GShotwell/vitamin_d_covid
Commenter:
Commenter's Conflict of Interests: RJ discloses application of a patent on vitamin K in Covid-19 for prognostic and therapeutic purposes.
Commenter: Erik Painter
The commenter has declared there is no conflict of interests.
Miso soup also has K2 (not as high -6%DV) and most people have it twice a day, 34gms of miso.
Aomori Prefecture has the highest nattō consumption, about 1.5 nattō packs per week (150 gms), 6800 gms/year. It has a population of 1.249 million. It has had one death from covid-19, and 27 confirmed cases. It has had little shutdown. Schools closed from April 20 to May 7.
Miyagi, Niigata, Gunma, and Ibaraki Prefecture also have high consumption. Miyagi has had 88 cases and one death (2.306 million). Niigata has had 82 cases and no deaths (Population: 2.227 million). Gunma as had 151 cases and 19 deaths (Population: 1.938 million). Ibaraki has had 168 cases and 10 deaths (Population: 2.871 million).
The lowest natto consumption areas in Japan still eat about 2200gms per year.
Commenter: Dr Kevin Maguire
The commenter has declared there is no conflict of interests.
"[X] levels were significantly higher in COVID-19 patients (1,673±1,584 pmol/L) compared to healthy controls (536±291 pmol/L, p<0.0005)."
Using the propagation of errors formula:
100% correlation: (1137 +/- 1581)
0% correlation: (1137 +/- 1610)
So not significant. It's completely wrong to say this result is significant. The quoted p-value is not explained and seems impossible.
Commenter:
Commenter's Conflict of Interests: RJ discloses application of a patent on vitamin K in Covid-19 for prognostic and therapeutic purposes.
We are going to submit our article today for peer review. If accepted, we'll make our data set public so everyone with statistical knowledge can perform their own tests.
Commenter: Puya Dehgani-Mobaraki
The commenter has declared there is no conflict of interests.
Focusing just on the activity of Vit K on liver will move the relationship that Vitamin K represents on blood vessels and lungs.
Since the lockdown announcement our lifestyle changed so much, and we never considered the possibility that this would have led to and imbalance of our entire system.
Now the key is to look at prevention and get our body prepared to fight against the Monster.
I would love to collaborate for a study on this, we are actually working on the final demonstration of the neurotropism of the virus through the olfactory cells to prove that our paper on the Lancet was correct (but already published a study on autopsies that confirming on 32).
Great effort, my compliments