Dramatic Decrease of Vitamin K2 Subtype Menaquinone-7 in COVID-19 Patients

Abstract

(1) Background: Vitamin K (VK) is a fat-soluble compound with a common chemical structure, a 2-methyl-1,4-naphthoquinone ring, and a variable aliphatic side-chain. VK is involved in the synthesis of blood-clotting proteins, bone stability, anti-oxidative, and immune inflammatory-modulatory functions. Vitamin K also activates protein S, which acts as an antioxidant and anti-inflammatory. The fact that cytokine overproduction, oxidative stress, and disturbed microcirculation by thrombogenicity play a central role in severe COVID-19 prompted us to analyze this vitamin. (2) Methods: We analyzed by a validated liquid-chromatography tandem mass-spectrometry method serum vitamin K1, MK4, MK7, and VK epoxide levels in 104 healthy controls, 77 patients with non-COVID-19 pneumonia, and 135 hospitalized COVID-19 patients with potentially fatal outcomes admitted to our University Hospital between April and November 2020. We included the quotient between VK and triglyceride (TG, nmol/mmol/L) values in the analyses with respect to the TG trans-porter function for all VK subtypes. Additionally, we assessed anthropometric, routine laboratory, and clinical data from the laboratory and hospital information systems. (3) Results: The COVID-19 patients had significantly lower MK7 levels than non-COVID-19 pneumonia patients and healthy controls. COVID-19 and non-COVID-19 pneumonia patients had significantly lower vitamin K1 and significantly higher MK4 compared to healthy controls, but did not differ significantly from each other. Between COVID-19 non-survivors (n = 30) and survivors (n = 105) no significant differences were seen in all vitamin K subtypes, despite the fact that non-survivors had higher peak concentrations of IL-6, CRP, d-dimer, and higher oxygen needs, respectively. (4) Conclusions: The present data identified significantly decreased vitamin K1, K2 (MK7), and increased MK4 levels in patients with COVID-19 compared to healthy controls. Vitamin K2 (MK7) was lowest in COVID-19 patients irrespective of potentially fatal courses, indicating consumption of this VK subtype by COVID-19 immanent effects, most probably inflammatory and oxidative stress factors.