Altered Insulin, IRS/PI3K/AKT/mTOR Signaling, ACE2 and Angiotensin II, Correlating with Vitamin K Status and Severity in Metabolically Disordered COVID-19 Egyptian patients

Aims: Metabolic disorders are essential risks of adverse outcomes in coronavirus disease 2019 (COVID-19). Vitamin K status might play an important role in metabolic regulation and influence the severity of COVID-19. This research shed light on vitamin K status in association with some metabolic pathways; pancreatic beta-cell function, insulin resistance, PI3K/AKT/mTOR signaling, and the angiotensin-converting enzyme 2 (ACE2)/angiotensin II in the context of COVID-19 and its metabolic effects in metabolically disordered patients. Main methods: This study included hospital-confirmed COVID-19 patients with or without obesity and/or diabetes mellitus (DM) and control subjects. The effect of viral infection on PERK double-stranded RNA-dependent protein kinase (PKR) and ACE2 was regressed against insulin resistance and blood pressure, respectively. Demographic and clinical characteristics, blood, and, clinical indices, were collected. Key findings: A total of 90 hospital-confirmed COVID-19-positive patients were eligible for our study. COVID-19 patients with obesity and DM showed poor vitamin K status which is correlated with severely compromised insulin signaling and inflammatory and immune states. It is also adversely associated with the existence of hypertension comorbidities. PKR levels significantly (P<0.05) and negatively predicted IRS (R 2 = 0.598) explaining 59.8% of the variance in IRS. Also, ACE2 is significantly (P<0.05) and negatively predicted systolic blood pressure and explained 45.6% of the variance in SBP (R 2 =0.456). Significance: Our study indicated that poor vitamin K status might be an important risk factor for severe adverse outcomes in COVID-19 patients with pre-existing obesity and type 2 diabetes. Also, metabolically disordered patients are highly susceptible to COVID-19 infection and its related adverse metabolic effects.