Effects of VDR polymorphisms on the COVID-19 Symptoms

ABSTRACT

Vitamin D [25 (OH)D] plays a role in many of biological processes, such as bone metabolism, immunomodulation, cell proliferation, differentiation, and regulation. Also, it has anti-inflammatory, antifibrotic, and antioxidant effects. Due to the immunomodulatory effects of 25 (OH)D, its deficiency is blamed for a higher risk for COVID-19 infection. Serum concentrations of 25 (OH)D were inversely associated with proinflammatory cytokines such as increased IL-6, CRP levels, and increased risk of pneumonia or ARDS. Lower 25 (OH)D concentrations are associated with a higher risk for infections, especially from the respiratory tract [1]. Chronic vitamin D deficiency can induce the renin-angiotensin system activation and leads to fibrotic changes that can cause lung injury by inducing proinflammatory cytokine production in human monocytes/macrophages (2). Increased frequency of COVID-19 infection at high latitudes and worse prognosis of these cases made clinicians to think that 25 (OH)D levels may affect the risk and prognosis of COVID-19 infection [3]. In previous reports, in the early pandemic, a higher prevalence of vitamin D deficiency has been reported to be related to high rates of COVID-19 infection, higher risk of invasive mechanical ventilation (IMV), and mortality [6]. Whilst, it is reported that 25 (OH)D may not protect against COVID-19 infection in recent studies. Moreover, it was not associated with disease severity or lethality [4-6]. The active form of vitamin D binds to its receptor (VDR) and modulates its responses. VDR is located on chromosome 12q13, consisting of 9 exons. Vitamin D-VDR signaling regulates the expression of a wide range of physiological functions. Herein, VDR polymorphisms cause a dysfunctional receptor that affects VDR activity. Both innate and adaptive immune responses can vary according to different polymorphisms of VDR. Also VDR polymorphisms have been previously found to be associated with bacterial infections such as tuberculosis [7] and severe Respiratory Syncytial Virus (RSV) bronchiolitis in respect to vitamin D deficiency [8]. Moreover, it was demonstrated that different VDR polymorphisms such as FokI, BsmI, ApaI, and TaqI could change the course of RSV infection in several studies, respectively [8-10]. This study aimed to evaluate if there is any association between the VDR gene polymorphism at FokI, TaqI, BsmI, and ApaI alleles and the prognosis of COVID-19 in respect to vitamin D deficiency. Two-hundred ninety-seven (n=297) patients with reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 who were admitted to Marmara University Education and Research Hospital between April and October 2020 were enrolled. The severity of COVID-19 patients was classified into 1-10 according to WHO criteria. The patients' requirement for noninvasive mechanical ventilation (NIMV) or reservoir mask, their requirement for admission to intensive care unit (ICU), mortality, and WHO clinical progression scales were reviewed. Four variant regions of vitamin D receptor (VDR);FokI, BsmI, ApaI, and TaqI were determined using the Restriction Fragment Length Polymorphism (RFLP) technique. To conclude;The effect of VDR polymorphisms on the receptor function causes intensive care unit treatment, disease severity and mortality differences among patients with covid-19 infection in the clinical set-up. VDR Ff genotype was related with disease severity, TT with disease severity and aa with mortality respectively. As a result we have detected that 25 (OH)D levels were not related to COVID-19 infection severity and mortality. Additionally, it indicated that VDR polymorphisms are independently associated with the severity of COVID-19 and the survival of patients. More extensive studies are needed to determine the impact of polymorphisms on COVID-19 and explain the underlying cause.