Low 25-Hydroxyvitamin D Levels on Admission to the Intensive Care Unit May Predispose COVID-19 Pneumonia Patients to a Higher 28-Day Mortality Risk: A Pilot Study on a Greek ICU Cohort

Abstract: Hellenic Journal of Cardiology 62 (2021) 381e383 Contents lists available at ScienceDirect Hellenic Journal of Cardiology journal homepage: http://www.journals.elsevier.com/ hellenic-journal-of-cardiology/ Correspondence Vitamin D deficiency correlates with a reduced number of natural killer cells in intensive care unit (ICU) and non-ICU patients with COVID-19 pneumonia Keywords: COVID-19 Vitamin D Natural killer cells Regulation of immune function continues to be one of the most well-recognised extra-skeletal actions of vitamin D. In vitro data have shown that vitamin D modulates immune cells and induces immune tolerance, while in vivo data from animal studies and from vitamin D supplementation human studies have shown beneficial effects of vitamin D on immune function, particularly in the context of autoimmunity.1 In the present study, we examined whether vitamin D deficiency modulates the number of immune cells in COVID-19 patients. This observational, single-centre study included consecutive COVID-19 intensive care unit (ICU) patients (N ¼ 29) and consecutive patients hospitalised in a specialised non-ICU COVID-19 ward (N ¼ 10) who were discharged from the hospital without being transferred to the ICU, from March 18th 2020 to May 25th 2020. The study was approved by the Hospital's Research Ethics Committee (129/19-3-2020), and all procedures carried out on patients were in compliance with the Helsinki Declaration. Informed written consent was obtained from all patients or patients' next-ofkin. Total 25-hydroxyvitamin D was measured on hospital admission using the electrochemiluminescence immunoassay method (Cobas E602, Roche Diagnostics International Ltd). Immune phenotyping was performed by flow cytometric analysis (Navios EX flow cytometer, Beckman Coulter). Vitamin D levels positively correlated with subpopulations of immune cells, namely, cytotoxic T cells (rs ¼ 0.344, p ¼ 0.032), natural killer (NK) cells (rs ¼ 0.496, p ¼ 0.001), NK-T cells (rs ¼ 0.325, p ¼ 0.044) and regulatory T cells (rs ¼ 0.333, p ¼ 0.038). With respect to all other clinical and laboratory parameters, vitamin D levels correlated only with albumin (rs ¼ 0.387, p ¼ 0.018). To further explore these associations, we divided our cohort into two groups based on their vitamin D levels; we classified them as vitamin D deficient (19.9 ng/ml, N ¼ 32) and vitamin D insufficient (20-29.9 ng/ml, N ¼ 7). Demographics, clinical and biochemical characteristics on hospital admission and important outcomes Peer review under responsibility of Hellenic Society of Cardiology. of the two patient groups are listed in Table 1. As expected, hypertension was the most common comorbidity.2 The two groups differed only in the number of NK cells (Table 1 and Figure 1). Cytotoxic T cells, NK-T cells and regulatory T cells did not differ in the two groups. It should also be noted that the two patient groups did not differ with respect to hospital mortality or disease severity. The beneficial effects of vitamin D on protective immunity are due in part to its effects on the innate immune system. In vitro studies have reported contradictory results on the role of vitamin D on NK cell function, but whether vitamin D induces or inhibits NK cell function in vivo remains unclear.3 NK cells are a type of cytotoxic lymphocytes that are critical to the innate immune system and secrete many cytokines and chemokines. Despite their vital role in viral infections, the contribution of NK cells in..