Abstract: Archives of Microbiology https://doi.org/10.1007/s00203-021-02482-5 ORIGINAL PAPER The sufficient vitamin D and albumin level have a protective effect on COVID‑19 infection Somaieh matin1,2 · Nasrin Fouladi3,4 · Yasamin Pahlevan5 · Vahid Asghariazar5,6 · Soheila Molaei5,7 · Hamid Afzoun khiavi 6 · Mohamad Negaresh8 · Elham Safarzadeh9 Received: 15 March 2021 / Revised: 3 July 2021 / Accepted: 7 July 2021 © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021 Abstract There is limited information regarding the protective factors of SARS-CoV-2 infection. This research is focused on analyzing the role of vitamin D and albumin in the severity, progression, or possible prevention of COVID-19 infection. In this case–control study, 191 patients and 203 healthy individuals were enrolled. Blood samples were taken to test the albumin and vitamin D levels of both groups. Our results show a direct association of vitamin D deficiency with the infection of COVID-19 and severity. According to our findings, 84.4% of patients with COVID-19 in this study had vitamin D deficiency. Moreover, the average level of albumin was significantly decreased in those infected patients who had respiratory symptoms. In the present study, a considerable negative correlation was established between the levels of vitamin D and the severity of COVID-19 infection. This reflects on the immunomodulatory and inhibitory nature of vitamin D to the viral replication. Keywords COVID-19 · Vitamin D · Albumin · Coronavirus Communicated by Erko Stackebrandt. * Elham Safarzadeh E.safarzadeh@arums.ac.ir Abbreviations ACE-2 Angiotensin-converting enzyme-2 CYP27B1 Vitamin D activating enzyme 1-α-hydroxylase VDR Vitamin D receptor NET Neutrophil extracellular traps ROS Reactive oxygen species RT-PCR Real-time reverse transcriptase polymerase chain reaction CT Computed tomography GGO Ground-glass opacity ORs Odds ratios VDR Vitamin D and its functional receptors VDRGS Vitamin D-related genes 1 Department of Internal Medicine, Imam khomeini hospital, Ardabil University of Medical Sciences, Ardabil, Iran 2 Gastrointestinal and Liver Disease Research Center, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran 3 School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran 4 Social Determinants of Health Research Center, Ardabil University of Medical Sciences, Ardabil, Iran 5 Deputy of Research and Technology, Ardabil University of Medical Sciences, Ardabil, Iran