Abstract: Vitamin D Deficiency is Associated with Increased COVID-19 Severity: Prospective Screening of At-Risk Groups is Medically Indicated Samuel H Pepkowitz MD (  Samuel.Pepkowitz@cshs.org ) Cedars-Sinai Medical Center https://orcid.org/0000-0002-8384-3227 Calvin J Hobel MD Cedars-Sinai Medical Center James M Mirocha MS Cedars-Sinai Medical Center Kimia.Sobhani PhD Cedars-Sinai Medical Center Carissa A Huynh BS Cedars-Sinai Medical Center Harneet Jawanda MD Cedars-Sinai Medical Center Wohaib Hasan PhD Cedars-Sinai Medical Cente Research Article Keywords: COVID-19, Vitamin D Deficiency, Pulmonary Inflammation, ICU Care Posted Date: September 29th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-83262/v1 License:   This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/10 Abstract Non-classical actions of Vitamin D are involved in regulation of the immune system including a role in mitigation of excessive inflammation. We hypothesized that vitamin D deficiency existing prior to SARSCoV-2 infection could contribute to patients developing severe pulmonary compromise as a result of dysfunctional hyperinflammation. Serum vitamin D concentrations of patients experiencing such severe COVID-19 manifestations that they required ICU care at any point of their hospitalization were compared to serum vitamin D concentrations of patients achieving discharge without the need for any ICU care. Having serum vitamin D < 20 ng/mL was significantly associated with increased COVID-19 severity, p=0.001. It is conjectured that population groups know to have low serum vitamin D should be prospectively screened for deficiency and if found emergently treated. Such action could both decrease the maximum severity suffered by infected individuals and lessen the strain on medical resources by decreasing the percentage of COVID-19 hospital admissions requiring ICU care. Background SARS-CoV-2 infection (COVID-19) manifests itself on a clinical spectrum ranging from asymptomatic carriage to life-threatening disease with catastrophic compromise often due to a hyperinflammatory necrotizing pneumonitis [1,2]. African Americans, Native Americans, Hispanic Americans, obese individuals and the elderly are among groups experiencing disproportionately high levels of severe disease compared a to younger, normal Body Mass Index (BMI), Caucasian control population [3,4,5,6,7]. However, instead of attributing these discrepancies to genetic susceptibility or unavoidable effects of aging there is an evolving recognition that asymmetries of socioeconomic status , chronic stress, the availability of routine and acute medical care, and exposure to toxic environmental factors may be primarily responsible for the increased morbidity being suffered by these groups [3,8]. These same groups are also known to be disproportionately 25-hydroxyvitamin D (25VD) insufficient (serum levels of 20-30 ng/dL) or deficient (serum levels<20 ng/dL) [9,10,11]. While the etiology of the necrotizing pulmonary process is no doubt multifactorial, vitamin D deficiency has been targeted as is a candidate factor for abetting some of the dysfunctional hyperinflammation [12,13] occurring in these patients. Vitamin D deficiency affects various macrophage populations generally leading to a dampening of local production of 1,25-dihydroxyvitamin D (1,25VD), the effector molecule of intracrine, autocrine and paracrine actions of vitamin D [14]. Specifically, vitamin D..