Our findings strongly suggest that pre-existing VD deficiency is at least in part responsible for increased COVID-19 severity and acts synergistically with, but also independently of obesity. Graphic representation of our results are shown in Figures 1, 2, 3 and 4.
Although we are reporting on only 37 patients they were all from one institution, were admitted in a restricted time-window to limit the effect of changing therapy on disease evolution, and were under the care of a limited staff of Acute-Care/Pulmonary specialists all using the same criteria for ICU admission and the same standards-of-care for hospitalized COVID-19 patients. This uniformity of evaluation and treatment lends an added level of confidence to our statistical analysis. Our conclusion supports and expands that of a recent study by De Smet et al from Belgium [21] demonstrating that vitamin D deficiency (also using at a cut-off of 20 ng/mL) is associated with more advanced COVID-19 related pulmonary disease as determined by chest CT. Appraising our findings in conjunction with those of De Smet it is compelling to conclude that the clinically severe physiologic compromise necessitating ICU care of our 25VD deficient patients is a direct manifestation of the disease process reflected in their radiologic findings and that preexisting vitamin D deficiency is very likely an easily remediable factor contributing to increased disease severity. Additional investigation is needed to determine whether 25VD deficient patients already infected with SARS-CoV-2 would benefit from correction of their deficiency.
A recent advisory from Public Health England of 06/29/2020 [22] states there is “no evidence to support taking vitamin D supplements to specifically prevent of treat COVID-19”. The ‘Joint Statement on Vitamin D in the Era of COVID-19’ released 07/09/2020 by the Endocrine Society and five other organizations [23] stresses the need for individuals to maintain sun exposure and to supplement with 400-1000 IU of vitamin D daily. Our conclusions are not at odds with these two statements but rather addresses the need for prompt anticipatory evaluation of serum 25VD for members of groups known to be at increased risk for 25VD deficiency. Unfortunately, routine vitamin D supplementation is often ineffective [24] for older individuals such that follow-up monitoring is required to assure that sufficient serum levels are attained. This need to evaluate the outcome of supplementation should probably apply to all individuals being urgently screened for 25VD deficiency. If ongoing patient follow-up studies demonstrate that significant multi-system complications result from even mild-to-moderate COVID-19 [25,26] universal prospective vitamin D screening should become a standard component of preventative medical care.
Our recommendation is to expeditiously screen groups known to have both disproportionately high rates of severe COVID-19 relative to their population percentages and vitamin D deficiency. Up to 40% of African Americans are suspected to be vitamin D deficient at random seasonal testing [10] but this percentage that may reach 65 % in winter months [27]. Native Americans have been infrequently evaluated for their 25VD status but a report from Oklahoma found that two-thirds of apparently healthy individuals had 25VD below 20 ng/dL [9]. Nursing home residents not taking vitamin D supplementation may have a deficiency rate over 60%; even with standard supplementation up to 16% remain deficient [28]. Profound vitamin D deficiency, though of variable percentage depending on the country of origin, has been substantiated in recent immigrants to Minnesota, Calgary, and Amsterdam [29,30,31]. Pregnant women and obese individuals are two additional population groups of concern. Evaluating healthy pregnant women from Pennsylvania in 2007 Bodnar et al [32] found 29% of black women and 5% of white women were 25VD deficient at delivery. By 2015 the obstetric situation was minimally changed: healthy women from the state of Washington, assessed at various times in pregnancy, were studied by Flood-Nichols et al [33] who found 19% of black women and 7% of white women to be vitamin D deficient. In light of an MMWR comment of 8/27/20 [34] suggesting that SARS-CoV-2 infected pregnant women “are more likely to be hospitalized and are at increased risk for ICU admission and receipt of mechanical ventilation than nonpregnant women” pregnancy does not appear to be a condition in which vitamin D deficiency should be neglected as part of routine care. Increasing obesity correlates with decreasing serum 25VD but total-body deficiency is rarely encountered due to modified distribution into differentially increased volumes of various tissues [35]. However, as mentioned in our RESULTS section, for the same BMI a higher 25VD was mildly protective of ICU admission suggesting that attempting correction of a recognized deficiency may be indicated.
NEW CONTRIBUTION to the LITERATURE
Prospective screening and remediation of vitamin D deficiency in groups at high-risk for severe COVID-19 disease is likely to attenuate an individual patient’s peak physiologic compromise from subsequent SARS-CoV-2 infection. From a Public Health and medical-systems perspective the percentage of COVID-19 patients requiring ICU care would be diminished. Though relying predominantly on North American data to reach our conclusions, the testing implications apply to the many vitamin D deficient people throughout the world.