Association between population vitamin D status and SARS-CoV-2 related serious-critical illness and deaths: An ecological integrative approach

In this ecological study analyzing the relationship between European population data for serum vitamin D concentrations [25(OH)D] and the number of total cases/million (M), recovered/M, deaths/M and serious-critically ill/M from COVID-19, a higher 25(OH)D concentration may protect from serious-critical illness and death from COVID-19 disease – even more in the elderly – but does not seem to prevent SARS-CoV-2 from spreading.

• From the 26 European countries included in the analysis, with a total population of 714.661 M, nine (54.17%, 387.15 M) had a vitamin D deficient status, eight an insufficient status (33.58%, 240.022 M), eight a mild insufficiency status (11.48%, 82.023 M) and only one country, Slovakia, a sufficient status (0.76%, 5.459 M).
• Linear regression found no correlation between population vitamin D concentrations and total cases/M or the recovered/M.
• Models that increased population vitamin D concentrations predicted a reduction in serious-critical illnesses/M and in deaths/M. These relationships were further enhanced when adjusting for life expectancy, if 25(OH)D concentrations were to reach and be sustained at 100-150 nmol/L (40-60 ng/ml) by August 15, 2020.

Population data for 24 European countries with population > 4 M and published vitamin D status data. The analysis included 714.6 M European citizens.

• Because it is an ecological study that is based on population data, the results do not mean that individuals with vitamin D deficiency are at increased risk of COVID-19 infection and mortality or the converse.
• Only European countries with available population estimates for 25(OH)D deficiency were included in this study, making the results of this analysis applicable only to the European population. An analysis of all countries with reported COVID-19 data or a different subset of countries would potentially alter the conclusions.

Achieving circulating concentrations of 25(OH)D in the range of 100-150 nmol/L (40-60 ng/mL) appears to optimize vitamin D’s ability to improve immune function, thereby substantially reducing the risk for serious-critical illness, particularly from SARS-CoV-2, and to potentially modulate the immune response to prevent cytokine storm, an event that often leads to COVID-19 related deaths.

• Data on European countries at the Worldometer website was accessed, on June 19, 2020, for 26 European countries with populations > 4 M. Sweden was excluded due to its decision not to lock down and Moldova was excluded because no published vitamin D status data were found.
• For the remaining 24 countries, linear regression was used to explore the correlation between published representative standardized population vitamin D concentrations and the number of total cases/million (M), recovered/M, deaths/M and serious-critically ill/M from COVID-19.
• Because mortality from COVID-19 disease has been shown to increase rapidly with respect to age, life expectancy (LE), an age-related index, was analyzed using a semi-parametric regression approach using Worldometer data.
• Weighted analysis of variance/analysis of covariance evaluated serious-critical/M and deaths/M by the vitamin D population status – deficient: < 50 nmol/l (20 ng/ml), insufficient: 50-62.5 nmol/l (20-25 ng/ml), mildly insufficient > 62.5-75 nmol/l (25-30 ng/ml), and sufficient > 75 nmol/L (>30 ng/ml) – while controlling for life expectancy for deaths/M.

Papadimitriou DT, Vassaras AK, Holick MF. Association between population vitamin D status and SARS-CoV-2 related serious-critical illness and deaths: An ecological integrative approach. World J Virol. 2021 May 25;10(3):111-129. doi: 10.5501/wjv.v10.i3.111. PMID: 34079693; PMCID: PMC8152454.