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Evidence Supports a Causal Role for Vitamin D Status in Global COVID-19 Outcomes
Gareth Davies
Attila R Garami
Joanna Byers
Acceso Abierto
Atribución-NoComercial-SinDerivadas
https://doi.org/10.1101/2020.05.01.20087965
https://www.medrxiv.org/content/10.1101/2020.05.01.20087965v3
Background The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 seemed to affect locations in the northern hemisphere most severely appearing to overlap with the pattern of seasonal vitamin D deficiency. Integrating available knowledge, we hypothesised that vitamin D status could play a causal role in COVID-19 outcomes. Objectives We set out to analyse the relationship between COVID-19 severity and latitude, and construct a causal inference framework to validate this hypothesis. Methods We analysed global daily reports of fatalities and recoveries from 239 locations from 22nd Jan 2020 to 9th April 2020. We quantified local COVID-19 outbreak severity to clearly distinguish the latitude relationship and identify any outliers breaking this pattern, and analysed the timeline of spread. We then used a causal inference framework to distinguish correlation from cause using observational data with a hypothetico-deductive method of proof. We constructed two contrasting directed acyclic graph (DAG) models, one causal and one acausal with respect to vitamin D and COVID-19 severity, allowing us to make 19 verifiable and falsifiable predictions for each. Results Our analysis confirmed a striking correlation between COVID-19 severity and latitude, and ruled out the temporal spread of infection as an explanation. We compared observed severity for 239 locations with our contrasting model. In the causal model, 16 predictions matched observed data and 3 predictions were untestable; in the acausal model, 14 predictions strongly contradicted observed data, 2 appeared to contradict data, and 3 were untestable. Discussion We show in advance of RCTs that observed data strongly match predictions made by the causal model but contradict those of the acausal model. We present historic evidence that vitamin D supplementation prevented past respiratory virus pandemics. We discuss how molecular mechanisms of vitamin D action can prevent respiratory viral infections and protect against ARDS. We highlight vitamin D’s direct effect on the renin-angiotensin-system (RAS), which in concert with additional effects, can modify host responses thus preventing a cytokine storm and SARS-CoV-2-induced pathological changes. Emerging clinical research confirms striking correlations between hypovitaminosis D and COVID-19 severity, in full alignment with our study. Conclusions Our novel causal inference analysis of global data verifies that vitamin D status plays a key role in COVID-19 outco
bioRxiv
13-06-2020
Preimpreso
Inglés
Público en general
VIRUS RESPIRATORIOS
Versión publicada
publishedVersion - Versión publicada
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