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expert reaction to preprint on calcifediol (vitamin D metabolite) treatment and COVID-19-related outcomes, data from Barcelona

A preprint, an unpublished non-peer reviewed study, looks at calcifediol treatment and COVID-19-related outcomes in Barcelona.


Prof Naveed Sattar, Professor of Metabolic Medicine, University of Glasgow, said:

“This is interesting but a huge dose of scepticism in the top line results is warranted as this is NOT a randomised controlled trial with no information on process of randomisation, and lack of placebo.  It also does not appear to be registered as a trial.  Also, baseline differences in more females in the vitamin D3 (calcifediol) group plus higher vitamin D levels, could easily confound the results.  There is also no reason to relate vitamin D levels to outcomes as that is observational and tells us nothing new as we know vitamin D levels are lower in sicker patients – we have known this for decades in many conditions.

“In short, this is not a useful study as it falls well short of a well conducted randomised trial.  Whilst many wish to believe Vitamin D is the cure to covid-19 or an exciting treatment, this ‘trial’ cannot allow any such inference.  We must await robust randomised trials to form appropriate conclusions.”


Prof Adrian Martineau, Clinical Professor of Respiratory Infection and Immunity, Queen Mary University of London, said:

“This manuscript reports findings of a study designed to investigate effects of administering calcifediol (25-hydroxyvitamin D) on COVID-19 outcomes.  Some dramatic positive findings are presented, but important methodological details are missing.

“First, it is not clear whether or how the randomisation was done.  The abstract mentions randomisation – but Methods do not describe how it was done – they simply state that ‘551 received calcifediol at admission to the hospital and 379 were not treated (control group).’ Two features in particular suggest that there may have been issues with the randomisation:

a) intervention and control groups were not evenly balanced in size;

b) intervention and control groups were not evenly balanced with regard to key baseline characteristics (sex composition, baseline vitamin D levels).

“Second, 50 patients in the control group received the vitamin D metabolite calcifediol during ICU admission ‘at the discretion of the treating physicians and outside the original protocol’.  This represents a pretty significant breach of the protocol, and calls into question the validity of the study’s results.

“Third, I could not find the registration for the trial.  It is standard practice to register clinical trials before they start recruiting, and it’s not clear whether this was done.

“Overall, more methodological detail is needed before the claims of treatment benefit can be substantiated.”



All our previous output on this subject can be seen at this weblink:



Declared interests

Prof Naveed Sattar: “No COI.”

Prof Adrian Martineau: “I am Chief Investigator of the CORONAVIT trial – the UK’s national clinical trial of vitamin D supplementation to reduce risk and/or severity of COVID-19.

I am the senior author on the meta-analysis by Jolliffe et al (, which demonstrates a modest protective effect of vitamin D supplements on acute respiratory infections other than COVID-19, and which is referenced in the updated NICE guideline.”


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