PLOS ONE has issued an expression of concern for a paper it published last month suggesting that vitamin D might protect against severe COVID-19.
Central to the concerns is that the authors seem to have been too far out over their skis in asserting a link between the vitamin and the response to the infection. But as the EoC reveals, many of the potential problems can fairly be attributed to porous peer review as much as over-ambitious authors.
The article, “Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection,” came from a group at Tehran University of Medical Sciences in Iran and Boston University in the United States. According to the authors:
Based on CDC criteria, among our study patients, 74% had severe COVID-19 infection and 32.8% were vitamin D sufficient. After adjusting for confounding factors, there was a significant association between vitamin D sufficiency and reduction in clinical severity, inpatient mortality serum levels of C-reactive protein (CRP) and an increase in lymphocyte percentage. Only 9.7% of patients older than 40 years who were vitamin D sufficient succumbed to the infection compared to 20% who had a circulating level of 25(OH)D< 30 ng/ml. The significant reduction in serum CRP, an inflammatory marker, along with increased lymphocytes percentage suggest that vitamin D sufficiency also may help modulate the immune response possibly by reducing risk for cytokine storm in response to this viral infection.
Therefore, it is recommended that improving vitamin D status in the general population and in particular hospitalized patients has a potential benefit in reducing the severity of morbidities and mortality associated with acquiring COVID-19.
The paper caught some notice on social media, including this lengthy post-publication analysis by Gideon Meyerowitz-Katz, an epidemiologist in Australia, who called the findings “wildly unimpressive.”
After this article [1] was published, concerns were raised about the validity of results and conclusions reported in the article and about undisclosed competing interests.
Specifically,
Concerns were raised about the reported study’s sample size and whether it was adequate to address the aims of the study.
Questions were raised about whether the statistical analyses and results were sufficiently robust to support the article’s conclusions, and about how potential confounds were addressed in the data analyses. As one aspect of this, it was raised that vitamin D levels may be indicative of co-morbidities that may themselves impact COVID outcomes.
There are statements in the article, including in its title and conclusions, that suggest a causal relationship between vitamin D levels and the clinical outcome of COVID-19 infections which is not supported by the data.
Of the participants in the study, only 31.06% had RT-PCR tests confirming a COVID-19 diagnosis. As such, the COVID-19 status of other participants is in question, although in the article all are reported as patients with COVID-19. This is not taken into consideration in the subgroup analyses as reported in the article, and calls into question the overall interpretation of the results.
The article’s Competing Interests statement says, “The authors have declared that no competing interests exist.” However, publicly available information indicates that corresponding author MFH may have potential competing interests that include non-financial interests based on his vitamin D research and other activities focused on vitamin D; contributions to an app that tracks vitamin D; and interests that include consultancies, funding support, and authorship of books related to vitamin D usage.
The notice also includes a rebuttal from the researchers:
The authors commented that the article did not claim a causal role of vitamin D on clinical outcomes, and that the limitations of the study were clearly described in the Discussion which said, “we cannot explain the cause and effect relationship of vitamin D sufficiency and the reduced risk of severity from a COVID-19 infection.” [1] They also stated that COVID-19 diagnoses were made by infectious disease specialists per WHO interim guidance and recommendations of the Iranian National Committee of COVID-19 [2].
We asked David Knutson, the senior manager for communications at PLOS, about the notice, and whether the peer review process might have identified some of the concerns prior to publication. He told us:
Concerns raised via social media in late September prompted a reassessment of this article. Some of the scientific issues noted in the Expression of Concern were raised during peer review. However, we identified several concerns during our post-publication assessment and determined that this work, including aspects discussed during peer review, warrants further editorial consideration. We are currently following up on this case with high priority in light of the public health implications of the article’s results.
Here’s our list of papers about COVID-19 that have been retracted or subjected to expressions of concern.
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Have you reviewed the clinical study done by staff at Reina Sofia University Hospital in Spain on Vitamin-D status and severity of Covid-19 infection?
Nah, we are waiting for some guy/gal on Twitter to do the review on 123 tweets so we can make a full assessment on it.
As typical of such retractions / “debunking” etc., important information is being ignored. The Tehran study is NOT the only one done. Several other clinical observations exist that also include people with serum D25 at levels of 50 or more did not contract covid19 despite being in daily close contact with people verified as ill with the virus.
Citing the Lancet to debunk is a loser, being as too many of their “debunking” in the past couple decades has been debunked.
I used to read the Lancet when I was al young lad, Dan Dare was my hero.
You should be asking this to @GidMK. This is not a peer review website. Here we are just making note of the EoC, which seems to have been earned because of the overambitious title on the paper.
It is far better to not do anything at all about covid and just take your chances with it, than to take vitamin D. Covid might kill you or make you wish you were dead by causing long term consequences from the blood clots, but at least you won’t have to worry about that nasty vitamin D. No, no, we are far better off not having any outpatient treatments available, and while we are at it let’s not even get a vaccine for 7 years. Like they say, masks and social distancing offer more protection than any vaccine ever could. Let’s just lock down society for 7 years and wait this thing out. Keep living in limbo and putting things off like cancer screenings for 7 years.
Because vaccines and “cancer screenings” (distinct from “cancer diagnosis in response to symptoms”) are provided to healthy people with no symptoms, the bar for side effects and false positives is set high. “Cancer screenings” are another of the lucrative but useless medical practices (like vitamin D and other dietary supplements) that are so unlikely to provide medical benefit relative to the medical (and financial) costs and side effects that they are not advocated by most conscientious MDs. But Jeff you go ahead believing there are no false positives, and that there are not costs or side effects to this quackery. And also you should keep ignoring the many advances in covid care over the last 8 months – those are the “outpatient treatments” your looking for, and are the reason why mortality rates are lower now even while infection rates have increased. Not this dopey vitamin D fantasy.
I can’t understand why this comment passed moderation— unless the moderators have a sick sense of humor.
Appreciate your honest sarcasm. I have still not heard of any fatalities from someone with normal or higher levels of vitamin D.
Who pays you? Wait it out. NO SUCH THING AS HERD-IMMUNITY w/ SARS/ MERS. Sombody continues to add to the mix and the U.S can’t find the source? Why disband the Covid-19 team Pres. Obama had working on the case, unless you need more to die.Why ignore the “What to do in case of a pandemic” notebook left by Pres. Obama/Biden? Unless you want people to die. Why stop testing or skip-tracing..unless u want people to die. Why stop people on FB from posting about the young white people who’ve had Double-Lung transplant, can no longer walk, on oxygen and Dyalysis
& 15 meds a day, like my relative w/ GANGRENE eating away their bodies….?
A strike down the middle!!! Yes we.MUST be “concerned” about vitamin D…which we are already deficient/insufficient in. In fact let’s research it for the next 5 years because god forbid a rsearcher might have a been overly optimistic in their title. We should all be extremely concerned. What a total joke.
Brilliant comment Jeff. The snobbery of self-blinding clones like Mike does double time as a foil versus good sense, making him and his nerdy dork-alikes unable to recognize and appreciate practical logic instead of striking out from their artificial island comfort of reductionist fantasy.
Thanks Tony. Sticks and stones eh? But seriously: wear a mask, wash your hands, stay away from other people who don’t do those things, and I hope you won’t catch the virus and get sick. Good luck!
You need to improve your sarcasm. That won’t do.
Vitamin-D supplements, especially for the elderly may well eventually be double blind tested proven efficacious to boost the immune system re: Covid-19. If you have a clinical deficiency of Vitamin-D (as a majority of seniors do) then what have you got to lose taking a low-cost supplement and having your levels measured? Surely it’s another layer to defence in depth, etc., etc.
The stock in trade here at RW is epistemology: how do we know what we think we know about the world (in this case, the world of coronavirus disease and treatment)? False steps in knowledge lead to retractions. Waiting for dependable advances in knowledge before committing to a course of treatment or prevention is sensible. Arguments based on “may well eventually be double blind tested” and “what have you got to lose” do not fall in that category of dependable advances in knowledge. Instead they’re just a form of Pascal’s wager. And as Voltaire said of that wager, “The interest I have to believe a thing is no proof that such a thing exists”.
What have you got to lose, Dennis? Oh, about 8 cents a day. I’m 66 and take 10,000IU. My Vitamin D level is 66ng/ml. The same as younger men who work outdoors all day. I’m not waiting for the vaccine and at 66 I’m not putting my life on hold, either.
Do all the studies you need to. In the end, you will find that higher levels of the supplement do, in deed, offer protection from virus whether Covid-19, the flu or the common cold.
I’m betting my life on it.
Dead right George, I live in the UK, am 82 with heart failure and implanted defib, been taking between 4000 and 8000 VitD for the last 2.5 years. Had covid twice, treated EARLY with HCQ + zinc + Doxycycline, obviously still here. Not jabbed and never worn a mask, never social distanced other than the first 3 months of covid, did my research early, started from 1870 with Quinine. Treat all disease early, that has always been the key other than for covid.
Bravo! But your thought is way too obviously logical for the ivory towered reasoning that passes for expert advice.
Holick has 2 other papers on PubPeer, including another published in PLOSONE.
https://pubpeer.com/search?q=Holick
I think if vitamin d will help or not take it anyway I take it I am 72 years old.
Study of 216 COVID-19 patients found 82% were vitamin D deficient. Nearly twice the percentage as the control group. https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgaa733/5934827
Pretty sure in future we will have evidence that thousands of lives could have been saved from covid if public health officials had advocated vitamin D supplementation.
All this blagh,. Just eat a varied diet to stay healthy. Brisk walk twice a day. Enjoy your life, without doing harm to yourself and others. Keep living , keep loving. Be wary of falsehood. Question everything .