A high dose of vitamin D from the diagnosis of Covid-19 limits deaths, according to a COVIT-TRIAL study promoted by the Angers University Hospital and labelled a national research priority by the State. Explanations.
Vitamin D is finally recognized as effective in the fight against Covid-19! A COVIT-TRIAL study (COvid-19 and high-dose VITamin D supplementation TRIAL in high-risk older patients) has confirmed this. Conducted by 73 experts and six learned societies gathered around Prof. Cédric Annweiler, head of the geriatrics department at the University Hospital of Angers, and Prof. Jean-Claude Souberbielle of the functional explorations department at the Necker-Enfants malades hospital in Paris, this study demonstrates the interest of vitamin D in the fight against Covid-19 and its authors call for supplementing the entire French population.
For two years already…
This is what a scientific publication signed by Emmanuelle Faucon and Jean-Marc Sabatier revealed in March-April 2020. In December 2020, Dr. Jean-Michel Wendling, scientific advisor for infodujour published a paper entitled “Covid: The incredible French discoveries“. In January 2021, this title: “Vitamin D: A massive plan against Covid-19” in which, already, we evoked the benefits of vitamin D in these terms: “Henceforth, several scientific studies confirm the beneficial role of vitamin D in the prevention of Covid-19” by evoking the work of Prof. Cédric Annweiler and Jean-Claude Souberbielle.
Information completed and argued by Jean-Marc Sabatier in our article vilified by the AFP-Factuel in a fake fact-checking to which we answered shortly after, point by point.
“A very high level of evidence”
Today, the Angers University Hospital is making a dramatic announcement. “While the latest wave of the Covid-19 epidemic is running out of steam, hospitalizations of Covid-19 patients, especially the elderly, have never stopped. This is why the results of the COVIT-TRIAL study, promoted by the Angers University Hospital and labeled a national research priority by the State, represent a lever for the care of elderly patients at high risk of death. COVIT-TRIAL, whose findings are published in the scientific journal Plos Medicine this Tuesday, May 31, 2022, shows with a very high level of evidence the benefit of a high dose of vitamin D, administered within 72 hours of the diagnosis of Covid-19, to frail elderly people who have contracted the infection. The results report a significant reduction in the rate of death in patients who received a high dose of vitamin D compared with those who received a standard dose of vitamin D. Nine French hospitals and their EHPADs participated in this study initiated by Prof. Cédric Annweiler, head of the geriatrics department at the CHU in Angers.”
Vitamin D, a natural hormone, is known for its effects on calcium metabolism and fracture risk, but also for its anti-inflammatory properties in infectious and cancerous diseases. For example, it helps prevent winter respiratory infections, which had been observed long before the Covid-19 era.
“We learned quite quickly during the first wave of the Covid-19 pandemic that SARS-CoV2 (coronavirus 2) causes deregulation of the renin-angiotensin system via the ACE2 receptor, the virus’s gateway to the body, causing a risk of inflammatory chain reactions (“cytokine storm”) and a risk of acute respiratory distress syndrome (ARDS) that is often fatal. However, vitamin D has recognized anti-inflammatory effects and participates in the regulation of the renin-angiotensin system. This is why we quickly imagined, as early as March 2020, that vitamin D could help fight against severe forms of Covid-19″, reminds Prof. Cédric Annweiler.
To examine the efficacy of vitamin D supplementation, tolerance and mortality
The COVIT-TRIAL study was therefore launched in April 2020, during the first wave of Covid-19, with the support of the Research and Innovation Department of the Angers University Hospital.
The main objectives of this multicenter, randomized, controlled, intention-to-treat trial were:
- to examine the effect on 14-day mortality of high-dose vitamin D supplementation versus standard dose in elderly patients with COVID-19 at risk of severe progression.
- to clarify the safety and tolerability of high-dose vitamin D supplementation compared with standard-dose vitamin D supplementation.
260 patients included in France
260 patients will be included between April and December 2020 (before the arrival of the vaccines in France) by the 9 participating French centers (the University Hospital Centres of Angers, Bordeaux, Limoges, Nantes, Nice, Saint-Etienne, Tours, and the University Hospital Centres of Le Mans and Saumur) and in the dependent EHPADs of these institutions.
Their profile? “Either patients aged 65 years and over with Covid-19 with criteria of unfavorable evolution (notably oxygen dependence), or patients aged 75 years and over with Covid-19 without any other risk factor,” explains Professor Cédric Annweiler.
These patients were then randomly divided into 2 groups:
- the group called “Intervention” received a single dose of 400,000 IU of vitamin D (= high dose of vitamin D) within 72 h of their diagnosis of Covid-19
- the “Control” group received a single dose of 50,000 IU within 72 hours of their diagnosis of Covid-19
Investigators and patients were aware of the treatment being administered. In parallel to the study, all patients in both groups of course continued to receive the best known Covid-19 care (corticosteroids, oxygen, etc.).
Efficacy of vitamin D on mortality demonstrated by day 6 of treatment
Compared to the “Control” group, the administration of high-dose vitamin D in the “Intervention” group resulted in a large and statistically significant reduction in the risk of death, and this as early as day 6 after the start of treatment, i.e. at the time when the cytokine storm is likely to worsen the disease.
“This result is important and consistent with what we knew about the anti-inflammatory effects of vitamin D, by very significantly reducing the risk of death at 14 days, and by clearly avoiding the inflammatory runaway and cytokine storm observed in severe forms of Covid-19,” observes Prof. Cédric Annweiler.
This superiority of efficacy of the high dose of vitamin D effectively persists on all-cause mortality within 14 days (primary endpoint) without causing more adverse effects than the standard dose.
Of note, secondary analyses showed a decrease in efficacy at 28 days, which could be expected given the lifetime of vitamin D taken as a single dose early in the disease course. The efficacy of continuous maintenance therapy (daily or weekly vitamin D supplementation) following the first dose will be studied further.
The authors’ recommendations
As an adjunct to standard treatments for Covid-19, early administration (within 72 h of diagnosis) of high-dose vitamin D is a simple and safe treatment that demonstrates its value in preventing severe forms of Covid-19 in elderly patients facing the emergence of new variants and the risk of immune escape.
At the end of the COVIT-TRIAL study, the authors strongly recommend that a satisfactory vitamin D status be achieved as soon as possible in elderly people with Covid-19, using high-dose vitamin D supplementation as soon as Covid-19 is diagnosed.
How can vitamin D affect Covid-19?
Vitamin D is a seco-steroid hormone. It is capable of activating or repressing several hundred genes, and can thus theoretically prevent and/or improve severe forms of Covid-19 by :
- modulating the activity of the renin-angiotensin system and in particular the expression of ACE2 (used by SARS-CoV-2 to infect host cells) and repressing renin synthesis. CEA2 has protective effects against inflammation in several organs, including the lungs. During Covid-19, down-regulation of CEA2 by SARS-CoV-2 results in an inflammatory chain reaction, called a cytokine storm, which can be complicated by acute respiratory distress syndrome with a high risk of death.
- regulating innate and adaptive cellular immunity: synthesis of antimicrobial peptides with direct antiviral activity and anti-inflammatory action.
- Finally, hypovitaminosis D appears to be an independent risk factor for severe Covid-19. This point is potentially very interesting because, unlike the other risk factors for severe Covid-19 (advanced age, obesity, multiple comorbidities) on which there is little (or no) possibility of acting, hypovitaminosis D is a risk factor that can be very easily modified by simple drug supplementation.
Vitamin D, an expertise from Angers
More than a year ago, on January 8, 2021, 73 experts gathered around Prof. Annweiler and Prof. Souberbielle co-signed a consensus article in La Revue du Praticien supported by 6 French national learned societies (*). They called for ensuring that the entire French population has a satisfactory level of vitamin D in the dual context of the Covid-19 pandemic and the winter period during which vitamin D levels naturally decrease.
A growing number of scientific studies already showed at the time that vitamin D supplementation (without replacing vaccination) contributed to preventing the risk of severe forms of Covid-19 and of passages in intensive care related to this virus.
The published results of the COVIT-TRIAL study now confirm, with a high level of evidence, the efficacy of high-dose vitamin D supplementation in reducing the risk of death in elderly people who have contracted the infection.
(*) The French Association of Anti-Rheumatic Diseases (AFLAR), the French Society of Endocrinology (SFE), the French Society of Geriatrics and Gerontology (SFGG), the French Society of Pediatrics (SFP), the French Society of Pediatric Endocrinology and Diabetology (SFEDP), the French Society of Nephrology, Dialysis and Transplantation (SFNDT)