May 16, 2023 — Patients with long COVID had lower levels of vitamin D than patients who had recovered from COVID-19, a new study shows, suggesting taking vitamin D supplements may help prevent or ease the debilitating condition.

The lower levels of vitamin D in patients with long COVID — where effects of the initial COVID infection last more than 12 weeks — were most notable in those with “brain fog.” 

These findings by Luigi di Filippo, MD, and colleagues, were recently presented at the European Congress of Endocrinology in Istanbul, and the study was also published in the Journal of Clinical Endocrinology & Metabolism.

“Our data suggest that vitamin D levels should be evaluated in COVID-19 patients after hospital discharge,” the researchers from San Raffaele Hospital, in Milan, Italy, wrote.

The researchers highlighted as a strength that this controlled study included patients with multiple symptoms of long COVID, and it had a longer follow-up than most previous studies (6 months vs. 3 months).

“The highly controlled nature of our study helps us better understand the role of vitamin D deficiency in long COVID and establish that there is likely a link between vitamin D deficiency and long COVID,” senior author Andrea Giustina, MD, said in a news release.

But, he said, “it is not yet known whether vitamin D supplements could improve the symptoms or reduce this risk altogether.”  

Supplement if Deficient? 

Amiel Dror, MD, PhD, who led a related study that showed that people with a vitamin D deficiency were more likely to have severe COVID, agreed. 

“The novelty and significance of this [new] study lie in the fact that it expands on our current understanding of the interplay between vitamin D and COVID-19, taking it beyond the acute phase of the disease,” said Dror, who’s with the Azrieli Faculty of Medicine at Bar-Ilan University in Safed, Israel.

“It’s striking to see how vitamin D levels continue to influence patients’ health even after recovery from the initial infection,” he said. 

“The findings certainly add weight to the argument for conducting a randomized, controlled trial,” he said, which “would enable us to conclusively determine whether vitamin D supplementation can effectively reduce the risk or severity of long COVID.” 

“In the interim,” Dror said, “given the safety profile of vitamin D and its broad health benefits, it could be reasonable to test for vitamin D levels in patients admitted with COVID-19. If levels are found to be low, supplementation could be considered.” 

“However, it’s important to note that this should be done under medical supervision,” he said, “and further studies are needed to establish the optimal timing and dosage of supplementation.” 

Low Vitamin D and Risk of Long COVID

Low levels of vitamin D have been associated with increased likelihood of needing mechanical ventilation and worse survival in patients hospitalized with COVID, but the risk of long COVID associated with vitamin D is not well known. 

The researchers analyzed data from adults age 18 and older who had been hospitalized at San Raffaele Hospital with a confirmed COVID diagnosis and then discharged during the first pandemic wave from March to May 2020, and then seen 6 months later at a follow-up clinic.

Patients were excluded if they had been admitted to the intensive care unit during their hospitalization or if they had missing medical data or blood samples available to determine vitamin D levels at admission and at the 6-month follow-up.

Guidelines from the UK National Institute for Health and Care Excellence were used to define long COVID as the presence of at least two or more of 17 symptoms that were absent prior to the COVID infection and could only be attributed to that acute disease.

The researchers identified 50 patients with long COVID at the 6-month follow-up and matched them with 50 patients without long COVID at that same point in time based on age, sex, other medical conditions, and need for noninvasive mechanical ventilation. 

The patients had an average age of 61 and 56% were men; 28% had been on a ventilator during their hospitalization for COVID.

The most frequent symptoms at 6 months in the patients with long COVID were weakness (38%), bad taste in the mouth (34%), shortness of breath (34%), and loss of sense of smell (24%).

Most symptoms were related to the cardiorespiratory system (42%), the feeling of well-being (42%), or the senses (36%), and fewer patients had symptoms related to neurocognitive impairment (headache or brain fog, 14%), or ear, nose, and throat (12%) or the gastrointestinal system (4%).    

Patients with long COVID had lower average vitamin D levels than patients without long COVID, and vitamin D levels were significantly lower in patients with symptoms like headache or brain fog. 

The researchers used a type of analysis called multiple regression that showed vitamin D at follow-up was the only variable that was significantly associated with long COVID. 

The findings “strongly reinforce the clinical usefulness of … vitamin D evaluation as a possible modifiable pathophysiological factor underlying this emerging worldwide critical health issue,” the researchers concluded. 

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