Low Vitamin D Levels are Associated with Long COVID Syndrome in COVID-19 Survivors

This study, conducted in Italy, found that patients with long COVID symptoms, and in particular neurocognitive symptoms, had significantly lower 25(OH) vitamin D levels than patients without long COVID symptoms.

• At the 6-month follow-up, subjects with long COVID had significantly lower 25(OH) vitamin D levels than those without (20.1 vs. 23.2 ng/mL, P = .03).  
• Lower vitamin D levels were observed in those with neurocognitive symptoms at follow-up than those without (14.6 ng/mL vs. 20.6 ng/mL, P = .042).  
• In patients with vitamin D deficiency at both admission and at follow-up, those with long COVID had lower 25(OH) vitamin D levels at follow-up than those without (12.7 vs 15.2 ng/mL, P = .041).  
• Multiple regression analyses revealed that lower 25(OH) levels at follow-up were the only variable significantly associated with long COVID. 

100 subjects in Italy with and without long COVID symptoms 6 months after hospitalization. 

This study included a relatively small number of subjects, due to the stringent inclusion criteria, and was a single center study. 

In conclusion, we have reported that patients with long COVID re-assessed 6 months after hospital discharge are characterized by lower 25(OH) vitamin D levels; lower vitamin D were an independent risk factor for the occurrence of this syndrome. Differently from other previous reports, we observed these findings in a controlled study with a homogeneous population; we did not limit our evaluation during follow-up visits to specific health areas but performed a multidisciplinary evaluation, including the collection of a broad spectrum of symptoms and signs reported by patients with long COVID. Furthermore, the medium-long term follow-up used in our study could probably better identify and characterize patients with post-infection recovery impairment, and thus those who needed more intensive follow-up, possibly requiring preventive and therapeutic strategies, including also vitamin D supplementation. This aspect strongly reinforces the clinical usefulness of 25(OH) vitamin D evaluation as a possible modifiable pathophysiological factor underlying this emerging worldwide critical health issue.

• This retrospective study evaluated the association between 25(OH) vitamin D levels and the risk of long COVID occurrence in patients previously hospitalized for COVID-19 and reassessed 6 months after hospital discharge. 
• 50 adult subjects with long COVID and 50 subjects without were matched 1:1 for age, sex, comorbidities, and acute disease severity. 
• Exclusion criteria included therapies or comorbidities affecting calcium/vitamin D/ bone metabolism, and/or admission to ICU during hospitalization. 
• 25(OH) Vitamin D was measured at hospital admission and 6 months after discharge. 
• To minimize the effects of seasonality on 25(OH) levels, long COVID patients were matched with non-long COVID subjects admitted to the hospital, and evaluated at 6-month follow-up, in the same time period (same week). 

di Filippo L, Frara S, Nannipieri F, Cotellessa A, Locatelli M, Rovere Querini P, Giustina A. Low vitamin D levels are associated with Long COVID syndrome in COVID-19 survivors. J Clin Endocrinol Metab. 2023 Apr 13:dgad207. doi: 10.1210/clinem/dgad207.