Response to the Letter to the Editor From Min et al: Low Vitamin D Levels are Associated With Long COVID Syndrome in COVID-19 Survivors Free

We found all points raised by Min et al of value. The main finding of our paper is that, among COVID-19 survivors, patients with Long COVID have lower 25(OH) vitamin D than patients without Long COVID (1). As noted, this work fits into the well-studied negative impact of low vitamin D on acute COVID-19 (2), which, however, did not necessarily translate into a protective role of vitamin D supplementation (3) likely due to factors such as doses, type and route of administration of vitamin D as well as enrollment of patients without vitamin D deficiency at baseline and use of vitamin D in prevention vs treatment (4). Our study suggests that vitamin D levels should be evaluated in COVID-19 patients after hospital discharge (1). We agree with Min et al that although our data give a rationale for vitamin D supplementation as a preventive strategy in COVID-19 sequelae, this should be tested in ad hoc randomized controlled trials.

As noted in the letter, one of the strengths of the study is careful matching of a Long COVID vs a non-Long COVID group. Our very stringent inclusion criteria on the one hand led to enrollment of a relatively limited number of patients but, on the other hand, allowed us to avoid the influence of several factors on our data already proposed as possible determinants for Long Covid such as age, severity of acute disease, and coexistent comorbidities (1). In this regard, Min et al correctly noted a high prevalence of overweight/obesity in both studied groups, but this is in line with the epidemiology of acute COVID-19 (5). Moreover, it is correct that overweight/obese patients had, as expected (5), at hospitalization but not at follow-up visit, more frequent vitamin D deficiency than normal-weight subjects. However, since Long COVID and non-Long COVID patients were also matched for body mass index (BMI) and for prevalence of overweight/obesity at follow-up (1), and BMI did not associate with Long COVID occurrence in multiple regression logistic analysis, it seems unlikely that our findings could have been influenced by reverse causality linked to overweight/obesity.

We also agree that, due to a change over time of leading SARS-CoV-2 variants, there is the theoretical possibility that results of a study performed in a restricted time frame could not be automatically translated into other periods (1). However, Long COVID seems to occur regardless SARS-CoV-2 variants (6), and the restricted time period of our study contributes to data consistency, also avoiding the impact of seasonality on vitamin D levels (1).

Finally, in our study, only post-acute COVID-19 onset neurocognitive symptoms were evaluated as part of a Long COVID assessment (1). We concur that also sociopsychological factors could be associated with higher risk for or occur de novo in Long COVID (1). However, at the time of the first evaluation of our patients, ie, at hospital admission for acute COVID-19, psychological manifestations could have been due to acute illness. Nevertheless, we agree that the role of low vitamin D in a psychological area of Long COVID is worth investigating due to the reported effect of vitamin D on both depression and anxiety (7).

Funding

No funding to declare.

Author Contributions

All authors contributed equally.

Disclosures

A.G. is a consultant for Abiogen and Takeda and received a research grant to his institution from Takeda. All other authors have no conflicts of interest to declare and no competing interests. The work submitted for publication is original and has not been published in any language or format and has not been submitted elsewhere for print or electronic publication consideration.

References