Abstract: Journal of Infection xxx (xxxx) xxx–xxx
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Journal of Infection
journal homepage: www.elsevier.com/locate/jinf
Letter to the Editor
Effect of calcifediol supplementation as add-on therapy on the
immune repertoire in recipients of the ChAdOx1 nCoV-19
vaccine: A prospective open-label, placebo-controlled, clinical
trial
Dear Editor,
Coronavirus disease 2019 (COVID-19) has caused formidable
global health crisis, and multiple vaccination programs have been
rolled out to curb the spread of the pandemic. Genetic disorders like
primary immunodeficiency diseases severely compromise the gen
eration of protective immunity following vaccinations. The spectrum
also includes those genetic disorders that have a lesser impact on
immunological memory such as Down Syndrome (DS). In a recent
study, Valentini et al.1 confirmed that the serological efficacy of
COVID-19 vaccination is least affected by DS. The authors included a
substantial number of subjects and further observed that the older
subjects exhibit lower anti-SARS-CoV-2 antibody titers 6 months
after vaccination. Earlier, Yarci-Carrion et al.2 had also reported that
DS and non-DS subjects develop similar anti-SARS-CoV-2 titers after
the third dose of vaccine that decline with age. However, the same
group demonstrated that DS subjects develop milder T cell responses
to the standard 2-dose vaccine.3 Valentini et al.1 further denote that
the factors modifying immune responses to vaccination in such
disorders are less explored. This may include nutritional deficiencies
like vitamin D [25(OH)D]. Indeed, reports have shown that hypovi
taminosis D is quite frequent in subjects with DS.4
It is also known that individuals with low 25(OH)D levels have a
higher risk of acquiring severe COVID-19 and stimulation of vitamin
D receptor can reduce COVID-19-associated hospitalization and
mortality.5,6 However, studies on vitamin D supplementation in
COVID-19 vaccination have yielded conflicting results with some
reporting improvement, while others observing lack of association
between 25(OH)D status and antibody titers post vaccination.7,8
Most of these studies, however, did not assess cellular immune re
sponses, which are more likely to be influenced by vitamin D. Cal
cifediol [25(OH)D3], the immediate precursor of 1,25(OH)2D3 leads
to a faster achievement of desired levels and biodistribution of cir
culating 1,25(OH)2D3 as compared to cholecalciferol (vitamin D3).9
There are reports on favorable outcomes of calcifediol supple
mentation in COVID-19,10 but there are no data on its utility in im
proving efficacy of COVID-19 vaccines. Therefore, we evaluated the
efficacy of calcifediol supplementation on cell-mediated immune
responses besides anti-SARS-CoV-2 titers post COVID-19 vaccina
tion. We carried an open-label, placebo-controlled clinical trial to
assess the impact of calcifediol supplementation on the efficacy of
ChAdOx1 nCoV-19 vaccine in terms of, protection from break
through infection and COVID-19 disease, anti-SARS-CoV-2 antibody
titers, SARS-CoV-2 specific lymphocyte proliferation and cytokine
secretion.
Herein 580 adult subjects receiving ChAdOx1 nCoV-19 vaccine
were recruited at the Post Graduate Institute of Medical Education
and Research (PGIMER), Chandigarh, India. The subjects received
either calcifediol (50 µg/day) or placebo, orally for 6 months
(Supplementary Fig. 1, Supplementary Table 1) and divided in 3
groups [SARS-CoV-2 unexposed,..
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