Normal T and B Cell Responses Against SARS-CoV-2 in a Family With a Non-Functional Vitamin D Receptor: A Case Report

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has severely impacted daily life all over the world. Any measures to slow down the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to decrease disease severity are highly requested. Recent studies have reported inverse correlations between plasma levels of vitamin D and susceptibility to SARS-CoV-2 infection and COVID-19 severity. Therefore, it has been proposed to supplement the general population with vitamin D to reduce the impact of COVID-19. However, by studying the course of COVID-19 and the immune response against SARS-CoV-2 in a family with a mutated, non-functional vitamin D receptor, we here demonstrate that vitamin D signaling was dispensable for mounting an efficient adaptive immune response against SARS-CoV-2 in this family. Although these observations might not directly be transferred to the general population, they question a central role of vitamin D in the generation of adaptive immunity against SARS-CoV-2.

Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a non-functional vitamin D receptor: A case report

“…Importantly, it was found that vitamin D is required for IFNg-mediated enhancement of cathelicidin. This is in agreement with studies showing that vitamin D deficiency is associated with impaired expression of cathelicidin and increased susceptibility to some infectious diseases, including TB (8)(9)(10)(11)(12)(13)(14)(15). This could also be an important mechanism explaining the beneficial role of vitamin D in TB prevention and treatment (16,17).…”

Vitamin D and SARS‐CoV‐2

“…33,44 In contrast, other CD4 + T cell subsets such as T H 2 and T H 17 do not seem to play a protective role for SARS-CoV-2 infections. 33,44 These findings are consistent with a classical function of T H 1 cells in antiviral immune responses, as T H 1 cells generally have direct antiviral functions, recruit monocytes to infected tissues and/or help activation and expansion of antiviral CD8 + T cells. Indeed, SARS-CoV-2-specific CD8 + T cells are also detected in the majority of COVID-19 convalescent individuals.…”

“…To resolve the controversy outlined above, we and others have investigated the impact of VDR signalling on the immune response against SARS-CoV-2. 44,90 We have recently identified and described a female patient suffering from hereditary vitamin D resistant rickets (HVDRR) (OMIM: 277440). HVDRR is an autosomal recessive disorder where mutations in the VDR render the receptor dysfunctional.…”

Low Serum Vitamin D in COVID-19 Patients Is Not Related to Inflammatory Markers and Patients’ Outcomes—A Single-Center Experience and a Brief Review of the Literature

“…Interestingly, a recent paper by Kongsbak-Wismann et al showed a normal T cell and B cell response during a SARS-CoV-2 infection in one homozygous and two heterozygous patients for mutations in VDR. These mutations totally abolish transcriptional activity after the vitamin D binds the receptor [ 37 ]. In the above-mentioned patients, the specific T cell response characterized by IFN gamma, IL-2, and TNF secretion as well as B cell response characterized by anti-RBD IgG antibodies were preserved [ 37 ].…”

“…These mutations totally abolish transcriptional activity after the vitamin D binds the receptor [ 37 ]. In the above-mentioned patients, the specific T cell response characterized by IFN gamma, IL-2, and TNF secretion as well as B cell response characterized by anti-RBD IgG antibodies were preserved [ 37 ]. This demonstrates that an efficient immune response during SARS-CoV-2 infection does not require vitamin D signaling; however, vitamin D may influence the course of the disease by modulating other antiviral mechanisms, such as antibacterial peptides [ 14 ].…”