doi: 10.1016/j.nfs.2020.06.001.
Epub 2020 Jun 7.
Vitamin D deficiency and co-morbidities in COVID-19 patients - A fatal relationship?
Affiliations
- PMID: 40476932
- PMCID: PMC7276229
- DOI: 10.1016/j.nfs.2020.06.001
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Vitamin D deficiency and co-morbidities in COVID-19 patients - A fatal relationship?
NFS J.
2020 Aug.
No abstract available
Conflict of interest statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Figures
In the classical RAS pathway Renin, expressed from the renin gene induces cleavage of Angiotensinogen to Angiotensin I which is converted to Angiotensin II via Angiotensin converting enzyme (ACE). Ang II activates the Angiotensin 1 receptor which results in an increase of blood pressure and further effects on the vascular system. In addition, Ang II suppresses renin synthesis via AT1R. To keep the system in balance a counter regulatory pathway exists. This pathway is activated through cleavage of Ang I to Ang1–9 via ACE2 or AT2R activation or Ang II to Ang1–7 which counter regulates via Mas receptor. This helps the system to stay within a homoeostatic balance, as long as the RAS activity is controlled.
If the system is dysbalanced this may result in a rising formation of Ang II and a higher renin synthesis which at least increases inflammatory responses. This is important in cases of a poor vitamin D status because vitamin D (1,25(OH)2D) can counteract the disbalance via negative expression of the renin gen which results in lower renin synthesis independent from Ang II. An increase of aldosterone will block the activities of the ACE2 and as a consequence attenuate the counter regulatory balance. If the counter regulatory circle is disrupted via ACE2 dysfunction due to SARS-CoV2 infection an uncontrolled classical pathway will run out of control and increase proinflammatory reactions and blood pressure and contribute to a couple of problems (e.g. cardiovascular, ARDS, Kawasaki disease). Ang II activates NFκB through AT1 receptors [194]. This and further interactions of the RAS with inflammatory stimuli results in an increasing and less controlled inflammatory reaction. Beside its effect on renin expression vitamin D can effectively inhibit NFκB activation [195]. This is especially efficient when the VDR is upregulated, which also plays an important role in other processes in the immune system through vitamin D activity.
Ang II leads to a series of pro-inflammatory stimuli in the immune system via the activation of AT1R. These include an increase in the expression of MCP-1 as well as the chemokine receptor CCR2, which lead to a massive infiltration of the endothelium with macrophages. The same applies to the activation, migration and maturation of dendritic cells (DC) and the antigen (Ag) presentation. The negative effect on T lymphocytes as well as on T regulatory cells further promotes a pro-inflammatory state. A number of other proinflammatory processes are triggered by AT1R and favor the development of inflammation, hypertension and diabetes. Vitamin D is considered to counteract this reaction by contributing to a normalization of immune function through a variety of processes. However, it should not be overlooked that most processes in the immune system initiated by vitamin D occur together with vitamin A [196].
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