Vitamin D can reduce severity in COVID-19 through regulation of PD-L1.

COVID-19 is a highly contagious viral infection that has killed millions of people around the world. The most important diagnostic feature of COVID-19 is lymphocyte depletion, particularly the depletion of T cells. In COVID-19 infections, there is a link between destruction of T cells and increased expression of inhibitory immune checkpoint molecules (PD-1/PD-L1) on T cell surfaces. It was shown that PD-1/PD-L1 levels increase in severely COVID-19 infected individuals. Higher proinflammatory cytokine levels cause increased PD-1/PD-L1 expression. In severe COVID-19, higher proinflammatory cytokine levels may increase PD-1/PD-L1. Vitamin-D is an important immune regulator. It is known that the numbers of CD4+ and CD8+ T lymphocytes decrease in vitamin D deficiency while vitamin D supplementation increases CD + 4 lymphocytes. Vitamin D can increase regulatory T cell (Treg) activity. Vitamin D also has a diminishing effect on proinflammatory cytokines. In severe COVID-19 cases, vitamin D supplementation may inhibit the increase of PD-L1 expression through reducing proinflammatory cytokine levels. Thus, vitamin D supplementation could eliminate the suppressive effect of PD-L1 on CD4+ and CD8+ T cells, preventing lymphopenia and reducing disease severity and mortality in patients infected with COVID-19. Besides, vitamin D supplementation can reduce inflammation by increasing Treg activity. The aim of this letter is to discuss the functions of inhibitory immune checkpoint molecules and their effects on dysfunction and depletion of T-cells as well as to explain the possible modulatory effect of vitamin D on these checkpoints and T cells.

Vitamin D may prevent COVID-19 induced pregnancy complication.

SARS-CoV-2 enters target cells via the ACE2 receptor and downregulates it. ACE2 exhibits high catalytic activity to produce Angiotensin 1-7 (Ang-1-7), which has a vasodilator effect and also inactivates the vasoconstrictor Angiotensin II. In normal pregnancy ACE2 expression is raising in the uterus and placenta. Ang-1-7 levels in plasma are significantly higher in third-trimester pregnant women when compared to non-pregnant women. This may be contributing to systemic vasodilation and reduced blood pressure and modulating hemodynamics during pregnancy. Interestingly, Ang-1-7 plasma levels are lower in pregnancies complicated by pre-eclampsia than normal pregnancies. COVID-19 infection increased the inflammatory cytokines and reduced ACE2 level. This may lead to pre-eclampsia or hypertensive pregnancies, then increasing the perinatal and maternal mortality and morbidity. Vitamin D increased ACE2 expression and Ang-1-7 plasma levels and also decreased Ang II level in plasma. Moreover, Vitamin D reduced the inflammatory cytokine storm. So, Vitamin D supplementation can prevent the risk of preeclampsia or hypertension in pregnant women with COVID-19.

Vitamin D deficiency is associated with COVID-19 positivity and severity of the disease.

The present study examined the relationship between polymerase chain reaction (PCR) test positivity and clinical outcomes of vitamin D levels measured within the 6 months before the PCR test in coronavirus disease 2019 (COVID-19)-positive patients. In this retrospective cohort study, COVID-19 (227) and non-COVID-19 patients (260) were divided into four groups according to their vitamin D levels: Group I (0-10 ng/ml), Group II (10-20 ng/ml), Group III (20-30 ng/ml), and Group IV (vitamin D > 30 ng/ml). Laboratory test results and the radiological findings were evaluated. In addition, for comparative purposes, medical records of 1200 patients who had a hospital visit in the November 1, 2019-November 1, 2020 period for complaints due to reasons not related to COVID-19 were investigated for the availability of vitamin D measurements. This search yielded 260 patients with tested vitamin D levels. Vitamin D levels were below 30 ng/ml in 94.27% of 227 COVID-19-positive patients (average age, 46.32 ± 1.24 years [range, 20-80 years] and 56.54% women) while 93.07% of 260 non-COVID-19 patients (average age, 44.63 ± 1.30 years [range, 18-75 years] and 59.50% women) had vitamin D levels below 30 ng/ml. Nevertheless, very severe vitamin D deficiency (<10 ng/ml) was considerably more common in COVID-19 patients (44%) (average age, 44.15 ± 1.89 years [range, 23-80 years] and 57.57% women) than in non-COVID-19 ones (31%) (average age, 46.50 ± 2.21 years [range, 20-75 years] and 62.5% women). Among COVID-19-positive patients, the group with vitamin D levels of >30 ng/ml had significantly lower D-dimer and C-reactive protein (CRP) levels, number levels, number of affected lung segments and shorter hospital stays. No difference was found among the groups in terms of age and gender distribution. Elevated vitamin D levels could decrease COVID-19 PCR positivity, D-dime and CRP levels and the number of affected lung segments in COVID-19-positive patients, thereby shortening the duration of hospital stays and alleviating the intensity of COVID-19.

Vitamin D can prevent COVID-19 infection-induced multiple organ damage.

Vitamin D is an immunomodulator hormone with an anti-inflammatory and antimicrobial effect with a high safety profile. A lot of COVID-19 infected patients develop acute respiratory distress syndrome (ARDS), which may lead to multiple organ damage. These symptoms are associated with a cytokine storm syndrome. The aim of this letter is to note the 5 crucial points that vitamin D could have protective and therapeutic effects against COVID-19. For that reason, COVID-19 infection-induced multiple organ damage might be prevented by vitamin D.