Vitamin D deficiency is frequently reported in patients with SARS-CoV-2 infection. The aim of this study was to correlate serum 25OH-vitamin D concentrations with clinical parameters of pulmonary involvement in elderly patients hospitalized with COVID-19.
Sixty-five consecutive patients with COVID-19 (mean age 76 ± 13 years) were analyzed retrospectively and compared with sixty-five control subjects paired by sex and age (CNT).
The following clinical parameters were collected: type of pulmonary involvement, respiratory parameters (PaOtwo, ONLYtwo, Pacetwo, Breadtwo/ Wiretwo), Laboratory parameters (including 25OH-vitamin D, D-dimer, C-reactive protein), as well as the duration of hospitalization and the duration of symptoms of COVID-19.
The results revealed that significantly lower serum vitamin D levels were found in patients with COVID-19 than in CNT (median 7.9 vs 16.3 ng / mL, p = 0.001) and a statistically significant positive correlation was observed between serum levels of vitamin D and PaOtwo(P = 0.03), SOtwo(P = 0.05), and PaOtwo/ Wiretwo(P = 0.02).
A statistically significant negative correlation was found between serum levels of vitamin D and D-dimer (p = 0.04), C-reactive protein (p = 0.04) and percentage of OtwoVenturi mask (p = 0.04).
A negative correlation was also observed between serum vitamin D levels and the severity of radiological lung involvement, assessed by computed tomography: in particular, vitamin D was found to be significantly lower in patients with COVID-19 with multiple pulmonary consolidations (p = 0.0001) or diffuse / severe interstitial lung involvement than in those with mild involvement (p = 0.05).
Finally, significantly lower serum vitamin D levels were found in elderly patients with COVID-19 who died during hospitalization, compared with those who survived (median 3.0 vs 8.4 ng / mL, p = 0.046).
The researchers concluded that this study confirms that 25OH-vitamin D deficiency in serum is associated with more severe pulmonary involvement, longer disease duration and risk of death in elderly patients with COVID-19.
The detection of low levels of vitamin D also in younger patients with COVID-19 with less comorbidities further suggests vitamin D deficiency as a crucial risk factor at any age.
The report states that the results are likely linked to the role played by the biologically active metabolite of vitamin D [1,25(OH)2-D] which, as a steroid hormone, is involved in the regulation of growth and the differentiation of various types of immune cells.
This study has some limitations, including the small number of patients analyzed and the great variability of the data: for this reason the correlation coefficients are relatively small. Therefore, randomized and robust clinical trials are needed, including a larger number of patients.
Research Fund
This is the latest in a deluge of studies that link vitamin D deficiency to COVID-19 severity. Researchers and healthcare professionals are calling on governments around the world to add vitamin D supplementation to their virus-fighting strategies.
Vitamin D has been associated with COVID-19 infection, in terms of greater risk of developing the disease, greater severity of the disease, greater frequency of admission to the intensive care unit and greater risk of death.
The results of the current study are quite similar to those of a recent study reporting serum vitamin D levels <50 nmol / L (<20 ng / mL) in 61% of hospitalized patients (mean age 76 years). They observed a significantly higher prevalence of vitamin D deficiency (<50 nmol / L) in patients requiring intensive treatment than in those without (81% of patients).
Likewise, another study reported 25OHD deficiency in 67% of patients with mild SARS-CoV-2 disease, but in 80% of patients who required mechanical ventilation.
A recent systematic review analyzed seven studies on the severity of COVID-19, intensive care treatment and mortality (1368 patients were included) and detected an average vitamin D level of 22.9 nmol / L (9.16 ng / mL) , higher, but similar to that of our cohort of patients (7.9 ng / mL). Patients with a good prognosis had significantly higher levels of vitamin D compared to those with a poor prognosis.
A low PaO2 / FiO2 ratio was detected as an independent risk factor for death in patients with COVID-19. Our study detected a statistically significant positive correlation between serum 25OHD levels and PaO2 / FiO2 values. This observation is in line with the results of another study that reported a high prevalence of hypovitaminosis D in patients with COVID-19 with a low PaO2 / FiO2 ratio.
How vitamin D interferes with the progression of COVID-19 is not fully understood, but this report aims to elucidate some pathways.
“1,25 (OH) 2-D plays an antiviral role, regulating the inflammatory response by modulating Toll-like receptor expression and NK cell function, and suppressing overexpression of pro-inflammatory cytokines. 1,25 (OH) 2-D also increases defense by inducing the release of antimicrobial peptides, such as catelicidin, which leads to viral destruction and clearance and facilitates the recruitment of monocytes, macrophages, neutrophils and dendritic cells.
“Therefore, 1.25 (OH) 2-D can regulate innate / adaptive responses and can interfere with the maturation of dendritic cells and their ability to present antigen to T cells, changing the profile of the T-cells of the pro-inflammatory Th1 and Th17 subsets for Th2 and Treg subsets, thus inhibiting pro-inflammatory processes.
“In addition to the immunomodulatory and antiviral effects, 1,25 (OH) 2-D modulates the renin-angiotensin system, which also plays a key role in the pathogenesis of COVID-19. ACE2 appears to be the main host cell receptor that mediates infection by SARS-CoV-2: the virus binds to ACE2 through its peak glycoprotein to enter the cell, thereby reducing the expression of ACE2.
“Vitamin D suppresses renin at the transcriptional level and, consequently, the expression of angiotensin and increases the expression of ACE2, possibly restoring the physiological concentration of down regulated ACE2 by the virus.
“In the lung, several types of alveolar cells express the ACE2 receptor. These cells play an important role in the production of surfactant, capable of regulating alveolar surface tension. SARS-CoV-2 can infect alveolar cells by binding ACE2 and suppressing the production of surfactant. Loss of alveolar cells results in lung damage and respiratory failure due to loss of pulmonary surfactant. These damages can be prevented with vitamin D.
“Interestingly … vitamin D deficiency is associated with an increased risk of thrombotic events. As is known, patients with COVID-19 often suffer from microthrombotic complications, which can contribute to worsening lung disease and death. The main findings Histological findings from autopsy report sequential alveolar damage, characterized mainly by focal capillary microthrombosis. “
Source: Nutrients
Cutolo. M., et al
“Vitamin D and pulmonary outcomes in elderly patients with COVID-19”
https://doi.org/10.3390/nu13030717