Study: Vitamin D influences the immune status of COVID-19-patients

reference

Karonova TL, Golovatyuk Ka, Kudryavtsev IV, et al. Effect of the Cholecalciferol Supplementation on the clinical features and inflammatory markers in hospitalized covid 19 patients: a randomized, open, monocentric study.Nutrients. 2022; 14 (13): 2602.

Study goal

To evaluate the effect of vitamin D₃Dietary supplementation influences clinical features and inflammatory markers in Covid-19 patients

Key to take away

Supplement with 10,000 IE/day vitamin D₃In patients with vitamin D deficiency or deficiency, the number of C-reactive protein (CRP) and the white blood cells improved compared to the control persons.

design

Randomized, single-center, open study

Participant

The study comprised 129 hospitalized patients in St. Petersburg, Russia, aged 18 to 75 (49 % female, 51 % male), in which Covid-19 was diagnosed by polymerase chain reaction (PCR) and/or breast computed tomography (CT).

The study excluded patients who were 1,000 IE vitamin D or more income, those in whom the intake of vitamin D was contraindicated, and patients with an estimated glomerular filtration rate (EGFR) <40 ml/min/1.73 m²Gastrointestinal and liver diseases, granulomatous diseases, cancer (less than 5 years), immune deficiency as well as drug or alcohol addiction.

intervention

Vitamin D₃10,000 IE/day for 9 days or no nutritional supplement

Evaluated study parameters

The investigators assessed the following parameters:

• Veränderungen der 25(OH)D-Spiegel im Serum
• Komplettes Blutbild (CBC)
• C-reaktives Protein (CRP)
• B-Zell-Untergruppen auf der 9^Th Tag des Krankenhausaufenthaltes im Vergleich zum 1^st Tag
• Schwere der Erkrankung
• Sauerstoffergänzung
• Aufnahmequote auf der Intensivstation
• Klinische Ergebnisse
• Dauer des Krankenhausaufenthaltes

Primary results

The researchers evaluated the following measurements:

• Veränderungen der 25(OH)D-Spiegel im Serum
• CBC
• CRP
• B-Zell-Untergruppen auf der 9^Th Tag des Krankenhausaufenthaltes im Vergleich zum 1^st Tag

Most important knowledge

Changes in serum 25(OH)D levels

On the 9th day, significantly fewer patients in the intervention group had a vitamin D deficiency (P<0.01).

After 9 days of supplement with vitamin D₃increased the mean 25(OH)D level from 16.4 ng/ml to 22.8 ng/ml (P<0.001). In contrast, the control group experienced an average decrease in their 25(OH)D levels of 2.6 ng/ml (13.9 ng/ml to 10.6 ng/ml), or -18.2%, over the same period.

In addition, after supplementing the middle serum-25 (OH) D level in the treatment group compared to the control group was significantly higher: 22.8 ng/ml vs. 10.6 ng/ml (P<0.001)

CBC

After 9 days of vitamin D supplementation, neutrophil and lymphocyte counts were significantly higher compared to controls.

The mean neutrophilic number in the intervention group was 8.6 x 10⁹/L compared to 6.4 x 10⁹/L in the control group (P= 0.04).

The mean lymphocyte count in the intervention group was 1.8 x 10⁹/L compared to 1.58 x 10⁹/L in the control group (P=0.02).

However, the mean neutrophil-to-lymphocyte ratio (NLR) was not significantly different between the two groups: 4.5 in the treatment group vs. 4.4 in the control group (P=0.71).

CRP

After 9 days of vitamin D supplementation, CRP was significantly lower compared to controls (P= 0.02). In addition, CRP was negatively associated with the CRP values ​​(R = –0.28,P= 0.02).

The middle CRP in the intervention group was 2 mg/l compared to 3 ng/ml in the control group (P=0.02).

B cell subsets

On the 9th^ThDay of hospitalization compared to the 1st^stDay:

• Die Häufigkeit von CD38++CD27-Übergangszellen war in der Behandlungsgruppe im Vergleich zur Kontrollgruppe signifikant geringer (1,43 % bzw. 2,74 %; P=0,006).
• Die Häufigkeit reifer naiver CD27-CD38+-B-Zellen war in der Behandlungsgruppe im Vergleich zur Kontrollgruppe signifikant niedriger (57,57 % bzw. 67,03 %; P=0,02)
• CD27-CD38-doppelnegative (DN) B-Zellen waren in der Behandlungsgruppe im Vergleich zur Kontrollgruppe signifikant höher (6,21 % vs. 4,19 %); P=0,02)

Sleeping day

In the intervention group there was a negative connection between Serum 25 (OH) D on 9^ThDay and the number of bed days (r = −0.23,P= 0.006); However, there were no significant differences between the groups with regard to the number of bed days or the percentage of the dismissed patients (P=0.87 andP= 0.93).

transparency

The other authors did not explain any conflict of interest; Bio-Tech Pharmacal, Inc (Fayetteville, AR), however, finances the Sunlight, Nutrition and Health Research Center, which employs co-author William A. Grant.

Effects and restrictions for practice

The coronavirus (SARS-CoV)-related severe acute respiratory syndrome (SARS) pandemic (Covid-19), discovered in 2019, initiated a global search for risk factors and ways to prevent and treat the infection and its consequences.

Studies have consistently shown a reverse connection between low vitamin D serum mirrors and the severity of Covid-19 and the mortality risk.¹They have also shown an inverse association with Covid-19 positivity rates. In a large, retrospective, observational analysis of 191,779 patients whose samples were processed by Quest Diagnostics, each 1 ng/mL increase in serum 25(OH)D was associated with an unadjusted odds ratio of 0.97 (95% CI: 0.977-0.980). for a positive SARS-CoV-2 PCR test result. The decrease in positivity rate associated with serum 25(OH)D reached a plateau at 55 ng/mL.²

While the current study showed improvement in laboratory markers, the lack of significant improvement in clinical outcomes may be due to (1) too low a dose being administered or (2) the incorrect form of vitamin D being used.

The current study achieved a mean serum 25(OH)D level of 22.8 ng/mL in the intervention group; However, this value may be too low to provide clinical benefit.

In addition, taking vitamin D3 was associated with a 2.14-fold lower risk of death than taking without vitamin D3.

An earlier, prospective study resulted in vitamin D₃to 95 hospitalized Covid patients for up to 14 days.³All patients in the treatment group had to increase Serum-25 (0H) D levels of 30 ng/ml at the beginning of the course. The entire vitamin D₃The amounts received during the treatment period varied between 224,000 IU and 320,000 IU.

Compared to patients with a serum-25 (oh) d> 30 ng/ml, a serum-25 (oh) d <30 ng/ml was associated with a 1.9 times higher risk of staying in the hospital for more than 8 days (P= 0.02). Additionally preserved vitamin D₃was associated with a 2.14 times lower risk of death than not receiving vitamin D₃(P= 0.03, 95 %KI: 1.0585 to 4.3327).

The form of vitamin D can also be an important consideration. In acute hospital settings, research may eventually confirm that administration of calcifediol (vitamin D₂) instead of cholecalciferol (vitamin D).₃) is superior. Vitamin D₂increases serum 25(OH)D faster than vitamin D₃. In a pharmacokinetic study in 35 healthy women aged 50 to 70 years, serum 25(OH)D was 28% higher after 1 year^stDose of vitamin D₂compared to vitamin D₃and 123 % higher after 15 weeks.⁴

Vitamin D₂was examined in a retrospective, multicenter cohort study of covid patients. Oral vitamin D₂(532 mcg) was administered at hospital admission, then 266 mcg on days 3 and 7, then 266 mcg weekly until discharge or ICU admission. A total of 73 patients (mean age 69 years, 53% male) received vitamin D₂. After 30 days, the risk of death was significantly lower for those who took vitamin D₂(OR 0.22 (95% CI, 0.08-0.61),P<0.01) compared to patients who did not receive vitamin D₂.⁵Unfortunately, the vitamin concentrations in the serum were neither available at the beginning of the study nor at any other time of this study. Based on previous studies, however, the authors speculate that the dose they have given was sufficient to raise the Serum-25 (OH) D level from 3 to over 30 to 40 ng/ml^approxTreatment day.

Positive clinical results have been achieved by supplementing Covid-19 patients with vitamin D (as D₂or d₃). While it seems that a serum concentration over 30 ng/ml could be the threshold for the achievement of clinical results, the optimal form, the dosage scheme and the desired serum concentration for the best results are still unknown.