. 2023 Apr;93(5):1383-1390.

doi: 10.1038/s41390-022-02275-6. Epub 2022 Sep 9.

Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19

Nancy M S Zeidan¹, Hanan M Abd El Lateef², Dalia M Selim², Suzan A Razek², Ghada A B Abd-Elrehim³, Mohamed Nashat⁴, Noha ElGyar⁵, Nevin M Waked⁶, Attia A Soliman⁷, Ahmed A Elhewala⁷, Mohamed M M Shehab⁷, Ahmed A A Ibraheem⁷, Hassan Shehata⁷, Yousif M Yousif⁷, Nagwa E Akeel⁷, Mustafa I A Hashem⁷, Amani A Ahmed⁷, Ahmed A Emam⁸, Mohamed M Abdelmohsen⁹, Mohamed F Ahmed⁹, Ahmed S E Saleh¹⁰, Heba H Eltrawy¹¹, Gehan H Shahin¹², Rehab M Nabil¹³, Thoraya A Hosny¹³, Mohamed R Abdelhamed¹⁴, Mona R Afify¹⁵, Mohanned T Alharbi¹⁵, Mohammed K Nagshabandi¹⁵, Muyassar K Tarabulsi¹⁵, Sherif F Osman¹⁶, Amal S M Abd-Elrazek¹⁷, Manal M Rashad¹⁸, Sonya A A El-Gaaly¹⁹, Said A B Gad²⁰, Mohamed Y Mohamed²¹, Khalil Abdelkhalek¹, Aly A Yousef²²

Affiliations

¹ Department of Pediatrics, Faculty of Medicine, Cairo University, Giza, Egypt.
² Department of Pediatrics, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
³ Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt.
⁴ Department of Pediatrics, Faculty of Medicine, Aswan University, Aswan, Egypt.
⁵ Department of Pediatrics, Faculty of Medicine, Assuit University, Assuit, Egypt.
⁶ Department of Pediatrics, Faculty of Medicine, October 6 University, 6th of October City, Egypt.
⁷ Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
⁸ Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt. ahmedemam1111@yahoo.com.
⁹ Department of Pediatrics, Faculty of Medicine for Boys, Al-Azhar University, Cairo, Egypt.
¹⁰ Department of Otorhinolaryngology, Faculty of Medicine, Benha University, Benha, Egypt.
¹¹ Department of Chest Diseases, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.
¹² Department of Clinical Pathology, Faculty of Medicine, Cairo University, Giza, Egypt.
¹³ Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
¹⁴ Department of Clinical Pathology, Al-Azhar Faculty of Medicine, Cairo, Egypt.
¹⁵ Department of Medical Microbiology and Parasitology, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia.
¹⁶ Department of Radiology, Texas Tech University Health Sciences Center, El Paso, TX, USA.
¹⁷ Department of Radio-Diagnosis, Menoufia University, Shibin Al Kawm, Egypt.
¹⁸ Department of Anesthesia, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
¹⁹ Department of Internal Medicine, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
²⁰ Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
²¹ Department of Psychiatry, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
²² Department of Pediatrics, Faculty of Medicine, Helwan University, Helwan, Egypt.

PMID: 36085364
PMCID: PMC9461391
DOI: 10.1038/s41390-022-02275-6

Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19

Nancy M S Zeidan et al. Pediatr Res. 2023 Apr.

. 2023 Apr;93(5):1383-1390.

doi: 10.1038/s41390-022-02275-6. Epub 2022 Sep 9.

Authors

Affiliations

¹ Department of Pediatrics, Faculty of Medicine, Cairo University, Giza, Egypt.
² Department of Pediatrics, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
³ Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt.
⁴ Department of Pediatrics, Faculty of Medicine, Aswan University, Aswan, Egypt.
⁵ Department of Pediatrics, Faculty of Medicine, Assuit University, Assuit, Egypt.
⁶ Department of Pediatrics, Faculty of Medicine, October 6 University, 6th of October City, Egypt.
⁷ Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
⁸ Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt. ahmedemam1111@yahoo.com.
⁹ Department of Pediatrics, Faculty of Medicine for Boys, Al-Azhar University, Cairo, Egypt.
¹⁰ Department of Otorhinolaryngology, Faculty of Medicine, Benha University, Benha, Egypt.
¹¹ Department of Chest Diseases, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.
¹² Department of Clinical Pathology, Faculty of Medicine, Cairo University, Giza, Egypt.
¹³ Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
¹⁴ Department of Clinical Pathology, Al-Azhar Faculty of Medicine, Cairo, Egypt.
¹⁵ Department of Medical Microbiology and Parasitology, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia.
¹⁶ Department of Radiology, Texas Tech University Health Sciences Center, El Paso, TX, USA.
¹⁷ Department of Radio-Diagnosis, Menoufia University, Shibin Al Kawm, Egypt.
¹⁸ Department of Anesthesia, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
¹⁹ Department of Internal Medicine, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
²⁰ Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
²¹ Department of Psychiatry, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
²² Department of Pediatrics, Faculty of Medicine, Helwan University, Helwan, Egypt.

PMID: 36085364
PMCID: PMC9461391
DOI: 10.1038/s41390-022-02275-6

Abstract

Background: Given the sparse data on vitamin D status in pediatric COVID-19, we investigated whether vitamin D deficiency could be a risk factor for susceptibility to COVID-19 in Egyptian children and adolescents. We also investigated whether vitamin D receptor (VDR) FokI polymorphism could be a genetic marker for COVID-19 susceptibility.

Methods: One hundred and eighty patients diagnosed to have COVID-19 and 200 matched control children and adolescents were recruited. Patients were laboratory confirmed as SARS-CoV-2 positive by real-time RT-PCR. All participants were genotyped for VDR Fok1 polymorphism by RT-PCR. Vitamin D status was defined as sufficient for serum 25(OH) D at least 30 ng/mL, insufficient at 21-29 ng/mL, deficient at <20 ng/mL.

Results: Ninety-four patients (52%) had low vitamin D levels with 74 (41%) being deficient and 20 (11%) had vitamin D insufficiency. Vitamin D deficiency was associated with 2.6-fold increased risk for COVID-19 (OR = 2.6; [95% CI 1.96-4.9]; P = 0.002. The FokI FF genotype was significantly more represented in patients compared to control group (OR = 4.05; [95% CI: 1.95-8.55]; P < 0.001).

Conclusions: Vitamin D deficiency and VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents.

Impact: Vitamin D deficiency could be a modifiable risk factor for COVID-19 in children and adolescents because of its immune-modulatory action. To our knowledge, ours is the first such study to investigate the VDR Fok I polymorphism in Caucasian children and adolescents with COVID-19. Vitamin D deficiency and the VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. Clinical trials should be urgently conducted to test for causality and to evaluate the efficacy of vitamin D supplementation for prophylaxis and treatment of COVID-19 taking into account the VDR polymorphisms.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1**
Vitamin D status among the studied subjects (P < 0.001).

**Fig. 2**
Mean serum 25(OH) D among the studied patients’ VDR Fok I genotypes.

See this image and copyright information in PMC

Comment in

Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19: correspondence.
Mungmunpuntipantip R, Wiwanitkit V. Mungmunpuntipantip R, et al. Pediatr Res. 2023 Apr;93(5):1110. doi: 10.1038/s41390-022-02348-6. Epub 2022 Oct 19. Pediatr Res. 2023. PMID: 36261502 Free PMC article. No abstract available.

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References

1. World Health Organization. WHO coronavirus (COVID-19) dashboard. https://covid19.who.int (2022).
1. Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. - PMC - PubMed
1. Hoffmann M, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271.e8–280.e8. - PMC - PubMed
1. Guan WJ, et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020;382:1708–1720. - PMC - PubMed
1. Wang D, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069. - PMC - PubMed

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Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19

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Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19

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