Investigating the Potential Impact of CCR5-Δ32 Variant on COVID-19 Outcome: A Case-Control Study in Iranian Population
-
Parisa Mashayekhi
,
Mir Davood Omrani
,
Asma Olhosna Amini
,
Mohammad Amin Omrani
,
Shahla Ganbari Milani
Abstract
Background: The impact of CCR5-Δ32 on COVID-19 outcomes has been the focus of much research. This genetic variant may protect against SARS-CoV-2 infection, while others have produced conflicting results. Given the controversial results of previous research on different populations, we aimed to investigate the possible association between the CCR5-Δ32 variant and COVID-19 severity in an Iranian population.
Methods: This case-control study was conducted between 25th of April till 10th of October 2021 at Rasoul Akram Hospital of Iran University of Medical Sciences, Tehran, Iran. We investigated the association between CCR5-Δ32 genotype and COVID-19 severity in 200 unrelated Iranian patients. The patients were divided into 2 groups: 100 patients with severe COVID-19 (case group) and 100 patients with mild COVID-19 (control group). Genotyping of CCR5-Δ32 was performed using the polymerase chain reaction (PCR) technique.
Results: The frequency of CCR5-Δ32 allele was 11 in the case group and 16 in the control group. However, no significant association was found between this genetic variant and the clinical outcomes of COVID-19.
Conclusion: The CCR5-Δ32 variant cannot serve as a reliable predictive factor for identifying individuals prone to developing severe COVID-19 in Iranian population. Additionally, targeting CCR5 would not be a viable treatment approach for COVID-19 in Iranians.
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21. Jasinska AJ, Pandrea I, Apetrei C (2022). CCR5 as a coreceptor for human immunodeficiency virus and simian immunodeficiency viruses: A prototypic love-hate affair. Front Immunol, 13:835994.
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24. Hubacek JA, Dusek L, Majek O, et al (2021). CCR5Δ32 deletion as a protective factor in Czech first-wave COVID-19 subjects. Physiol Res, 70 (1):111-115.
25. Čizmarević NS, Tota M, Ristić S (2020). Does the CCR5-Δ32 mutation explain the variable coronavirus-2019 pandemic statistics in Europe? Croat Med J, 61 (6):525-526.
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27. Brodin P (2021). Immune determinants of COVID-19 disease presentation and severity. Nat Med, 27 (1):28-33.
28. Bajaj V, Gadi N, Spihlman AP, et al (2021). Aging, immunity, and COVID-19: how age influences the host immune response to coronavirus infections? Front Physiol, 11:571416.
29. Statsenko Y, Al Zahmi F, Habuza T, et al (2022). Impact of age and sex on COVID-19 severity assessed from radiologic and clinical findings. Front Cell Infect Microbiol, 11: 777070.
30. Karimi Z, Masjedi F, Doostkam A, Roozbeh J, Malekmakan L (2022). Investigating the Association between Gender and Age Distribution with Severity of COVID-19: A Single-Center Study from Southern Iran. Women’s Health Bulletin, 9 (4):207-215.
31. Barek MA, Aziz MA, Islam MS (2020). Impact of age, sex, comorbidities and clinical symptoms on the severity of COVID-19 cases: A meta-analysis with 55 studies and 10014 cases. Heliyon, 6 (12): e05684.
2. Fatmawati F, Mulyanti S (2023). Risk Factors Associated with the Severity of COVID-19. Malays J Med Sci, 30 (3):84-92.
3. Ahmad FB, Cisewski JA, Miniño A, Anderson RN (2021). Provisional mortality data—united states, 2020. MMWR Morb Mortal Wkly Rep, 70(14):519-522.
4. Proportions V (2022). COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#datatracker-home
5. Velavan TP, Pallerla SR, Rüter J, Augustin Y, Kremsner PG, Krishna S, Meyer CG (2021). Host genetic factors determining COVID-19 susceptibility and severity. EBioMedicine, 72: 103629.
6. Karlsen TH (2022). Understanding COVID-19 through genome-wide association studies. Nat Genet, 54 (4):368-369.
7. Glessner JT, Chang X, Mentch F, Qu H, Abrams DJ, Thomas A, Sleiman P, Hakonarson H (2022). COVID-19 in pediatrics: Genetic susceptibility. Front Genet, 13:928466.
8. Ellinghaus D (2020). Genomewide association study of severe Covid‐19 with respiratory failure. N Engl J Med, 383(16):1522-1534.
9. Chien H-C, Chan P-C, Tu C-C, Day Y-J, et al (2018). Importance of PLC-dependent PI3K/AKT and AMPK signaling in RANTES/CCR5 mediated macrophage chemotaxis. Chin J Physiol, 61 (5):266-279.
10. Zhao Y, Qin L, Zhang P, Li K, et al (2020). Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease. JCI Insight, 5 (13): e139834.
11. Ellwanger JH, Kulmann-Leal B, de Lima Kaminski V, et al (2020). Beyond HIV infection: neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases. Virus Res, 286:198040.
12. Ellwanger JH, Kaminski VdL, Rodrigues AG, et al (2020). CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box. Int J Immunogenet, 47 (3):261-285.
13. Ruiz-Mateos E, Tarancon-Diez L, Alvarez-Rios AI, et al (2018). Association of heterozygous CCR5Δ32 deletion with survival in HIV-infection: A cohort study. Antiviral Res, 150:15-19.
14. Falcon A, Cuevas MT, Rodriguez-Frandsen A, et al (2015). CCR5 deficiency predisposes to fatal outcome in influenza virus infection. J Gen Virol, 96 (8):2074-2078.
15. Glass WG, McDermott DH, Lim JK, et al (2006). CCR5 deficiency increases risk of symptomatic West Nile virus infection. J Exp Med, 203 (1):35-40.
16. Panda AK, Padhi A, Prusty BAK (2020). CCR5 Δ32 minorallele is associated with susceptibility to SARS-CoV-2 infection and death: An epidemiological investigation. Clin Chim Acta, 510:60-61.
17. Patterson BK, Seethamraju H, Dhody K, et al (2021). CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14. Int J Infect Dis, 103:25-32.
18. Sandford AJ, Zhu S, Bai TR, et al (2001). The role of the CC chemokine receptor-5 Δ32 polymorphism in asthma and in the production of regulated on activation, normal T cells expressed and secreted. J Allergy Clin Immunol, 108 (1):69-73.
19. Ishak A, Mehendale M, AlRawashdeh MM, et al (2022). The association of COVID-19 severity and susceptibility and genetic risk factors: A systematic review of the literature. Gene, 836:146674.
20. Klein RS (2008) A moving target: the multiple roles of CCR5 in infectious diseases. J Infect Dis, 197(2):183-6.
21. Jasinska AJ, Pandrea I, Apetrei C (2022). CCR5 as a coreceptor for human immunodeficiency virus and simian immunodeficiency viruses: A prototypic love-hate affair. Front Immunol, 13:835994.
22. Čizmarević NS, Kapović M, Rončević D, Ristić S (2021). Could the CCR5-Δ32 mutation be protective in SARS-CoV-2 infection? Physiol Res, 70 (S 2):S249-S252.
23. Gómez J, Cuesta-Llavona E, Albaiceta GM, et al (2020). The CCR5-delta32 variant might explain part of the association between COVID-19 and the chemokine-receptor gene cluster. medRxiv, doi: 10.1101/2020.11.02.20224659.
24. Hubacek JA, Dusek L, Majek O, et al (2021). CCR5Δ32 deletion as a protective factor in Czech first-wave COVID-19 subjects. Physiol Res, 70 (1):111-115.
25. Čizmarević NS, Tota M, Ristić S (2020). Does the CCR5-Δ32 mutation explain the variable coronavirus-2019 pandemic statistics in Europe? Croat Med J, 61 (6):525-526.
26. Bernas SN, Baldauf H, Wendler S, et al (2021). CCR5Δ32 mutations do not determine COVID-19 disease course. Int J Infect Dis, 105:653-655.
27. Brodin P (2021). Immune determinants of COVID-19 disease presentation and severity. Nat Med, 27 (1):28-33.
28. Bajaj V, Gadi N, Spihlman AP, et al (2021). Aging, immunity, and COVID-19: how age influences the host immune response to coronavirus infections? Front Physiol, 11:571416.
29. Statsenko Y, Al Zahmi F, Habuza T, et al (2022). Impact of age and sex on COVID-19 severity assessed from radiologic and clinical findings. Front Cell Infect Microbiol, 11: 777070.
30. Karimi Z, Masjedi F, Doostkam A, Roozbeh J, Malekmakan L (2022). Investigating the Association between Gender and Age Distribution with Severity of COVID-19: A Single-Center Study from Southern Iran. Women’s Health Bulletin, 9 (4):207-215.
31. Barek MA, Aziz MA, Islam MS (2020). Impact of age, sex, comorbidities and clinical symptoms on the severity of COVID-19 cases: A meta-analysis with 55 studies and 10014 cases. Heliyon, 6 (12): e05684.
| Files | ||
| Issue | Vol 53 No 8 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v53i8.16292 | |
| Keywords | ||
| Severe COVID-19 Iranian population Virus | ||
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How to Cite
1.
Mashayekhi P, Omrani MD, Amini AO, Omrani MA, Ganbari Milani S. Investigating the Potential Impact of CCR5-Δ32 Variant on COVID-19 Outcome: A Case-Control Study in Iranian Population. Iran J Public Health. 2024;53(8):1864-1870.
