Genetika COVID-19: Zašto neki ljudi razviju teške simptome

Advanced age and comorbidities are known to be high risk factors for COVID-19. Does genetski make-up predispose some people making them more susceptible to severe symptoms? Conversely, does genetic make-up enable some people to have innate immunity making them immune against COVID-19 implying such people may not require vaccines. Identifying people with genetic susceptibility (by way of genome analysis) may provide for a more efficient personalised/precision medicine approach to combat this pandemic and other high burden diseases like cancer.  

Covid-19 is known to disproportionately affect elderly and people with comorbidities however there seems to be another pattern. Apparently, some people are genetski more prone and predisposed to develop severe life-threatening symptoms ¹ kao što je navedeno u prijavljenim slučajevima kao što su tri brata u sličnoj dobnoj skupini (koji su živjeli odvojeno i bili su normalnog zdravlja) koji su podlegli COVID-19 ². Ova mala skupina ljudi pati od hiperinflamacije, kliničkog pogoršanja i višeorganskog zatajenja uzrokovanog razvojem Citokinska oluja (CS) u kojem je interleukin-6 (IL-6) središnji posrednik. Dva uobičajena polimorfizma gena koja predisponiraju hiperupalu su obiteljska mediteranska groznica (FMF) i nedostatak glukoza-6-fosfat dehidrogenaze (G6PD) koji u kombinaciji s pretilošću dodatno povećava rizik ³.  

A systematic review links susceptibility to genetski variants in immune response genes. Forty genes were found to be associated with susceptibility and 21 of these genes had relation with development of severe symptom ⁴. Druga studija podržava gledište da ACE2 gen polimorfizam doprinosi osjetljivosti na COVID-19 ⁵. The virus responsible for COVID-19 uses the angiotensin-converting enzyme 2 (ACE2) receptor protein present on the cell surface to enter the cell. Any variation in the ACE2 gene would have strong bearing on predisposition to COVID.  The role of host-genetika in susceptibility to COVID-19 is investigated at the level of structural variants (SV) in a study reported in preprint recently by Sahajpal NS, et al. In this study, the researchers performed genome analysis on 37 severely ill COVID-19 patients. This patient-centric investigation identified 11 large structural variants involving 38 genes with a potential role in development of severe symptoms of COVID-19 ⁶. 

The fast-evolving knowledge base about role of host-genetika in Covid-19 disease progression may indicate appropriate shift of focus towards targeted approach to prevention and treatment of COVID-19. It may be possible to think of precisely targeted interventions to unique genetski-makeup of individuals ⁷. Međutim, personalizirani, precizni tretmani ili intervencije zahtijevali bi podatke analize genoma na individualnoj razini. Možda postoji problem privatnosti za rješavanje, međutim, dugoročno, to bi se moglo pokazati učinkovitijim i troškovno.  

Trenutno postoje neke komercijalne organizacije koje pružaju osobne usluge koje pokrivaju osnovne zdravstvene predispozicije za pojedince. Međutim, bili bi potrebni organiziraniji napori u javnom sektoru kako bi se izgradila baza znanja i infrastruktura kako bi personalizirana precizna medicina postala stvarnost. GEN-COVID Multicentrična studija ⁸ kojima je cilj izvući fenotipske i genotipske podatke na individualnoj razini putem biobanke i zdravstvenih zapisa kako bi podaci bili dostupni Covid-19 istraživača širom svijeta je korak naprijed u tom smjeru.  

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Reference:  

1. Kaiser J., 2020. Koliko će vas razboljeti koronavirus? Odgovor je možda u vašim genima. Znanost. Objavljeno 27. ožujka 2020. DOI: https://doi.org/10.1126/science.abb9192 

2. Yousefzadegan S. i Rezaei N., 2020. Izvještaj o slučaju: Smrt od COVID-19 u Three Brothers. American Journal of Tropical Medicine and Hygiene. Svezak 102: Broj 6 Stranica(e): 1203–1204. Objavljeno online: 10. travnja 2020. DOI: https://doi.org/10.4269/ajtmh.20-0240 

3. Woo Y., Kamarulzaman A., et al 2020. A genetski predisposition for Cytokine Storm in life-threatening COVID-19 infection. OSFPreprints. Created: April 12, 2020. DOI: https://doi.org/10.31219/osf.io/mxsvw    

4. Elhabyan A., Elyaacoub S., et al, 2020. The role of host genetika in susceptibility to severe viral infections in humans and insights into host genetics of severe COVID-19: A systematic review, Virus Research, Volume 289, 2020. Available online 9 September 2020. DOI: https://doi.org/10.1016/j.virusres.2020.198163 

5. Calcagnile M. i Forgez P., 2020. Simulacija molekularnog spajanja otkriva ACE2 polimorfizme koji mogu povećati afinitet ACE2 s proteinom SARS-CoV-2 Spike. Biochimie, svezak 180, siječanj 2021., stranice 143-148. Dostupno online 9. studenog 2020. DOI: https://doi.org/10.1016/j.biochi.2020.11.004   

6. Sahajpal NS, Lai CJ, dr. 2021. Analiza strukturnih varijacija genoma domaćina pomoću optičkog mapiranja genoma pruža klinički vrijedne uvide u gene koji su uključeni u kritične imunološke, virusne infekcije i puteve replikacije virusa u pacijenata s teškim COVID-19. Preprint medRxiv. 8. siječnja 2021. DOI: https://doi.org/10.1101/2021.01.05.21249190 

7. Zhou, A., Sabatello, M., Eyal, G. i sur. Je li precizna medicina relevantna u doba COVID-19? Genet Med (2021). Objavljeno: 13. siječnja 202. DOI:  https://doi.org/10.1038/s41436-020-01088-4 

8. Daga, S., Fallerini, C., Baldassarri, M. et al. Employing a systematic approach to biobanking and analyzing clinical and genetski data for advancing COVID-19 research. Eur J Hum Genet (2021). Published: 17 January 2021.  https://doi.org/10.1038/s41431-020-00793-7  

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