Genetske varijante ljudskog domaćina koje utječu na fenotipove povezane s koronavirusom (SARS, MERS i COVID-19): brzi sistematski pregled i sinopsis na terenu.
Human genomics
Sažetak istraživanja
Pandemija COVID-19 ojačala je interes za biološke mehanizme koji leže u osnovi složene interakcije između infektivnih agenasa i ljudskog domaćina. Spektar fenotipova povezanih sa infekcijom SARS-CoV-2, u rasponu od odsustva simptoma do teških sistemskih komplikacija, postavio je pitanje u kojoj mjeri na varijabilni odgovor na koronaviruse (CoVs) utječe varijabilnost genetske pozadine domaćina. Da bismo istražili trenutna saznanja o ovom pitanju, osmislili smo sistematski pregled objavljene naučne literature Janpas3 do 2. lipnja 00. 2020. uključiti studije o savremenim epidemijama uzrokovanim SARS-CoV-1, MERS-CoV i SARS-CoV-2 (odnosno bolesti SARS, MERS i COVID-19). Studije su bile prihvatljive ako su ljudske genetske varijante testirane kao prediktori kliničkih fenotipova. Ad hoc protokol za proces brzog pregleda je dizajniran prema PRISMA paradigmi i registrovan u bazi podataka PROSPERO (ID: CRD42020180860). Sistematski tok posla pružio je 32 članka prihvatljivih za apstrakciju podataka (28 o SARS-u, 1 o MERS-u, 3 o COVID-19) u kojima se izvještavaju podaci o 26 kohorti otkrića. Većina studija je definitivnu kliničku dijagnozu smatrala primarnim ishodom, promjenjivo u kombinaciji s drugim ishodima (ozbiljnost je najčešće analizirana). Deset studija analiziralo je HLA haplotipove (1 kod pacijenata sa COVID-19) i nije dalo dosljedne signale povezanosti s fenotipovima povezanim s bolešću. Od 22 prihvatljiva članka koji su istraživali gene kandidate (2 povezana s COVID-19), najbolje rangirani geni u broju studija bili su ACE2, CLEC4M (L-SIGN), MBL, MxA (n = 3), ACE, CD209, FCER2, OAS-1, TLR4, TNF-α (n). U najmanje dvije studije pronađene su samo varijante MBL i MxA kao moguće upletene u fenotipove povezane s CoV. Broj studija za svaki prediktor bio je nedovoljan za sprovođenje meta-analize. Studije koje prikupljaju velike kohorte iz različitih predaka su potrebne da bi se dodatno razjasnila uloga genetskih varijanti domaćina u određivanju odgovora na infekciju CoV-om. Zajamčeni su rigorozni dizajn i robusne statističke metode.
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Genetic variants of the human host influencing the coronavirus-associated phenotypes (SARS, MERS and COVID-19): rapid systematic review and field synopsis.
The COVID-19 pandemic has strengthened the interest in the biological mechanisms underlying the complex interplay between infectious agents and the human host. The spectrum of phenotypes associated with the SARS-CoV-2 infection, ranging from the absence of symptoms to severe systemic complications, raised the question as to what extent the variable response to coronaviruses (CoVs) is influenced by the variability of the hosts' genetic background.To explore the current knowledge about this question, we designed a systematic review encompassing the scientific literature published from Jan. 2003 to June 2020, to include studies on the contemporary outbreaks caused by SARS-CoV-1, MERS-CoV and SARS-CoV-2 (namely SARS, MERS and COVID-19 diseases). Studies were eligible if human genetic variants were tested as predictors of clinical phenotypes.An ad hoc protocol for the rapid review process was designed according to the PRISMA paradigm and registered at the PROSPERO database (ID: CRD42020180860). The systematic workflow provided 32 articles eligible for data abstraction (28 on SARS, 1 on MERS, 3 on COVID-19) reporting data on 26 discovery cohorts. Most studies considered the definite clinical diagnosis as the primary outcome, variably coupled with other outcomes (severity was the most frequently analysed). Ten studies analysed HLA haplotypes (1 in patients with COVID-19) and did not provide consistent signals of association with disease-associated phenotypes. Out of 22 eligible articles that investigated candidate genes (2 as associated with COVID-19), the top-ranked genes in the number of studies were ACE2, CLEC4M (L-SIGN), MBL, MxA (n = 3), ACE, CD209, FCER2, OAS-1, TLR4, TNF-α (n = 2). Only variants in MBL and MxA were found as possibly implicated in CoV-associated phenotypes in at least two studies. The number of studies for each predictor was insufficient to conduct meta-analyses.Studies collecting large cohorts from different ancestries are needed to further elucidate the role of host genetic variants in determining the response to CoVs infection. Rigorous design and robust statistical methods are warranted.
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- DOI
- 10.1186/s40246-020-00280-6
- PMID
- 32917282
- PMCID
- PMC7484929
- Provjereno
- 2026-07-26
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