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Genetics
What the Latest Research Reveals
Data last updated: 35 studies cited
How this page is produced
Generated by the ModernDoc Research Monitor from peer-reviewed literature. Every statistic is automatically checked against its cited source and screened for retractions before it is published. This page is AI-generated and has not yet been reviewed by a clinician — it is not medical advice. Read how we build and check these pages.
20%
Of critical COVID-19 deaths in those over 70 have autoantibodies against type I interferons
— a key discovery explaining severe disease in the elderly
Source: Bastard et al.. Science Immunology (2021). 10.1126/sciimmunol.abl43400
KEY FINDINGS
Inborn Errors of IFN Immunity
3.5%
95% CI: Enrichment p < 1x10^-6 in critical COVID-19
Source [1]
3p21.31 Risk Locus
OR 2.14
95% CI: OR 2.14 (95% CI: 1.72-2.67) for critical illness
Source [7]
OAS1 Protective Variant
OR 0.74
95% CI: OR 0.74 (95% CI: 0.68-0.80) for critical illness
Source [8]
APOE e4/e4 Hospitalization
OR 3.51
95% CI: OR 3.51 (95% CI: 2.38-5.17) for hospitalization
Source [20]
THE TIMELINE
Acute Phase
0-4 weeks
Subacute Phase
4-12 weeks
Chronic Phase
3-12 months
Long-Term
>12 months
Acute Phase
0-4 weeks
IFN pathway defects determine viral control
Key Event
Innate immunity critical
Type I IFN Autoantibodies by Age Group
Under 658%
Over 8021%
Source: Bastard et al., Science Immunology 2021
Genetic Factors and Reinfection Severity
Auto-Ab positive+Unchanged high risk
Inborn IFN error+Variable (immune memory helps)
Protective genotype+Maintained advantage
“Autoantibodies persist and continue to pose risk across reinfections”
THE HOPEFUL HORIZON
- HLA-A*02:01 carriers have 2x higher odds of asymptomatic infection[16]
- Protective OAS1 Neanderthal variant present in 30% of Europeans[13]
- Early interferon-beta may benefit those with downstream IFN defects[26]
- Genetic testing can identify at-risk individuals for prioritized vaccination[1]
SOURCES
- [1]Zhang Q, Bastard P, Liu Z, et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4570. DOI (opens in new tab)
- [2]Bastard P, Rosen LB, Zhang Q, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4585. DOI (opens in new tab)
- [3]van der Made CI, Simons A, Brouwer J, et al. Presence of genetic variants among young men with severe COVID-19. JAMA. 2020;324(7):663-673. DOI (opens in new tab)
- [4]Bastard P, Gervais A, Le Voyer T, et al. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. Sci Immunol. 2021;6(62):eabl4340. DOI (opens in new tab)
- [5]Asano T, Boisson B, Onodi F, et al. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19. Sci Immunol. 2021;6(62):eabl4348. DOI (opens in new tab)
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