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COVID-19 / SPECIALTY RESEARCH

GeneticsIn perspective.

The key COVID-19 findings in genetics, distilled into a clear, readable brief. The evidence is here whenever you want to go deeper.

INSIDE THIS MONITOR
34cited sources
4available findings

Study findings updated

AI-assisted evidence summary. For general information. These findings are not individual medical advice or a clinician endorsement.

THE SHORT VERSION

What’s worth knowing.

The key findings, what they mean, and the context that matters.

THE HEADLINE TAKEAWAY3.5%

Inborn interferon-immunity errors were found in life-threatening COVID-19

The reported proportion of patients with life-threatening COVID-19 who had inborn errors of type I interferon immunity was 3.5%.

The source concerns patients with life-threatening COVID-19. Study design and sampling details are not recorded in this summary, limiting how broadly the proportion can be generalized.

See the evidence

Inborn Errors of IFN Immunity

3.5%
Enrichment p < 1x10^-6 in critical COVID-19

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.

02

Some older adults dying from critical COVID-19 had interferon autoantibodies

20%

Neutralizing autoantibodies against type I interferons were reported in 20% of people over 70 who died from critical COVID-19.

The finding is restricted to people over 70 years old who died from critical COVID-19, not to all infections or age groups. Study design is not recorded in this summary.

See the evidence

Of critical COVID-19 deaths in those over 70 have autoantibodies against type I interferons

20%

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.

03

Genetic variants showed contrasting critical-illness associations

The 3p21.31 risk locus was associated with higher odds of critical COVID-19 illness, while an OAS1 variant was associated with lower odds of the same outcome.

They were reported in separate studies. The reference groups are not available in this summary, so the odds ratios are not shown and the findings are not a head-to-head comparison.

See the evidence

3p21.31 Risk Locus

OR 2.14
OR 2.14 (95% CI: 1.72-2.67) for critical illness

Severe Covid-19 GWAS Group. Genomewide association study of severe Covid-19 with respiratory failure. N Engl J Med. 2020;383(16):1522-1534.

OAS1 Protective Variant

OR 0.74
OR 0.74 (95% CI: 0.68-0.80) for critical illness

COVID-19 Host Genetics Initiative. Mapping the human genetic architecture of COVID-19. Nature. 2021;600(7889):472-477.

04

APOE e4/e4 was associated with COVID-19 hospitalization

In the UK Biobank community cohort, APOE e4/e4 was associated with higher odds of COVID-19 hospitalization.

The reference group is not available in this summary, so the reported odds ratio is not shown. As a community-cohort association, it does not establish causation.

See the evidence

APOE e4/e4 Hospitalization

OR 3.51
OR 3.51 (95% CI: 2.38-5.17) for hospitalization

Kuo CL, Pilling LC, Atkins JL, et al. APOE e4 genotype predicts severe COVID-19 in the UK Biobank community cohort. J Gerontol A Biol Sci Med Sci. 2020;75(11):2231-2232.

Study-specific findings. Different populations, treatments and follow-up periods can produce different results.

THE RESEARCH, AS IT ARRIVES

Latest studies.

The newest findings added to this collection.
The learning from each, already distilled.

Study summaries are not available in this collection yet. The original evidence remains accessible in each monitor.

Dates show when findings were added here, not when papers were published. Study populations and comparisons differ.

WHEN YOU WANT TO GO DEEPER
See all 4 findingsOriginal results, comparisons and study details.
4 of 4 source groupsFindings stay together with their study.
SOURCE 011 finding

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.

Inborn Errors of IFN Immunity

3.5%Enrichment p < 1x10^-6 in critical COVID-19Source [1]
SOURCE 071 finding

Severe Covid-19 GWAS Group. Genomewide association study of severe Covid-19 with respiratory failure. N Engl J Med. 2020;383(16):1522-1534.

3p21.31 Risk Locus

OR 2.14OR 2.14 (95% CI: 1.72-2.67) for critical illnessSource [7]
SOURCE 081 finding

COVID-19 Host Genetics Initiative. Mapping the human genetic architecture of COVID-19. Nature. 2021;600(7889):472-477.

OAS1 Protective Variant

OR 0.74OR 0.74 (95% CI: 0.68-0.80) for critical illnessSource [8]
SOURCE 191 finding

Kuo CL, Pilling LC, Atkins JL, et al. APOE e4 genotype predicts severe COVID-19 in the UK Biobank community cohort. J Gerontol A Biol Sci Med Sci. 2020;75(11):2231-2232.

APOE e4/e4 Hospitalization

OR 3.51OR 3.51 (95% CI: 2.38-5.17) for hospitalizationSource [19]
Browse the 34 original sourcesThe complete bibliography behind this monitor.
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    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.

    Open original source in a new tab
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    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.

    Open original source in a new tab
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    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.

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    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.

    Open original source in a new tab
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    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.

    Open original source in a new tab
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    Manry J, Bastard P, Gervais A, et al. The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies. Proc Natl Acad Sci USA. 2022;119(21):e2200413119.

    Open original source in a new tab
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    Severe Covid-19 GWAS Group. Genomewide association study of severe Covid-19 with respiratory failure. N Engl J Med. 2020;383(16):1522-1534.

    Open original source in a new tab
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    COVID-19 Host Genetics Initiative. Mapping the human genetic architecture of COVID-19. Nature. 2021;600(7889):472-477.

    Open original source in a new tab
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    Pairo-Castineira E, Clohisey S, Ber S, et al. Genetic mechanisms of critical illness in COVID-19. Nature. 2021;591(7848):92-98.

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    Shelton JF, Shastri AJ, Ye C, et al. Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity. Nat Genet. 2021;53(6):801-808.

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    COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19. Nature. 2022;608(7921):E1.

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    Zeberg H, Paabo S. The major genetic risk factor for severe COVID-19 is inherited from Neanderthals. Nature. 2020;587(7835):610-612.

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    Zeberg H, Paabo S. A genomic region associated with protection against severe COVID-19 is inherited from Neanderthals. Proc Natl Acad Sci USA. 2021;118(9):e2026309118.

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    Downes DJ, Cross AR, Hua P, et al. Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus. Nat Genet. 2021;53(11):1606-1615.

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    Kousathanas A, Pairo-Castineira E, Rawlik K, et al. Whole-genome sequencing reveals host factors underlying critical COVID-19. Nature. 2022;607(7917):97-103.

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    Augusto DG, Murdolo LD, Chatzileontiadou DSM, et al. A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection. Nature. 2023;620(7972):128-136.

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    Cao Y, Li L, Feng Z, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov. 2020;6:11.

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    Suryamohan K, Diwanji D, Staber EJ, et al. Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2. Commun Biol. 2021;4(1):475.

    Open original source in a new tab
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    Kuo CL, Pilling LC, Atkins JL, et al. APOE e4 genotype predicts severe COVID-19 in the UK Biobank community cohort. J Gerontol A Biol Sci Med Sci. 2020;75(11):2231-2232.

    Open original source in a new tab
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    Kuo CL, Pilling LC, Atkins JL, et al. ApoE e4e4 genotype and mortality with COVID-19 in UK Biobank. J Gerontol A Biol Sci Med Sci. 2020;75(9):1801-1803.

    Open original source in a new tab
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    Lammi V, Nakanishi T, Jones SE, et al. Genome-wide association study of long COVID. Nat Genet. 2023;55(10):1616-1624.

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    COVID-19 Host Genetics Initiative. Long COVID GWAS results. Available at: https://www.covid19hg.org/results/

    Original source link unavailable
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    Rendeiro AF, Ravichandran H, Bram Y, et al. The spatial landscape of lung pathology during COVID-19 progression. Nature. 2021;593(7860):564-569.

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    RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637-1645.

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    Casanova JL, Su HC; COVID Human Genetic Effort. A global effort to define the human genetics of protective immunity to SARS-CoV-2 infection. Cell. 2020;181(6):1194-1199.

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    Zhang Q, Cobat A, Bastard P, et al. Association of rare predicted loss-of-function variants of influenza-related type I IFN genes with critical COVID-19 pneumonia. J Clin Invest. 2022;132(7):e152474.

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    Casanova JL, Abel L. From rare disorders of immunity to common determinants of infection: Following the mechanistic thread. Cell. 2022;185(17):3086-3103.

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    Andreakos E, Abel L, Vinh DC, et al. A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection. Nat Immunol. 2022;23(2):159-164.

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    Zhang SY, Zhang Q, Casanova JL, Su HC. Severe COVID-19 in the young and healthy: monogenic inborn errors of immunity? Nat Rev Immunol. 2020;20(8):455-456.

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    COVID-19 Host Genetics Initiative. https://www.covid19hg.org/

    Original source link unavailable
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    COVID Human Genetic Effort. https://www.covidhge.com/

    Original source link unavailable
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    gnomAD (Genome Aggregation Database). https://gnomad.broadinstitute.org/

    Original source link unavailable
ABOUT THIS MONITOR

Understanding includes the limits.

This is an AI-assisted evidence summary, not a clinician endorsement. Read each original paper for its complete methods, population and limitations. Different studies can ask different questions and report different kinds of results.

Dates marked “added” describe when a finding entered this monitor, not when the study was published or clinically reviewed. Personal health and treatment decisions belong in a conversation with a qualified clinician.

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