ReviewNature2022
Human genetic and immunological determinants of critical COVID-19 pneumonia.
Review in Nature, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
238 citing papers in PubMed, 1 synthesis or guideline pooled it, 384 citations in OpenAlex.
- A genome-wide association study of survival in patients with sepsis.Critical care (London, England) · 2022Pooled it
- Influence of grandchildren on COVID-19 vaccination uptake among older adults in China: a parallel-group, cluster-randomized controlled trial.Nature aging · 2024Trial
- Prevalence of neutralizing autoantibodies against type I interferon in dengue patients.Journal of human immunity · 2026Article
- Biallelic loss-of-function PTPN6 variants lead to inflammatory lung disease and hemolytic anemia.The Journal of experimental medicine · 2026Article
- Viral syncytia evolve to resist interferon.Nature communications · 2026Article
- Identification and functional characterization of regulatory variants in DPP9 associated with COVID-19 severity.Genome medicine · 2026Article
- Four doses of coronavirus disease 2019 vaccination for patients with inborn errors of immunity compared to 3 doses for healthy individuals.The journal of allergy and clinical immunology. Global · 2026Article
- Affinity-matured B cell responses neutralizing type-I interferons underlie severe viral infections.Cell · 2026Article
- Article
- The Open Reading Frame 7b of the SARS-CoV-2 Disperse Trans-Golgi and Activate the NLRP3 Inflammasome.Journal of medical virology · 2026Article
- Defective RNA Polymerase III sensing of mitochondrial DNA in pulmonary epithelial cells impairs type I IFN immunity to SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Unique Patient Stratification Method Combined with a Machine Learning Approach Identifies Novel Genetic Susceptibility and Protective Factors for Severe COVID-19 in a Hungarian Population.International journal of molecular sciences · 2026Article
- Autoantibodies neutralizing type I IFNs in a fatal case of H5N1 avian influenza.The Journal of experimental medicine · 2026Article
- Viral infection and brain inflammation with seizures in PARK7 deficiency.Journal of human immunity · 2026Article
- Single-cell RNA sequencing data analysis reveals differential expressions of ion channels in immunity response to pulmonary COVID-19 infection.Biochemical and biophysical research communications · 2026Article
- Chromatin-mediated anticipatory control of type I interferon production in plasmacytoid dendritic cells.Immunity · 2026Article
- Genetic contribution to severe COVID-19 in adults under 60 years without major comorbidities in the German National Pandemic Cohort Network (NAPKON).Human genomics · 2026Article
- Stealth replication of SARS-CoV-2 Omicron in the nasal epithelium at physiological temperature.Journal of virology · 2026Article
- The OAS-RNase L pathway: Insights from experiments of nature.Science immunology · 2026Review
- Auto-Abs against type I IFNs: Strong, common, and global determinants of severe arboviral diseases.Journal of human immunity · 2026Review
178 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 20 institutions in 35 countries.
Funding
Abstract
SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFNα, IFNβ and/or IFNω, which are more common in men than in women, are found in approximately 15-20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.