Two new studies report specific mechanisms of impaired type I interferon (IFN) signaling in some hospitalized patients suffering from severe cases of COVID-19, suggesting that screens for these defects could help identify patients at the highest risk of life-threatening complications from SARS-CoV-2 infection.
The results of the paired studies - which report that mutations in type I IFN-associated genes and high titers of neutralizing autoantibodies against type I IFNs may both be associated with severe COVID-19 respiratory symptoms - also suggest that administering specific type I IFNs to select high-risk patients could offer therapeutic benefits, especially early in the course of the disease.
To test whether severe COVID-19 respiratory symptoms may be associated with the genetics of type I IFN signaling, the authors performed whole-genome or whole-exome sequencing of 659 patients hospitalized with life-threatening COVID-19 pneumonia and 534 patients with asymptomatic or mild infection. Focusing on 13 gene loci known to govern TLR3- and IRF7-dependent type I IFN immunity to influenza virus, the researchers found rare loss-of-function gene variants in 3.5% of the patients with severe COVID-19 symptoms, but not in the asymptomatic/mild cohort. This subgroup of patients (23 in total) ranged in age from 17 to 77, with representation of both sexes and various ancestries.
Based on their findings, the researchers suggest that mutations in other type I IFN-related genes may exist in other patients with life-threatening COVID-19 symptoms. In a related study,
In the second study the authors investigated whether neutralizing autoantibodies (which aberrantly recognize, bind to, and neutralize a patient's own proteins) against type I IFNs might also underlie severe COVID-19 pneumonia. In a screen of 987 patients with dire cases of COVID-19, the researchers found that 101 patients had autoantibodies against IFN-ω, IFN-a, or both. In contrast, 663 patients with asymptomatic or mild cases of COVID-19 had none of the autoantibodies, and only 4 of 1,227 healthy individuals, sampled before the pandemic, had one or more of the autoantibody types.
Based on their findings, the authors. conclude that "the neutralizing [autoantibodies] against type I IFNs, like inborn errors of type I IFN production, tip the balance in favor of the virus, resulting in devastating disease, with insufficient, and even perhaps deleterious, innate and adaptive immune responses."
https://www.niaid.nih.gov/news-events/scientists-discover-genetic-and-immunologic-underpinnings-some-cases-severe-covid-19
https://science.sciencemag.org/content/early/2020/09/23/science.abd4570
https://science.sciencemag.org/content/early/2020/09/23/science.abd4585
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Finborn-errors-of-type-i&filter=22
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fauto-antibodies-against&filter=22
Impaired type I interferon signaling may contribute to severe COVID-19 symptoms
- 996 views
- Added
Edited
Latest News
Protein found in brain link…
By newseditor
Posted 09 Dec
Calcium acts as missing lin…
By newseditor
Posted 09 Dec
How repeated traumatic brai…
By newseditor
Posted 08 Dec
Metformin rescues neuronal…
By newseditor
Posted 08 Dec
Variants in the genome inte…
By newseditor
Posted 08 Dec
Other Top Stories
How secondary structure RNA elements control the cleavage activity…
Read more
Transcription factors regulate distinct segments of the distal neph…
Read more
Single-molecule FRET illuminate mechanisms of GPCR activation
Read more
How hormones define brain sex differences
Read more
CDC7-independent G1/S transition revealed by targeted protein degra…
Read more
Protocols
Brain-wide circuit-specific…
By newseditor
Posted 05 Dec
Cheap, cost-effective, and…
By newseditor
Posted 03 Dec
Temporally multiplexed imag…
By newseditor
Posted 02 Dec
Efficient elimination of ME…
By newseditor
Posted 01 Dec
Personalized drug screening…
By newseditor
Posted 30 Nov
Publications
Extracellular calcium funct…
By newseditor
Posted 09 Dec
TAF15 amyloid filaments in…
By newseditor
Posted 09 Dec
Metformin rescues migratory…
By newseditor
Posted 08 Dec
Oral magnesium prevents ace…
By newseditor
Posted 08 Dec
GDF15 is a major determinan…
By newseditor
Posted 08 Dec
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar