Genetic Screening for TLR7 Variants in Young and Previously Healthy Men With Severe COVID-19
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Loss-of-function TLR7 variants have been recently reported in a small number of males to underlie strong predisposition to severe COVID-19. We aimed to determine the presence of these rare variants in young men with severe COVID-19.
Methods
We prospectively studied males between 18 and 50 years-old without predisposing comorbidities that required at least high-flow nasal oxygen to treat COVID-19. The coding region of TLR7 was sequenced to assess the presence of potentially deleterious variants.
Results
TLR7 missense variants were identified in two out of 14 patients (14.3%). Overall, the median age was 38 (IQR 30-45) years. Both variants were not previously reported in population control databases and were predicted to be damaging by in silico predictors. In a 30-year-old patient a maternally inherited variant [c.644A>G; p.(Asn215Ser)] was identified, co-segregating in his 27-year-old brother who also contracted severe COVID-19. A second variant [c.2797T>C; p.(Trp933Arg)] was found in a 28-year-old patient, co-segregating in his 24-year-old brother who developed mild COVID-19. Functional testing of this variant revealed decreased type I and II interferon responses in peripheral mononuclear blood cells upon stimulation with the TLR7 agonist imiquimod, confirming a loss-of-function effect.
Conclusions
This study supports a rationale for the genetic screening for TLR7 variants in young men with severe COVID-19 in the absence of other relevant risk factors. A diagnosis of TLR7 deficiency could not only inform on treatment options for the patient, but also enables pre-symptomatic testing of at-risk male relatives with the possibility of instituting early preventive and therapeutic interventions.
Article activity feed
-
-
SciScore for 10.1101/2021.03.14.21252289: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Informed consent was obtained from all patients and relatives, and the IDIBELL Research Ethics Committee approved this study (PR152/20). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Ten male patients fulfilled all selection criteria (Table 1). Table 2: Resources
Software and Algorithms Sentences Resources Mutation Surveyor software was used to detect variants and nomenclature was given according to HGVS guidelines. Mutation Surveyorsuggested: (Mutation Surveyor, RRID:SCR_001247)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open …
SciScore for 10.1101/2021.03.14.21252289: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Informed consent was obtained from all patients and relatives, and the IDIBELL Research Ethics Committee approved this study (PR152/20). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Ten male patients fulfilled all selection criteria (Table 1). Table 2: Resources
Software and Algorithms Sentences Resources Mutation Surveyor software was used to detect variants and nomenclature was given according to HGVS guidelines. Mutation Surveyorsuggested: (Mutation Surveyor, RRID:SCR_001247)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
-
