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4bases’ paper of the month – October 2021 – Update on human genetic susceptibility to COVID-19: susceptibility to virus and response

Our team’s reading recommendation for this month goes to “Update on human genetic susceptibility to COVID-19: susceptibility to virus and response”[1] by Colona et al., an extremely useful editorial published in “Human genomics”.

With a focus on genetic and genomics susceptibility factors to COVID-19, this paper summarizes the current knowledge as shared in the literature and provides an updated, easy to consult and constantly revised tool, through a recently reviewed table (which the authors commit to constantly update) that can be consulted through the following link

Their review underlines that:

  • Genome-wide association studies led to the identification of susceptibility alleles in several genes, which are linked to severe and/or life-threatening phenotypes, but more research is needed
  • Innate immune system deficits can be the basis of heterogeneity in clinical phenotypes and of the outcome of patients affected by COVID-19, and the functional role of rare variants needs to be further explored
  • The presence of alleles underpinning altered type 1b Interferon (IFN-1b) response in critical patients was described. The fact that anti-interferon antibodies in the serum of affected individuals in critical conditions are capable of halting the IFN activity was proven
  • Other potential susceptibility alleles were identified – and are listed in the table – in a British study on 2,244 severely affected patients, many of which are involved in the IFN type I immune response pathway
  • The authors also particularly mention DDP9 and TLR7, the latter being identified through a well-known study on two couples of young male siblings with no reported comorbidities and displaying a severe COVID-19 phenotype
  • The potential relevance of HLA complex polymorphisms for SARS-CoV-2 susceptibility, evoked in several studies is also mentioned
  • On another hand, 13 novel susceptibility loci have been linked to several aspects of SARS-CoV-2 infection as a result of a recent meta-analysis performed by COVID-19 Host Genetics Initiative, some of them overlapping/confirming the previously presented results
  • It has been proved that expression levels of genes encoding for proteins involved in the viral uptake (e.g., ACE2, TMPRSS2, FURIN) change with age, which depicts a biological rationale for the broad phenotypic spectrum of COVID-19

As mentioned by the authors of this review, there still are many questions to answer in this very complex field, and the outstanding cooperation between highly skilled research laboratories all around the world, that has proven its capability to achieve extraordinary results, needs to be maintained.

We at 4bases are proud to support research by developing new molecular diagnostic tools to allow a better understanding of the genetic susceptibility to COVID.

We’re getting ready for the future.

[1] Colona VL, Vasiliou V, Watt J, Novelli G, Reichardt JKV. Update on human genetic susceptibility to COVID-19: susceptibility to virus and response. Hum Genomics. 2021 Aug 25;15(1):57. doi: 10.1186/s40246-021-00356-x. Erratum in: Hum Genomics. 2021 Sep 18;15(1):59. PMID: 34429158; PMCID: PMC8384585.

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