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July 24, 2020

Molecular Underpinnings of Severe Coronavirus Disease 2019

Author Affiliations
  • 1Research & Early Development, Bristol Myers Squibb, Cambridge, Massachusetts
JAMA. Published online July 24, 2020. doi:10.1001/jama.2020.14015

The molecular underpinnings of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the disease it causes, coronavirus disease 2019 (COVID-19), are poorly understood. Inherited genetic variation is an important tool to disentangle cause and consequence, which in turn can generate insights to guide therapeutic interventions to prevent or treat disease. To date, little is known about genetic susceptibility to SARS-CoV-2 infection and severe forms of COVID-19.1,2

In this issue of JAMA, van der Made and colleagues3 describe 2 independent families with rare germline variants in an innate immune-sensing gene, toll-like receptor 7 (TLR7), that lead to severe disease in males who inherit the mutated gene on a single copy of their X chromosome. The study implicates TLR7 as a critical node in recognizing SARS-CoV-2 and initiating an early immune response to clear the virus and prevent the development of COVID-19.