MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study

Area of Science:

• Immunology
• Genetics
• Infectious Diseases

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can trigger a cytokine storm, a key factor in severe Coronavirus Disease 2019 (COVID-19) pathogenesis.
• The mammalian target of rapamycin (mTOR) pathway regulates innate immune responses, including cytokine production, and is often dysregulated in severe COVID-19.
• Individual genetic variations may influence the severity of the immune response to SARS-CoV-2.

Purpose of the Study:

• To investigate the association between specific genetic variants in the MTOR gene and COVID-19 outcomes.
• To determine if MTOR variants contribute to the severity of COVID-19 infection.

Main Methods:

• Genotyping of MTOR variants (rs1057079 and rs2536) in individuals with severe (n=285) and mild (n=207) COVID-19.
• Logistic regression analysis and Kaplan-Meier survival curves were used to assess the association between variants and outcomes.
• Measurement of plasma levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6), and application of a genotyping risk score.

Main Results:

• The T allele of MTOR rs1057079 was associated with an increased likelihood of severe COVID-19.
• The T allele of MTOR rs2536 was linked to higher IL-6 levels and increased COVID-19 mortality.
• A cumulative risk was observed when these MTOR variants were inherited together.

Conclusions:

• MTOR gene variants may play a pathogenetic role in severe COVID-19.
• These findings could aid in predicting severe outcomes of COVID-19 infection.
• Identifying at-risk individuals may allow for more effective allocation of healthcare resources.