COVID-19 and platelet traits: A bidirectional Mendelian randomization study

Area of Science:

• Genetics
• Hematology
• Epidemiology

Background:

• Host genetic factors influence susceptibility and severity of coronavirus disease 2019 (COVID-19).
• Platelet traits are implicated in the pathophysiology of viral infections and thrombotic complications.

Purpose of the Study:

• To investigate the causal relationship between host genetic liability for COVID-19 severity and platelet traits using Mendelian randomization.
• To explore potential genetic links between COVID-19 and platelet parameters like mean platelet volume (MPV), plateletcrit, platelet distribution width, and platelet count.

Main Methods:

• A bidirectional two-sample Mendelian randomization (MR) approach was employed.
• Summary statistics from large genome-wide association studies for COVID-19 severity (N ≈ 1.5 million) and platelet traits (N ≈ 408,000) were utilized.
• Inverse-variance weighted (IVW), median weighted, MR-Egger, and contamination mixture methods were applied for robust causal inference.

Main Results:

• No significant causal associations were found between genetic liability for SARS-CoV-2 infection or COVID-19 hospitalization and platelet traits.
• Significant causal associations were observed between genetic liability for severe COVID-19 and increased MPV (β_IVW = 0.01, p = 3.51×10^-4) and decreased platelet count (β_IVW = -0.009, p = 0.008).
• Conversely, no significant causal associations were detected for platelet traits influencing COVID-19 traits.

Conclusions:

• Host genetic predisposition to severe COVID-19 is causally associated with altered platelet parameters, specifically increased MPV and reduced platelet count.
• These findings may offer valuable insights into the mechanisms underlying hypercoagulability and thromboembolic events in severe COVID-19 patients.
• The study highlights the complex interplay between host genetics, platelet function, and COVID-19 severity.