Pattern recognition receptor-associated immuno-thrombotic transcript changes in platelets and leukocytes with...

Area of Science:

• Immunology
• Hematology
• Infectious Diseases

Background:

• Respiratory infections, including COVID-19, are linked to increased thrombosis risk.
• Platelet-leukocyte interactions via pattern recognition receptors (PRRs) are implicated in this process.
• Understanding PRR expression changes and their functional consequences is crucial for managing COVID-19 complications.

Purpose of the Study:

• To characterize COVID-19-induced alterations in PRR expression on platelets and leukocytes.
• To investigate the association of PRR expression with thrombotic/coagulation transcriptional programs.
• To correlate PRR levels with COVID-19 patient outcomes, including disease severity, coagulopathy, and liver inflammation.

Main Methods:

• Amplicon RNA sequencing of platelets and leukocytes from COVID-19 patients and healthy donors.
• Analysis of PRR expression patterns and their correlation with thrombotic/coagulation transcripts.
• Assessment of platelet-leukocyte aggregates and extracellular vesicles.
• Correlation of specific PRR levels with clinical outcomes (severity, survival, INR, ALT).
• Bioinformatic analysis of publicly available whole-blood RNA-seq data.

Main Results:

• COVID-19 significantly altered PRR expression in platelets (increased TLR9, RIG-I, CGAS, TLR1) and leukocytes (decreased TLR6, TLR8).
• Platelet PRRs (MDA5, RIG-I, LGP2) associated with thrombotic/coagulation transcripts in COVID-19, unlike in healthy donors (TLR9).
• Leukocyte PRR associations with coagulation transcripts diminished in COVID-19.
• Platelet-TLR3 and leukocyte-TLR5 correlated with COVID-19 severity/survival; leukocyte-TLR7 showed inverse correlation.
• Specific PRRs linked to coagulopathy (platelet-TLR4, leukocyte-TLR10) and liver inflammation (LGP2, TLR3, TLR6, TLR7, RIG-I).

Conclusions:

• Platelets and leukocytes exhibit distinct, COVID-19-dependent PRR expression profiles and associations with thrombotic/coagulation pathways.
• Specific PRRs on platelets and leukocytes serve as potential biomarkers for COVID-19 severity, coagulopathy, and liver damage.
• The findings highlight the complex interplay of PRRs in COVID-19 pathogenesis and thrombosis, suggesting therapeutic targets.