A macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia

Area of Science:

• Immunology
• Hematology
• Virology

Background:

• Bacterial pneumonia involves neutrophilic infiltration, while SARS-CoV-2 viral pneumonia is characterized by macrophage infiltration.
• Macrophages in SARS-CoV-2 pneumonia are rich in tissue factor, contributing to a prothrombotic state and extra-pulmonary organ damage.
• Elevated ferritin, acute phase proteins, and d-dimers in severe COVID-19 patients suggest immune overreaction and clotting activation.

Purpose of the Study:

• To investigate the role of soluble fibrin monomer complexes (SFMC) in severe COVID-19 pneumonia.
• To correlate SFMC levels with immune activation markers and disseminated intravascular coagulation (DIC) in COVID-19 patients.
• To clarify the frequency and potential causes of DIC in severe COVID-19 pneumonia.

Main Methods:

• Utilized an in-house assay to measure whole blood SFMC levels, a marker for incipient DIC.
• Monitored SFMC levels in tandem with immune activation assays and d-dimer levels.
• Compared SFMC levels with clinical presentation of clotting and defibrination.

Main Results:

• Classical DIC with intravascular clotting and thrombocytopenia was rarely observed.
• Three patients exhibited acute defibrination, with fibrinogen rapidly converting to SFMC and depositing in the vasculature.
• SFMC levels were five times higher than normal during the defibrination process in these patients.

Conclusions:

• Severe COVID-19 patients with hyperactive immune responses can experience defibrination linked to markedly elevated SFMC levels.
• High SFMC levels may precipitate as microclots, leading to damage in multiple organs (heart, kidney, brain).
• SFMC monitoring is crucial for understanding and potentially managing thrombotic complications in severe COVID-19.