COVID-19 and erythrocrine function: The roller coaster and danger

Area of Science:

• Hematology
• Virology
• Immunology

Background:

• Erythrocytes synthesize and release signaling molecules like ATP and nitric oxide (NO), crucial for regulating blood flow and preventing hypoxia.
• Erythrocrine function, the signaling capacity of red blood cells, is increasingly recognized for its role in physiological regulation.

Purpose of the Study:

• To investigate the impact of SARS-CoV-2 infection on erythrocrine function.
• To elucidate the mechanisms by which SARS-CoV-2 alters erythrocyte physiology and contributes to COVID-19 pathogenesis.

Main Methods:

• Analysis of erythrocyte interactions with SARS-CoV-2, including binding to band3 protein and activation of protein kinase C alpha (PKC-α).
• Examination of the effects of SARS-CoV-2 ORF8 protein on hemoglobin and erythrocyte hemolysis.
• Assessment of changes in the release of signaling molecules (NO, ATP, S1P) from erythrocytes.

Main Results:

• SARS-CoV-2 binds to erythrocyte band3 protein, altering oxygen transport and leading to hypoxia.
• Viral infection activates erythrocyte PKC-α, significantly impacting red blood cell functions.
• SARS-CoV-2 binding to erythrocytes facilitates virus delivery to macrophages, suggesting a role in viral clearance.
• ORF8 protein binding to hemoglobin causes hemolysis and reduces oxygen-carrying capacity.
• Erythrocrine function is impaired, with reduced release of NO, S1P, and ATP, contributing to inflammation and endothelial dysfunction.

Conclusions:

• SARS-CoV-2 infection disrupts erythrocrine function, leading to hypoxia, hemolysis, and reduced oxygen transport.
• The deficiency in protective signaling molecules (NO, S1P, ATP) released by erythrocytes contributes to inflammatory complications and endothelial dysfunction in COVID-19.
• Further in vitro, preclinical, and clinical studies are essential to fully understand and address the consequences of altered erythrocrine function in SARS-CoV-2 infection.