Impact of SARS CoV-2 in Hemoglobinopathies with Immune Disfunction and Epidemiology. A Protective Mechanism from Beta Chain Hemoglobin Defects?

摘要

A novel coronavirus (SARS-CoV-2) has rapidly overspread infecting in few months all continents and representing a medical emergency, with 20% of patients with severe clinical manifestations. The pathogenesis of SARS include mechanisms involving both direct effects on target cells and indirect immune effects.1 The virus binds to extracellular receptors on the host cell, fuses to the membrane and enters the cytoplasm where it is released and starts replication. Anti-viral drug therapy targets typically include blocking receptor binding in the cell surface, or molecular steps of transcription, translation and protein processing.2 The transcribed, non-structural SARS-CoV- 2 proteins ORF 8, 3a, and 10 play critical roles during infection (viral replication) and disease pathogenesis (stimulate NF-kB mediated inflammation and immune responses).3 ORFs interact with Beta Chain Hemoglobin (BCH) to dissociate iron and form porphyrin,4 and that results in hemoglobin dysfunction, with lung cells failing to exchange carbon dioxide and oxygen and respiratory failure.5 Chloroquine, currently used to treat SARS-CoV-2 patients, prevents ORF proteins from attacking heme and forming porphyrin.6 Thus, might abnormalities of BCH, quantitative in thalassemias, and qualitative in Sickle-Cell-Disease (SCD), influence the outcome? However, the impact of SARS-CoV-2 in those patients is still unknown.