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

Abstract

Erythrocrine function refers to erythrocytes’ ability to synthesize and release active signaling molecules such as ATP and nitric oxide (NO). Erythrocyte NO regulates its deformability and increases its perfusion and circulation that prevent tissue hypoxia. Recently, there is a connotation between SARS-CoV-2 infection and erythrocrine function due to alteration in the release of NO and ATP from erythrocytes. SARS-CoV-2 binds erythrocyte band3 protein, which has a similar characteristic of ACE2, leading to alteration of erythrocyte physiology like oxygen transport with development of hypoxia. Similarly, SARS-CoV-2 infection activates erythrocyte protein kinase C alpha (PKC-α), causing significant changes in the erythrocyte functions. The erythrocytes can bind SARS-CoV-2 and its active particles with subsequent virus delivery to the liver and spleen macrophages. Thus, the erythrocytes act as elimination for SARS-CoV-2 in COVID-19. Moreover, the erythrocyte stored, release sphingosine-1 phosphate (S1P) improves endothelial and regulates lymphocyte functions. SARS-CoV-2 ORF8 protein binds the porphyrin part of hemoglobin heme at the β1 chain, causing hemolysis and dysfunctional hemoglobin to reduce oxygen-carrying capacity. In conclusion, SARS-CoV-2 infection and associated pro-inflammatory disorders lead to abnormal erythrocrine function with subsequent inflammatory complications and endothelial dysfunction due to deficiency of protective released molecules (NO, G1P, and ATP) from functional erythrocytes. In vitro, preclinical, and clinical studies are mandatory in this regard.

Pathophysiology of Post-COVID syndromes: a new perspective

“…PCS was initially defined in relation to post-acute COVID-19 as persistence symptoms for > 3 weeks from the onset of COVID-19 or chronic COVID-19 as persistence symptoms for > 12 weeks from the onset of COVID-19 [ 22 , 23 ]. Yong defined PCS or long-term COVID-19 as symptoms that persist for more than 3 months after the onset of COVID-19 [ 24 , 25 ].…”

Role of Neuropilin 1 in COVID-19 Patients with Acute Ischemic Stroke

“…In SARS-CoV-2 infection, hypoxia due to cardio-respiratory insufficiency induces cell death and apoptosis, releasing damage-associated molecule patterns (DAMPs), which activate the transcription of HIF-α1. The hypoxia also stabilizes HIF-α1 by the inhibition of prolyl hydroxylase mRNA through the activation of endothelial TLR4 [ 20 ]. Moreover, HIF-α1 reduces the entry of SARS-CoV-2 through the inhibition of ACE2, and transmembrane protein serine 2 (TMPPSS2) through the activation of ADAM17 [ 20 ].…”

“…The hypoxia also stabilizes HIF-α1 by the inhibition of prolyl hydroxylase mRNA through the activation of endothelial TLR4 [ 20 ]. Moreover, HIF-α1 reduces the entry of SARS-CoV-2 through the inhibition of ACE2, and transmembrane protein serine 2 (TMPPSS2) through the activation of ADAM17 [ 20 ]. However, prolonged HIF-α1 effect may lead to the development of ARDS due to the augmented release of pro-inflammatory cytokines and glycolysis-dependent generation of ROS [ 139 ].…”

“…For example, Hu et al revealed that procalcitonin serum level was correlated with COVID-19 severity and mortality [ 19 ]. In addition, N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin-T, lactate dehydrogenase (LDH), and creatin kinase (CK) levels reflect the severity of the acute cardiac injury, ARDS, and MOF [ 20 , 21 , 22 ].…”

Pregnancy and COVID-19: high or low risk of vertical transmission

“…The connotation between over-expression of ACE2 and COVID-19 severity is weak since the ACE2 protein is located on the X chromosome, which is more abundant in females. Despite the low expression of ACE2, the COVID-19 fatality rate is higher in males, and the severity of COVID-19 in elderly patients is high [ 99 , 100 ]. Also, ACE2 has a protective role against ALI in influenza [ 22 ].…”