Could COVID-19 Be a Hemoglobinopathy?

Abstract

The world is struggling to deal with the corona pandemic. Effective therapies are still awaited due to the lack of understanding of the pathophysiological mechanism of the disease. Bearing recent research and clinical observations in mind, the authors propose a novel physiological mechanism of COVID-19 and explain development of COVID-19 related acute respiratory distress syndrome (ARDS) secondary to COVID-19 related hemoglobinopathy. It is a consistent observation that the radiological picture of COVID-19 related ARDS bears more resemblance to high altitude pulmonary edema (HAPE) than typical ARDS. There has been great controversy regarding this proposed similarity. The main argument from those objecting to this comparison is that the etiology is hypoxia in case of HAPE and inflammation in COVID-19 related ARDS. We propose that considering the recent bioinformatics prediction models, COVID-19 might first infect red blood cells via CD147 and cause hemoglobin damage. The resulting hypoxemia may cause pulmonary hypoxic vasoconstriction leading to HAPE-like lung lesions. The now introduced alveolar hypoxia further exaggerates hemoglobinopathy hypoxemia leading to a vicious cycle. In this review, the authors recommend laboratory experiments to prove these hypotheses. The proposed physiological mechanism has significant therapeutic implications. If proven, the authors suggest the use of exchange transfusion as adjunct therapy and development of anti-CD147 drugs.

Common Variable Immunodeficiency: Predisposing or Protective Factor for Severe Complications of COVID-19?

“…Therefore, it seems that SARS-CoV-2 induces severe inflammatory response through macrophage activation, which leads to a cytokine storm [10][11][12] . Some authors even suggest COVID-19 hemoglobinopathy and resulting hypoxia as one of the leading causes of COVID-19 related ARDS 13 . CVID patients possess dysfunctional B-lymphocytes, which may contribute to poor cytokine response.…”

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

“…133 Overall, scientific research has early focused on the possible role of hemoglobin morpho-functional alterations in this disease, as reported above, though a homogenous and direct evidence about hemoglobin dysregulation in COVID-19 has not been reached; similarly, literature reports contrasting papers about the related hypoxia and about the altered hemoglobin dissociation-curves. 4,[134][135][136][137][138][139][140][141] At the same time, also the critical debate about hypoxemic hypoxia and about the high-altitude pulmonary edema (HAPE)-like condition in COVID-19 patients has attracted some scientific interest. [142][143][144] In fact, the dysfunctionality of RBC and hemoglobin has been proposed as primary cause of hypoxemic hypoxia, in presence of normal lung functionality during the early phase of COVID-19; the subsequent lung parenchyma deterioration in the late phase, with pneumolysis and interstitial pneumonia, would finally contribute to the ARDS phenomenon and to the deteriorated hypoxic state.…”

Pentraxin 3 Levels Correlate well with Disease Severity at Admission in COVID-19 Patients

“…In a study, red cell distribution width, mean platelet volume and platelet volume index were found to offer an inexpensive and effective method to predict the severity of the disease ( 6 ). In addition, the oxygenation index in COVID-19 does not correlate with disease severity as in typical ARDS ( 7 ).…”