Red Blood Cell Morphology in Severe COVID-19: Insights from Low-Voltage Scanning Electron Microscopy


Since the emergence of the COVID-19 pandemic in 2020, scientists and researchers worldwide have been grappling with the complexities of the virus’s impact on the human body.

While much attention has been devoted to studying the immune response, cytokine storms, and inflammatory markers associated with SARS-CoV-2 infection, relatively few investigations have explored the effects on red blood cells (RBCs).

Given the respiratory nature of COVID-19, which often leads to hypoxia and systemic oxygen imbalances, it is essential to understand whether the virus affects the fundamental transporters of oxygen – erythrocytes. This article delves into the intricate details of a study that sought to identify changes in RBC morphology during COVID-19-induced cytokine storms.

Using Low-Voltage Scanning Electron Microscopy (LVSEM) images, the study conducted a comparative analysis of RBC morphology between healthy donors and COVID-19 patients.


The Impact of SARS-CoV-2 on Red Blood Cells

The impact of SARS-CoV-2 on red blood cells remains a subject of ongoing research and debate. Most studies in the early phases of the pandemic focused on immunological parameters, leaving limited data available for analysis. The study at hand, utilizing LVSEM, offers a more precise examination of RBC morphology. However, it’s crucial to recognize that comparing findings from LVSEM with those obtained through traditional light microscopy presents challenges, as the criteria for categorizing abnormal erythrocyte shapes differ.

Acanthocytes and Potential Associations

One notable observation in the study was a significant increase in the percentage of acanthocytes in COVID-19 patients. Acanthocytes are typically associated with various medical conditions, such as severe liver dysfunction, neuroacanthocytosis, and malnutrition. Liver dysfunction can lead to an accumulation of lipoproteins in plasma, resulting in abnormal cholesterol levels in RBCs, ultimately causing acanthocyte formation.

Interestingly, several of these conditions are linked to protein or lipid disorders, both of which are known risk factors in COVID-19. This suggests a possible connection between these underlying conditions and the observed increase in acanthocytes in COVID-19 patients.

Spherocytes and Potential Explanations

Conversely, the study found a lower percentage of spherocytes among COVID-19 patients. This phenomenon could be attributed to the hyperactive immune response and cytokine storm during acute infection, potentially leading to the rapid elimination of spherocytes by splenic and liver macrophages. This increased clearance rate might explain the reduced presence of spherocytes in the peripheral blood of COVID-19 patients.

Erythrocyte Size and Red Cell Distribution Width (RDW)

The research also revealed a significant increase in erythrocyte size among COVID-19 patients, a finding consistent with previous studies that demonstrated elevated red cell distribution width (RDW) values in severe COVID-19 cases. Higher RDW values have been associated with disease severity and an increased risk of mortality. This increase in erythrocyte size may be linked to several pathogenetic pathways.

Possible Pathogenetic Mechanisms

One potential mechanism is related to increased sensitivity of COVID-19 patients’ RBCs to mechanical stress, leading to elevated apoptotic markers. Increased intracellular calcium content in RBCs can activate processes resulting in cell shrinkage, cytoskeleton destruction, membrane blebbing, and microvesiculation. However, the study did not find evident signs of cell shrinkage. Instead, poikilocytes were observed, which could be a manifestation of cytoskeleton disruption.

Another possible mechanism is the direct infection of RBC precursors by SARS-CoV-2 due to the presence of ACE2 receptors. This viral infection may lead to iron dysmetabolism, impairing oxygen-binding capacity in severely ill COVID-19 patients, exacerbating hypoxia, and triggering an accelerated erythropoietic response. This response may produce immature erythrocytes that contribute to the observed increase in erythrocyte size.


In conclusion, this study employing low-voltage scanning electron microscopy sheds light on the impact of severe COVID-19 on red blood cells. The findings indicate an increase in erythrocyte size, dispersion, and the presence of acanthocytes, along with a decrease in spherocytes.

These observations offer valuable insights into the pathophysiological mechanisms at play during a cytokine storm in COVID-19 patients and emphasize the need for further research to unravel the intricate interplay between the virus and red blood cells.

Understanding these mechanisms could pave the way for more effective therapeutic interventions and a deeper comprehension of the multifaceted nature of COVID-19.


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