: The COVID-19 pandemic, which began in 2020, has been a relentless and formidable force, challenging our understanding of viral infections and the human immune response. As researchers worldwide delve into the complexities of this disease, much of the focus has centered on the immune system and cytokine storm associated with COVID-19. While these aspects are critical, there has been a notable lack of attention given to the impact of the virus on red blood cells (RBCs). Given that COVID-19 primarily affects the respiratory system and can lead to hypoxia, it is reasonable to suspect that the virus might influence the very carriers of oxygen in our bodies - the erythrocytes.
Morphological types of erythrocytes of five patients with severe COVID-19.
Images obtained by LVSEM. White segment is equal to 1 µm.
This COVID-19 News
report explores a recent study conducted by researchers from City Hospital, St. Petersburg-Russia, Military Medical Academy, Petersburg-Russia, and Saint-Petersburg State University-Russia, shedding light on the alterations in RBC morphology caused by severe COVID-19.
The Research Quest: Examining COVID-19's Influence on RBC Morphology
While much research has focused on the immune response to COVID-19, fewer studies have ventured into the realm of red blood cells. The researchers embarked on a mission to explore the changes that occur in RBCs during the cytokine storm induced by SARS-CoV-2 infection. To achieve this, the study team employed a powerful tool - Low-Voltage Scanning Electron Microscopy (LVSEM) images. Their goal was to not only identify these changes but also to compare RBC morphology between healthy donors and COVID-19 patients, potentially unveiling novel insights into the disease.
Poikilocytes: The Enigmatic Red Blood Cell Aberrations
The impact of SARS-CoV-2 on red blood cells has remained enigmatic, primarily due to the overwhelming emphasis on immunological parameters in COVID-19 research. The researchers' study revealed a plethora of features that could potentially be associated with conditions beyond COVID-19. Surprisingly, they did not uncover any unique pathologic RBC forms. It's essential to note that many studies assessing poikilocytosis in COVID-19 and other diseases rely on light microscopy, which may not offer the precision required to identify subtle changes in cell morphology. LVSEM, on the other hand, provides a more accurate depiction of cell morphology, but the criteria for categorizing various types of poikilocytes differ from those used in light microscopy. This subtle difference emphasizes the importance of the methodology employed in such investigations.
Acanthocytes: Clues to Underlying Health Conditions
In their study, the researchers observed a significant increase in the percentage of acanthocytes among COVID-19 patients. Acanthocytes are typically associated with various health conditions such as severe liver dysfunction, neuroacanthocytosis, abetalipoproteinemia, malnutrition, hypothyroidism, and post-splenectomy conditions.
The formation of acanthocytes primarily stems from abnormalities in membrane lipids or structural proteins. Notably, many of these conditions are characterized by protein or lipid disorders, which are also known risk factors in COVID-19. While the exact connection between COVID-19 and acanthocyte formation remains uncertain, it suggests that the virus may exacerbate underlying health issues, thereby impacting RBC morphology.
The Mystery of Decreased Spherocytes
Curiously, the researchers found a decrease in the number of spherocytes among COVID-19 patients. Spherocytes are spherical RBCs commonly found in certain conditions like hereditary spherocytosis or autoimmune hemolytic anemia. One plausible explanation for this observation could be that during pyrexia, cytokine storm, and heightened immune reactivity, spherocytes are eliminated more rapidly by splenic and liver macrophages. This heightened clearance may lead to a reduced presence of spherocytes in the peripheral blood of COVID-19 patients, but further research is needed to confirm this hypothesis.
The Enigma of Enlarged Erythrocytes
Perhaps the most striking finding of the study was the significant increase in the size of erythrocytes among COVID-19 patients. This observation aligns with similar findings reported by other research groups regarding Red Cell Distribution Width (RDW). Elevated RDW has been associated with increased disease severity in COVID-19 patients. Several potential mechanisms may explain this phenomenon. One possibility is that SARS-CoV-2 infection affects RBCs, leading to increased hemolysis markers and sensitivity to mechanical stress. This heightened sensitivity may result in cell shrinkage, cytoskeleton destruction, membrane blebbing, and microvesiculation. However, the study did not observe evident signs of cell shrinkage. Alternatively, COVID-19-associated coagulopathy and microvascular thrombi formation could directly damage RBCs. This theory is supported by the virus's ability to infect type II pneumocytes via ACE2, which are closely connected to the alveolar vascular network, potentially leading to microvascular thrombosis. However, this study did not find microscopic evidence of coagulopathy in RBCs.
The Caspase Conundrum
Another intriguing aspect of the research revolves around elevated caspase-3/7 levels in RBCs of COVID-19 patients. Caspases are enzymes involved in apoptosis, and their presence in RBCs suggests a potential role in erythropoiesis. It is hypothesized that immature forms of RBCs may enter the bloodstream due to SARS-CoV-2's affinity for ACE2 receptors found on RBC precursors. This hypothesis could explain the significant increase in erythrocyte size observed in COVID-19 patients. However, more research is needed to fully understand this complex phenomenon.
Conclusion: Unveiling the Mysteries of COVID-19's Impact on RBCs
In conclusion, this groundbreaking research employing low-voltage scanning electron microscopy has provided crucial insights into the impact of severe COVID-19 on red blood cell morphology. Notably, the study revealed an increase in erythrocyte size, a rise in acanthocytes, and a decrease in spherocytes among COVID-19 patients. These findings open doors to further investigations into the mechanisms underlying these alterations and their potential implications for disease severity and patient outcomes. As we continue to unravel the mysteries of COVID-19, this research reminds us that the virus's effects extend beyond the respiratory system, reaching even the smallest but essential components of our circulatory system - our red blood cells.
The study findings were published on a preprint server and are currently being peer reviewed.
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