Since the onset of the COVID-19 pandemic in early 2020, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the global population has been grappling with the far-reaching impacts of this highly infectious and easily transmissible virus.
A consistent observation among COVID-19 patients, whether severe or mild, is a reduction in fitness, possibly linked to compromised oxygen transport and/or release by red blood cells (RBC). Research has demonstrated that SARS-CoV-2 can invade erythroid precursors and progenitors, inducing hematopoietic stress and leading to abnormalities in RBC morphology and their ability to respond to environmental cues.
This article discusses the long-term hematological and hemorheological effects of mild COVID-19 infections, exploring how these alterations may contribute to persistent symptoms and the emerging phenomenon of Long-COVID.
Hematological Changes in COVID-19 Patients
In the acute phase of COVID-19, patients exhibit a distinctive hematological profile, characterized by lower RBC count, mean cellular hemoglobin concentration (MCHC), hemoglobin concentration (Hb), and hematocrit (Hct).
Additionally, decreased mean cellular volume (MCV) and mean cellular hemoglobin (MCH) and an increased red blood cell distribution width (RDW) have been observed.
These hematological alterations are associated with functional changes in RBC, such as reduced deformability, increased blood viscosity, and enhanced RBC aggregation. These changes have been attributed to membrane lipid remodeling and structural protein damage, particularly affecting the RBC cytoskeleton. Impaired deformability is linked to decreased oxygen transport and tissue hypoxia, with potential involvement of beta-chain hemoglobin damage and elevated methemoglobin formation.
Hematological Changes in Mild COVID-19
Interestingly, these RBC alterations have been reported not only in severe COVID-19 cases but also in patients with mild disease courses. Furthermore, the persistence of COVID-19 symptoms beyond the acute phase, even in cases with initially mild symptoms, raises questions about the long-term effects of the virus on the RBC system.
Long-Term Hematological and Hemorheological Effects
The study presented in this article aimed to investigate the persistence of hematological and hemorheological changes in individuals who had experienced mild COVID-19 infection after a 4-month follow-up period. The findings revealed that many of the previously described alterations were still evident, suggesting that the virus can induce long-term modifications in the RBC.
Hematological Parameters: Hemoglobin and RBC Volume
The study confirmed lower hemoglobin-related parameters and reduced RBC volume in COVID-19 patients compared to control subjects, indicating ongoing alterations in RBC characteristics. While MCV increased four months after infection, hemoglobin parameters continued to decrease, possibly due to the interaction of the S1 spike protein of the virus with RBC membrane proteins like Band-3 and protoporphyrin IX.
This interaction can cause hemoglobin denaturation, affecting oxygen transport. An elevated oxygen affinity of hemoglobin might be a compensatory mechanism, advantageous for loading hemoglobin in the lungs but potentially impairing oxygen unloading at target cells. The observed alterations in specific hematological parameters might contribute to long-term symptoms like loss of lung function and cardiorespiratory capacity, given the RBC’s lifespan of approximately 120 days.
RBC deformability, crucial for microcirculatory function, was reduced in COVID-19 patients during the acute phase and remained impaired at the study’s outset (T0). However, the data suggested that deformability tended to improve and approach control levels over the 4-month follow-up period. Even RBC with minor deformability impairments might persist in the circulation, possibly inducing mechanical stress and affecting spleen function, which could contribute to long-term symptoms. Deformability measurements showed that changes in RBC properties might be reversible in the long term.
RBC aggregation, which influences blood flow properties, was found to increase four months after COVID-19 infection. The high individual variability in this parameter suggests that additional factors, including physical activity, might be involved in this change. Physical exercise could positively affect RBC aggregation and might explain the improvement in deformability observed during the follow-up period.
Sex-based differences in hematological and rheological parameters are well-documented. The study results indicated that the differences between healthy controls and COVID-19 patients were more pronounced in males than females. This may reflect the known variations in hematological parameters between the sexes. Hemoglobin concentration, for instance, was frequently below the normal range in male COVID-19 patients, suggesting that men may be more affected by the virus. This is consistent with observations of higher disease severity and mortality rates in older males compared to females, children, and adolescents.
Limitations and Conclusion
While this study provides valuable insights into the long-term effects of mild COVID-19 on the RBC system, there are limitations. The small number of female participants and the absence of a comparative measurement for the control group after four months raise some questions. However, previous research suggests that hematological values remain relatively stable over an extended period.
In conclusion, these findings emphasize the enduring impact of mild COVID-19 infections on hematological and hemorheological parameters, potentially contributing to persistent symptoms seen in Long-COVID patients. Understanding these long-term effects is crucial for patient management and healthcare strategies as the pandemic continues to unfold.
reference link: https://www.mdpi.com/2038-8330/15/4/57