Red Blood Cell Morphology Is Associated with Altered Hemorheological Properties and Fatigue in Patients with Long COVID

SARS-CoV-2 alters the properties of oxygen-carrying red blood cells (RBCs) through a possible deterioration of hemorheological properties, such as aggregation and deformability. However, long-term changes in these properties and a possible association with morphological abnormalities remain unknown. Therefore, this study aims to investigate changes in the above-mentioned RBC properties in Long-COVID (LC). Venous blood was collected from n = 30 diagnosed LC and n = 30 non-Long-COVID controls (non-LC). Hematological parameters were measured, as well as the aggregation, deformability, and morphology of the RBCs and the mechanical sensitivity index (MS), which reflects the functional capacity of RBCs to deform. The results indicate that hematological parameters were not altered in LC. However, LC showed higher overall aggregation parameters. RBC deformability was higher in LC compared to non-LC; however, MS was limited in this group. LC showed a higher percentage of RBCs with abnormal shapes, which was related to MS and to fatigue, which is considered the leading symptom of LC. It is concluded that the symptoms of LC and changes in the blood flow determining the properties of RBCs are related to the morphological changes in RBCs. Future studies should investigate the underlying causes in order to develop appropriate therapies for this relatively new disease.

Background: SARS-CoV-2 infection adversely affects rheological parameters, particularly red blood cell (RBC) aggregation and deformability, but whether these changes persist in patients suffering from Long-COVID (LC) and whether these changes are related to RBC morphology remain unknown.

Methods: Venous blood was collected from n = 30 diagnosed LC patients and n = 30 non-LC controls and RBC deformability, RBC aggregation, and hematological parameters were measured. In addition, RBCs were examined microscopically for morphological abnormalities. The mechanical sensitivity index (MS) was assessed in n = 15 LC and n = 15 non-LC samples.

Results: Hematological parameters did not differ between the groups. However, LC showed higher aggregation-related parameters. Although RBC deformability was higher in LC, MS, reflecting the functional capacity to deform, was limited in this group. RBCs from LC showed significantly more morphological abnormalities. The extent of morphological abnormalities correlated with MS and the FACIT-Fatigue score of the LC patients.

Conclusion: RBCs from LC show a high degree of morphological abnormalities, which might limit the blood flow determining RBC properties and also be related to fatigue symptomatology in LC. Approaches are now needed to understand the underlying cause of these alterations and to ameliorate these permanent changes.