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Increased median deformation of red blood cells in children and adolescents after SARS-CoV-2 infection or COVID-19 vaccination

The red blood cells (RBCs) play a key role in microcirculation and tissue oxygenation. The alterations in RBCs induced by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may seriously impact microcirculation. The mechanical properties of RBCs are closely associated with cell functionality, so, there is an increasing interest in their characterization in COVID-19 patients. Several studies showed changes in the number and morphology of peripheral blood cells in patients with COVID-19. In this study, researchers from Germany and Switzerland used a new technique, real-time deformability cytometry (RT-DC), to investigate morphological and mechanical characteristics of RBCs in children and adolescents infected with SARS-CoV-2 or following a COVID-19 vaccination. 

SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA virus. Its genome encodes four structural proteins, namely the spike (S), envelope (E), nucleocapsid (N), and membrane (M) protein. The S protein appears to be a major pathogenic factor that contributes to the unique pathogenesis of SARS-CoV-2. The S protein is a glycosylated homotrimer with each monomer composed of subunits S1 and S2, separated by host cell proteases.

A real-time deformability cytometry (RT-DC) can assess morphological changes in peripheral blood cells and detect altered mechanical properties associated with specific disease pathologies. Previous RT-DC analysis of peripheral blood cells from adult COVID-19 patients demonstrated more heterogeneous and deformed RBCs.

About the study

This study investigated morphological and mechanical changes in RBCs of children and adolescents who were seronegative or seropositive for SARS-CoV-2. The presence of IgG antibodies specific for S1 and S2 subunits of the S protein defined SARS-CoV-2 seropositivity. The two groups did not differ in terms of age or gender.

Participants were further categorized based on the time from infection into two groups: those who tested seropositive more than six months ago (n = 21) and those who tested seropositive within the past six months (n = 18).

Nine participants reported complete COVID-19 vaccination status at the time of blood collection. They were older than SARS-CoV-2 seronegative participants. The subjects with only one vaccination dose were not included in the study.


The study included 121 participants, 49 were SARS-CoV-2 seronegative and 63 were SARS-CoV-2 seropositive. The mean age was 14.93 years, ranging between 11 and 18 years.

The results of RT-DC of peripheral blood cells showed a significant increase in median deformation of RBCs in participants seropositive for SARS-CoV-2 compared to seronegative participants. In addition, the median deformation of RBCs was significantly higher in participants with complete COVID-19 vaccination than in seronegative participants.

The higher median deformation of RBCs in seropositive and vaccinated participants than in seronegative participants has been found only if the SARS-CoV-2-seroconversion had occurred within the past six months. There was no significant difference in the median deformation of RBCs between participants if the SARS-CoV-2-seroconversion occurred more than six months ago. 

Since the results demonstrated higher deformation of RBCs in participants with complete COVID-19 vaccination compared to seronegative participants, the authors speculated that increased deformation of RBCs might be a direct consequence of the SARS-CoV-2 S protein presentation and a component of the immune response against SARS-CoV-2. This observation needs to be confirmed further because a small number of participants in this study had been fully vaccinated against COVID-19.

The RBCs were significantly brighter in both subgroups who tested seropositive (more than six months and within six months) than seronegative subjects, regardless of the time from SARS-CoV-2-seroconversion. The brightness of RBCs did not differ significantly between the two seropositive subgroups. The authors noted that these findings could be due to various SARS-CoV-2 effects, such as direct infection of RBCs or changes in hemoglobin.

The researchers discussed possible mechanisms that caused a loss of membrane integrity and increased deformation of RBCs. These mechanisms might include the fragmentation of the membrane-bound protein band-3 that coordinates the shape of RBCs, deposition of immune complexes on the membrane of RBCs, mechanical damage of RBCs through capillary shear stress, the release of NO from endothelial cells, and physiological compensatory mechanisms that prevent microthrombosis and hypoxemia during the infection. Accordingly, the observed increase in median deformation of RBCs in seropositive children and adolescents with asymptomatic to mild COVID-19 may represent the maximum capacity of these compensatory mechanisms in young and healthy organisms.


These findings demonstrated that increased deformation of RBCs, measured by the RT-DC, has been found in children and adolescents after SARS-CoV-2 infection and COVID-19 vaccination. The median deformation of RBCs was higher in seropositive and vaccinated participants than in seronegative participants within six months following SARS-CoV-2 infection. 

This article was published in Scientific Reports.

Journal Reference

Eder al. Increased red blood cell deformation in children and adolescents after SARS-CoV-2 infection. Sci Rep 13, 9823 (2023) (Open Access)

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