@article{3034145,
    title = "Red Blood Cell Abnormalities as the Mirror of SARS-CoV-2 Disease
Severity: A Pilot Study",
    author = "Bouchla, Anthi and Kriebardis, Anastasios G. and Georgatzakou, Hara T. and and Fortis, Sotirios P. and Thomopoulos, Thomas P. and Lekkakou, Leoni and and Markakis, Konstantinos and Gkotzias, Dimitrios and Panagiotou, and Aikaterini and Papageorgiou, Effie G. and Pouliakis, Abraham and and Stamoulis, Konstantinos E. and Papageorgiou, Sotirios G. and Pappa, and Vasiliki and Valsami, Serena",
    journal = "FRONTIERS IN PHYSIOLOGY",
    year = "2022",
    volume = "12",
    publisher = "Frontiers Media SA",
    doi = "10.3389/fphys.2021.825055",
    keywords = "COVID-19; red blood cell; disease severity; hemolysis; SARS-CoV-2; chest
infiltration; free hemoglobin",
    abstract = "PurposeUnraveling the pathophysiology of COVID-19 disease is of crucial
importance for designing treatment. The purpose of this study is to
investigate the effects of the disease on erythrocytes (RBCs) and to
correlate the findings with disease severity. Materials and
MethodsHospitalized patients (n = 36) with COVID-19 and control group of
healthy volunteers (n = 18) were included in the study. Demographic
data, clinical, laboratory and chest Computed Tomography (CT) findings
at time of admission were recorded. Laboratory measurements included:
Hemoglobin (H b), indirect billirubin, LDH, D-Dimers, and plasma free
hemoglobin (plasma free-Hb). On RBCs were performed: osmotic fragility
(MCF), Free-Hb after mechanical stress (Free-Hb-MECH), intracellular RBC
concentration of calcium ions (iCa(2+)), intracellular ROS (iROS), G6PD,
intracellular active caspase-3 (RBC-caspase-3), IgG immunoglobulins
(RBC-IgGs), which are bound on RBCs’ senescent neo-antigen proteins and
RBC surface phosphatidylserine (RBC-PS). ResultsThe percentage of males
was 50 and 66% and the mean age was 65.16 +/- 14.24 and 66.33 +/- 13.48
years among patients and controls respectively (mean +/- SD, p = 0.78).
Upon admission patients’ PO2/FiO(2) ratio was 305.92 +/- 76.75 and
distribution of infiltration extend on chest CT was: 0-25% (N = 19),
25-50%: (N = 7), and 50-75% (N = 9). Elevated hemolysis markers (LDH
and plasma free-Hb) were observed in patients compared to the control
group. Patients’ RBCs were more sensitive to mechanical stress, and
exhibited significantly elevated apoptotic markers (iCa(2+), RBC-PS).
Plasma free Hb levels correlated with the extend of pulmonary
infiltrates on chest CT in COVID-19 patients. Surprisingly, patients’
RBC-iROS were decreased, a finding possibly related with the increased
G6PDH levels in this group, suggesting a possible compensatory mechanism
against the virus. This compensatory mechanism seemed to be attenuated
as pulmonary infiltrates on chest CT deteriorated. Furthermore, RBC-IgGs
correlated with the severity of pulmonary CT imaging features as well as
the abnormality of lung function, which are both associated with
increased disease severity. Lastly, patients’ D-Dimers correlated with
RBC surface phosphatidylserine, implying a possible contribution of the
red blood cells in the thrombotic diathesis associated with the
SARS-CoV-2 disease. ConclusionThis pilot study suggests that SARS-CoV-2
infection has an effect on red blood cells and there seems to be an
association between RBC markers and disease severity in these patients."
}