Red Blood Cell Abnormalities as the Mirror of SARS-CoV-2 Disease Severity: A Pilot Study

Anthi Bouchla; Anastasios G Kriebardis; Hara T Georgatzakou; Sotirios P Fortis; Thomas P Thomopoulos; Leoni Lekkakou; Konstantinos Markakis; Dimitrios Gkotzias; Aikaterini Panagiotou; Effie G Papageorgiou; Abraham Pouliakis; Konstantinos E Stamoulis; Sotirios G Papageorgiou; Vasiliki Pappa; Serena Valsami

doi:10.3389/fphys.2021.825055

Red Blood Cell Abnormalities as the Mirror of SARS-CoV-2 Disease Severity: A Pilot Study

Front Physiol. 2022 Jan 20:12:825055. doi: 10.3389/fphys.2021.825055. eCollection 2021.

Authors

Anthi Bouchla¹, Anastasios G Kriebardis², Hara T Georgatzakou², Sotirios P Fortis², Thomas P Thomopoulos¹, Leoni Lekkakou¹, Konstantinos Markakis¹, Dimitrios Gkotzias¹, Aikaterini Panagiotou¹, Effie G Papageorgiou², Abraham Pouliakis³, Konstantinos E Stamoulis⁴, Sotirios G Papageorgiou¹, Vasiliki Pappa¹, Serena Valsami⁵

Affiliations

¹ Second Department of Internal Medicine, Attikon Hospital, Research Institute, National and Kapodistrian University of Athens, Athens, Greece.
² Laboratory of Reliability and Quality Control in Hematology (HemQcR), Department of Biomedical Sciences, School of Health, and Caring Sciences, University of West Attica (UniWA), Egaleo, Greece.
³ Second Department of Pathology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
⁴ National Blood Center, Athens, Greece.
⁵ Hematology Laboratory - Blood Bank, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Abstract

Purpose: Unraveling 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 methods: Hospitalized 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 (iCa²⁺), 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).

Results: The 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/FiO₂ 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 (iCa²⁺, 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.

Conclusion: This 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.

Keywords: COVID-19; SARS-CoV-2; chest infiltration; disease severity; free hemoglobin; hemolysis; red blood cell.