Abstract
Previous case reports have described patients with COVID-19-associated autoimmune hemolytic anemia (AIHA), and cold agglutinin disease (CAD) which is characterized by a positive direct antiglobulin (DAT) or “Coombs” test, yet the mechanism is not well understood. To investigate the significance of Coombs test reactivity among COVID-19 patients, we conducted a retrospective study on hospitalized COVID-19 patients treated at NMC Royal Hospital between 15 April and 30 May 2020. There were 27 (20%) patients in the Coombs-positive group and 108 (80%) in the Coombs-negative group. The cold agglutinin titer was examined in 22 patients due to symptoms suggestive of cold agglutinin disease, and all tested negative. We demonstrated a significant association with reactive Coombs test results in univariate analysis through clinical findings such as ICU admission rate, the severity of COVID-19, and several laboratory findings such as CRP, D-dimer, and hemoglobin levels lactate dehydrogenase, and RDW-CV. However, only hemoglobin levels and disease severity had a statistically significant association in multivariate analysis. A possible explanation of COVID-19-associated positive Coombs is cytokine storm-induced hyperinflammation, complement system activation, alterations of RBCs, binding of SARS-CoV-2 proteins to hemoglobin or its metabolites, and autoantibody production. Coombs-positive patients were tested for hemolysis using indirect bilirubin, consumed haptoglobin, and/or peripheral smear that ruled out any evidence of hemolysis. Understanding this etiology sheds new light on RBC involvement as a pathophysiological target for SARS-CoV-2 by interfering with their function; consequently, therapies capable of restoring RBC function, such as erythrocytapheresis, could be repurposed for the treatment of worsening severe and critical COVID-19.
Keywords: Anemia; Antiglobulin (Coombs) test; Erythrocytapheresis; Hemoglobinopathy; Hemolysis; Red blood cell.
【저자키워드】 Anemia, Hemolysis, Hemoglobinopathy, Antiglobulin (Coombs) test, Erythrocytapheresis, Red blood cell., 【초록키워드】 COVID-19, Treatment, SARS-CoV-2, therapy, disease severity, CRP, D-dimer, cytokine, Symptom, lactate dehydrogenase, Case report, Laboratory, Retrospective study, severity of COVID-19, hyperinflammation, Patient, ICU admission, understanding, Autoimmune, metabolites, hemoglobin, etiology, disease, Critical, mechanism, COVID-19 patients, binding, red blood cell, association, hospitalized COVID-19 patient, Evidence, CAD, Analysis, autoantibody, hemolytic anemia, peripheral smear, Clinical finding, alteration, worsening, SARS-CoV-2 protein, Univariate analysis, positive, RBCs, RBC, reactive, complement system activation, tested, described, examined, conducted, characterized, treated, demonstrated, reactivity, statistically significant, Antiglobulin, indirect bilirubin, pathophysiological, 【제목키워드】 reactivity, patients with COVID-19,