The significance of antiglobulin (Coombs) test reactivity in patients with COVID-19.

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.

• Authors: Wael Hafez, Mohamad Azzam Ziade, Arun Arya, Husam Saleh, Ahmed Abdelrahman
• Journal: Immunobiology (Immunobiology) Vol. 227 Issue 4 Pg. 152240 (07 2022) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 35839729 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.

Chemical References

• Antibodies, Anti-Idiotypic
• Hemoglobins

Topics

• Anemia, Hemolytic, Autoimmune (diagnosis, drug therapy)
• Antibodies, Anti-Idiotypic (therapeutic use)
• COVID-19
• Coombs Test (methods)
• Hemoglobins
• Hemolysis
• Humans
• Retrospective Studies
• SARS-CoV-2