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. 2022 Jul;227(4):152240.
doi: 10.1016/j.imbio.2022.152240. Epub 2022 Jul 6.

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

Wael Hafez  1 , Mohamad Azzam Ziade  2 , Arun Arya  2 , Husam Saleh  2 , Ahmed Abdelrahman  3
Affiliations

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

Wael Hafez et al. Immunobiology. 2022 Jul.

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.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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