key: cord-0774014-zr59mmrt
authors: Hendrickson, Jeanne E.; Tormey, Christopher A.
title: COVID-19 and the Coombs test
date: 2020-08-06
journal: Blood
DOI: 10.1182/blood.2020007483
sha: f6330d59dc41eea7cba6eaa5ba661baaf3540cf7
doc_id: 774014
cord_uid: zr59mmrt

In this issue of Blood, Berzuini et al(1) describe immunoglobulin G (IgG) bound to the red blood cells (RBCs) of patients with COVID-19 and associate this bound IgG with increased RBC transfusion requirements. The intrigue behind these observations is not just the high (46%) direct antiglobulin test (DAT) positivity rate, but also the novel finding that eluates (ie, antibodies stripped from the surface of the reactive RBCs) from these DAT-positive patients react not with standard-reagent RBCs but exclusively with RBCs from DAT-negative COVID-19 patients.

thus a durable treatment strategy. Broadly, COVID-19 presents a rare opportunity to study CP. If shown to be effective, CP would offer a scalable model that could be applied both to the current pandemic as well as to future emerging infectious diseases. It could also facilitate development of hyperimmune globulin and vaccine design. Clinical trials are already under way to address the uncertainty of use. Nonetheless, harmonization of efforts is needed along with creative approaches to overcome looming obstacles, such as pairing of trials of similar design and/or metanalysis. We must not be left wondering whether the intervention worked after the pandemic wanes. positivity rate, but also the novel finding that eluates (ie, antibodies stripped from the surface of the reactive RBCs) from these DAT-positive patients react not with standard-reagent RBCs but exclusively with RBCs from DAT-negative COVID-19 patients.

Although the association of DAT positivity and anemia is limited by study design, the serologic findings may be teaching us something important about modifications to RBCs that occur in COVID-19. The authors are to be congratulated on the rapid dissemination of these data and on the clever idea of using RBCs from COVID-19 patients as blood bank reagents in addition to standard, commercially available reagent RBCs. Moreover, complement receptors on RBC surfaces are important in the clearance of immune complexes in infectious or inflammatory disease. 6 It is possible, but purely speculative, that there may be alterations of complement receptors on the RBC surface of COVID-19 patients, contributing not only to the DAT positivity but also to the pattern of eluate reactivity. Future studies of the roles that complement and complement receptors may play in COVID-19, through the lectin pathway, the classical pathway, or the alternative pathway, 7 are eagerly awaited.

Although Berzuini et al did not find a relationship between DAT positivity and any of the medications administered, the possibility of a drug effect cannot be fully discounted because an IgG-positive DAT with a negative eluate against standardreagent RBCs may be drug associated until proven otherwise. 8 In their article, it is unclear what drugs the 5 COVID-19-positive patients whose RBCs were used for eluate testing might have been taking. Repeating the eluate testing using RBCs from different COVID-19-positive donors who were not taking any drugs could be one way to investigate this possibility, although by definition such individuals would be less ill. Alternatively, the authors could incorporate select, commonly identified drugs into the eluate testing with standard-reagent RBCs to evaluate for a drug-dependent effect.

In sum, the Coombs test results and associated clinical data described by Berzuini et al in hospitalized patients with COVID-19 add to our growing understanding of hematologic manifestations of SARS-CoV-2. Given the time-sensitive nature of the COVID-19 pandemic, the data from the samples collected over a 1-week period are not exhaustive and the conclusions are not definitive. However, the described results are thoughtprovoking, and they join the findings of other rapidly written manuscripts in raising important questions to be investigated by the hematology and transfusion medicine communities in the years to come.

Conflict-of-interest disclosure: The authors declare no competing financial interests. n

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Elution studies are performed to separate bound Ig from a patient's RBCs in the setting of an IgG-positive DAT; this separation is typically accomplished using pH or temperature changes. As depicted, the eluates from COVID-19 patients with an IgG-positive DAT did not show agglutination after incubation with commercially available reagent RBCs. However, the same eluates incubated with RBCs derived from other COVID-19 patients showed agglutination. Professional illustration by Patrick Lane