Autoimmune hemolytic anemia in COVID-19 patients, the « transmissible » direct Coombs test

Abstract

Background: Like other viruses, the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) appears to be responsible for several autoimmune complications. The occurrence of autoimmune hemolytic anemia has been described in several case reports. This AIHA was also noticeable by the important number of blood transfusions required for COVID-19 (coronavirus disease 2019) patients. By investigating RBC coating autoantibodies, this article attempts to clarify the autoimmune aspect of the anemia in the context of SARS-CoV-2 infection. Results: A large population of COVID-19 patients selected at Saint-Luc University Hospital showed an average of 44% DAT positivity. In this population, the intensive care patients were more prone to DAT positivity than the general ward patients (statistically significant result). The positive DAT appeared « transmissible » to other RBCs via COVID-19 DAT-positive patient’s plasma. Conclusion: The strongest hypothesis explaining this observation is the targeting of cryptic antigens by autoantibodies in COVID-19 patients.

Hemolytic Anemia Complicating COVID-19 Infection

“…The exact mechanism of AIHA in the setting of COVID-19 infection remains unknown. One proposed mechanism is that the SARS-CoV-2 cytokine-rich inflammatory environment causes alteration in antigen presentation creating cryptic antigens [ 21 ]. Those cryptic antigens stimulate T lymphocytes which in turn activates autoreactive B lymphocytes to produce antibodies against those antigens [ 21 - 23 ].…”

“…One proposed mechanism is that the SARS-CoV-2 cytokine-rich inflammatory environment causes alteration in antigen presentation creating cryptic antigens [ 21 ]. Those cryptic antigens stimulate T lymphocytes which in turn activates autoreactive B lymphocytes to produce antibodies against those antigens [ 21 - 23 ]. These antibodies then coat the red blood cells (RBCs) causing the positive DAT in around 44-46% of COVID-19 patients [ 21 , 24 ].…”

“…Those cryptic antigens stimulate T lymphocytes which in turn activates autoreactive B lymphocytes to produce antibodies against those antigens [ 21 - 23 ]. These antibodies then coat the red blood cells (RBCs) causing the positive DAT in around 44-46% of COVID-19 patients [ 21 , 24 ]. The importance of the COVID-induced inflammatory milieu in exposing cryptic antigens was further emphasized by demonstrating that the DAT can be “transmitted” to allogeneic RBCs that have been in contact with the plasma of DAT-positive COVID-19 patients [ 21 , 23 ].…”

“…These antibodies then coat the red blood cells (RBCs) causing the positive DAT in around 44-46% of COVID-19 patients [ 21 , 24 ]. The importance of the COVID-induced inflammatory milieu in exposing cryptic antigens was further emphasized by demonstrating that the DAT can be “transmitted” to allogeneic RBCs that have been in contact with the plasma of DAT-positive COVID-19 patients [ 21 , 23 ]. In their study, Brochier et al reported a negative eluate among all of the 99 hospitalized COVID-19 patients who had a positive DAT [ 21 ], a finding similar to that of our patient.…”

“…The importance of the COVID-induced inflammatory milieu in exposing cryptic antigens was further emphasized by demonstrating that the DAT can be “transmitted” to allogeneic RBCs that have been in contact with the plasma of DAT-positive COVID-19 patients [ 21 , 23 ]. In their study, Brochier et al reported a negative eluate among all of the 99 hospitalized COVID-19 patients who had a positive DAT [ 21 ], a finding similar to that of our patient. The number of COVID-19 patients with positive DAT who would eventually develop clinically significant hemolysis remains unknown.…”