Anti-SARS-CoV2 antibody-mediated cytokine release syndrome in a patient with acute promyelocytic leukemia

Abstract

Background Passive immunization against SARS-CoV-2 limits viral burden and death from COVID-19; however, it poses a theoretical risk of disease exacerbation through antibody-dependent enhancement (ADE). ADE after anti-SARS-CoV2 antibody treatment has not been reported, and therefore the potential risk and promoting factors remain unknown. Case presentation A 75-year-old female was admitted to the emergency room with recurrent, unexplained bruises and leukocytopenia, anemia, and thrombocytopenia. Evaluation of a bone marrow biopsy established the diagnosis of an acute promyelocytic leukemia (APL). SARS-CoV-2 RT-PCR testing of nasal and throat swabs on admission was negative. During the routine SARS-CoV-2 testing of inpatients, our patient tested positive for SARS-CoV-2 on day 14 after admission without typical COVID-19 symptoms. Due to disease- and therapy-related immunosuppression and advanced age conferring a high risk of progressing to severe COVID-19, casirivimab and imdevimab were administered as a preemptive approach. The patient developed immune activation and cytokine release syndrome (CRS) occurring within four hours of preemptive anti-SARS-CoV2 antibody (casirivimab/imdevimab) infusion. Immune activation and CRS were evidenced by a rapid increase in serum cytokines (IL-6, TNFα, IL-8, IL-10), acute respiratory insufficiency, and progressive acute respiratory distress syndrome. Discussion and conclusion The temporal relationship between therapeutic antibody administration and the rapid laboratory, radiological, and clinical deterioration suggests that CRS was an antibody-related adverse event, potentially exacerbated by APL treatment-mediated differentiation of leukemic blasts and promyelocytes. This case highlights the need for careful assessment of life-threatening adverse events after passive SARS-CoV-2 immunization, especially in the clinical context of patients with complex immune and hematological landscapes.

Theoretical Explanation for the Rarity of Antibody-Dependent Enhancement of Infection (ADE) in COVID-19

“…A marked decline in pneumocyte survival will only be observable when the binding affinity between the viral epitope and the antibody is very high. This suggestion is indirectly supported by a clinical case in which an acute myeloid leukemia patient might have suffered ADE shortly after being treated with high-affinity anti-COVID-19 therapy [ 41 ].…”

A Review: Understanding Molecular Mechanisms of Antibody-Dependent Enhancement in Viral Infections

“…The intrinsic ADE can be evinced from a case study where the cytokine release syndrome (CRS) arises after infusion of an anti-SARS-CoV-2 antibody in a 75 year old patient. An increased level of the IL-6, TNFα, IL-8, and IL-10 cytokines in serum contributed to the immune activation and, finally, the progressive acute respiratory distress syndrome [ 43 ]. As a result of the findings from the aforementioned studies, it is important to evaluate the mechanism of ADE in the case of SARS-CoV-2 and its effects on the severity of the disease.…”

Antibody dependent enhancement-induced hypoxic respiratory failure: A case report

“…There are previous reports of ADE after both the COVID-19 vaccine and monoclonal antibody treatment and vaccine. 8 , 9 Because of the temporal relationship of the reaction following the infusion, the adverse event confirmed by objective evidence on the CT scan, a Naranjo Adverse Drug Reaction Probability Scale reveals the monoclonal antibody was the possible cause of the patients deterioration. 10 As for alternative causes for the acute hypoxia, the patient had no other signs or symptoms of an acute allergic reaction—such as hives or flushing.…”