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

• Published in: BMC infectious diseases Vol. 22; no. 1; p. 537
• Main Authors: Hegazy, Ahmed N, Krönke, Jan, Angermair, Stefan, Schwartz, Stefan, Weidinger, Carl, Keller, Ulrich, Treskatsch, Sascha, Siegmund, Britta, Schneider, Thomas
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.06.2022; BioMed Central; BMC
• Subjects: Acute promyelocytic leukemia; Acute promyeloid leukemia; Adverse events; Aged; Anemia; Antibiotics; Antibodies; Antibodies, Monoclonal, Humanized; Antibody-dependent enhancement; Biopsy; Blood pressure; Bone marrow; Bone marrow examination; Case Report; Case reports; Coronavirus disease 2019; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - diagnosis; COVID-19 Testing; Cytokine release syndrome; Cytokine Release Syndrome - diagnosis; Cytokine Release Syndrome - drug therapy; Cytokine Release Syndrome - etiology; Cytokine storm; Cytokines; Cytomegalovirus; Emergency medical care; Emergency medical services; Female; Health aspects; Health risks; Health services; Heart rate; Humans; Immune response; Immunization; Immunization (passive); Immunosuppression; Infections; Infectious diseases; Interleukin 10; Interleukin 6; Interleukin 8; Leukemia; Leukemia, Promyelocytic, Acute - complications; Leukemia, Promyelocytic, Acute - diagnosis; Leukemia, Promyelocytic, Acute - drug therapy; Leukopenia; Measurement; Methods; Oxygen saturation; Pathogens; Patients; Preempting; Promyeloid leukemia; Pulmonary arteries; Respiratory Distress Syndrome; Risk; Risk assessment; Risk factors; SARS-CoV-2; SARS-CoV2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; Thrombocytopenia; Tumor necrosis factor-α; Viral diseases; Viral infection; Viral infections; Germany; SARS-CoV2; Case report; Cytokine release syndrome; Acute promyelocytic leukemia; Coronavirus disease 2019; Antibody-dependent enhancement; Viral infection
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-022-07513-0

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. 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. 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.