key: cord-0907052-z9angxwn authors: Faguer, Stanislas; Del Bello, Arnaud; Abravanel, Florence; Nicolau-Travers, Marie-Laure; Kamar, Nassim title: Tocilizumab for Hemophagocytic Syndrome in a Kidney Transplant Recipient With COVID-19 date: 2020-05-18 journal: Ann Intern Med DOI: 10.7326/l20-0419 sha: 7e1e3f17fddddfe60ec4dd9fb627c73f6d7e07c8 doc_id: 907052 cord_uid: z9angxwn nan Background: A subset of patients with coronavirus disease 2019 (COVID-19) will develop acute respiratory distress syndrome and require mechanical ventilation. Studies suggest that many patients with COVID-19 and acute respiratory distress syndrome experience a cytokine storm characterized by fever; hyperferritinemia; and a massive release of inflammatory cytokines, including interleukin-6, tumor necrosis factor-␣, and monocyte chemoattractant proteins (1) . These findings led to the hypothesis that biological agents targeting specific cytokine or inflammatory pathways may improve the respiratory outcomes of patients with the most severe forms of COVID-19 (2) . Objective: To describe a patient with COVID-19 and overt hemophagocytic syndrome whose response to treatment was consistent with this hypothesis. Case Report: A 51-year-old man who had received a kidney transplant was referred to our intensive care unit for cough, fever, and shortness of breath leading to the presumptive diagnosis of COVID-19. On day 1, acute respiratory failure required mechanical ventilation and prone positioning. Therapy with dexamethasone (5 mg twice daily), ceftriaxone (2 g/d), and spiramycin (1.5 million units 3 times daily) was initiated. Tacrolimus and mycophenolate mofetil were withdrawn. On day 2, the patient developed refractory multiorgan failure characterized by an inflammatory state, heart failure, stage 3 acute-on-chronic kidney injury, acute liver failure, nonregenerative anemia, thrombocytopenia, and lactic acidosis. The C-reactive protein level was 262 mg/L, and the ferritin level was 52 005 μg/L. We considered a diagnosis of hemophagocytic syndrome because the patient had underlying immunosuppression; fever of 39°C; a serum ferritin level above 6000 μg/L; a hemoglobin level below 92 g/L; a platelet count below 110 × 10 9 cells/L; high levels of serum triglycerides; and aspartate aminotransferase with an HScore of 253, which indicated that the probability of having hemophagocytic syndrome was 99.5% (3). Bone marrow aspiration and liver biopsy confirmed the presence of hemophagocytosis (Figure) . Polymerase chain reaction identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in bronchoalveolar fluid (cycle threshold 21) and blood. Given the salutary effects of interleukin-6 receptor inhibition in the treatment of secondary hemophagocytic syndromes (4) and chimeric antigen receptor T cell-related cyto-This article was published at Annals.org on 18 May 2020. kine release syndromes (5), we treated the patient with tocilizumab (8 mg/kg intravenously, once) as salvage therapy, instead of etoposide, and we withdrew dexamethasone. Tocilizumab administration was followed by dramatic improvement of the respiratory, hemodynamic, and liver conditions and correction of the ferritin levels (Table) . Three days after tocilizumab administration, we observed normalization of circulating levels of CD3 -CD16 + CD56 + natural killer cells and effector CD8 + CD56 + and CD8 + CD57 + perforin-positive, granzyme-positive T cells. Discussion: In this report, we describe an immunocompromised patient with COVID-19 and a related hemophagocytic syndrome whom we treated with tocilizumab. The cytokine storm and multiorgan failure rapidly reversed, and the patient made a speedy recovery. On hospital day 30, the patient was breathing spontaneously with protective tracheotomy, and rehabilitation is ongoing. On the basis of this experience, we suggest that clinicians who have similar patients consider using drugs that inhibit interleukin-6 to treat these patients while waiting for the results of the randomized controlled trials that are now evaluating tocilizumab in patients with COVID-19 and respiratory failure. Clinical features of patients infected with 2019 novel coronavirus in Wuhan The cytokine release syndrome (CRS) of severe COVID-19 and interleukin-6 receptor (IL-6R) antagonist tocilizumab may be the key to reduce the mortality Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome The authors thank Dr. Emmanuel Treiner, Prof.