key: cord-0692641-oqeoawny authors: De Luna, Gonzalo; Habibi, Anoosha; Odièvre, Marie‐Hélène; Guillet, Henri; Guiraud, Vincent; Cougoul, Pierre; Carpentier, Benjamin; Loko, Gylna; Guichard, Isabelle; Ourghanlian, Clément; Pawlotsky, Jean Michel; Mahevas, Matthieu; Limal, Nicolas; Michel, Marc; Mekontso‐Dessap, Armand; Arlet, Jean‐Benoît; Bartolucci, Pablo title: Blood exchange transfusion with dexamethasone and Tocilizumab for management of hospitalized patients with sickle cell disease and severe COVID‐19: Preliminary evaluation of a novel algorithm date: 2022-04-15 journal: Am J Hematol DOI: 10.1002/ajh.26563 sha: fa08747a63c9e528a28c637c441cfb1cb3561abc doc_id: 692641 cord_uid: oqeoawny nan Blood exchange transfusion with dexamethasone and Tocilizumab for management of hospitalized patients with sickle cell disease and severe COVID-19: Preliminary evaluation of a novel algorithm To the Editor: Sickle cell disease (SCD) is a severe hemoglobin (Hb) disorder characterized by hemolytic anemia, recurrent painful vaso-occlusive events, and ischemia/reperfusion-driven inflammation. Acute chest syndrome (ACS) is a common and potentially life-threatening form of acute lung injury that can be triggered by infectious conditions. Coronavirus disease 2019 (COVID-19) infection represents a significant mortality risk for SCD patients, as death or required mechanical ventilation was reported for 5.6% of patients in the largest cohort of SCD patients hospitalized for COVID-19. 1 In this cohort, ACS was described for 30% of patients. For SCD patients hospitalized with severe COVID-19 requiring supplemental oxygen, current therapeutic strategies may include corticosteroids, the interleukin-6 (IL-6) inhibitor Tocilizumab, or anticoagulant agents. Selection of the appropriate therapies may have a critical impact on patient outcome, due to the complex relationship between the drugs' mechanism of action and SCD pathophysiology. For instance, the use of corticosteroids in SCD patients should be approached with caution, as corticosteroids are associated with an increased risk of hospitalization for vaso-occlusive crises (VOC) or ACS. 2 In contrast, Odièvre et al. reported dramatic improvement after Tocilizumab in COVID-19-related ACS in a pediatric SCD patient, 3 as was also previously described in an adult SCD patient, suggesting that IL-6 could play an essential role in ACS pathophysiology. We propose here a treatment algorithm for SCD patients hospitalized with severe COVID-19. The aim of the algorithm is to minimize the worsening of SCD patients' clinical course related to corticosteroid therapy by proposing a prior blood exchange transfusion (BET); Tocilizumab is considered as alternative when transfusion is not recommended due to immunization against red blood cell (RBC) antigens. This algorithm was developed taking into consideration multiple aspects of SCD pathophysiology and of COVID-19 in SCD. . Percentages do not always equal 100% because of rounding. Around 11 patients were collected from March 13, 2020 to 17 January 2022 with a median age of 40 [17-50] years, 54% female; one pregnant woman is described. Concerning genotype HbSS was reported in 64%, HbSC in 27% and one HbS/BetaThal°; median IMC was 23.9 kg/m 2 , Hydroxyurea (HU) treatment was reported in 62% of HbSS and HbS/BetaThal°genotype. The median length of hospitalization stay was 12.5 days , with intensive care unit admission in 73%. ACS related to COVID-19 was reported in eight patients with blood exchange transfusion (BET) performed in 75% of them and no BET in 25% due to dramatic improvement after Tocilizumab (one Jehovah's Witness patient is described). VTE or PE was reported in 27%. Tocilizumab infusion was related to history of DHTR (n = 1), high DHTR risk development (n = 5) and BET not available in the 24 h before corticosteroid infusion (n = 5). Corticosteroids were prescribed in 27% after BET due to infection severity despite Tocilizumab, required mechanical ventilation in 45% and extracorporeal membrane oxygenation (ECMO) in 18%. Two death were reported in a 48 years-old kidney transplant homozygous (HbSS) patient, and in a 50 years-old heterozygous (HbSC) patient with a severe PE successive to COVID-19 infection deformable cells and by suppressing the formation of sickled erythrocytes. Stroke and ACS are examples of acute organ damage that benefit from transfusion. BET aims to reduce the percentage of sickle hemoglobin (HbS) and attain <30% of HbS. This threshold is based on expert consensus rather than findings from randomized trials, and can be achieved by repeated manual exchange transfusions (RMET) or by erythrocytapheresis, a technique that removes sickled erythrocytes but maintains baseline hematocrit. In our experience, an HbS threshold of 30%-40% may be reached after two RMET cycles (using 2 RBC transfused units in each cycle) in a homozygous SCD patient with no previous transfusion. tening complication of transfusions in SCD, which is induced by immunization against RBC antigens. Risk of DHTR can be assessed with a predictive score based on DHTR history, number of units previously transfused and immunization status before transfusion. 6 We propose here a therapeutic algorithm ( Figure 1A) for SCD patients hospitalized with severe COVID-19 treated by corticosteroid therapy, with the goal of minimizing VOC complications related to corticosteroids. The algorithm is based on DHTR risk profile and transfusion availability, and includes suggestions for VTE management. • Before corticosteroid therapy (total daily dose dexamethasone 6 mg or equivalencies for up to 10 days or until hospital discharge) is prescribed, according to oxygen needs, a prior BET must be per- We applied this therapeutic algorithm to our cohort of sickle cell patients hospitalized with COVID-19 and we describe here a preliminary evaluation of patients treated by Tocilizumab ( Figure 1C ). Around 11 patients, with a median age of 40 years , treated according to this algorithm between March 13th, 2020 and January 17th, 2022 were analyzed. Mechanical ventilation (MV) was required in 45% and extracorporeal membrane oxygenation (ECMO) in 18%. Tocilizumab infusion was related to history of DHTR (n = 1), high DHTR risk development (n = 5) and BET not available in the 24 h before corticosteroid infusion (n = 5). Corticosteroids were prescribed in 27% after BET due to infection severity despite In conclusion, severity of COVID-19 infection, ACS diagnosis and history of transfusion reactions must be taken into account when considering the use of corticosteroids for the management of severe COVID-19 pneumonia in SCD patients. Blood exchange transfusion must be considered prior to dexamethasone use in order to minimize the risk of VOC complications; IL-6 inhibitors should be proposed as an alternative to dexamethasone for patients at high risk for DHTR for whom transfusion must be avoided. Pr Bartolucci discloses the following: (a) consulting agreement for A single investigator (GDL) collected the data from patient interviews and chart reviews between March 13th, 2020 and January 17th, 2022. Clinical data were collected using a standardized form. All consecutive adult patients with SS-homozygous and S-heterozygous (S/β, Risk factors for severe COVID-19 in hospitalized sickle cell disease patients: a study of 319 patients in France Etude SISTER: sickle cell disease and steroïds Risque d'hospitalisation pour crise vaso-occlusive chez les patients atteints de drépanocytose après exposition ambulatoire aux corticoïdes systémiques en France Dramatic improvement after Tocilizumab of severe COVID-19 in a child with sickle cell disease and acute chest syndrome IL-6 levels are dramatically high in the sputum from children with sickle cell disease during acute chest syndrome Tocilizumab for severe acute chest syndrome in a child with sickle cell disease and dramatically high interleukin-6 values in endotracheal and pleural fluids Incidence and predictive score for delayed hemolytic transfusion reaction in adult patients with sickle cell disease Jean-Benoît Arlet https://orcid.org/0000-0003-2608-302X