The consequences of COVID-19 pandemic on patients with monoclonal gammopathy–associated systemic capillary leak syndrome (Clarkson disease)
2021; Elsevier BV; Volume: 10; Issue: 2 Linguagem: Inglês
10.1016/j.jaip.2021.11.023
ISSN2213-2201
AutoresMarc Pineton de Chambrun, Quentin Moyon, Stanislas Faguer, G. Urbanski, Alexis Mathian, Noémie Zucman, Marie Werner, Charles‐Édouard Luyt, Franco Verlicchi, Zahir Amoura, Marc Pineton de Chambrun, Marie Gousseff, Wladimir Mauhin, A. Hot, Jean‐Christophe Lega, M. Lambert, Sophie Rivière, Antoine Dossier, M. Ruivard, François Lhote, Thomas Gille, Sybille Merceron, Nathalie Zapella, Laurent Alric, C. Agard, Mathieu Lacout, David Saadoun, J. Graveleau, Martin Soubrier, Julien Haroche, J. Boileau, Marie-Josée Lucchini-Lecomte, Thomas Hanslik, Christine Christides, H. Lévesque, Aline Talasczka, Caroline Bulte, É. Hachulla, Olivier Decaux, Romain Sonneville, Florent Ibouanga, Bertrand Arnulf, Marcel Bénédit, Jean‐François Viallard, N. Tieulié, Fadi Haddad, Bruno Moulin, Fleur Cohen-Aubert, Pierre‐Yves Lovey, S. Le Moal, B. Bibes, Georges‐Étienne Rivard, Éric Rondeau, Giuseppe Malizia, P. Debourdeau, P. Abgueguen, A. Bosseray, Jérôme Devaquet, Claire Presne, François Liferman, Nicolas Limal, Laurent Argaud, Romain Hernu, Sylvie de la Salle, Stanislas Faguer, G. Urbanski, Noémie Zucman, Marie Werner, Charles‐Édouard Luyt, Quentin Moyon, Franco Verlicchi, Jorge Álvarez Troncoso, John T. Harty, Pascal Godmer, Miguel Hie, T. Papo, Pierre‐Yves Hatron, Alexis Mathian, Zahir Amoura,
Tópico(s)Muscle and Compartmental Disorders
ResumoClinical ImplicationsSevere acute respiratory syndrome coronavirus 2 infection and coronavirus disease 2019 vaccination can trigger severe relapse of systemic capillary leak syndrome (Clarkson disease). The systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the presence of a monoclonal gammopathy. Viral infections, especially influenza virus, are known to reveal the disease and to elicit its recurrence.1Druey K.M. Parikh S.M. Idiopathic systemic capillary leak syndrome (Clarkson disease).J Allergy Clin Immunol. 2017; 140: 663-670Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 2Pineton de Chambrun M. Luyt C.-E. Beloncle F. Gousseff M. Mauhin W. Argaud L. et al.The clinical picture of severe systemic capillary-leak syndrome episodes requiring ICU admission.Crit Care Med. 2017; 45: 1216-1223Crossref PubMed Scopus (36) Google Scholar, 3Pineton de Chambrun M. Mathian A. Luyt C.-E. Combes A. Amoura Z. EurêClark Study GroupMyocardial dysfunction is frequent in systemic capillary-leak syndrome (Clarkson disease) severe episodes.J Allergy Clin Immunol. 2018; 141: 1539-1540Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Patients are asymptomatic between episodes. Monoclonal gammopathy of undetermined significance occurs in 3.2% of persons 50 years of age or older and in 5.3% of those 70 years of age or older.4Kyle R.A. Larson D.R. Therneau T.M. Dispenzieri A. Kumar S. Cerhan J.R. et al.Long-term follow-up of monoclonal gammopathy of undetermined significance.N Engl J Med. 2018; 378: 241-249Crossref PubMed Scopus (266) Google Scholar However, the incidence and prevalence of Clarkson’s disease in this population is unknown, certainly very low.1Druey K.M. Parikh S.M. Idiopathic systemic capillary leak syndrome (Clarkson disease).J Allergy Clin Immunol. 2017; 140: 663-670Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar The prevention of severe episodes relies on chronic perfusion of high-dose intravenous immunoglobulins (IVIg).5Pineton de Chambrun M. Gousseff M. Mauhin W. Lega J.-C. Lambert M. Rivière S. et al.Intravenous immunoglobulins improve survival in monoclonal gammopathy-associated systemic capillary-leak syndrome.Am J Med. 2017; 130 (1219.e19-27)Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar Aside IVIg and a modest effect of terbutaline, no other treatment have shown to prevent recurrence. Moreover, despite some promising drugs, none have been proven effective in reducing capillary leak during severe episodes. Several pathophysiological pathways, such as phosphodiesterase inhibition, are candidates for the treatment of severe episodes. The coronavirus disease 2019 (COVID-19) and its preventive vaccines have been recently reported to trigger first episodes and relapses of Clarkson disease.6Pineton de Chambrun M. Cohen-Aubart F. Donker D.W. Cariou P.-L. Luyt C.-E. Combes A. et al.SARS-CoV-2 induces acute and refractory relapse of systemic capillary leak syndrome (Clarkson’s disease).Am J Med. 2020; 133: e663-e664Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar,7Matheny M. Maleque N. Channell N. Eisch A.R. Auld S.C. Banerji A. et al.Severe exacerbations of systemic capillary leak syndrome after COVID-19 vaccination: a case series.Ann Intern Med. 2021; 174: 1476-1478Crossref PubMed Scopus (19) Google Scholar We aimed to describe the outcome of European patients with Clarkson disease from the EurêClark registry during the COVID-19 pandemic. All patients with a diagnosis of monoclonal gammopathy–associated SCLS included in the EurêClark registry and alive at the start of COVID-19 pandemic (February 1, 2020) were included and evaluated until July 10, 2021 (Table I). Thirty patients were included, with a female-to-male ratio of 1.3 and a mean ± standard deviation age of 58 ± 14 years. Every patient had an IgG gammopathy with kappa (n = 24) or lambda light chain (n = 7). Most patients were under long-term treatment with IVIg (n = 27, 90%). Five patients (17%) experienced a relapse related to a proven (n = 3) or highly probable (see footnotes in Table I) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with a fatal outcome in 4 patients. None had evidence of COVID-19 pneumonia, and all experienced typical flare of Clarkson’s disease with severe hypovolemic shock and refractory multiple-organ failure. Twenty patients underwent COVID-19 vaccination with BNT162b2 (Pfizer-BioNTech, Pfizer Inc, New York City, NY), n = 17; Ad26.COV2.S (Janssen Pharmaceuticals, Beerse, Belgium), n = 1; and mRNA-1273 (Moderna Inc, Cambridge, MA), n = 2. Vaccination was uneventful in 18 patients, including 2 not receiving IVIg. Two patients treated with IVIg had a relapse after a second dose of mRNA vaccine, with a favorable outcome in both cases. During the time of the study, 5 patients had a new diagnosis of Clarkson disease and were reported to the EurêClark registry (Table II). All required intensive care unit management, and 1 died during this opening episode. Four had their first flare triggered by a polymerase chain reaction–confirmed COVID-19 infection. The last patient, previously known to have a monoclonal gammopathy, had a typical opening flare of SCLS 3 days after the first injection of ChAdOx1 (AstraZeneca).Table IConsequences and outcome of patients with known Clarkson’s disease during the COVID-19 pandemic (2020-2021)PatientsSexAgeDiagnosisMonoclonal gammopathyIVIgDateDoseCOVID-19COVID-19 vaccineFlareInterval∗Interval between COVID-19 infection or COVID-19 vaccination and Clarkson’s disease flare.ICU†Admission to the ICU.Outcome1F452013IgG K120130.5 g/kg/4 wkPCR +–YesConcomitantYesDead2M622015IgG K120152 g/kg/4 wk–BNT162 b2No––Alive3M532010IgG K120110.5 g/kg/4 wk–BNT162 b2No––Alive4F812012IgG K and L120120.5 g/kg/12 wk–BNT162b2No––Alive5M762004IgG K120211 g/kg/4 wk––No––Alive6M752007IgG L120090.5 g/kg/16 wk–BNT162b2No––Alive7M562010IgG K120101 g/kg/4 wkPCR +–YesConcomitantYesAlive8F542008IgG L120080.5 g/kg/6 wkProbable‡Two patients died during severe flare of Clarkson’s disease complicated by refractory cardiac arrest probably related to an undiagnosed COVID-19 infection. Both had fever and viral symptoms on emergency department admission that happened respectively during the epidemic peak of the first wave in France (March 23, 2020) and of the third wave in Italy (March 5, 2021). As cardiac arrest occurred very early in both patients, deep airway COVID-19 PCR could not be taken.–YesConcomitantYesDead9M612011IgG K120120.7 g/kg/6 wk–BNT162b2No––Alive10M672003IgG K120052 g/kg/4 wk–BNT162b2No––Alive11F812013IgG K120140.5 g/kg/6 wk–BNT162b2No––Alive12F802013IgG K120141 g/kg/4 wk–BNT162b2No––Alive13F592009IgG K0–––BNT162b2No––Alive14F622002IgG K120071 g/kg/8 wk–mRNA-1273No––Alive15F732011IgG L120112 g/kg/6 wk–BNT162b2No––Alive16M732015IgG L120150.5 g/kg/8 wk–Ad26.COV2.SNo––Alive17M512008IgG K120081 g/kg/4 wk––No––Alive18F682016IgG L120160.5 g/kg/4 wk––No––Alive19F592008IgG K120080.5 g/kg/4 wk–BNT162b2No––Alive20M592012IgG K120122 g/kg/4 wkPCR +–YesConcomitantYesDead21F402017IgG K120181 g/kg/4 wk–BNT162b2No––Alive22F462016IgG K120190.5 g/kg/4 wk–BNT162b2Yes2 d after second doseNoAlive23F522018IgG K0–––BNT162b2No––Alive24F612003IgG K0––Probable‡Two patients died during severe flare of Clarkson’s disease complicated by refractory cardiac arrest probably related to an undiagnosed COVID-19 infection. Both had fever and viral symptoms on emergency department admission that happened respectively during the epidemic peak of the first wave in France (March 23, 2020) and of the third wave in Italy (March 5, 2021). As cardiac arrest occurred very early in both patients, deep airway COVID-19 PCR could not be taken.–YesConcomitantYesDead25M432021IgG L120212 g/kg/4 wk–BNT162b2No––Alive26M452020IgG K120212 g/kg/4 wk–BNT162b2No––Alive27M602019IgG K120191 g/kg/3 wk–BNT162b2No––Alive28F272021IgG K120212 g/kg/4 wk––No––Alive29F372016IgG K120161 g/kg/4 wk–mRNA-1273Yes3 d after second doseYesAlive30F432011IgG K120111 g/kg/6 wk––No––AliveEurêClark registry was approved by local review boards and by the Commission Nationale de l’Informatique et des Libertés n°1001704; no AP-HP 14 in 1997.COVID-19, Coronavirus disease 2019; F, female; g/kg/wk, gram per kilogram of body weight delivered every x weeks; ICU, intensive care unit; IgG, immunoglobulin G; IVIg, intravenous immunoglobulins; K, kappa light chain; L, lambda light chain; M, male; PCR, polymerase chain reaction.∗ Interval between COVID-19 infection or COVID-19 vaccination and Clarkson’s disease flare.† Admission to the ICU.‡ Two patients died during severe flare of Clarkson’s disease complicated by refractory cardiac arrest probably related to an undiagnosed COVID-19 infection. Both had fever and viral symptoms on emergency department admission that happened respectively during the epidemic peak of the first wave in France (March 23, 2020) and of the third wave in Italy (March 5, 2021). As cardiac arrest occurred very early in both patients, deep airway COVID-19 PCR could not be taken. Open table in a new tab Table IINew diagnosis of Clarkson’s disease during the COVID-19 pandemic (2020-2021)PatientsSexAge (y)Monoclonal gammopathyCOVID-19COVID-19 vaccineFlareInterval∗Interval between COVID-19 infection or COVID-19 vaccination and Clarkson’s disease flare.ICU†Admission to the ICU.Hb‡Hemoglobin highest value during the episode. (g/dL)MVRRTCompartment syndromeOutcomeAM44?§Monoclonal gammopathy could not be found during the acute episode and will be tested few weeks/month after the flare.PCR +–YesConcomitantYes23YesYes4 limbsAliveBF47?‖Monoclonal gammopathy could not be found during the acute episode and the patient died.PCR +–YesConcomitantYes19YesYesNoDeadCM56IgG K–ChAdOx1Yes3 d after first doseYes23NoNoNoAliveDM35IgG LPCR +–YesConcomitantYes25YesYes4 limbsAliveEM38IgG KPCR +–YesConcomitantYes26YesNoLower limbsAliveCOVID-19, Coronavirus disease 2019; F, female; Hb, hemoglobin; ICU, intensive care unit; IgG, immunoglobulin G; K, kappa light chain; L, lambda light chain; M, male; MV, mechanical ventilation; PCR, polymerase chain reaction; RRT, renal replacement therapy.∗ Interval between COVID-19 infection or COVID-19 vaccination and Clarkson’s disease flare.† Admission to the ICU.‡ Hemoglobin highest value during the episode.§ Monoclonal gammopathy could not be found during the acute episode and will be tested few weeks/month after the flare.‖ Monoclonal gammopathy could not be found during the acute episode and the patient died. Open table in a new tab EurêClark registry was approved by local review boards and by the Commission Nationale de l’Informatique et des Libertés n°1001704; no AP-HP 14 in 1997. COVID-19, Coronavirus disease 2019; F, female; g/kg/wk, gram per kilogram of body weight delivered every x weeks; ICU, intensive care unit; IgG, immunoglobulin G; IVIg, intravenous immunoglobulins; K, kappa light chain; L, lambda light chain; M, male; PCR, polymerase chain reaction. COVID-19, Coronavirus disease 2019; F, female; Hb, hemoglobin; ICU, intensive care unit; IgG, immunoglobulin G; K, kappa light chain; L, lambda light chain; M, male; MV, mechanical ventilation; PCR, polymerase chain reaction; RRT, renal replacement therapy. Our results highlight the burden of the COVID-19 pandemic for patients with Clarkson disease. They face the threat of both the infection and its preventive vaccine. Moreover, IVIg seems to protect them imperfectly against these foes. Several lessons can be drawn from our results jointly with previous reports. First, COVID-19 infection seems to induce very frequently a relapse of Clarkson disease. Every patient from our cohort with a proven or suspected SARS-CoV-2 infection had a severe flare, fatal in 80% of cases. To the best of our knowledge and in the published literature, there is no report of uneventful SARS-CoV-2 infection in these patients. As previously reported, viral infection frequently elicits relapse in patients with Clarkson disease. However, vascular leakage seems to play a major role in COVID-19 pathophysiology and may explain the high relapse risk during SARS-CoV-2 infection. Although IVIg have been shown to prevent severe episodes8Gousseff M. Arnaud L. Lambert M. Hot A. Hamidou M. Duhaut P. et al.The systemic capillary leak syndrome: a case series of 28 patients from a European registry.Ann Intern Med. 2011; 154: 464-471Crossref PubMed Scopus (103) Google Scholar and to improve survival,5Pineton de Chambrun M. Gousseff M. Mauhin W. Lega J.-C. Lambert M. Rivière S. et al.Intravenous immunoglobulins improve survival in monoclonal gammopathy-associated systemic capillary-leak syndrome.Am J Med. 2017; 130 (1219.e19-27)Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar they failed to prevent the COVID-19-related relapses in 4 of our patients, including 1 treated with full dose (2 g/kg/4 weeks). The tapered dose in the 3 others might have lowered their preventive effect. The lack of SARS-CoV-2 specific immunoglobulins in available preparations of IVIg could explain this lower efficacy.6Pineton de Chambrun M. Cohen-Aubart F. Donker D.W. Cariou P.-L. Luyt C.-E. Combes A. et al.SARS-CoV-2 induces acute and refractory relapse of systemic capillary leak syndrome (Clarkson’s disease).Am J Med. 2020; 133: e663-e664Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar A recent study revealed the apparition of anti-SARS-CoV-2 nucleocapsid protein and spike protein receptor binding domain antibodies in IVIg preparation containing plasma collected in Italy after March 2020.9Pisani G, Cristiano K, Simeoni M, Martina A, Pati I, Carocci A, et al. Detection of antibodies against SARS-CoV-2 both in plasma pools for fractionation and in commercial intravenous immunoglobulins produced from plasma collected in Italy during the pandemic. Blood Transfus. Published online May 27, 2021. https://doi.org/10.2450/2021.0055-21Google Scholar Yet, it cannot be denied that some patients from our cohort might have had asymptomatic COVID-19 during the time of the study. Second, although the incidence of Clarkson disease is unknown, being probably very low, this pandemic has been associated with an elevated number of new diagnoses in a short period of time. This finding highlights the critical role of viral triggers in the onset of SCLS. Third, although we usually recommended vaccination in our patients (especially against influenza virus), COVID-19 vaccines have been shown to trigger Clarkson disease episodes. All 4 vaccines authorized by the European Medicines Agency (EMA, BNT162b2, Ad26.COV2.S, mRNA-1273, and ChAdOx1) have been incriminated and not solely ChAdOx1 (AstraZeneca) for which this adverse effect was recently pointed out by the EMA’s safety committee. Conversely, with cases reported by Druey et al,7Matheny M. Maleque N. Channell N. Eisch A.R. Auld S.C. Banerji A. et al.Severe exacerbations of systemic capillary leak syndrome after COVID-19 vaccination: a case series.Ann Intern Med. 2021; 174: 1476-1478Crossref PubMed Scopus (19) Google Scholar our 2 patients relapsing after vaccination were given IVIg regularly. Furthermore, 18 patients, including 2 not receiving IVIg, had no adverse event after COVID-19 vaccination. This study has several strengths and limitations. First, the small sample size of this series should be put in perspective with the rarity of the disease. Second, although the retrospective nature of this work is inevitably associated with selection bias, most information originates from prospectively collected data. Third, only symptomatic episodes after vaccination were monitored but not any other vaccine adverse reactions. Last, we did not evaluate the anti-spike antibody response to confirm that vaccination participates in prevention of relapse of Clarkson disease. In conclusion, the COVID-19 pandemic has serious consequences in patients with SCLS. SARS-CoV-2 infection is associated with a high risk of relapse, and all COVID-19 vaccines can trigger episodes. High-dose IVIg remains the only effective preventive treatment and should not be stopped during the pandemic. In our opinion, the benefit/risk ratio favors COVID-19 vaccination in our patients under IVIg, but further data are needed to determine its safest modalities. Marc Pineton de Chambrun (Service de Médecine Interne 2, CHU La Pitié-Salpêtrière, APHP, Paris, France; Service de Médecine Intensive-Réanimation, Hôpital La Pitié-Salpêtrière, Paris, France); Marie Gousseff (Service de Médecine Interne, CH Bretagne Atlantique, Vannes, France); Wladimir Mauhin (Service de Médecine Interne 2, CHU La Pitié-Salpêtrière, APHP, Paris, France); Arnaud Hot (Service de Médecine Interne, CHU Edouard Herriot, Lyon, France); Jean-Christophe Lega (Service de Médecine Interne et Vasculaire, CHU Lyon Sud, Lyon France); Marc Lambert (Service de Médecine Interne, Hôpital Claude Huriez, CHRU Lille, Lille, France); Sophie Riviere (Service de Médecine Interne, Hôpital St-Eloi, CHRU Montpellier, Montpellier, France); Antoine Dossier (Service de Médecine Interne, CHU Bichat, Paris, APHP, France); Marc Ruivard (Service de Médecine Interne, Hôpital d'Estaing, CHU de Clermont-Ferrand, Clermont-Ferrand, France); François Lhote (Service de Médecine Interne, Hôpital Delafontaine, Saint-Denis, France); Gilles Blaison (Service de Médecine Interne et Rhumatologie, Hôpital Pasteur, Colmar, France); Sybille Merceron (Service de Réanimation Polyvalente, CH André Mignot, Versailles, France); Nathalie Zapella (Service de Réanimation Polyvalente, CH André Mignot, Versailles, France); Laurent Alric (Service de Médecine Interne, Pôle Digestif, CHU Purpan, Toulouse, France); Christian Agard (Service de Médecine Interne, CHU Hôtel-Dieu, Nantes, France); Mathieu Lacout: Service de Médecine Interne, CHU Hôtel-Dieu, Nantes, France); David Saadoun (Service de Médecine Interne et Immunologie Clinique, CHU La Pitié-Salpêtrière, APHP, Paris, France); Julie Graveleau (Service de Médecine Polyvalente, CH Saint-Nazaire, Saint-Nazaire, France); Martin Soubrier (Service de Rhumatologie, Hôpital Gabriel-Montpied, CHU Clermont-Ferrand, Clermont-Ferrand, France); Julien Haroche (Service de Médecine Interne, CH Morlaix, Morlaix, France); Julien Boileau (Service de Médecine Interne, CH Morlaix, France); Marie-Josee Lucchini-Lecomte (Service de Médecine Interne, CH Notre-Dame de la Miséricorde, Ajaccio, France); Thomas Hanslik (Service de Médecine Interne, CHU Ambroise Paré, Boulogne-Billancourt, France); Christine Christides (Service de Médecine Interne, CH Avignon, Avignon, France); Hervé Levesque (Service de Médecine Interne, Hôpital de Bois-Guillaume, CHU de Rouen, Rouen, France); Aline Talasczka (Service de Médecine Interne, CH Roubaix, Roubaix, France); Caroline Bulte (Service de Médecine Interne, Hôpital de Bois-Guillaume, CHU de Rouen, Rouen, France); Eric Hachulla (Service de Médecine Interne, Hôpital Claude Huriez, CHRU Lille, Lille, France); Olivier Decaux (Service de Médecine Interne, Hôpital Pontchaillou, CHU Rennes, Rennes, France); Romain Sonneville (Service de Médecine Interne, CHU Bichat, Paris, APHP, France); Florent Ibouanga (Service de Médecine Interne, CH Saint-Omer, Saint-Omer, France); Bertrand Arnulf (Service d'Immunologie Clinique, CHU Saint-Louis, Paris, APHP, France); Marcel Benedit (Service de Réanimation Polyvalente, CH Moulins, Moulins, France); Jean François Viallard (Service de Médecine Interne, Hôpital Haut-Lévêque, CHU Bordeaux Sud, Pessac, France); Nathalie Tieulie (Service de Rhumatologie, Hôpital Pasteur 2, CHU Nice, Nice, France); Fadi Haddad (Service de Médecine Interne, Hôtel-Dieu de France, Beirut, Lebanon); Bruno Moulin (Service de Néphrologie Dialyse Transplantation Rénale, Hôpital Civil, CHU de Strasbourg, Strasbourg, France); Fleur Cohen-Aubert (Service de Médecine Interne 2, CHU La Pitié-Salpêtrière, APHP, Paris, France); Pierre-Yves Lovey (Service d'Hématologie, CH Sion, Sion, Switzerland); Sylvie le Moal (Service de Médecine Interne, CH de Saint-Brieuc, Saint-Brieuc, France); Béatrice Bibes (Service de Médecine Interne, CHP Saint-Grégoire, Saint-Gregoire, France); Georges-Etienne Rivard (Service d'Hématologie, CHU Saint-Justine, Montréal, Canada); Eric Rondeau (Service d'Urgences Néphrologiques et de Transplantation Rénale, CHU Tenon, France); Giuseppe Malizia (Divisione di Medicina, Ospedale V. Cervello, Palermo, Italy); Philippe Debourdeau (Institut Sainte-Catherine, Avignon, France); Pierre Abgueguen (Service des Maladies Infectieuses et Tropicales, CHU d'Angers, Angers, France); Annick Bosseray (Service de Médecine Interne, CHU Grenoble Alpes, La Tronche, France); Jérôme Devaquet (Service de Réanimation Polyvalente, CH Foch, Suresnes, France); Claire Presne (Service de Néphrologie, Hôpital Sud, CHU Amiens, Salouël, France); François Liferman (Service de Médecine Interne, CH Dax, Dax, France); Nicolas Limal (Service de Médecine Interne, CHU Henri Mondor, APHP, Créteil, France); Laurent Argaud (Service de Réanimation Médicale, CHU Edouard Herriot, Lyon, France); Romain Hernu (Service de Réanimation Médicale, CHU Edouard Herriot, Lyon, France); Sylvie de la Salle (Service de Réanimation Médicale, CHU Edouard Herriot, Lyon, France); Stanislas Faguer (Département de Néphrologie et Transplantation d'Organes, CHU de Toulouse, Toulouse, France); Geoffrey Urbanski (Service de Médecine Interne et d’Immunologie Clinique, CHU d’Angers, Angers, France); Noémie Zucman (Service de Médecine Intensive Réanimation, Hôpital Louis Mourier, Colombes, France); Marie Werner (Service de Réanimation Chirurgicale Adulte, Le Kremlin-Bicêtre, France); Charles-Edouard Luyt (Service de Médecine Intensive-Réanimation, Hôpital La Pitié-Salpêtrière, Paris, France); Quentin Moyon (Service de Médecine Interne 2, CHU La Pitié-Salpêtrière, APHP, Paris, France; and Service de Médecine Intensive-Réanimation, Hôpital La Pitié-Salpêtrière, Paris, France); Franco Verlicchi (Transfusion Service, Romagna Local Health Unit, Ravenna, Italy); Jorge Álvarez Troncoso (Medicina Interna, Unidad de Enfermedades Autoinmunes Sistémicas, Hospital Universitario La Paz-Cantoblanco-Carlos III, Madrid, Spain); John Harty (Daisy Hill Hospital, Newry, Ireland); Pascal Godmer (Service de Médecine Interne, CH Bretagne Atlantique, Vannes, France); Miguel Hie (Service de Médecine Interne 2, CHU La Pitié-Salpêtrière, APHP, Paris, France); Thomas Papo (Service de Médecine Interne, CHU Bichat, Paris, APHP, France); Pierre-Yves Hatron (Service de Médecine Interne, Hôpital Claude Huriez, CHRU Lille, Lille, France); Alexis Mathian (Service de Médecine Interne 2, CHU La Pitié-Salpêtrière, APHP, Paris, France); and Zahir Amoura (Service de Médecine Interne 2, CHU La Pitié-Salpêtrière, APHP, Paris, France).
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