Retour d'experience sur la prise en charge de myocardite aigue dite << Kawasaki-like >> associee a la COVID-19 : respect du bon usage et de la juste prescription des immunoglobulines intraveineuses

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Heterogeneite phenotypique des myocardites fulminantes induites par la COVID-19 chez l'adulte

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Myocardites fulminantes associées aux auto-anticorps Anti-ARN-polymérases III

La myocardite fulminante associée aux auto-anticorps anti-ARN polymérases III (ARNpol3) est une entité récemment décrit associant la survenue de myocardites aiguës fulminantes et/ou de péricardites sévères, principalement d'origine grippale et volontiers récidivantes, chez des patients présentant des ARNpol3 sans sclérodermie systémique évidente. La gravité de cette maladie procède à la fois de la sévérité des épisodes de myocardites et du risque de récidive à chaque nouvelle infection virale. La physiopathologie de cette maladie est inconnue. L'objectif de cette étude était de poursuivre la description de cette entité pour mieux en connaître les contours et le pronostic. Nous avons conduit une étude rétrospective monocentrique entre janvier 2013 et janvier 2022 incluant les patients admis dans le service de Médecine Intensive-Réanimation ou de Médecine Interne d'un centre hospitalier universitaire tertiaire et présentant une myocardite fulminante et/ou une péricardite sévère en présence d'ARNpol3. Pendant la durée de l'étude, 25 patients (femme 80 %, âge moyen au premier épisode 35 ± 11,4) ont pu être inclus. Après un suivi de 39 [6–50] mois, 7 (28 %) patients étaient décédés, d'un premier épisode de myocardite (n = 2), d'une récidive fatale (n = 4) ou d'une autre cause (n = 1). Le nombre moyen d'épisodes par malade était de 1,6 ± 0,9 et le taux de récidive de 40 %. Tous les patients ont nécessité au moins une fois l'admission en soins critiques, pour une durée de 9 [5–14] jours en médiane. La fraction d'éjection ventriculaire minimale était de 5 [5–10] % et le zénith de troponine de 82 [19-370] fois la valeur supérieure de la normale. Un épanchement péricardique significatif était présent chez 94 % des patients, nécessitant un drainage dans 40 % des cas. Les marqueurs inflammatoires à l'admission étaient peu élevés : CRP 7 [5–14] mg/L, procalcitonine 0,1 [0,06–0,4] ng/mL et fibrinogène 3 [2,4–3,4] g/L. Les troubles de conduction et du rythme étaient rares : 3 et 7 % respectivement. Au cours de leurs séjours, les fréquences des traitements des défaillances d'organes étaient : dobutamine 83 %, ECMO-VA 77 %, amines vasopressives 70 %, ventilation mécanique 67 % et épuration extra-rénale 30 %. Deux patients ont été transplantés en raison d'une non récupération de la fonction ventriculaire gauche. En dehors de ces deux malades, tous les survivants ont récupéré une fonction cardiaque normale. Les causes des myocardites étaient : grippale 52 %, COVID-19 44 %, virus inconnu 12 %, autre virus 4 %. Quatre patients ont présenté une myocardite grippale et une myocardite de COVID-19. Les ARNpol3 étaient confirmés positifs à distance chez tous les malades (n = 17) après un délai médian de 8 [2,5–16,5] mois. Seuls deux patients avaient un score de classification de sclérodermie systémique ≥9 sans atteinte viscérale ou signe d'évolutivité. Un patient avait un antécédent de cancer en rémission complète. Deux patients ont reçu un traitement préventif des récidives par immunoglobulines intraveineuses. La myocardite associée aux ARNpol3 est une entité en cours d'exploration. Cette étude montre que la grippe et la COVID-19 sont les principales causes de myocardites. De plus, nombre important de nouveaux malades ont été diagnostiqués à l'occasion de la pandémie de COVID-19. La physiopathologie de cette maladie est inconnue et nécessite d'être étudiée. (French) [ FROM AUTHOR] Copyright of Revue de Médecine Interne is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Longitudinal measurement of whole blood viscoelastic properties throughout the course of extracorporeal membrane oxygenation in COVID-19 patients with severe acute respiratory distress syndrome

Background : Venovenous (vv)-extracorporeal membrane oxygenation (ECMO) support is used as rescue therapy in COVID-19 patients with severe acute respiratory distress syndrome (ARDS). However, COVID-19 is associated with a hypercoagulable state with high rates of thrombosis. Whether ECMO implantation exacerbates COVID-19-associated coagulopathy is unknown. Aims : To perform a longitudinal evaluation of whole blood viscoelastic properties throughout the course of vv-ECMO in COVID-19 ARDS patients. Methods : 20 COVID-19 patients undergoing vv-ECMO were included in this prospective study. Blood was sampled before ECMO implantation and then 24 h and 7 days after ECMO implantation. SEER Sonorheometry was performed on a Quantra ® hemostasis analyzer with the QPlus ® Cartridge (HemoSonics LLC). All patients received UFH to a target anti-Xa activity of 0.3-0.5 IU/mL. Results : The median age was 48 (42-58) years, with a median body mass index of 30.5 (28.2-38.5) Kg/m2, and 15 (71%) patients were men. The median SAPSII and SOFA scores on admission were 52.5 (44.3-65.5) and 12.0 (8.5-15.8), respectively. Baseline clot times (CT) and baseline clot times with heparinase (CTH) were within the normal range [median 150 (127-178) s and 129 (118-151) s, respectively] and did not vary throughout the course of ECMO. COVID-19 patients exhibited markedly increased baseline values of clot stiffness [CS, median 49.9 (35.5-69.2 hPA)], fibrinogen contribution to CS [FCS, median 12.80 (6.20-20.10) hPA] and platelet contribution to CS [PCS, median 38.5 (28.7-52.4) hPA]. CS, FCS and PCS decreased from baseline to day 7. CT significantly correlated with aPTT ( r = 0.75, P < 0.0001), FCS with fibrinogen levels ( r = 0.81, P < 0.0001) and PCS with platelet count ( r = 0.85, P < 0.0001) but result delivery was much faster with the Quantra ® analyzer compared to conventional tests (∼15 versus ∼60 min). Conclusions : COVID-19 patients with ARDS exhibited a pronounced baseline procoagulant state that partially resolved over the first 7 days of ECMO support.

Extracorporeal membrane oxygenation induces early alterations in coagulation and fibrinolysis profiles in COVID-19patients with acute respiratory distress syndrome

Background : Extracorporeal membrane oxygenation (ECMO) support induces complex hemostatic changes that have been yet poorly described, particularly in COVID-19 patients. Aims : To comprehensively analyze changes in coagulation and fibrinolysis profiles occurring during ECMO support in COVID-19 and non-COVID-19 patients with severe acute respiratory distress syndrome (ARDS). Methods : All consecutive patients with ARDS undergoing ECMO were eligible to participate in this prospective monocentric study. Clinical characteristics were recorded on admission. Blood was sampled before and then 24 h, 7 and 14 days after ECMO implantation for longitudinal measurement of coagulation and fibrinolysis markers. Clinical outcomes were prospectively assessed until discharge from the ICU or death. Results : We included 20 COVID-19 and 10 non-COVID-19 participants. The median age was 47 (35-56) years, with a median body mass index of 30 (27-35) kg/m, and a SOFA score of 12 (8-16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1+2, thrombin-antithrombin, D-Dimers and PAI-1 were elevated in both groups, indicating that endothelial activation, endogenous thrombin generation and fibrinolysis shut-down occur in all ARDS patients before ECMO implantation. From baseline to day 7, platelet count ( P < 0.0001) and fibrinogen level ( P < 0.001) significantly decreased, resulting from increases in thrombin generation (prothrombin F1+2, P < 0.01) and fibrin formation (fibrin monomers, P < 0.001). PAI-1 levels significantly decreased from baseline to day 7 ( P < 0.0001) in all ARDS patients. These changes were more marked in COVID-19 patients, resulting in 3 fatal bleeding. Conclusions : ECMO circuit triggers early coagulation activation, resulting in significant fibrinogen and platelets consumption, with subsequent hypofibrinogenemia and thrombocytopenia, which may have contributed to the high prevalence of bleeding complications observed in COVID-19 ARDS patients rescued by ECMO. Additional studies are warranted to determine whether individualized anticoagulation might help to reduce bleeding complications during ECMO support. For now, daily monitoring of platelet count and fibrinogen should be part of ECMO management.

Ventilator-associated pneumonia in patients with SARS-COV-2-associated acute respiratory failure requiring mechanical ventilation: A retrospective cohort study

Background: Data on incidence, clinical presentation and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. Methods: Case series of patients with COVID-19 pneumonia admitted to a single ICU in France. All consecutive patients requiring MV with RT-PCR-confirmed SARS-CoV-2 infection between March 12th and April 24th, 2020 were included. Frequency, clinical characteristics, responsible pathogens and outcomes of VAP were assessed, and compared to an historical cohort of patients with severe influenza-associated pneumonia requiring MV admitted to the same ICU during the preceding three winter seasons. Results: Fifty-four consecutive patients with COVID-19-associated respiratory failure requiring MV were included (median (IQR) age 48 (42-58) years;74% male;93% requiring veno-venous ECMO). VAP occurred in 46 (85%) of them (median (IQR) prior MV duration before the first episode, 11 (8-16) days) (Table 1). Pathogens responsible for VAP were predominantly Enterobacteriaceae (72%), and particularly inducible AmpC-cephalosporinase producers (41%), followed by Pseudomonas aeruginosa (35%) (Table 2). Pulmonary infection recurrence and death were observed in 46 (85%) and 17 (31%) patients, respectively. Details on recurrent episodes and pathogens responsible for recurrences are given in Table 3. Most recurrences were relapse (i.e. infection with the same pathogen), with a high proportion occurring during antimicrobial treatment despite its adequacy. Despite a high rate of P. aeruginosa VAP in patients with influenza-associated ARDS, pulmonary infection recurrence rate was significantly lower than in patients with COVID-19. Overall mortality was similar in the two groups. Baseline characteristics of patientsConclusion: Patients with severe COVID-19-associated respiratory failure requiring MV had a very high late-onset VAP rate. Inducible AmpC cephalosporinase- producing Enterobacteriaceae and Pseudomonas aeruginosa appeared to be frequently responsible for VAP, with multiple subsequent episodes and difficulties to eradicate the pathogen from the lung.

[COVID-19 and mechanical circulatory support]. / COVID-19 et assistance circulatoire.

Extracorporeal membrane oxygenation (ECMO) is mainly used as a rescue therapy in COVID-19 patients with severe acute respiratory distress syndrome (ARDS). More rarely, COVID-19 can be complicated by hemodynamic failure due to fulminant myocarditis or massive pulmonary embolism necessitating the implantation of venous-arterial ECMO. The management of ECMO during the COVID-19 pandemic is challenging due to some specificities related to the disease characteristics, such as the management of anticoagulation in patients with a hypercoagulable state and an increased risk of venous thromboembolism. In large retrospective cohorts, survival of ECMO-rescued COVID-19 patients with ADRS was reported to be similar to that reported in previous studies on ECMO support for severe ARDS. Full consideration of ECMO candidacy is crucial for appropriate allocation of resources.

Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): a systematic review and pooled analysis.

BACKGROUND: Several observational studies have reported elevated baseline D-dimer levels in patients hospitalized for moderate to severe coronavirus disease 2019 (COVID-19). These elevated baseline D-dimer levels have been associated with disease severity and mortality in retrospective cohorts. OBJECTIVES: To review current available data on the association between D-Dimer levels and mortality in patients admitted to hospital for COVID-19. METHODS: We performed a systematic review of published studies using MEDLINE and EMBASE through 13 April 2020. Two authors independently screened all records and extracted the outcomes. A random effects model was used to estimate the standardized mean difference (SMD) with 95% confidence intervals (CI). RESULTS: Six original studies enrolling 1355 hospitalized patients with moderate to critical COVID-19 (391 in the non-survivor group and 964 in the survivor group) were considered for the final pooled analysis. When pooling together the results of these studies, D-Dimer levels were found to be higher in non-survivors than in-survivors. The SMD in D-Dimer levels between non-survivors and survivors was 3.59µg/L (95% CI 2.79-4.40µg/L), and the Z-score for overall effect was 8.74 (P<0.00001), with a high heterogeneity across studies (I2=95%). CONCLUSIONS: Despite high heterogeneity across included studies, the present pooled analysis indicates that D-Dimer levels are significantly associated with the risk of mortality in COVID-19 patients. Early integration of D-Dimer testing, which is a rapid, inexpensive, and easily accessible biological test, can be useful to better risk stratification and management of COVID-19 patients.