ABSTRACT
Background. Lung reactivations of Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) have been reported in Covid-19 patients. Whether or not those viral reactivations are more frequent than in other patients is not known. Methods. Retrospective monocentric cohort study of 145 patients with severe Covid-19 pneumonia requiring invasive mechanical ventilation and who were tested for HSV and CMV in bronchoalveolar lavage performed during fiberoptic bronchoscopy for ventilator-associated pneumonia suspicion. Rates of HSV and CMV lung reactivations, and HSV bronchopneumonitis were assessed and compared with an historical cohort of 89 patients with severe influenza pneumonia requiring invasive mechanical ventilation. Results. Among the 145 Covid-19 patients included, 50% and 42 % had HSV and CMV lung reactivations, respectively;whereas among the 89 influenza patients, 63% and 28% had CMV lung reactivations, respectively. Cumulative incidence of HSV lung reactivation (taking into account extubation and death as competing events) was higher in influenza than in Covid-19 patients (p = 0.03, see figure 1), whereas the rate of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively). Cumulative incidence of CMV lung reactivation (taking into account extubation and death as competing events) was similar in Covid-19 and influenza patients (p=0.07). Outcomes of patients with HSV or CMV lung reactivations were similar to that of patients without, whatever the underlying conditions, i.e., in Covid-19 patients, in influenza patients, or when all patients were grouped. Estimated cumulative incidence of herpes simplex virus (HSV) lung reactivation, extubation or death in Covid-19 and influenza patients, taking into account only the first event that occurred. p values for differences between Covid-19 and influenza patients were 0.03 for HSV reactivation, 0.53 for death and 0.87 for extubation. Conclusion. HSV andCMVlung reactivations are frequent in Covid-19 patients, but not more frequent than in patients with influenza-associated severe pneumonia, despite a higher severity of illness at intensive care unit (ICU) admission of the latter and a longer duration of mechanical ventilation of the former. Although no impact on outcome of HSV and CMV lung reactivations was detected, the effect of antiviral treatment against these Herpesviridae remains to be determined in these patients. (Figure Presented).
ABSTRACT
Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets. Copyright © 2022
ABSTRACT
Introduction: Dexamethasone decreases mortality in patients with severe COVID-19. The effects of dexamethasone on inflammation and repair in patients with severe COVID-19 are not well understood. We integrated tracheal aspirate (TA) and peripheral blood bulk/single-cell RNA sequencing to study the effect of dexamethasone on patients with COVID-19 ARDS. Methods: We studied selected patients from a cohort of adults with COVID-19 admitted to three hospitals in San Francisco, California from April 2020 to February 2021. Immunosuppression was not used to treat COVID-19 ARDS at these hospitals prior to July 2020, but was routinely used in these patients after this date. For this analysis, we included patients who were mechanically ventilated for COVID-19 ARDS for whom sequencing samples were available within four days of intubation. We excluded patients who received steroids prior to July 2020, subjects who received immunosuppression other than dexamethasone (e.g., tocilizumab) prior to sample collection, and chronically immunosuppressed subjects. We compared bulk RNASeq from TA and single cell RNASeq from TA and whole blood from subjects who received dexamethasone to subjects who did not receive dexamethasone. In addition, we studied the effect of dexamethasone on peripheral blood cytokine concentrations to confirm the effects of observed changes in gene expression. Results: TA bulk RNASeq was available from 20 subjects (six dexamethasone, 14 non-dexamethasone). There was no significant difference in age, sex, smoking, or BMI between groups. After correcting for multiple comparisons, 947 genes were differentially expressed in TA from subjects who received dexamethasone. Ingenuity Pathway Analysis predicted decreased activation of interferon, JAK/STAT, and NLRP12 signaling in subjects who received dexamethasone (Figure 1A). TA scRNASeq samples were available from ten dexamethasone-treated subjects and nine non-dexamethasone subjects. Whole blood scRNAseq samples were available for seven dexamethasone and eight non-dexamethasone subjects (Figure 1B). Eight subjects (three treated with dexamethasone) had both TA and whole blood scRNAseq samples available for analysis. Dexamethasone had distinct effects on the proportions of immune cells in tracheal aspirates and whole blood (Figure 1C). In 36 dexamethasone vs 42 non-dexamethasone subjects, treatment with dexamethasone was associated with significantly increased concentrations of IL-10 and decreased concentrations of IL-6 (Figure 1D). Conclusions: Dexamethasone decreases pro-inflammatory gene expression in the respiratory tract and peripheral blood of patients with COVID-19 ARDS. The effect of dexamethasone on specific cell populations may be distinct in the respiratory tract and peripheral blood.
ABSTRACT
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.)
ABSTRACT
Introduction Prédire le devenir des patients gravement malades hospitalisés en unité de soins intensifs (USI) et atteints de la maladie du coronavirus 19 (COVID-19) est un défi majeur pour éviter les séjours futiles et prolongés en USI. L'objectif de cette recherche était de développer des modèles de prédictifs de la survie à 90 jours applicable à ce type de patients à différents moments de leur séjour en USI. Methodes Sur la base de la cohorte nationale multicentrique COVID-ICU, qui a recueilli de manière prospective les caractéristiques, la prise en charge et le devenir des patients atteints de COVID-19 et hospitalisés en USI pendant la première vague de la pandémie, nous avons utilisé un algorithme d'apprentissage automatique (eXtreme Gradient Boosting) pour développer des modèles destinés à prédire la mortalité à 90 jours à l'aide d'informations recueillies à J1, J7 ou J14 du séjour du patient, en tenant compte des données manquantes (que ce soit pendant l'estimation, ou lors de l'utilisation de ces modèles sur de nouveaux individus). Ces modèles ont été évalués par une double validation interne (bootstrap et échantillon de validation) et l'estimation de l'aire sous la courbe ROC, la courbe de calibration, et le score de Brier. Resultats Les scores Survival Of Severely Ill COVID (SOSIC)-1, SOSIC-7 et SOSIC-14 ont été construits et validés avec 4244, 2877 et 1349 patients respectivement. Dans l’échantillon de validation, l'aire sous la courbe ROC de SOSIC-7 était légèrement supérieure (0,80 [0,74-0,86]) à celles de SOSIC-1 (0,76 [0,71-0,81]) et de SOSIC-14 (0,76 [0,68-0,83]). SOSIC-1 et SOSIC-7 présentaient d'excellentes courbes de calibration, avec des scores de Brier similaires pour les trois modèles. Conclusion Les scores SOSIC-1, -7 et -14 ont globalement montré une bonne capacité discriminante et une bonne calibration. D'autres études sont maintenant nécessaires pour évaluer la validité externe de ces scores dans des cohortes plus récentes de patients hospitalisés en USI. L'application web disponible publiquement (sosic.shinyapps.io/shiny) devrait faciliter cet objectif. Légende de la figure : Calibration et discrimination des scores SOSIC-1, SOSIC-7, and SOSIC-14 dans l’échantillon de validation Mots clés Syndrome de détresse respiratoire aiguë ;COVID-19 ;Score prédictif Déclaration de liens d'intérêts Les auteurs n'ont pas précisé leurs éventuels liens d'intérêts
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.