Post-traumatic stress among COVID-19 survivors: A descriptive study of hospitalized first-wave survivors

Introduction: The coronavirus Severe Acute Respiratory Syndrome Coronavirus Type 1 induces a severe respiratory disease, coronavirus disease 2019 (COVID-19). After Severe Acute Respiratory Syndrome Coronavirus Type 1 and Middle East Respiratory Syndrome infection, increased post-traumatic stress disorder (PTSD) rates were described. Methods: This single-centred, prospective study aimed to evaluate the rates of PTSD in patients who were hospitalized for COVID-19. Inclusion criteria were COVID-19 patients hospitalized in the intensive care unit (ICU) or in a standard unit with at least 2 L/min oxygen. Six months post-hospitalization, subjects were assessed for PTSD using a validated screening tool, the Post-Traumatic Stress Checklist-5 (PCL-5). Results: A total of 40 patients were included. No demographic differences between the ICU and non-ICU groups were found. The mean PCL-5 score for the population was 8.85±10. The mean PCL-5 score was 6.7±8 in the ICU group and 10.5±11 in the non-ICU group (P=0.27). We screened one patient with a positive PCL-5 score and one with a possible PCL-5 cluster score. Nine patients had a PCL-5 score of up to 15. Seven patients reported no symptoms.Seven patients accepted a psychological follow-up: one for PTSD, three for possible PTSD and three for other psychological problems. Discussion: The PCL-5 tool can be used by lung physicians during consultations to identify patients for whom follow-up mental health assessment and treatment for PTSD are warranted. Conclusion: Lung physicians should be aware of the risk of PTSD in patients hospitalized for COVID-19 and ensure appropriate screening and follow-up care

BMJ Med

OBJECTIVE: To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial). DESIGN: Open label, randomised clinical trial. SETTING: CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021. PARTICIPANTS: 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms 40. MAIN OUTCOME MEASURES: Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids. RESULTS: 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10). CONCLUSIONS: In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further. TRIAL REGISTRATION: ClinicalTrials.gov NCT04345991

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Étude de la réponse immunitaire au traitement antirétroviral au cours de l'infection par le virus de l'immunodéficience humaine

More than 30 years after the discovery of HIV, between 20 and 30% of patients on highly active antiretroviral therapy (ART) do not recover normal levels of CD4 T lymphocytes (CD4). This immunological non response (INR) to ART is associated with an increased morbidity and mortality. There are many conflicting results in the literature related the role of T cells immune activation of T regulator cells (Treg), in INR. In order to clarify the links between INR, immune activation and Treg, we made two hypotheses: (i) there is a link between Treg’s percentage, immune activation of CD4 and / or CD8, and INR; and (ii) the percentage of Treg measured at ART introduction can be used as an independent predictor for INR. To test our hypotheses, we initially improved the immunophenotyping of Treg in daily practice, by comparing different Treg’s phenotype, and by validating in clinical samples a new « one step» staining method of intracellular FoxP3. Then we analyzed in a crosssectionnal study the links between INR, immune activation, different Treg’s subpopulations and detection of very low level viremia, in a population of HIV-1 infected patients, under suppressive ART for many years. Predictive factors associated with the INR were analyzed using multivariate analysis. Simultaneously, we performed a prospective study to analyse the prognostic role of Treg’s percentage at ART introduction on the CD4 reconstitution within 2 years. We have shown that INR after 7 years of ART was independently associated with CD4 nadir and Treg’s percentage. We found in INR patients a significant increase of CD4 immune activation, but not of CD8. Finally, we showed that the Treg’s percentage and the CD4 nadir were independant predictors of INR within 2 years from the start of ART. The effect of Treg at baseline on CD4 evolution was as lower as the CD4 nadir was higher. Measuring the percentage of Treg at ART introduction could be a simple and easy tool to use in daily routine. It could help to better target patients at risk of INR in association with the measurement of CD4 nadir. A follow-up of the cohort will confirm these results in the long term. Further studies will be conducted, focusing on patients with a low CD4 nadir, and on older patients, in order to explore the interactions between immunosenescence, immune activation and TregPlus de 30 ans après la découverte du virus de l'immunodéficience humaine (VIH), entre 20 et 30% des patients sous trithérapie anti rétrovirale (TARV) ne récupèrent pas un taux normal de lymphocytes (LT) CD4, ce qui est associé à une plus grande morbi-mortalité. Il existe de nombreux résultats discordants dans la littérature concernant le rôle joué par l'activation immunitaire des LT CD4 et CD8, ainsi que des incertitudes sur celui des LT régulateurs (Treg), dans cette non réponse immunologique (NRI). Dans le but de clarifier les liens entre NRI, activation immunitaire et Treg, nous avons formulé deux hypothèses : (i) il existe un lien entre le pourcentage de Treg, l'activation immune des LT CD4 et/ou LT CD8, et NRI; et (ii) le pourcentage de Treg mesuré à l'introduction de la TARV est utilisable en tant que marqueur indépendant de risque de NRI à la TARV. Afin de tester nos hypothèses, nous avons dans un premier temps amélioré le phénotypage des Treg en pratique quotidienne, d'abord en comparant différents phénotypes de Treg, puis en validant dans des échantillons cliniques une nouvelle méthode de marquage de FoxP3 intracellulaire en un temps. Puis nous avons analysé dans une étude transversale les liens entre NRI, activation immune, différentes sous populations de Treg et la détection d'une virémie résiduelle, au sein d'une population de patients infectés par le VIH-1, en succès virologique sous TARV depuis de nombreuses années. Les facteurs prédictifs associée à la NRI ont été analysés au moyen d'une analyse multivariée. Nous avons parallèlement étudié au moyen d'une étude prospective le rôle pronostic de la mesure du pourcentage de Treg à l'introduction de la TARV, sur la réponse immune en LT CD4 dans les 2 ans suivant le début du traitement. Nous avons montré que la NRI après 7 ans de TARV en moyenne était associée de façon indépendante au nadir de LT CD4 et au pourcentage de Treg. Nous avons retrouvé une augmentation significative de l'activation immune des LT CD4 en cas de NRI, mais pas des LT CD8. Enfin, nous avons montré que le pourcentage de Treg était, avec le nadir de LT CD4, un facteur prédictif de NRI dans les 2 ans suivant le début de la TARV, et que son impact sur la réponse immune était d'autant plus marqué que le nadir de CD4 était bas. La mesure du pourcentage de Treg à l'introduction de la TARV pourrait être un outil simple et facilement utilisable en routine pour mieux cibler les patients à risque de NRI, en association avec la mesure du nadir des LT CD4. Un suivi de la cohorte permettra de confirmer ces résultats à plus long terme. D'autres études devront être conduites, en se focalisant sur les patients avec un nadir de LT CD4 bas, ainsi que chez des patients plus âgés, afin d'explorer les interactions entre immunosénescence, activation immune et Tre

Immune response to antiretroviral therapy during HIV infection

Plus de 30 ans après la découverte du virus de l'immunodéficience humaine (VIH), entre 20 et 30% des patients sous trithérapie anti rétrovirale (TARV) ne récupèrent pas un taux normal de lymphocytes (LT) CD4, ce qui est associé à une plus grande morbi-mortalité. Il existe de nombreux résultats discordants dans la littérature concernant le rôle joué par l'activation immunitaire des LT CD4 et CD8, ainsi que des incertitudes sur celui des LT régulateurs (Treg), dans cette non réponse immunologique (NRI). Dans le but de clarifier les liens entre NRI, activation immunitaire et Treg, nous avons formulé deux hypothèses : (i) il existe un lien entre le pourcentage de Treg, l'activation immune des LT CD4 et/ou LT CD8, et NRI; et (ii) le pourcentage de Treg mesuré à l'introduction de la TARV est utilisable en tant que marqueur indépendant de risque de NRI à la TARV. Afin de tester nos hypothèses, nous avons dans un premier temps amélioré le phénotypage des Treg en pratique quotidienne, d'abord en comparant différents phénotypes de Treg, puis en validant dans des échantillons cliniques une nouvelle méthode de marquage de FoxP3 intracellulaire en un temps. Puis nous avons analysé dans une étude transversale les liens entre NRI, activation immune, différentes sous populations de Treg et la détection d'une virémie résiduelle, au sein d'une population de patients infectés par le VIH-1, en succès virologique sous TARV depuis de nombreuses années. Les facteurs prédictifs associée à la NRI ont été analysés au moyen d'une analyse multivariée. Nous avons parallèlement étudié au moyen d'une étude prospective le rôle pronostic de la mesure du pourcentage de Treg à l'introduction de la TARV, sur la réponse immune en LT CD4 dans les 2 ans suivant le début du traitement. Nous avons montré que la NRI après 7 ans de TARV en moyenne était associée de façon indépendante au nadir de LT CD4 et au pourcentage de Treg. Nous avons retrouvé une augmentation significative de l'activation immune des LT CD4 en cas de NRI, mais pas des LT CD8. Enfin, nous avons montré que le pourcentage de Treg était, avec le nadir de LT CD4, un facteur prédictif de NRI dans les 2 ans suivant le début de la TARV, et que son impact sur la réponse immune était d'autant plus marqué que le nadir de CD4 était bas. La mesure du pourcentage de Treg à l'introduction de la TARV pourrait être un outil simple et facilement utilisable en routine pour mieux cibler les patients à risque de NRI, en association avec la mesure du nadir des LT CD4. Un suivi de la cohorte permettra de confirmer ces résultats à plus long terme. D'autres études devront être conduites, en se focalisant sur les patients avec un nadir de LT CD4 bas, ainsi que chez des patients plus âgés, afin d'explorer les interactions entre immunosénescence, activation immune et TregMore than 30 years after the discovery of HIV, between 20 and 30% of patients on highly active antiretroviral therapy (ART) do not recover normal levels of CD4 T lymphocytes (CD4). This immunological non response (INR) to ART is associated with an increased morbidity and mortality. There are many conflicting results in the literature related the role of T cells immune activation of T regulator cells (Treg), in INR. In order to clarify the links between INR, immune activation and Treg, we made two hypotheses: (i) there is a link between Treg’s percentage, immune activation of CD4 and / or CD8, and INR; and (ii) the percentage of Treg measured at ART introduction can be used as an independent predictor for INR. To test our hypotheses, we initially improved the immunophenotyping of Treg in daily practice, by comparing different Treg’s phenotype, and by validating in clinical samples a new « one step» staining method of intracellular FoxP3. Then we analyzed in a crosssectionnal study the links between INR, immune activation, different Treg’s subpopulations and detection of very low level viremia, in a population of HIV-1 infected patients, under suppressive ART for many years. Predictive factors associated with the INR were analyzed using multivariate analysis. Simultaneously, we performed a prospective study to analyse the prognostic role of Treg’s percentage at ART introduction on the CD4 reconstitution within 2 years. We have shown that INR after 7 years of ART was independently associated with CD4 nadir and Treg’s percentage. We found in INR patients a significant increase of CD4 immune activation, but not of CD8. Finally, we showed that the Treg’s percentage and the CD4 nadir were independant predictors of INR within 2 years from the start of ART. The effect of Treg at baseline on CD4 evolution was as lower as the CD4 nadir was higher. Measuring the percentage of Treg at ART introduction could be a simple and easy tool to use in daily routine. It could help to better target patients at risk of INR in association with the measurement of CD4 nadir. A follow-up of the cohort will confirm these results in the long term. Further studies will be conducted, focusing on patients with a low CD4 nadir, and on older patients, in order to explore the interactions between immunosenescence, immune activation and Tre

La virémie résiduelle détectée chez les patients en succès virologique après l'introduction des antirétroviraux est associée au sous-type non-B du VIH-1

LYON1-BU Santé (693882101) / SudocSudocFranceF

Unexpected severe native aortic subacute endocarditis due to Bartonella quintana in a 40-year-old woman with good socioeconomic condition

International audienc