Persistent COVID-19 symptoms have been reported up to 3 months after hospital discharge. Little is known on the frequency and the nature of persistent symptoms beyond 3 months. Here we have assessed, ...in the longitudinal prospective French COVID-19 cohort, symptoms that persisted 6 months after admission for COVID-19.
Hospitalized patients with virologically confirmed COVID-19 were enrolled. Follow-up was planned with a physician's visit at month (M)3 and M6 after admission. Associations between persistence of symptoms at M6 and clinical characteristics at admission were assessed through bivariate and multivariate logistic regression.
M6 data were available for 1137 participants. Median age was 61 years (IQR 51–71) and 288 (29%, 95% CI 26–32%) were admitted to intensive care unit (ICU) during the acute phase. Six hundred and fifty-five (68%, 95% CI 65–71%) and 639 (60%, 95% CI 57–63%) participants had at least one symptom at M3 and M6 visit, respectively, mostly fatigue, dyspnoea, joint pain and myalgia. At M6, 255 (24%, 95% CI 21–27%) of participants had three or more persistent symptoms. The presence of three or more symptoms at M6 was independently associated with female gender (adjusted odds ratio (aOR) 2.40, 95% CI 1.75–3.30), having three or more symptoms at admission (aOR 2.04, 95% CI 1.45–2.89) and ICU admission/transfer during acute phase (aOR 1.55, 95% CI 1.09–2.18), but not significantly with age or having two or more comorbidities. One hundred and twenty-five (29%, 95% CI 25–34%) of those who initially had a professional occupation were not back to work at M6.
A fourth of individuals admitted to hospital for COVID-19 still had three or more persistent symptoms at M6. Longitudinal follow-up of individuals with severe COVID-19 is warranted to better understand the pathophysiology underlying this long-term persistence.
The risk of congenital neurologic defects related to Zika virus (ZIKV) infection has ranged from 6 to 42% in various reports. The aim of this study was to estimate this risk among pregnant women with ...symptomatic ZIKV infection in French territories in the Americas.
From March 2016 through November 2016, we enrolled in this prospective cohort study pregnant women with symptomatic ZIKV infection that was confirmed by polymerase-chain-reaction (PCR) assay. The analysis included all data collected up to April 27, 2017, the date of the last delivery in the cohort.
Among the 555 fetuses and infants in the 546 pregnancies included in the analysis, 28 (5.0%) were not carried to term or were stillborn, and 527 were born alive. Neurologic and ocular defects possibly associated with ZIKV infection were seen in 39 fetuses and infants (7.0%; 95% confidence interval, 5.0 to 9.5); of these, 10 were not carried to term because of termination of pregnancy for medical reasons, 1 was stillborn, and 28 were live-born. Microcephaly (defined as head circumference more than 2 SD below the mean for sex and gestational age) was detected in 32 fetuses and infants (5.8%), of whom 9 (1.6%) had severe microcephaly (more than 3 SD below the mean). Neurologic and ocular defects were more common when ZIKV infection occurred during the first trimester (24 of 189 fetuses and infants 12.7%) than when it occurred during the second trimester (9 of 252 3.6%) or third trimester (6 of 114 5.3%) (P=0.001).
Among pregnant women with symptomatic, PCR-confirmed ZIKV infection, birth defects possibly associated with ZIKV infection were present in 7% of fetuses and infants. Defects occurred more frequently in fetuses and infants whose mothers had been infected early in pregnancy. Longer-term follow-up of infants is required to assess any manifestations not detected at birth. (Funded by the French Ministry of Health and others; ClinicalTrials.gov number, NCT02916732 .).
Contexte
L’alliance thérapeutique représente un objet très peu étudié quand il concerne les infirmiers et les soins prodigués par une équipe infirmière et dans le cadre de l’hospitalisation en soins ...aigus.
Objectif
L’objectif était d’étudier l’influence de facteurs sur l’alliance thérapeutique construite entre les infirmier(e)s et les aides-soignant(e)s et les patients adultes hospitalisés dans un service de soins aigus en psychiatrie générale de secteur.
Méthode
Il s’agit d’une étude prospective, observationnelle et transversale utilisant une échelle de mesure de l’alliance thérapeutique. Le score d’alliance thérapeutique (AT) a été mesuré à l’aide de l’échelle STAR-P sur un échantillon de 240 patients.
Résultats
Le score moyen obtenu est de 33,4 (±7,8) sur un score maximum théorique de 48. Le score global d’AT des patients âgés de 60 ans ou plus, est significativement plus élevé que celui des patients ayant entre 18 et 29 ans (p = 0,021). L’absence de suivi ambulatoire au cours des trois mois suivant la sortie d’hospitalisation n’est pas associée au score global d’AT (p = 0,73). Si les patients hospitalisés, quelques soit leurs troubles et les différentes formes de soins, sous obligation légale ou non, jugent plutôt bonne l’AT à l’issue de leur hospitalisation. Seuls des facteurs sociaux-démographiques comme, l’âge, les conditions d’hébergement (précaire ou durable), avoir ou non un emploi, vivre seul ou avec un partenaire influent sur l’AT et le suivi.
Conclusion
Les résultats convoquent les concepts d’anomie et d’attachement, qui semblent jouer un rôle important dans l’absence de suivi post-hospitalisation, ce qui indiquent la nécessaire approche globale des soins et une implication des professionnels de santé mais aussi du social où l’empathie doit trouver sa place.
In 2014-2015, we assessed favipiravir tolerance and efficacy in patients with Ebola virus (EBOV) disease (EVD) in Guinea (JIKI trial). Because the drug had never been used before for this indication ...and that high concentrations of the drugs were needed to achieve antiviral efficacy against EBOV, a pharmacokinetic model had been used to propose relevant dosing regimen. Here we report the favipiravir plasma concentrations that were achieved in participants in the JIKI trial and put them in perspective with the model-based targeted concentrations.
Pre-dose drug concentrations were collected at Day-2 and Day-4 of treatment in 66 patients of the JIKI trial and compared to those predicted by the model taking into account patient's individual characteristics. At Day-2, the observed concentrations were slightly lower than the model predictions adjusted for patient's characteristics (median value of 46.1 versus 54.3 μg/mL for observed and predicted concentrations, respectively, p = 0.012). However, the concentrations dropped at Day-4, which was not anticipated by the model (median values of 25.9 and 64.4 μg/mL for observed and predicted concentrations, respectively, p<10-6). There was no significant relationship between favipiravir concentrations and EBOV viral kinetics or mortality.
Favipiravir plasma concentrations in the JIKI trial failed to achieve the target exposure defined before the trial. Furthermore, the drug concentration experienced an unanticipated drop between Day-2 and Day-4. The origin of this drop could be due to severe sepsis conditions and/or to intrinsic properties of favipiravir metabolism. Dose-ranging studies should be performed in healthy volunteers to assess the concentrations and the tolerance that could be achieved with high doses.
ClinicalTrials.gov NCT02329054.
Viral haemorrhagic fevers are characterized by irregular outbreaks with high mortality rate. Difficulties arise when implementing therapeutic trials in this context. The outbreak duration is hard to ...predict and can be short compared to delays of trial launch and number of subject needed (NSN) recruitment. Our objectives were to compare, using clinical trial simulation, different trial designs for experimental treatment evaluation in various outbreak scenarios.
Four type of designs were compared: fixed or group-sequential, each being single- or two-arm. The primary outcome was 14-day survival rate. For single-arm designs, results were compared to a pre-trial historical survival rate p
. Treatments efficacy was evaluated by one-sided tests of proportion (fixed designs) and Whitehead triangular tests (group-sequential designs) with type-I-error = 0.025. Both survival rates in the control arm p
and survival rate differences Δ (including 0) varied. Three specific cases were considered: "standard" (fixed p
, reaching NSN for fixed designs and maximum sample size N
for group-sequential designs); "changing with time" (increased p
over time); "stopping of recruitment" (epidemic ends). We calculated the proportion of simulated trials showing treatment efficacy, with K = 93,639 simulated trials to get a type-I-error PI
of 0.024;0.026.
Under H
(Δ = 0), for the "standard" case, the type-I-error was maintained regardless of trial designs. For "changing with time" case, when p
> p
type-I-error was inflated, and when p
< p
it decreased. Wrong conclusions were more often observed for single-arm designs due to an increase of Δ over time. Under H
(Δ = + 0.2), for the "standard" case, the power was similar between single- and two-arm designs when p
= p
. For "stopping of recruitment" case, single-arm performed better than two-arm designs, and fixed designs reported higher power than group-sequential designs. A web R-Shiny application was developed.
At an outbreak beginning, group-sequential two-arm trials should be preferred, as the infected cases number increases allowing to conduct a strong randomized control trial. Group-sequential designs allow early termination of trials in cases of harmful experimental treatment. After the epidemic peak, fixed single-arm design should be preferred, as the cases number decreases but this assumes a high level of confidence on the pre-trial historical survival rate.
The aims of this study were, first, to identify risk factors for microbiology-proven postoperative pneumonia after cardiac surgery and, second, to develop and validate a preoperative scoring system ...for the risk of postoperative pneumonia.
A single-center cohort study.
All consecutive patients undergoing cardiac surgery between January 2006 and July 2011.
None.
Multivariate analysis of risk factors for postoperative pneumonia was performed on data from patients operated between January 2006 and December 2008 (training set). External temporal validation was performed on data from patients operated between January 2009 and July 2011 (validation set). Preoperative variables identified in multivariate analysis of the training set were then used to develop a preoperative scoring system that was validated on the validation set. Postoperative pneumonia occurred in 174 of the 5,582 patients (3.1%; 95% CI, 2.7-3.6). Multivariate analysis identified four risk factors for postoperative pneumonia: age (odds ratio, 1.02; 95% CI, 1.01-1.03), chronic obstructive pulmonary disease (odds ratio, 2.97; 95% CI, 1.8-4.71), preoperative left ventricular ejection fraction (odds ratio, 0.98; 95% CI, 0.96-0.99), and the interaction between RBC transfusion during surgery and duration of cardiopulmonary bypass (odds ratio, 2.98; 95% CI, 1.96-4.54). A 6-point score including the three preoperative variables then defined two risk groups corresponding to postoperative pneumonia rates of 1.8% (score < 3) and 6.5% (score ≥ 3).
Assessing preoperative risk factors for postoperative pneumonia with the proposed scoring system could help to implement a preventive policy in high-risk patients with a risk of postoperative pneumonia greater than 4% (i.e., patients with a score ≥ 3).
It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their differing antibody response profiles. Here, we performed a pilot ...study of four serological assays to assess the amounts of anti-SARS-CoV-2 antibodies in serum samples obtained from 491 healthy individuals before the SARS-CoV-2 pandemic, 51 individuals hospitalized with COVID-19, 209 suspected cases of COVID-19 with mild symptoms, and 200 healthy blood donors. We used two ELISA assays that recognized the full-length nucleoprotein (N) or trimeric spike (S) protein ectodomain of SARS-CoV-2. In addition, we developed the S-Flow assay that recognized the S protein expressed at the cell surface using flow cytometry, and the luciferase immunoprecipitation system (LIPS) assay that recognized diverse SARS-CoV-2 antigens including the S1 domain and the carboxyl-terminal domain of N by immunoprecipitation. We obtained similar results with the four serological assays. Differences in sensitivity were attributed to the technique and the antigen used. High anti-SARS-CoV-2 antibody titers were associated with neutralization activity, which was assessed using infectious SARS-CoV-2 or lentiviral-S pseudotype virus. In hospitalized patients with COVID-19, seroconversion and virus neutralization occurred between 5 and 14 days after symptom onset, confirming previous studies. Seropositivity was detected in 32% of mildly symptomatic individuals within 15 days of symptom onset and in 3% of healthy blood donors. The four antibody assays that we used enabled a broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in different subpopulations within one region.
The identification of patients with coronavirus disease 2019 and high risk of severe disease is a challenge in routine care. We performed cell phenotypic, serum, and RNA sequencing gene expression ...analyses in severe hospitalized patients (n = 61). Relative to healthy donors, results showed abnormalities of 27 cell populations and an elevation of 42 cytokines, neutrophil chemo-attractants, and inflammatory components in patients. Supervised and unsupervised analyses revealed a high abundance of CD177, a specific neutrophil activation marker, contributing to the clustering of severe patients. Gene abundance correlated with high serum levels of CD177 in severe patients. Higher levels were confirmed in a second cohort and in intensive care unit (ICU) than non-ICU patients (P < 0.001). Longitudinal measurements discriminated between patients with the worst prognosis, leading to death, and those who recovered (P = 0.01). These results highlight neutrophil activation as a hallmark of severe disease and CD177 assessment as a reliable prognostic marker for routine care.
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•Increase in B cells, activated CD8 T cells, NKT, and γδ T NKG2A + cells in severe COVID-19•Severe COVID-19 is characterized by an increase of neutrophil and inflammatory markers•Serum CD177 protein levels are increased in patients with COVID-19 in ICU•Sustained high levels of CD177 discriminated recovery and death of patients with COVID-19
Immunology; Virology
The chikungunya virus (CHIKV) is a re-emerging alphavirus that can cause chronic and potentially incapacitating rheumatic musculoskeletal disorders known as chronic chikungunya arthritis (CCA). We ...conducted a prospective cohort study of CHIKV-infected subjects during the 2013 chikungunya outbreak in Martinique. The aim of this study was to assess the prevalence of CCA at 12 months and to search for acute phase factors significantly associated with chronicity.
A total of 193 patients who tested positive for CHIKV RNA via qRT-PCR underwent clinical investigations in the acute phase (<21 days), and then 3, 6, and 12 months after inclusion. The Asian lineage was identified as the circulating genotype. A total of 167 participants were classified as either with or without CCA, and were analyzed using logistic regression models. The overall prevalence of CCA at 12 months was 52.1% (95%CI: 44.5-59.7). In univariate analysis, age (RD 9.62, 95% CI, 4.87;14.38, p<0.0001), female sex (RD 15.5, 95% CI, 1.03;30.0, p = 0.04), headache (RD 15.42, 95% CI, 0.65;30.18 p = 0.04), vertigo (RD 15.33, 95% CI, 1.47;29.19, p = 0.03), vomiting (RD 12.89, 95% CI, 1.54;24.24, p = 0.03), dyspnea (RD 13.53, 95% CI, 0.73;26.33, p = 0.04), intravenous rehydration (RD -16.12, 95% CI, -31.58; -0.66 p = 0.04) and urea (RD 0.66, 95% CI, 0.12;1.20, p = 0.02) were significantly associated with the development of CCA. For the subpopulation with data on joint involvement in the acute phase, the risk factors significantly associated with CCA were at least one 1 enthesitis (RD 16.7, 95%CI, 2.8; 30.7, p = 0.02) and at least one tenosynovitis (RD 16.8, 95% CI, 1.4-32.2, p = 0.04).
This cohort study conducted in Martinique confirms that CCA is a common complication of acute chikungunya disease. Our analysis emphasized the importance of age and female sex for CCA occurrence, and highlighted the aggravating role of dehydration during the acute phase. Early and adequate hydration were found to reduce the risk chronic chikungunya disorders.
clinicaltrials.gov (NCT01099852).
The aim of this study was to compare the diagnostic performances for the detection of myocardial ischemia of 82-Rb-PET-MPS and 99m-Tc-SPECT-MPS in overweight individuals and women.
Men with BMI ≥ 25 ...and women referred for MPS were considered for inclusion. All individuals underwent 99m-Tc-SPECT-MPS with CZT cameras and 82-Rb-PET-MPS in 3D-mode. Individuals with at least one positive MPS were referred for coronary angiography (CA) with FFR measurements. A criterion for positivity was a composite endpoint including significant stenosis on CA or, in the absence of CA, the occurrence of acute coronary event during the following year. 313 patients (46% women) with mean BMI of 31.8 ± 6.5 were included. Sensitivity for the detection of myocardial ischemia was higher with 82-Rb-PET-MPS compared with 99m-Tc-SPECT-MPS (85% vs. 57%, P < .05); specificity was equally high with both imaging techniques (93% vs. 94%, P > .05). 82-Rb-PET allowed for a more accurate detection of patients with a high-risk coronary artery disease (HR-CAD) than 99m-Tc-SPECT-MPS (AUC = 0.86 vs. 0.75, respectively; P = .04).
In women and overweight individuals, 82-Rb-PET-MPS provides higher sensitivity for the detection of myocardial ischemia than 99m-Tc-SPECT-MPS thanks to a better image quality and an improved detection of HR-CAD.
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