RESUMEN
BACKGROUND: Innate lymphoid cells (ILCs) are key organizers of tissue immune responses and regulate tissue development, repair, and pathology. Persistent clinical sequelae beyond 12 weeks following acute COVID-19 disease, named post-COVID syndrome (PCS), are increasingly recognized in convalescent individuals. ILCs have been associated with the severity of COVID-19 symptoms but their role in the development of PCS remains poorly defined. METHODS AND RESULTS: Here, we used multiparametric immune phenotyping, finding expanded circulating ILC precursors (ILCPs) and concurrent decreased group 2 innate lymphoid cells (ILC2s) in PCS patients compared to well-matched convalescent control groups at > 3 months after infection or healthy controls. Patients with PCS showed elevated expression of chemokines and cytokines associated with trafficking of immune cells (CCL19/MIP-3b, FLT3-ligand), endothelial inflammation and repair (CXCL1, EGF, RANTES, IL-1RA, PDGF-AA). CONCLUSION: These results define immunological parameters associated with PCS and might help find biomarkers and disease-relevant therapeutic strategies.
Asunto(s)
COVID-19 , Convalecencia , Citocinas , Linfocitos , Síndrome Post Agudo de COVID-19 , Humanos , COVID-19/inmunología , COVID-19/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Linfocitos/inmunología , Citocinas/inmunología , SARS-CoV-2/inmunología , Inmunidad Innata , Anciano , Quimiocinas/inmunologíaRESUMEN
There is a lack of interventions that treat the Post-Covid-19 Condition (PCC) itself. Accordingly, treatment guidelines recommend physiotherapy interventions to alleviate symptoms and enhance functioning. In cases where unimodal treatments prove ineffective, non-organ-specific multidisciplinary bio-psycho-social rehabilitation (MBR) programs are a suitable option. In a pilot observational study with assessments at the entry and end of treatment we aimed to evaluate the feasibility of a 3-week day clinic MBR program and explore its effects on physical functioning in PCC patients with fatigue and reduced physical capacity. Patient selection was based on an interdisciplinary assessment involving a physician, a psychologist and a physiotherapist. Feasibility was determined based on full participation (≥ 8 of 9 days) and maintenance of stable endurance in the 6-Minute Walk Test (6MWT). From 37 patients included in the study, 33 completed the MBR (mean age: 43 ± 12 years, 73% female). Four patients discontinued the MBR, with two of them having reported deterioration of PCC symptoms. The 6MWT showed a numerical improvement from 501 ± 97 m to 512 ± 87 m, although it did not reach statistical significance. These results support the feasibility of outpatient MBR with a focus on active physiotherapy interventions in PCC patients with fatigue. This study aligns with previous research supporting the effectiveness of physiotherapy and rehabilitation in PCC patients. However, further research is needed to address possible different treatment responses and varying treatment approaches in subgroups of PCC patients.
RESUMEN
Post COVID-19 conditions (PCC) present with a wide range of symptoms. Headache is one of the most frequently reported neurological symptoms by patients with PCC. We aimed to assess the prevalence of headache in patients with PCC who attended the Post-COVIDLMU outpatient department at LMU University Hospital in Munich. We hypothesized that headaches occur more frequently in patients with PCC than in the control group. Patients answered a questionnaire containing sociodemographic characteristics, their current symptoms, and prior psychiatric and somatic diagnoses, the WHO Quality of Life assessment (WHOQOL-BREF), 9-item Patient Health Questionnaire (PHQ-9), and the Fatigue Severity Scale (FSS). 188 PCC patients were included in this study and compared to a control group of patients with a history of COVID-19 or a different infectious disease - but no consecutive post-infectious condition (nc=27). 115 (61%) of our PCC patients were female. The median age was 41 years. 60 (32%, p = 0.001) had a pre-existing psychiatric diagnosis. PCC was associated with worse outcomes in all four domains of the WHOQOL-BREF (p < 0.001), high levels of fatigue (FSS; p < 0.001), and a higher likeliness for symptoms of depression (PHQ-9; p < 0.001). We were able to confirm that psychiatric disorders are more frequently associated with headaches in PCC patients. Headache should be assessed and treated in the context of PCC not only by neurologists but by multi-professional teams and regarding all PCC symptoms.
RESUMEN
Cognitive symptoms (CS) belong to the most common manifestations of the Post COVID-19 (PC) condition. We sought to objectify CS in PC patients using routine diagnostic assessments: neurocognitive testing (NCT) and brain imaging (BI). Further, we investigated possible associations of CS with patient reported outcomes (PROs), and risk factors for developing CS. Clinical data and PROs of 315 PC patients were assessed at a mean of 6 months after SARS-CoV-2 infection. 231 (73.3%) patients reported any sort of CS. Among them, 78 underwent NCT and 55 received BI. In NCT, the cognitive domains most affected were the working memory, attention, and concentration. Nonetheless, pathological thresholds were exceeded only in few cases. Neurocognitive performance did not differ significantly between patients complaining of severe (n = 26) versus non-severe (n = 52) CS. BI findings were abnormal in 8 (14.5%) cases with CS but were most likely not related to PC. Patients reporting high severity of CS scored worse in the PHQ-9, FSS, WHOQOL-BREF, were more likely to report impaired sleep, and had a higher prevalence of psychiatric diagnoses. Overall, NCT could confirm mild impairment in some but not all PC patients with CS, while BI studies were abnormal in only few cases. CS severity did not affect NCT results, but severe CS were associated with symptoms of depression (PHQ-9), fatigue (FSS), reduced quality of life (WHOQOL-BREF) and higher prevalence of psychiatric illnesses. These findings support the importance of NCT, BI, and neuro-psychological assessment in the work-up of PC patients reporting CS. TRIAL REGISTRATION: Trial registration number and date of registration: DRKS00030974, 22 Dec 2022, retrospectively registered.
RESUMEN
Our prototype system designed for clinical data acquisition and recording of studies is a novel electronic data capture (EDC) software for simple and lightweight data capture in clinical research. Existing software tools are either costly or suffer from very limited features. To overcome these shortcomings, we designed an EDC software together with a mobile client. We aimed at making it easy to set-up, modifiable, scalable and thereby facilitating research. We wrote the software in R using a modular approach and implemented existing data standards along with a meta data driven interface and database structure. The prototype is an adaptable open-source software, which can be installed locally or in the cloud without advanced IT-knowledge. A mobile web interface and progressive web app for mobile use and desktop computers is added. We show the software's capability, by demonstrating four clinical studies with over 1600 participants and 679 variables per participant. We delineate a simple deployment approach for a server-installation and indicate further use-cases. The software is available under the MIT open-source license. Conclusively the software is versatile, easily deployable, highly modifiable, and extremely scalable for clinical studies. As an open-source R-software it is accessible, open to community-driven development and improvement in the future.
Asunto(s)
Programas Informáticos , Humanos , Aplicaciones Móviles , Interfaz Usuario-Computador , Registros Electrónicos de Salud , Bases de Datos Factuales , Recolección de Datos/métodos , Configuración de Recursos LimitadosRESUMEN
Fair allocation of funding in multi-centre clinical studies is challenging. Models commonly used in Germany - the case fees ("fixed-rate model", FRM) and up-front staffing and consumables ("up-front allocation model", UFAM) lack transparency and fail to suitably accommodate variations in centre performance. We developed a performance-based reimbursement model (PBRM) with automated calculation of conducted activities and applied it to the cohorts of the National Pandemic Cohort Network (NAPKON) within the Network of University Medicine (NUM). The study protocol activities, which were derived from data management systems, underwent validation through standardized quality checks by multiple stakeholders. The PBRM output (first funding period) was compared among centres and cohorts, and the cost-efficiency of the models was evaluated. Cases per centre varied from one to 164. The mean case reimbursement differed among the cohorts (1173.21 [95% CI 645.68-1700.73] to 3863.43 [95% CI 1468.89-6257.96]) and centres and mostly fell short of the expected amount. Model comparisons revealed higher cost-efficiency of the PBRM compared to FRM and UFAM, especially for low recruitment outliers. In conclusion, we have developed a reimbursement model that is transparent, accurate, and flexible. In multi-centre collaborations where heterogeneity between centres is expected, a PBRM could be used as a model to address performance discrepancies.Trial registration: https://clinicaltrials.gov/ct2/show/NCT04768998 ; https://clinicaltrials.gov/ct2/show/NCT04747366 ; https://clinicaltrials.gov/ct2/show/NCT04679584 .