Project description:Accurate diagnosis and prognosis of disorders of consciousness is complicated by the variability amongst patients' trajectories. However, the majority of research and scientific knowledge in this field is based on cross-sectional studies. The translational gap in applying this knowledge to inform clinical management can only be bridged by research that systematically examines follow-up. In this study, we present findings from a novel longitudinal study of the long-term recovery trajectory of 39 patients, repeatedly assessed using the Coma Recovery Scale-Revised once every 3 months for 2 years, generating 185 assessments. Despite the expected inter-patient variability, there was a statistically significant improvement in behaviour over time. Further, improvements began approximately 22 months after injury. Individual variation in the trajectory of recovery was influenced by initial diagnosis. Patients with an initial diagnosis of unresponsive wakefulness state, who progressed to the minimally conscious state, did so at a median of 485 days following onset-later than 12-month period after which current guidelines propose permanence. Although current guidelines are based on the expectation that patients with traumatic brain injury show potential for recovery over longer periods than those with non-traumatic injury, we did not observe any differences between trajectories in these two subgroups. However, age was a significant predictor, with younger patients showing more promising recovery. Also, progressive increases in arousal contributed exponentially to improvements in behavioural awareness, especially in minimally conscious patients. These findings highlight the importance of indexing arousal when measuring awareness, and the potential for interventions to regulate arousal to aid long-term behavioural recovery in disorders of consciousness.
Project description:Since the Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), our understanding regarding the pathophysiology and clinical manifestations of this disease have been improving. However, we still have limited data on long-term effects and lingering symptoms of post COVID-19 recovery. Despite predilection of COVID-19 for lungs, multiple extra-pulmonary manifestations appear in multiple organs and biological systems and with continued infection and recovery worldwide. It is necessary that clinicians provide patients with previous SARS-CoV-2 infection with expectations of long-term effects during or after recovery from COVID-19. Herein, we review the long-term impact of COVID-19 on different organ systems reported from different clinical studies. Understanding risk factors and signs and symptoms of long-term consequences after recovery from COVID-19 will allow for proper follow-up and management of the disease post recovery.
Project description:Background and objectivesIn patients with severe coronavirus disease 2019 (COVID-19), disorders of consciousness (DoC) have emerged as a serious complication. The prognosis and pathophysiology of COVID-DoC remain unclear, complicating decisions about continuing life-sustaining treatment. We describe the natural history of COVID-DoC and investigate its associated brain connectivity profile.MethodsIn a prospective longitudinal study, we screened consecutive patients with COVID-19 at our institution. We enrolled critically ill adult patients with a DoC unexplained by sedation or structural brain injury and who were planned to undergo a brain MRI. We performed resting-state fMRI and diffusion MRI to evaluate functional and structural connectivity compared to healthy controls and patients with DoC resulting from severe traumatic brain injury (TBI). We assessed the recovery of consciousness (command following) and functional outcomes (Glasgow Outcome Scale Extended [GOSE] and the Disability Rating Scale [DRS]) at hospital discharge and 3 and 6 months after discharge. We also explored whether clinical variables were associated with recovery from COVID-DoC.ResultsAfter screening 1,105 patients with COVID-19, we enrolled 12 with COVID-DoC. The median age was 63.5 years (interquartile range 55-76.3 years). After the exclusion of 1 patient who died shortly after enrollment, all of the remaining 11 patients recovered consciousness 0 to 25 days (median 7 [5-14.5] days) after the cessation of continuous IV sedation. At discharge, all surviving patients remained dependent: median GOSE score 3 (1-3) and median DRS score 23 (16-30). Ultimately, however, except for 2 patients with severe polyneuropathy, all returned home with normal cognition and minimal disability: at 3 months, median GOSE score 3 (3-3) and median DRS score 7 (5-13); at 6 months, median GOSE score 4 (4-5), median DRS score 3 (3-5). Ten patients with COVID-DoC underwent advanced neuroimaging; functional and structural brain connectivity in those with COVID-DoC was diminished compared to healthy controls, and structural connectivity was comparable to that in patients with severe TBI.DiscussionPatients who survived invariably recovered consciousness after COVID-DoC. Although disability was common after hospitalization, functional status improved over the ensuing months. While future research is necessary, these prospective findings inform the prognosis and pathophysiology of COVID-DoC.Trial registration informationClinicalTrials.gov identifier: NCT04476589.
Project description:BackgroundAfter recovery from acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many patients experience long-term symptoms in different body systems. The aim of the present study was to identify these symptoms, their severity, and their duration as a first step in building a system to classify post-recovery long-term symptoms of coronavirus disease 2019 (COVID-19).MethodsAn online-based cross-sectional survey was administered between September and October 2020. Data regarding the severity of post-recovery symptoms and their duration were collected using an Arabic questionnaire divided into six categories encompassing the 20 most prevalent symptoms.ResultsA total of 979 patients recovered from COVID-19 in Saudi Arabia in the study period, of whom 53% were male and 47% were female. The most common symptoms included general fatigue and weakness (73% each), with moderate severity of neurological symptoms including mood changes (41%) and insomnia (39%). Among the special senses, loss of smell and taste of marked severity were reported by 64% and 55% among respiratory symptoms, cough of mild severity (47%), and dyspnea of moderate severity (43%). Loss of appetite of moderate severity was reported in 42%, and diarrhea, abdominal pain, and nausea of mild severity were reported by 53%, 50%, and 44% of respondents, respectively.ConclusionsLong-term symptoms after recovery from COVID-19 warrant patient follow-up. The authors propose a classification system as a starting point to guide the identification and follow-up of long-term symptoms post-recovery, and recommend larger-scale studies to broaden the definition of recovery from COVID-19, which appears to have two phases, acute and chronic.
Project description:ObjectivesThis study aimed to describe the burden of illness and impact on health and working situation among former intensive care patients treated for COVID-19.MethodsA prospective cohort study was performed at one intensive care unit of a university hospital in Sweden during the first wave of COVID-19 in spring 2020. The burden of illness in health status, cognitive, physical, and psychological outcomes, and working situation were assessed at four and 12 months after discharge from intensive care, using nine validated instruments.ResultsForty-six participants treated for COVID-19 participated in both follow-ups and were included in this study. General fatigue was reported by 37 of 46 participants (82%) at both follow-ups (p = 1.000). For overall health status 28 (61%) participants at the first follow-up and 26 (57%) (p = 0.414) at the second reported lower values than the general population. Cognitive impairment was seen in 22 (52%) participants at four months and in 13 (31%) at 12 months (p = 0.029). The proportion of participants on sick-leave decreased between the first and second follow-up (24% vs 13%, p = 0.025), but the proportion of participants working full-time was almost the same at both follow-ups (35% vs 37%, p = 0.317).ConclusionsThe burden of illness of patients treated in intensive care due to COVID-19 included cognitive, physical, and psychological impacts. Cognitive functions were improved after 12 months, but no clear improvements could be distinguished in the physical or psychological outcome. Higher burden of illness was associated with inability to return to work.
Project description:We performed the longitudinal peripheral blood transcriptome profiling after diagnosis in five patients, and found that patients' blood transcriptomes undergo dramatic and consistent changes in early recovery stage (ERS). Meanwhile, the blood transcriptome did not fully return to the healthy state even after more than one month of recovery. We also realized that differential expressed genes (DEGs) are enriched in biological processes of antigen processing and related processes, and promoter regions of these genes enrich key transcription factors (TFs) involved in T cell differentiation and activation. We further provided potential mechanisms underlying these orchestrated processes, by revealing these specific TFs mediated gene co-expression network.
Project description:The emergence of a new type of COVID-19 patients, who were retested positive after hospital discharge with long-term persistent SARS-CoV-2 infection but without COVID-19 clinical symptoms (hereinafter, LTPPs), poses novel challenges to COVID-19 treatment and prevention. Why was there such a contradictory phenomenon in LTPPs? To explore the mechanism underlying this phenomenon, we performed quantitative proteomic analyses using the sera of 12 LTPPs (Wuhan Pulmonary Hospital), with the longest carrying history of 132 days, and mainly focused on seven LTPPs without hypertension (LTPPs-NH).
Project description:BackgroundIt is unclear whether asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2.MethodsAll patients over 28 days old testing positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms.Results168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4.15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1.12 [95% CI 0.86, 1.45], p = .40). Among SARS-CoV-2-positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared with non-allergic asthma (OR 0.52 [0.28, 0.91], p = .026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared with patients with mild or asymptomatic disease, independent of asthma status (p = .0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms.ConclusionsAsthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared with non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with a more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms 3 months post-infection.
Project description:ObjectivesTo determine the health status, exercise capacity, and health related quality of life (HRQoL) of COVID-19 associated acute respiratory distress syndrome (ARDS) survivors, 8 months after diagnosis.MethodsAll eligible patients were interviewed and underwent a physical examination, chest X-ray, and 6 min walk test (6MWT). Scales to evaluate post-traumatic stress disorder, depression, anxiety, and HRQoL were applied.ResultsOf 1295 patients, 365 suffered ARDS and 166 survived to hospital discharge. Five died after discharge and 48 were lost to follow-up. Of the 113 remaining patients, 81% had persistent symptoms. More than 50% of patients completed less than 80% of the theoretical distance on the 6MWT, 50% had an abnormal X-ray and 93% of patients developed psychiatric disorders. Mean SF-36 scores were worse than in the general population. After multivariate regression analysis, female sex, non-Caucasian race, and Charlson index>2 were independent risk factors for a worse mental health component summary score on the SF-36, and age was associated with a better prognosis. Female sex and chronic obstructive pulmonary disease were independently associated with a worse physical component summary score.ConclusionCOVID-19 associated ARDS survivors have long-term consequences in health status, exercise capacity, and HRQoL. Strategies addressed to prevent these sequelae are needed.
Project description:BackgroundWhile acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking.MethodsA retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1-365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021.FindingsAdvanced age (HR 2.77, 95%CI 2.53-3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03-4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55-5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14-1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37-0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17-1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20-1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45-1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80-13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10-1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32-1.67) and 365 days (RR 1.54, 95%CI 1.21-1.96) compared to COVID-19 patients with no AKI.InterpretationCOVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery.FundingAuthors are supported by various funders, with full details stated in the acknowledgement section.