BACKGROUND: Postacute sequelae of COVID-19 (PASC), also known as long COVID, is a broad grouping of a range of long-term symptoms following acute COVID-19. These symptoms can occur across a range of biological systems, leading to challenges in determining risk factors for PASC and the causal etiology of this disorder. An understanding of characteristics that are predictive of future PASC is valuable, as this can inform the identification of high-risk individuals and future preventative efforts. However, current knowledge regarding PASC risk factors is limited.
OBJECTIVE: Using a sample of 55,257 patients (at a ratio of 1 patient with PASC to 4 matched controls) from the National COVID Cohort Collaborative, as part of the National Institutes of Health Long COVID Computational Challenge, we sought to predict individual risk of PASC diagnosis from a curated set of clinically informed covariates. The National COVID Cohort Collaborative includes electronic health records for more than 22 million patients from 84 sites across the United States.
METHODS: We predicted individual PASC status, given covariate information, using Super Learner (an ensemble machine learning algorithm also known as stacking) to learn the optimal combination of gradient boosting and random forest algorithms to maximize the area under the receiver operator curve. We evaluated variable importance (Shapley values) based on 3 levels: individual features, temporal windows, and clinical domains. We externally validated these findings using a holdout set of randomly selected study sites.
RESULTS: We were able to predict individual PASC diagnoses accurately (area under the curve 0.874). The individual features of the length of observation period, number of health care interactions during acute COVID-19, and viral lower respiratory infection were the most predictive of subsequent PASC diagnosis. Temporally, we found that baseline characteristics were the most predictive of future PASC diagnosis, compared with characteristics immediately before, during, or after acute COVID-19. We found that the clinical domains of health care use, demographics or anthropometry, and respiratory factors were the most predictive of PASC diagnosis.
CONCLUSIONS: The methods outlined here provide an open-source, applied example of using Super Learner to predict PASC status using electronic health record data, which can be replicated across a variety of settings. Across individual predictors and clinical domains, we consistently found that factors related to health care use were the strongest predictors of PASC diagnosis. This indicates that any observational studies using PASC diagnosis as a primary outcome must rigorously account for heterogeneous health care use. Our temporal findings support the hypothesis that clinicians may be able to accurately assess the risk of PASC in patients before acute COVID-19 diagnosis, which could improve early interventions and preventive care. Our findings also highlight the importance of respiratory characteristics in PASC risk assessment.
UNASSIGNED: RR2-10.1101/2023.07.27.23293272.

Tuberculosis (TB) survivors, especially children and adolescents, can develop chronic respiratory problems called post-tuberculosis lung disease (PTLD). We conducted a scoping review to identify the current knowledge gaps on PTLD definitions, measuring tools, and research specific to this age group. We searched MEDLINE, EMBASE, Global Health, CINAHL, and Web of Science for studies published between January 1, 2000, and March 1, 2024, and identified 16 studies. Our review found that no consistent definition of PTLD was used in the studies, and the measurement tools used varied widely. Moreover, there was a lack of research on children under five years old, who are disproportionately affected by TB. Also, symptom screening tools designed for adults were frequently used in these studies, raising concerns about their accuracy in detecting PTLD in children and adolescents. Several critical research gaps require attention to improve our understanding and treatment of PTLD. Firstly, the use of inconsistent definitions of PTLD across studies makes it challenging to compare research findings and gain a clear understanding of the condition. Therefore, we need to include an objective measurement of respiratory health, such as a comprehensive post-TB lung function assessment for children and adolescents. It is also crucial to determine the optimal timing and frequency of post-TB assessments for effective PTLD detection. Furthermore, we need more knowledge of the modifiable risk factors for PTLD. The scarcity of prospective studies makes it difficult to establish causality and track the long-term course of the disease in children and adolescents. Finally, current approaches to PTLD management often fail to consider patient-reported outcomes and strategies for social support. Addressing these research gaps in future studies can improve our understanding and management of paediatric PTLD, leading to better long-term health outcomes for this vulnerable population.

暂无摘要。

Despite the success of various cancer therapies on patient survival, these treatments can have negative side effects, particularly severe damage to the respiratory system. Given the rise in respiratory-associated illnesses in response to cancer treatment, we urge the field to consider a new discipline referred to as \'oncology-respirology\' (or onco-respirology).

Coronavirus disease 2019 (COVID-19) continues to cause morbidity and mortality worldwide; therefore, effective treatments remain crucial to controlling it. As interferon-alpha (IFN-α) and -beta (β) have been proposed as COVID-19 treatments, we sought to assess their effectiveness on respiratory, cardiovascular, neurological, and psychiatric signs and symptoms, as well as PASC and death, in hospitalized COVID-19 patients without multiple sclerosis (MS). Using a federated data research network (TriNetX), we performed a retrospective cohort study of hospitalized COVID-19 patients without MS who received IFN-α or -β treatment, comparing them to a similar cohort who did not receive treatment. Following propensity-score matched analyses, we demonstrate that hospitalized COVID-19 patients who were treated with IFN-α or -β had significantly higher odds of death. In contrast, there was no significant difference in any other outcomes between 1-30 days or 1 day to anytime afterward. Overall, hospitalized COVID-19 patients without MS who were treated with IFN-α or -β had similar short- and long-term sequelae (except for mortality) as those who did not receive treatment. The potential benefits of utilizing IFN-α or -β treatment as therapeutics remain to be realized, and our research highlights the need to explore repurposing drugs for COVID-19 using real-world evidence.

Chronic hepatitis C virus infection (HCV) causes liver inflammation and fibrosis, leading to the development of severe liver disease, such as cirrhosis or hepatocellular carcinoma (HCC). Approval of direct-acting antiviral drug combinations has revolutionized chronic HCV therapy, with virus eradication in >98% of the treated patients. The efficacy of these treatments is such that it is formally possible for cured patients to carry formerly infected cells that display irreversible transcriptional alterations directly caused by chronic HCV Infection. Combining differential transcriptomes from two different persistent infection models, we observed a major reversion of infection-related transcripts after complete infection elimination. However, a small number of transcripts were abnormally expressed in formerly infected cells. Comparison of the results obtained in proliferating and growth-arrested cell culture models suggest that permanent transcriptional alterations may be established by several mechanisms. Interestingly, some of these alterations were also observed in the liver biopsies of virologically cured patients. Overall, our data suggest a direct and permanent impact of persistent HCV infection on the host cell transcriptome even after virus elimination, possibly contributing to the development of HCC.

暂无摘要。

Burns are an underestimated serious injury negatively impacting survivors physically, psychologically and economically, and thus are a considerable public health burden. Despite significant advancements in burn treatment, many burns still do not heal or develop serious complications/sequelae. The nucleotide-binding oligomerization domain-like receptors (NLRs) family pyrin domain-containing 3 (NLRP3) inflammasome is a critical regulator of wound healing, including burn wound healing. A better understanding of the pathophysiological mechanism underlying the healing of burn wounds may help find optimal therapeutic targets to promote the healing of burn wounds, reduce complications/sequelae following burn, and maximize the restoration of structure and function of burn skin. This review aimed to summarize current understanding of the roles and regulatory mechanisms of the NLRP3 inflammasome in burn wound healing, as well as the preclinical studies of the involvement of NLRP3 inhibitors in burn treatment, highlighting the potential application of NLRP3-targeted therapy in burn wounds.

UNASSIGNED: Around twenty percent of meningitis survivors experience after-effects. However, very little research on their psychological impact has been conducted. This report details a small explorative investigation into these psychological impacts.
UNASSIGNED: To explore the impact sequelae have on the meningitis survivors affected.
UNASSIGNED: Thematic analysis of one-hundred individual user\'s blog posts, self-reporting one or more sequelae after a diagnosis of meningitis.
UNASSIGNED: Blog posters\' experiences varied greatly. Common trends in experience were mapped onto three themes. \'Struggling to Adjust to the New Normal\' captures blog posters\' struggles in returning to their lives post-hospitalization. \'Navigating Possibilities for Positivity\' explores how blog posters either reported positive change due to their illness experience or felt a pressure, or inability, to do so. \'The Impact of Knowledge and Support\' overarching two sub-themes; \'Lack of Awareness Causing Further Suffering\' and \'Validation Leads to Narrative Shift\'. These sub-themes contrast differences in experience blog posters reported, with and without knowledge, of the cause of their symptoms and support in dealing with the resulting difficulties.
UNASSIGNED: Consistent and structured after-care would benefit patients experiencing sequelae. Suggestions of a possible format this could take are put forward. In addition, self-regulatory models of illness perception help explain some variations in blog posters experiences, with possible intervention plans based on these models also suggested. However, limitations, including the comparatively small and highly selected sample, mean that further research is necessary to validate the findings and assess their validity, widespread applicability, and financial feasibility.

Following mass vaccinations for the control of the COVID-19 epidemic, a spectrum of cardiac and neurological disorders was reported among vaccinated individuals. This study examined the range of complications documented and factors related to their occurrence. Three electronic databases were searched for case reports and case series with descriptions of cardiac and/or neurological complications in COVID-19 vaccine recipients. A total of 698 vaccinees were included in this review, of which 259 (37.1%) had cardiac and 439 (62.9%) had neurological complications. Inflammatory conditions were the commonest among the cardiac complications; while polyneuropathy, demyelinating diseases and cerebrovascular disorders were the more common neurological complications. The mean age of those with cardiac complications (33.8 years) was much younger than those with neurological complications (49.7 years). There was no notable difference in the gender distribution between these two groups of vaccine recipients. mRNA vaccines (all brands) were associated with almost 90.0% of the cardiac complications, whereas viral vector vaccines were associated with slightly over half (52.6%) of the neurological complications. With regard to the dose, cardiac complications were more common after the second (69.1%), whereas neurological complications were more common after the first dose (63.6%). The majority of the cases had an uncomplicated clinical course. Nevertheless, 5.9% of cases with neurological complications and 2.5% of those with cardiac complications were fatal, underscoring the significance of the consistent surveillance and vigilant monitoring of vaccinated individuals to mitigate these occurrences.