Acute COVID-19 gene-expression profiles show multiple etiologies of long-term sequelae.
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ABSTRACT:
SUBMITTER: Thompson RC
PROVIDER: S-EPMC8509101 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Post-acute sequelae of SARS-CoV-2 infection are debilitating, clinically heterogeneous, and of unknown molecular etiology. A transcriptome-wide investigation was performed in acutely infected patients followed clinically into the post-acute period. Distinct gene-expression signatures of post-acute sequelae were already present in whole-blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell associated gene-expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in subjects with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development.
2022-12-06 | GSE215865 | GEO
Project description:Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
2022-02-01 | E-MTAB-10129 | biostudies-arrayexpress
Project description:Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae
| PRJNA891054 | ENA
Project description:Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
| S-EPMC8786632 | biostudies-literature
Project description:Although a substantial proportion of severe COVID-19 pneumonia survivors exhibit long-term pulmonary sequalae, the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high dimensional characterization of the pathophysiological and immune traits of aged COVID-19 convalescents, and correlated the local and systemic immune profiles with pulmonary function and lung imaging. In this cohort of aged COVID-19 convalescents, chronic lung impairment was accompanied by persistent systemic inflammation and respiratory immune alterations. Detailed evaluation of the lung immune compartment revealed dysregulated respiratory CD8+ T cell responses that likely underlie the impaired lung function following acute COVID-19 during aging. Single cell transcriptomic analysis identified the potential pathogenic subsets of respiratory CD8+ T cells causing persistent tissue conditions following COVID-19. Our results have revealed key pathophysiological and immune traits that support the development of lung sequelae following SARS-CoV2 pneumonia during aging, with implications for the treatment of chronic COVID-19 symptoms.
2021-09-17 | GSE176201 | GEO
Project description:Emerging as a new epidemic, long COVID or post-acute sequelae of coronavirus disease 2019 (COVID-19), a condition characterized by the persistence of COVID-19 symptoms beyond 3 months, is anticipated to substantially alter the lives of millions of people globally. Cardiopulmonary symptoms including chest pain, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia are common and associated with significant disability, heightened anxiety, and public awareness. A range of cardiovascular (CV) abnormalities has been reported among patients beyond the acute phase and include myocardial inflammation, myocardial infarction, right ventricular dysfunction, and arrhythmias. Pathophysiological mechanisms for delayed complications are still poorly understood, with a dissociation seen between ongoing symptoms and objective measures of cardiopulmonary health. COVID-19 is anticipated to alter the long-term trajectory of many chronic cardiac diseases which are abundant in those at risk of severe disease. In this review, we discuss the definition of long COVID and its epidemiology, with an emphasis on cardiopulmonary symptoms. We further review the pathophysiological mechanisms underlying acute and chronic CV injury, the range of post-acute CV sequelae, and impact of COVID-19 on multiorgan health. We propose a possible model for referral of post-COVID-19 patients to cardiac services and discuss future directions including research priorities and clinical trials that are currently underway to evaluate the efficacy of treatment strategies for long COVID and associated CV sequelae.
| S-EPMC8903393 | biostudies-literature
Project description:BackgroundAs the coronavirus disease 2019 (COVID-19) pandemic has progressed, there has been a growing awareness of the long-term impacts of the COVID-19 infection. However, until recently, there was no published study that investigated COVID-19-related sequelae and related factors for greater than six months from the onset of COVID-19 symptoms or the time of COVID-19 diagnosis in Korea.Materials and methodsOnline survey and statistical analysis were conducted by Kyungpook National University Hospital on 5,252 patients diagnosed as COVID-19 between February 18, 2020 and March 14, 2020. Responders aged between 16 and 70 years were included. Long-term sequelae were defined as persistent symptoms or signs ≥ 6 months after acute COVID-19 infection. The survey was conducted from September 8, 2020 to September 10, 2020. Clinical characteristics and self-reported clinical sequelae of the responders were analyzed to investigate the prevalence and factors associated with sequelae using descriptive and multivariate logistic regression analysis.ResultsThe median period from the date of the first symptom onset or COVID-19 diagnosis to the time of the survey was 195 (interquartile range [IQR] 191 - 200) days. The response rate was 17.1% (900 out of 5,252). The median age was 31 (IQR 24.0 - 47.0) years old, and 627 responders were female (69.7%). Regarding the disease severity, 29 (3.2%) were asymptomatic, 763 (84.8%) mild, 86 (9.6%) moderate, 17 (1.9%) severe, and 5 (0.6%) critical. In total, 591 (65.7%) responders suffered from COVID-19-related long-term sequelae and 78 (8.6%) responders were receiving outpatient treatment for COVID-19-related long-term sequelae. The most common symptoms identified during the isolation period were anosmia and ageusia at 44.5% and 43.5%, respectively. Fatigue was the most common long-term sequelae, accounting for 253 (26.2%) responders, followed by concentration difficulty, amnesia, cognitive dysfunction, anxiety, and depression, which accounted for over 20%. Female gender was identified as the factor associated with mental and psychological long-term sequelae (P <0.05).ConclusionThe results showed that the rate of COVID-19-related long-term sequelae was 65.7%. The most common long-term sequela was fatigue. The risk factor identified was female gender. It was found that the long-term sequelae had various manifestations, including mental and psychological aspects. To improve the care of COVID-19 recovered patients with COVID-19-related long-term sequelae, the participation of a comprehensive and an interdisciplinary group of researchers is required.
| S-EPMC8511373 | biostudies-literature
Project description:PurposeWe examine prevalence, characteristics, quality of life (QOL) assessments, and long-term effects of interventions for laryngeal dysfunction after recovery from COVID-19 infection.Materials and methods653 patients presenting to Yale's COVID clinic from April 2020 to August 2021 were identified retrospectively. Patients with PCR-positive COVID-19 who underwent evaluation by fellowship-trained laryngologists were included. Patient demographics, comorbidities, intubation/tracheostomy, strobolaryngoscopy, voice metrics, and management data were collected. Patient-reported QOL indices were Dyspnea Index (DI), Cough Severity Index (CSI), Voice Handicap Index-10 (VHI-10), Eating Assessment Tool-10 (EAT-10), and Reflux Symptom Index (RSI).Results57 patients met inclusion criteria: 37 (64.9 %) were hospitalized for COVID-19 infection and 24 (42.1 %) required intubation. Mean duration between COVID-19 diagnosis and presentation to laryngology was significantly shorter for patients who were intubated compared to non-intubated (175 ± 98 days versus 256 ± 150 days, respectively, p = 0.025). Dysphonia was diagnosed in 40 (70.2 %) patients, dysphagia in 14 (25.0 %) patients, COVID-related laryngeal hypersensitivity in 13 (22.8 %), and laryngotracheal stenosis (LTS) in 10 (17.5 %) patients. Of the 17 patients who underwent voice therapy, 11 (64.7 %) reported improvement in their symptoms and 2 (11.8 %) patients reported resolution. VHI scores decreased for patients who reported symptom improvement. 7 (70 %) patients with LTS required >1 procedural intervention before symptom improvement. Improvement across QOL indices was seen in patients with LTS.ConclusionsLaryngeal dysfunction commonly presents and is persistent for months after recovery from COVID-19 in non-hospitalized and non-intubated patients. Voice therapy and procedural interventions have the potential to address post-COVID laryngeal dysfunction.
| S-EPMC9798664 | biostudies-literature
Project description:The pandemic of coronavirus disease 2019 (COVID‑19), caused by a novel severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has caused an enormous impact on the global healthcare. SARS-CoV-2 infection primarily targets the respiratory system. Although most individuals testing positive for SARS-CoV-2 present mild or no upper respiratory tract symptoms, patients with severe COVID-19 can rapidly progress to acute respiratory distress syndrome (ARDS). ARDS-related pulmonary fibrosis is a recognized sequelae of COVID-19. Whether post-COVID-19 lung fibrosis is resolvable, persistent, or even becomes progressive as seen in human idiopathic pulmonary fibrosis (IPF) is currently not known and remains a matter of debate. With the emergence of effective vaccines and treatments against COVID-19, it is now important to build our understanding of the long-term sequela of SARS-CoV-2 infection, to identify COVID-19 survivors who are at risk of developing chronic pulmonary fibrosis, and to develop effective anti-fibrotic therapies. The current review aims to summarize the pathogenesis of COVID-19 in the respiratory system and highlights ARDS-related lung fibrosis in severe COVID-19 and the potential mechanisms. It envisions the long-term fibrotic lung complication in COVID-19 survivors, in particular in the aged population. The early identification of patients at risk of developing chronic lung fibrosis and the development of anti-fibrotic therapies are discussed.
| S-EPMC9988550 | biostudies-literature
Project description:The risk profiles of post-acute sequelae of COVID-19 (PASC) have not been well characterized in multi-national settings with appropriate controls. We leveraged electronic health record (EHR) data from 277 international hospitals representing 414,602 patients with COVID-19, 2.3 million control patients without COVID-19 in the inpatient and outpatient settings, and over 221 million diagnosis codes to systematically identify new-onset conditions enriched among patients with COVID-19 during the post-acute period. Compared to inpatient controls, inpatient COVID-19 cases were at significant risk for angina pectoris (RR 1.30, 95% CI 1.09-1.55), heart failure (RR 1.22, 95% CI 1.10-1.35), cognitive dysfunctions (RR 1.18, 95% CI 1.07-1.31), and fatigue (RR 1.18, 95% CI 1.07-1.30). Relative to outpatient controls, outpatient COVID-19 cases were at risk for pulmonary embolism (RR 2.10, 95% CI 1.58-2.76), venous embolism (RR 1.34, 95% CI 1.17-1.54), atrial fibrillation (RR 1.30, 95% CI 1.13-1.50), type 2 diabetes (RR 1.26, 95% CI 1.16-1.36) and vitamin D deficiency (RR 1.19, 95% CI 1.09-1.30). Outpatient COVID-19 cases were also at risk for loss of smell and taste (RR 2.42, 95% CI 1.90-3.06), inflammatory neuropathy (RR 1.66, 95% CI 1.21-2.27), and cognitive dysfunction (RR 1.18, 95% CI 1.04-1.33). The incidence of post-acute cardiovascular and pulmonary conditions decreased across time among inpatient cases while the incidence of cardiovascular, digestive, and metabolic conditions increased among outpatient cases. Our study, based on a federated international network, systematically identified robust conditions associated with PASC compared to control groups, underscoring the multifaceted cardiovascular and neurological phenotype profiles of PASC.
| S-EPMC9242995 | biostudies-literature