Persistent dysregulation of cellular immunity following COVID-19 recovery despite minimal post-COVID-19 sequelae manifestation.
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ABSTRACT:
SUBMITTER: Putri DU
PROVIDER: S-EPMC9942484 | biostudies-literature | 2023 May
REPOSITORIES: biostudies-literature
Publications
Persistent dysregulation of cellular immunity following COVID-19 recovery despite minimal post-COVID-19 sequelae manifestation.
Putri Denise Utami DU Huang Chun-Kai CK Ou Tsong-Yih TY Lin Chiou-Feng CF Lee Ming-Che MC Hung Ching-Sheng CS Lee Chih-Hsin CH
The Journal of infection 20230221 5
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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:ObjectiveIn this study of patients hospitalized during acute SARS-CoV2 infection with 6-months of follow-up data, we identified risk factors associated with the development of neuro-PASC.MethodsWe conducted an exploratory, observational single-center cohort study of patients hospitalized for COVID-19 from November 2020 to March 2022. Our primary outcome was persistent neurocognitive symptoms, defined as fatigue, headache, loss of taste/smell, brain fog, confusion, concentration/memory/word finding difficulty, and/or change in speech present at 1-month and persisting for 6-months following acute SARS-CoV2 infection. Secondary outcomes included persistent impairment scores on PROMIS cognitive function and abilities scales. Multivariate logistic regression analyses identified potential risk factors for neuro-PASC.ResultsOf 89 participants, 60% reported persistent neurocognitive symptoms at 6-months; fatigue was the most prevalent, occurring in 53% of participants, followed by brain fog in 34% of participants. Lower self-reported socioeconomic status and increased pre-COVID-19 anxiety scores on the Hospital Anxiety and Depression Scale were associated with increased odds of developing persistent neurocognitive symptoms. Being female and of Hispanic descent were associated with increased odds of persistent cognitive function and ability impairment.InterpretationSociodemographic factors and pre-COVID-19 anxiety symptoms may be important risk factors for neuro-PASC. These findings underscore the need to assess various sociodemographic factors in research on PASC. Our study also highlights premorbid mental health symptoms as a potential predictor of persistent neurocognitive symptoms following hospitalization with SARS-CoV2 infection.
| S-EPMC10351655 | 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:BackgroundA substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC).ObjectiveTo characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls.DesignCohort study. (ClinicalTrials.gov: NCT04411147).SettingNational Institutes of Health Clinical Center, Bethesda, Maryland.ParticipantsSelf-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area.MeasurementsAll participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations.Results189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC.LimitationsMost participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment.ConclusionA high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19.Primary funding sourceDivision of Intramural Research, National Institute of Allergy and Infectious Diseases.
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| S-EPMC9580466 | biostudies-literature
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| S-SCDT-10_1038-S44321-025-00215-5 | biostudies-other
Project description:A species of Galápagos tortoise endemic to Española Island was reduced to just 12 females and three males that have been bred in captivity since 1971 and have produced over 1700 offspring now repatriated to the island. Our molecular genetic analyses of juveniles repatriated to and surviving on the island indicate that none of the tortoises sampled in 1994 had hatched on the island versus 3% in 2004 and 24% in 2007, which demonstrates substantial and increasing reproduction in situ once again. This recovery occurred despite the parental population having an estimated effective population size <8 due to a combination of unequal reproductive success of the breeders and nonrandom mating in captivity. These results provide guidelines for adapting breeding regimes in the parental captive population and decreasing inbreeding in the repatriated population. Using simple morphological data scored on the sampled animals, we also show that a strongly heterogeneous distribution of tortoise sizes on Española Island observed today is due to a large variance in the number of animals included in yearly repatriation events performed in the last 40 years. Our study reveals that, at least in the short run, some endangered species can recover dramatically despite a lack of genetic variation and irregular repatriation efforts.
| S-EPMC3586625 | biostudies-literature
Project description:Our understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including prominent hyperactivation signatures in neutrophils and monocytes with anti-inflammatory features. We also leverage epigenomic analysis to identify loss of accessibility at NF-kB binding sites within pro-inflammatory cytokine gene loci as a potential mechanism for the striking lack of cytokine production observed in monocytes in severe and fatal COVID-19. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.
2021-05-08 | GSE174072 | GEO
Project description:BackgroundElevated D-dimer is known as predictor for severity of SARS-CoV2-infection. Increased D-dimer is associated with thromboembolic complications, but it is also a direct consequence of the acute lung injury seen in COVID-19 pneumonia.ObjectivesTo evaluate the rate of persistent elevated D-dimer and its association with thromboembolic complications and persistent ground glass opacities (GGO) after recovery from COVID-19.MethodsIn this post hoc analysis of a prospective multicenter trial, patients underwent blood sampling, measurement of diffusion capacity, blood gas analysis, and multidetector computed tomography (MDCT) scan following COVID-19. In case of increased D-dimer (>0,5 μg/ml), an additional contrast medium-enhanced CT was performed in absence of contraindications. Results were compared between patients with persistent D-dimer elevation and patients with normal D-dimer level.Results129 patients (median age 48.8 years; range 19-91 years) underwent D-Dimer assessment after a median (IQR) of 94 days (64-130) following COVID-19. D-dimer elevation was found in 15% (19/129) and was significantly more common in patients who had experienced a severe SARS-CoV2 infection that had required hospitalisation compared to patients with mild disease (p = 0.049). Contrast-medium CT (n = 15) revealed an acute pulmonary embolism in one patient and CTEPH in another patient. A significant lower mean pO2 (p = 0.015) and AaDO2 (p = 0.043) were observed in patients with persistent D-Dimer elevation, but the rate of GGO were similar in both patient groups (p = 0.33).ConclusionIn 15% of the patients recovered from COVID-19, persistent D-dimer elevation was observed after a median of 3 months following COVID-19. These patients had experienced a more severe COVID and still presented more frequently a lower mean pO2 and AaDO2.
| S-EPMC8553152 | biostudies-literature
Project description:IntroductionAfter the acute Sars-CoV-2-infection, some athletes suffer from persistent, performance-impairing symptoms, although the course of the disease is often mild to moderate. The relation between cardiopulmonary performance and persistent symptoms after the acute period is still unclear. In addition, information about the development of this relationship is lacking.ObjectiveTo assess the prevalence of persistent symptoms over time and their association with the performance capability of athletes.MethodsWe conducted two cardiopulmonary exercise tests (CPET) in a three months interval with 60 athletes (age: 35.2±12.1 years, 56.7% male) after infection with Sars-CoV-2 (t0: study inclusion; t1: three months post t0). At each examination, athletes were asked about their persistent symptoms. To evaluate the change of Peak VO2/BM (Body Mass) between the time before infection and the first examination, the VO2/BM (predVO2) before infection was predicted based on anthropometric data and exercise history of the athletes. For data analysis, athletes were grouped according to their symptom status (symptom-free, SF; persistent symptoms, PS) and its progression from the first to the second examination 1) SF-SF, 2) PS-SF and 3) PS-PS.ResultsComparing the SF and PS groups at t0, significant differences for Max Power/BM, Max Power/lbm (lean body mass), Peak VO2, Peak VO2/BM, Peak VO2/lbm, Peak VO2/HR, Peak VE, Peak Vt and VE/VCO2-Slope were observed. Regarding the progression over three months, an increase in Max Power/BM was shown in SF-SF and PS-SF (tendency). Max Power/lbm increased in SF-SF and PS-PS (tendency). A decrease of VE/VCO2-Slope in PS-PS was found.ConclusionCOVID-19 led to a decline in performance that was greater in PS than in SF. Additionally, PS had decreased ventilatory parameters compared to SF. Furthermore, an improvement over time was observed in some CPET parameters and a partial recovery was observed judging by the decrease in various symptoms.
| S-EPMC9728914 | biostudies-literature