Evidence of lung perfusion defects and ongoing inflammation in an adolescent with post-acute sequelae of SARS-CoV-2 infection.
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ABSTRACT:
SUBMITTER: Buonsenso D
PROVIDER: S-EPMC8324416 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
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Evidence of lung perfusion defects and ongoing inflammation in an adolescent with post-acute sequelae of SARS-CoV-2 infection.
Buonsenso Danilo D Di Giuda Daniela D Sigfrid Louise L Pizzuto Daniele Antonio DA Di Sante Gabriele G De Rose Cristina C Lazzareschi Ilaria I Sali Michela M Baldi Fabiana F Chieffo Daniela Pia Rosaria DPR Munblit Daniel D Valentini Piero P
The Lancet. Child & adolescent health 20210731 9
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Project description:RationaleSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes long-term pulmonary sequelae in adults, but little is known about pulmonary outcomes in pediatrics.Objective(s)The aim of this study was to describe long-term subjective and objective pulmonary abnormalities after SARS-CoV-2 infection in pediatric populations.MethodsSingle-center, retrospective cohort of patients seen in post-coronavirus disease 2019 (COVID-19) pulmonary clinic in 2021. Subjects evaluated had persistent pulmonary symptoms 4 weeks or more after initial infection. Clinical testing included a 6-min walk test (6MWT), chest X-ray, pre- and postbronchodilator spirometry, plethysmography, and diffusion capacity. Patients were followed 2-to-3-months after the initial visit with repeat testing. The primary outcome was the presence of abnormal pulmonary function testing. Secondary measures included variables associated with pulmonary outcomes.ResultsEighty-two adolescents were seen at a median of 3.5 months postinfection, with approximately 80% reporting two or more symptoms at clinic presentation (cough, chest pain, dyspnea at rest, and exertional dyspnea). At follow-up (~6.5 months) exertional dyspnea persisted for most (67%). Spirometry was normal in 77% of patients, but 31% had a positive bronchodilator response. No abnormalities were noted on plethysmography or diffusion capacity. Clinical phenotypes identified included inhaled corticosteroid responsiveness, paradoxical vocal fold motion disorder, deconditioning, and dysautonomia. Multivariable modeling demonstrated that obesity, anxiety, and resting dyspnea were associated with reduced 6MWT, while female sex and resting dyspnea were associated with higher Borg Dyspnea and Fatigues scores.ConclusionsThis is the largest study to date of pediatric patients with long-term pulmonary sequelae post-COVID-19. Identified clinical phenotypes and risk factors warrant further study and treatment.
| S-EPMC9349789 | biostudies-literature
Project description:BackgroundAcute COVID-19 infection has been shown to have significant effects on the cardiovascular system. Post-acute sequelae of SARS-CoV-2 (PASC) are being identified in patients; however, the cardiovascular effects are yet to be well-defined. The Post-COVID Cardiology Clinic at Washington University evaluates and treats patients with ongoing cardiovascular PASC.ObjectivesThis investigation aims to describe the phenotypes of cardiovascular symptoms of PASC in patients presenting to the Post-COVID Cardiology Clinic, including their demographics, symptoms, and the clinical phenotypes observed.MethodsThis was a retrospective analysis of symptoms, clinical findings, and test results from the first 100 consecutive adult patients who presented to the Post-COVID Cardiology Clinic at Washington University in St. Louis, between September 2020 to May 2021 with cardiovascular symptoms following COVID-19 infection.ResultsThe population (n = 100) had a mean age of 46.3 years and was 81% female. Most patients had mild acute illness, with only 23% of patients requiring hospitalization during acute COVID-19 infection. The most commonly reported PASC symptoms were chest pain (66%), palpitations (59%), and dyspnea on exertion (56%). Of those presenting with these symptoms, 74/98 patients (75.5%) were found to have a significant blood pressure elevation, considerable sinus tachycardia burden, reduced global longitudinal strain, increased indexed left-ventricular end-diastolic volume (LVEDVi) by echocardiogram, and/or cMRI findings consistent with possible active or healing myocarditis.ConclusionsOur findings highlight clinical phenotypes of the cardiovascular manifestations of PASC. Further studies are needed to evaluate the pathophysiology, treatment options and long-term outcomes for these patients.
| S-EPMC9278009 | biostudies-literature
Project description:ObjectiveTo assess the initial features and evolution of neurologic Postacute Sequelae of SARS-CoV-2 infection (neuro-PASC) in patients with and without prior neurologic disease.MethodsParticipants with neurologic symptoms following acute SARS-CoV-2 infection were recruited from October 9, 2020 to October 11, 2021. Clinical data included a SARS-CoV-2 infection history, neurologic review of systems, neurologic exam, Montreal cognitive assessment (MoCA), and symptom-based self-reported surveys at baseline (conducted after acute infection) and 6-month follow-up assessments.ResultsFifty-six participants (69% female, mean age 50 years, 29% with prior neurologic disease such as multiple sclerosis) were enrolled, of which 27 had completed the 6-month follow-up visit in this ongoing study. SARS-CoV-2 infection severity was largely described as mild (39.3%) or moderate (42.9%). At baseline, following acute infection, the most common neurologic symptoms were fatigue (89.3%) and headaches (80.4%). At the 6-month follow-up, memory impairment (68.8%) and decreased concentration (61.5%) were the most prevalent, though on average all symptoms showed a reduction in reported severity score at the follow-up. Complete symptom resolution was reported in 33.3% of participants by 6 months. From baseline to 6 months, average MoCA scores improved overall though 26.3% of participants' scores decreased. A syndrome consisting of tremor, ataxia, and cognitive dysfunction (PASC-TAC) was observed in 7.1% of patients.InterpretationEarly in the neuro-PASC syndrome, fatigue and headache are the most commonly reported symptoms. At 6 months, memory impairment and decreased concentration were most prominent. Only one-third of participants had completed resolution of neuro-PASC at 6 months, although persistent symptoms trended toward improvement at follow-up.
| S-EPMC9268882 | biostudies-literature
Project description:To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers. Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC.
| S-EPMC11358427 | biostudies-literature
Project description:Inflammation-associated gut microbiome in post-acute sequelae of SARS-CoV-2 points towards new therapeutic targets
| PRJEB56080 | ENA
Project description:BackgroundDespite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce.MethodsWe assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment.ResultsThe EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities.ConclusionsDifferent symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.
| S-EPMC9151630 | biostudies-literature
Project description:SARS-CoV-2 is thought to have originated in the human population from a zoonotic spillover event. Infection in humans results in a variety of outcomes ranging from asymptomatic cases to the disease COVID-19, which can have significant morbidity and mortality, with over two million confirmed deaths worldwide as of January 2021. Over a year into the pandemic, sequencing analysis has shown that variants of SARS-CoV-2 are being selected as the virus continues to circulate widely within the human population. The predominant drivers of genetic variation within SARS-CoV-2 are single nucleotide polymorphisms (SNPs) caused by polymerase error, potential host factor driven RNA modification, and insertion/deletions (indels) resulting from the discontinuous nature of viral RNA synthesis. While many mutations represent neutral 'genetic drift' or have quickly died out, a subset may be affecting viral traits such as transmissibility, pathogenicity, host range, and antigenicity of the virus. In this review, we summarise the current extent of genetic change in SARS-CoV-2, particularly recently emerging variants of concern, and consider the phenotypic consequences of this viral evolution that may impact the future trajectory of the pandemic.
| S-EPMC8290271 | biostudies-literature
Project description:Natural history and mechanisms for persistent cognitive symptoms (also known as “brain fog”) following acute and often mild COVID-19 are unknown. In a large prospective cohort of people who recovered from acute COVID-19 in the New York City/New Jersey area, we found the presence of cognitive dysfunction to closely associate with fatigue symptoms and, in some people, brain imaging abnormalities. In a smaller subset of people who underwent cerebrospinal fluid analysis at a median of 9 months after their initial infection, there was no evidence to suggest changes related to Alzheimer’s disease or neurodegeneration. However, single cell gene expression analysis of immune cells (T cells, border associated macrophages, microglia-like myeloid cells, myeloid dendritic cells) from the cerebrospinal fluid showed many changes seen in models of acute SARS-CoV-2 infection. Longitudinal follow-up additionally showed recovery from cognitive dysfunction to be very slow, and associate with greater – not less – activation of interferon-related inflammatory processes in both single cell transcriptomic and targeted fluid proteomic studies. These findings suggest persistent brain fog following COVID-19 to resemble more viral infection than autoimmune disorders.
2024-05-20 | GSE241385 | GEO
Project description:Muscle deconditioning and impaired vascular function in the lower extremities (LE) are among the long-term symptoms experienced by COVID-19 patients with a history of severe illness. These symptoms are part of the post-acute sequelae of Sars-CoV-2 (PASC) and currently lack evidence-based treatment. To investigate the efficacy of lower extremity electrical stimulation (E-Stim) in addressing PASC-related muscle deconditioning, we conducted a double-blinded randomized controlled trial. Eighteen (n = 18) patients with LE muscle deconditioning were randomly assigned to either the intervention (IG) or the control (CG) group, resulting in 36 LE being assessed. Both groups received daily 1 h E-Stim on both gastrocnemius muscles for 4 weeks, with the device functional in the IG and nonfunctional in the CG. Changes in plantar oxyhemoglobin (OxyHb) and gastrocnemius muscle endurance (GNMe) in response to 4 weeks of daily 1 h E-Stim were assessed. At each study visit, outcomes were measured at onset (t0 ), 60 min (t60 ), and 10 min after E-Stim therapy (t70 ) by recording ΔOxyHb with near-infrared spectroscopy. ΔGNMe was measured with surface electromyography at two time intervals: 0-5 min (Intv1 ) and: 55-60 min (Intv2 ). Baseline OxyHb decreased in both groups at t60 (IG: p = 0.046; CG: p = 0.026) and t70 (IG = p = 0.021; CG: p = 0.060) from t0 . At 4 weeks, the IG's OxyHb increased from t60 to t70 (p < 0.001), while the CG's decreased (p = 0.003). The IG had higher ΔOxyHb values than the CG at t70 (p = 0.004). Baseline GNMe did not increase in either group from Intv1 to Intv2 . At 4 weeks, the IG's GNMe increased (p = 0.031), whereas the CG did not change. There was a significant association between ΔOxyHb and ΔGNMe (r = 0.628, p = 0.003) at 4 weeks in the IG. In conclusion, E-Stim can improve muscle perfusion and muscle endurance in individuals with PASC experiencing LE muscle deconditioning.
| S-EPMC10006649 | biostudies-literature
Project description:Determinants of Post-Acute Sequelae of COVID-19 are not known. Here we show that 75% of patients with viral RNA in blood (RNAemia) at presentation were symptomatic in the post-acute phase. RNAemia at presentation successfully predicted PASC, independent of patient demographics, initial disease severity, and length of symptoms.
| S-EPMC8437320 | biostudies-literature