Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: A population-based, nested case-control study

PLoS Medicine, Год журнала: 2025, Номер 22(1), С. e1004511 - e1004511

Опубликована: Янв. 23, 2025

Background Self-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance sleep problems. The long-term prognosis of post-acute sequelae COVID-19/post-COVID-19 (PCS) is unknown, data finding correlating organ dysfunction pathology with self-reported symptoms in patients non-recovery from PCS scarce. We wanted to describe clinical characteristics diagnostic findings among persisting for >1 year assessed risk factors persistence versus improvement. Methods This nested population-based case-control study included subjects aged 18–65 years ( n = 982) age- sex-matched control without 576) according an earlier questionnaire (6–12 months after infection, phase 1) consenting provide follow-up information undergo comprehensive outpatient assessment, including neurocognitive, cardiopulmonary exercise, laboratory testing four university centres southwestern Germany (phase 2, another 8.5 [median, range 3–14 months] 1). mean age the participants was 48 years, 65% were female. At 67.6% at 1 developed persistent PCS, whereas 78.5% recovered remained free related PCS. Improvement associated mild index previous full-time employment, educational status, no specialist consultation not attending a rehabilitation programme. development new initially intercurrent secondary SARS-CoV-2 status. Patients less frequently never smokers (61.2% 75.7%), more obese (30.2% 12.4%) higher values body mass (BMI) fat, had lower status (university entrance qualification 38.7% 61.5%) than continued recovery. Fatigue/exhaustion, neurocognitive disturbance, chest symptoms/breathlessness anxiety/depression/sleep predominant symptom clusters. Exercise intolerance post-exertional malaise (PEM) >14 h compatible myalgic encephalomyelitis/chronic fatigue reported by 35.6% 11.6% patients, respectively. In analyses adjusted sex-age class combinations, centre qualification, significant differences between those recovery observed performance three different tests, scores perceived stress, subjective cognitive disturbances, dysautonomia, depression anxiety, quality, quality life. handgrip strength (40.2 [95% confidence interval (CI) [39.4, 41.1]] 42.5 CI [41.5, 43.6]] kg), maximal oxygen consumption (27.9 [27.3, 28.4]] 31.0 [30.3, 31.6]] ml/min/kg weight) ventilatory efficiency (minute ventilation/carbon dioxide production slope, 28.8 [28.3, 29.2]] 27.1 [26.6, 27.7]]) significantly reduced relative group adjustment centre, education, BMI, smoking use beta blocking agents. There measures systolic diastolic cardiac function rest, level N-terminal brain natriuretic peptide blood levels other measurements (including complement activity, markers Epstein–Barr virus [EBV] reactivation, inflammatory coagulation markers, serum cortisol, adrenocorticotropic hormone dehydroepiandrosterone sulfate). Screening viral (PCR stool samples spike antigen plasma) subgroup negative. Sensitivity (pre-existing illness/comorbidity, obesity, medical care infection) revealed similar findings. PEM pain worse results almost all tests. A limitation that we objective on exercise capacity cognition before infection. addition, did unable attend clinic whatever reason illness, immobility social deprivation exclusion. Conclusions this study, majority working recover second their illness. Patterns essentially similar, dominated complaints. Despite signs deficits capacity, there major investigations, our do support persistence, EBV adrenal insufficiency increased turnover pathophysiologically relevant history disease might help stratify cases severity.

Язык: Английский

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Small fiber neuropathy in the post‐COVID condition and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical significance and diagnostic challenges

European Journal of Neurology, Год журнала: 2025, Номер 32(2)

Опубликована: Янв. 31, 2025

Patients with post-COVID condition (PCC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) experience symptoms potentially associated small fiber neuropathy (SFN). A sample of 90 participants, comprising 30 PCC patients, ME/CFS healthy controls (HC), matched by sex age, was assessed. Neuropathic, autonomic, fatigue were measured TaskForce Monitor, the Sudoscan, heat cold evoked potentials, In Vivo Corneal Confocal Microscopy (IVCCM), specialized questionaries. patients demonstrated significantly higher levels autonomic (H = 39.89, p < 0.001), neuropathic 48.94, 49.29, 0.001) compared to HC. Quantitative sensory testing revealed significant differences in detection thresholds between HC (F 4.82; 0.01). Regarding corneal tortuosity, there statistically 6.80; 0.01), indicating pathological responses patients. Small tortuosity IVCCM identified as main discriminator (AUC 0.720; SFN, evidenced impaired increased fibers central subbasal plexus. The findings underscore importance a multimodal approach comprehensively detect characterize SFN. This study provides valuable scientific insights into manifestations these conditions.

Язык: Английский

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Mitochondrial oxidative stress, mitochondrial ROS storms in long COVID pathogenesis

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Дек. 22, 2023

Significance This review discusses the coronavirus disease 2019 (COVID-19) pathophysiology in context of diabetes and intracellular reactions by COVID-19, including mitochondrial oxidative stress storms, ROS long COVID. Recent advances The COVID is suffered ~10% COVID-19 patients. Even virus does not exist, patients suffer for even over a year, could be mitochondria dysregulation disease. Critical issues Patients who recover from can develop new or persistent symptoms multi-organ complications lasting weeks months, called underlying mechanisms involved still unclear. Once persist, they cause significant damage, leading to numerous, symptoms. Future directions A comprehensive map stages pathogenetic related effective drugs treat prevent it are required, which will aid development future treatments symptom relief.

Язык: Английский

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Similar Patterns of Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue and Post-COVID-19 Syndromes

Pathophysiology, Год журнала: 2024, Номер 31(1), С. 1 - 17

Опубликована: Янв. 5, 2024

Background: There is a considerable overlap between the clinical presentation of post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many their common symptoms can be linked to dysregulation autonomic nervous system (dysautonomia). This study aimed objectively assess function in general group patients with PCC ME/CFS whose disease was not related COVID-19. We hypothesize that similarity chronic extends objective abnormalities. Methods: Synchronous recordings an electrocardiogram continuous dynamics blood pressure digital artery using Penaz method were obtained spiroarteriocardiorhythmography 34 diagnosed ME/CFS, whom onset associated COVID-19, 29 meeting definition 32 healthy controls. Heart rate variability (HRV) systolic diastolic (BPV) assessed at rest tests fixed respiratory rates. Indicators baroreflex regulation (baroreflex effectiveness index sensitivity) additionally determined rest. Results: The total power low-frequency high-frequency RR interval as well sensitivity significantly lower both compared Several diagnostic prediction models for developed based on HRV parameters. During slow breathing, parameters returned normal but patients. correlation analysis revealed close relationship HRV, BPV fatigue, HADS depressive/anxiety Conclusions: A similar pattern failure signs pathological acceleration age-dependent dysautonomia identified clinical, therapeutic implications these findings are discussed, light previously described relationships inflammation, vascular pathology, atherosclerotic cardiovascular dysfunction.

Язык: Английский

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Post-COVID-19 Small Fiber Neuropathy as a New Emerging Quality of Life-Threatening Disease: A Systematic Review

Microorganisms, Год журнала: 2025, Номер 13(2), С. 328 - 328

Опубликована: Фев. 2, 2025

Post-acute sequelae of COVID-19 (PASC) syndrome is considered an emergent and diffuse multidisciplinary problem. Compelling evidence suggests that increases symptoms pre-existent small fiber neuropathy (SFN) might trigger de novo onset SFN. In this systematic review, for the first time, we provide a comprehensive overview clinical diagnostic features PASC-SFN, including accompanying disorders, disease evolution, possible treatments, described in recent literature. Following infection, many patients reported wide range complications, not self-limiting independent from previous infection severity. SFN begins more frequently with distal limb burning pain numbness, which accompany other dysautonomia, cognitive, visual, osteoarticular disorders involving multiple organ systems. initial suspicion, some tests be useful as complementary examinations, such nerve quantitative sensory testing, electromyography, optic tomography. Otherwise, definite diagnosis reached skin biopsy gold standard, along corneal vivo microscopy when ocular discomfort present. Being long-term condition, dissimilar symptomatic disease-modifying drugs were employed treatment condition achievement partial results, steroids, pregabalin, gabapentin, duloxetine, vitamins, homotaurine phosphatidylserine, alpha lipoic acid, immunosuppressants, intravenous immunoglobulin therapy. PASC-SFN complex emerging extremely challenging physicians. At present, only feasible management represented by tailored approach, future definitive protocols deemed essential.

Язык: Английский

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Efficacy of Vitamin D Replacement Therapy on 28 Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After COVID-19 Vaccination

Nutrition, Год журнала: 2025, Номер 134, С. 112718 - 112718

Опубликована: Фев. 19, 2025

Prolonged symptoms have been reported following both COVID-19 infection and vaccination, with some cases leading to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Of 80 patients presenting our hospital postvaccination syndrome, 28 met the diagnostic criteria for ME/CFS. We conducted a retrospective study on these patients. measured serum 25-hydroxyvitamin D levels in who developed ME/CFS after vaccination between August 2022 February 2024. Vitamin replacement therapy included dietary counseling, sun exposure recommendations, oral vitamin supplementation. evaluated changes blood symptom improvement. At initial visit, 27 of diagnosed had insufficient or deficient (16 ± 4 ng/mL, mean SD). Following therapy, we observed an increase (28 5 ng/mL) associated decrease (from 10.3 2.1 3.3 2.0). Notably, 23 (82%) no longer therapy. Among symptoms, sleep problems showed most improvement (71%), followed by autonomic (68%). For developing levels, appropriate under medical guidance may lead symptomatic relief. are preparing randomized controlled trial evaluate efficacy individuals deficiency vaccination.

Язык: Английский

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Analysis of 977 Long COVID Patients Reveals Prevalent Neuropathy and Association with Anti-Ganglioside Antibodies

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Abstract Background Long COVID (LC) is a novel condition that characterized by persistent symptoms last from months to years following SARS-CoV-2 infection. While LC vary widely, neuropathy one of the most prevalent and drastically affects patients’ quality life. However, underlying pathophysiology remains poorly understood. Here, we investigated prevalence potential mechanisms in largest cohort date. Methods We conducted an observational study 977 adults with at Dell Medical School. Participants underwent clinical assessments, skin punch biopsy, comprehensive metabolic, endocrine immunological profiling. A subset patients received treatment intravenous immunoglobulin (IVIG). Findings Neuropathic were reported 55% (534/977) participants, biopsy confirming small fiber 56.5% (48/85) cases, affecting both epidermal autonomic nerve fibers. Common risk factors for neuropathy, including metabolic disorders, did not fully explain neuropathic symptoms. general markers (lymphocyte, T cell, B cell count C reactive protein unremarkable, unexpectedly, detected anti-ganglioside antibodies (AGAs) 25% comparable rate other AGA-associated neuropathies. Longitudinal testing revealed AGA positivity, multiple elevated AGAs patients. In pilot eight patients, IVIG resulted improvement patient Interpretation Our findings reveal high LC, evidence suggesting autoimmune mechanism involving four The therapeutic response further supports pathophysiology, benefits immunomodulation

Язык: Английский

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Assessing Fatigue in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients before and after Treatment with Bright Light Therapy: a prospective randomized controlled crossover study

Sleep Medicine, Год журнала: 2025, Номер 129, С. 369 - 374

Опубликована: Март 14, 2025

The aim of the current study was to test effectiveness treatment with bright light therapy (BLT) on fatigue and cognitive function in patients Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A randomized-controlled cross-over design chosen order provide all access BLT account for placebo effects. In this study, a total 36 outpatients diagnosis ME/CFS according criteria Institute Medicine (2015) were randomly assigned starting out either or waitlist course 2 weeks washout phase between. Portable boxes emitting full-spectrum visible luminance intensity 10,000 lux used by participants at home. Primary outcome as assessed Chalder Score (CFQ) secondary variable per standardized battery (Test Attentional Performance - TAP). primary not significantly improved after compared wait list full crossover design, although scores immediately two BLT. Additionally, showed decreased reaction time subtest TAP list. Over 45 % diagnosed postural tachycardia syndrome. is effective ME/CFS, but it might have beneficial effects attention ME/CFS. clinical trial registered www. gov (NCT06635928).

Язык: Английский

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Oral SARS‐CoV‐2 Infection and Risk for Long Covid

Reviews in Medical Virology, Год журнала: 2025, Номер 35(2)

Опубликована: Март 1, 2025

ABSTRACT SARS‐CoV‐2 is an oral pathogen that infects and replicates in mucosal salivary epithelial cells, contributing to post‐acute sequelae COVID‐19 (PASC) other non‐oral pathologies. While pre‐existing inflammatory diseases provides a conducive environment for the virus, acute infection persistence of can also results microbiome dysbiosis further worsens poor health. Indeed, PASC includes periodontal diseases, dysgeusia, xerostomia, pharyngitis, keratoses, pulpitis suggesting significant bacterial contributions tissue tropism. Dysbiotic microbiome‐induced inflammation promote viral entry via angiotensin‐converting enzyme receptor‐2 (ACE2), serine transmembrane TMPRSS2 possibly non‐canonical pathways. Additionally, metabolites derived from dysbiotic alter physiological biochemical pathways related metabolism lipids, carbohydrates, amino acids. This may pro‐inflammatory microenvironment, leading immune exhaustion, loss tolerance, susceptibility variety pathogens, causing later chronic inflammation. Microbial release mimics host metallopeptidases furin, ADAM17 (A disintegrin metalloproteinase 17), glycoprotein aid attachment T cell immunoglobulin‐like (TIMs), enhancing while simultaneously depressing resistance clearance. Membrane reorganization characterised by neuroproteins, such as neuropilins, functionally assists with extends pathogenesis cavity brain, gut, or tissues. Thus, health, disrupted microbiomes tropism, weaken antiviral resistance, heightens infection. dysfunction increases risk additional infections, exacerbating conditions like endodontic diseases. These persistent health issues contribute systemic inflammation, creating bidirectional effects between tissues, potentially Post‐Acute Sequelae (PASC).

Язык: Английский

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Anästhesie bei Patient:innen mit postviralen Erkrankungen

Schmerz Nachrichten, Год журнала: 2025, Номер unknown

Опубликована: Март 20, 2025

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