Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or “long COVID”), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411 .

The aim of our study was to determine the impact of unsupervised Pulmonary Rehabilitation (uns-PR) on patients recovering from COVID-19, and determine its anthropometric, biological, demographic and fitness correlates. All patients (n = 20, age: 64.1 ± 9.9 years, 75% male) participated in unsupervised Pulmonary Rehabilitation program for eight weeks. We recorded anthropometric characteristics, pulmonary function parameters, while we performed 6 min walk test (6 MWT) and blood sampling for oxidative stress measurement before and after uns-PR. We observed differences before and after uns-PR during 6 MWT in hemodynamic parameters [systolic blood pressure in resting (138.7 ± 16.3 vs. 128.8 ± 8.6 mmHg, p = 0.005) and end of test (159.8 ± 13.5 vs. 152.0 ± 12.2 mmHg, p = 0.025), heart rate (5th min: 111.6 ± 16.9 vs. 105.4 ± 15.9 bpm, p = 0.049 and 6th min: 112.5 ± 18.3 vs. 106.9 ± 17.9 bpm, p = 0.039)], in oxygen saturation (4th min: 94.6 ± 2.9 vs. 95.8 ± 3.2%, p = 0.013 and 1st min of recovery: 97.8 ± 0.9 vs. 97.3 ± 0.9%), in dyspnea at the end of 6 MWT (1.3 ± 1.5 vs. 0.6 ± 0.9 score, p = 0.005), in distance (433.8 ± 102.2 vs. 519.2 ± 95.4 m, p < 0.001), in estimated O₂ uptake (14.9 ± 2.4 vs. 16.9 ± 2.2 mL/min/kg, p < 0.001) in 30 s sit to stand (11.4 ± 3.2 vs. 14.1 ± 2.7 repetitions, p < 0.001)] Moreover, in plasma antioxidant capacity (2528.3 ± 303.2 vs. 2864.7 ± 574.8 U.cor., p = 0.027), in body composition parameters [body fat (32.2 ± 9.4 vs. 29.5 ± 8.2%, p = 0.003), visceral fat (14.0 ± 4.4 vs. 13.3 ± 4.2 score, p = 0.021), neck circumference (39.9 ± 3.4 vs. 37.8 ± 4.2 cm, p = 0.006) and muscle mass (30.1 ± 4.6 vs. 34.6 ± 7.4 kg, p = 0.030)] and sleep quality (6.7 ± 3.9 vs. 5.6 ± 3.3 score, p = 0.036) we observed differences before and after uns-PR. Our findings support the implementation of unsupervised pulmonary rehabilitation programs in patients following COVID-19 recovery, targeting the improvement of many aspects of long COVID-19 syndrome.

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer’s disease, globally. Dopaminergic neuron degeneration in substantia nigra pars compacta and aggregation of misfolded alpha-synuclein are the PD hallmarks, accompanied by motor and non-motor symptoms. Several viruses have been linked to the appearance of a post-infection parkinsonian phenotype. Coronavirus disease 2019 (COVID-19), caused by emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has evolved from a novel pneumonia to a multifaceted syndrome with multiple clinical manifestations, among which neurological sequalae appear insidious and potentially long-lasting. Exosomes are extracellular nanovesicles bearing a complex cargo of active biomolecules and playing crucial roles in intercellular communication under pathophysiological conditions. Exosomes constitute a reliable route for misfolded protein transmission, contributing to PD pathogenesis and diagnosis. Herein, we summarize recent evidence suggesting that SARS-CoV-2 infection shares numerous clinical manifestations and inflammatory and molecular pathways with PD. We carry on hypothesizing that these similarities may be reflected in exosomal cargo modulated by the virus in correlation with disease severity. Travelling from the periphery to the brain, SARS-CoV-2-related exosomal cargo contains SARS-CoV-2 RNA, viral proteins, inflammatory mediators, and modified host proteins that could operate as promoters of neurodegenerative and neuroinflammatory cascades, potentially leading to a future parkinsonism and PD development.