Breathlessness and exercise with virtual reality system in long-post-coronavirus disease 2019 patients

Long-post-coronavirus disease-2019 (COVID-19) patients tend to claim residual symptomatology from various systems, most importantly the respiratory and central nervous systems. Breathlessness and brain fog are the main complaints. The pulmonary function pattern is consistent with restrictive defects, which, in most cases, are self-resolved, while the cognitive profile may be impaired. Rehabilitation is an ongoing field for holistic management of long-post-COVID-19 patients. Virtual reality (VR) applications may represent an innovative implementation of rehabilitation. We aimed to investigate the effect of exercise with and without the VR system and to assess further breathlessness and functional fitness indicators in long-post-COVID-19 patients with mild cognitive impairment after self-selected exercise duration using the VR system. Twenty long-post-COVID-19 patients were enrolled in our study (age: 53.9 ± 9.1 years, male: 80%, body mass index: 28.1 ± 3.1 kg/m2). Participants' anthropometric data were recorded, and they underwent pulmonary functional test evaluation as well as sleep quality and cognitive assessment. The participants randomly exercised with and without a VR system (VR vs. no-VR) and, later, self-selected the exercise duration using the VR system. The results showed that exercise with VR resulted in a lower dyspnea score than exercise without VR. In conclusion, VR applications seem to be an attractive and safe tool for implementing rehabilitation. They can enhance performance during exercise and benefit patients with both respiratory and cognitive symptoms.

Breathlessness and exercise with virtual reality system in long-post-coronavirus disease 2019 patients.

Long-post-coronavirus disease-2019 (COVID-19) patients tend to claim residual symptomatology from various systems, most importantly the respiratory and central nervous systems. Breathlessness and brain fog are the main complaints. The pulmonary function pattern is consistent with restrictive defects, which, in most cases, are self-resolved, while the cognitive profile may be impaired. Rehabilitation is an ongoing field for holistic management of long-post-COVID-19 patients. Virtual reality (VR) applications may represent an innovative implementation of rehabilitation. We aimed to investigate the effect of exercise with and without the VR system and to assess further breathlessness and functional fitness indicators in long-post-COVID-19 patients with mild cognitive impairment after self-selected exercise duration using the VR system. Twenty long-post-COVID-19 patients were enrolled in our study (age: 53.9 ± 9.1 years, male: 80%, body mass index: 28.1 ± 3.1 kg/m2). Participants' anthropometric data were recorded, and they underwent pulmonary functional test evaluation as well as sleep quality and cognitive assessment. The participants randomly exercised with and without a VR system (VR vs. no-VR) and, later, self-selected the exercise duration using the VR system. The results showed that exercise with VR resulted in a lower dyspnea score than exercise without VR. In conclusion, VR applications seem to be an attractive and safe tool for implementing rehabilitation. They can enhance performance during exercise and benefit patients with both respiratory and cognitive symptoms.

Cognitive impairment in COVID‐19 Survivors: Analysis and Extensions on Population Studies in Greece

Background The aim of our study was to investigate the prevalence and associations of cognitive impairment in COVID‐19 survivors in the post‐acute setting. Method Our study is conducted in three post‐COVID‐19 outpatient clinics in tertiary hospitals in Greece. Eligible subjects included previously hospitalized COVID‐19 survivors with mild to moderate disease, returning for follow‐up at least two months post‐discharge. Exclusion criteria included intensive care unit admission, intubation, a history of neurodegenerative disease and other significant comorbidities. Study measurements included demographics, clinical evaluation, medical, family history, anthropometrics, 6‐minute walk test (6MWT), 30 seconds sit‐to‐stand (30STS), handgrip strength, spirometry, Pittsburgh Sleep Quality Index (PSQI), the Montreal Cognitive Assessment (MoCA), reactive oxygen metabolites (dROMs) and plasma antioxidant capacity (PAT). Cognitive impairment was considered on MoCA ≤24. Result 142 COVID‐19 survivors were included in the study (110 Male, 32 Female;Mean age of 56.16±10.92). A total of 47.2% presented with cognitive decline (CD) as indicated by a MoCA score ≤24. Cognitive decline prevalence by SARS‐CoV‐2 variant of concern (VOC) was 39.5%, 50% and 62.5% for Alpha, Beta and Delta, correspondingly. A binary logistic regression model controlling for age, gender and VOC indicated that the diffusing capacity for carbon monoxide (DLCO) was independently associated with MoCA ≤24 (p = 0.014, OR = 0.669, 95%CI: 0.484‐0.923). Compared to severe untreated OSAS (n = 28), distinct domains but similar prevalence of cognitive impairment was noted. Conclusion Diffusion capacity abnormalities for carbon monoxide in COVID‐19 survivors as noted in other studies, may be implicated in the development of cognitive impairment.

Type I interferon signaling in SARS-CoV-2 associated neurocognitive disorder (SAND): Mapping host-virus interactions to an etiopathogenesis.

Epidemiological, clinical, and radiological studies have provided insights into the phenomenology and biological basis of cognitive impairment in COVID-19 survivors. Furthermore, its association with biomarkers associated with neuroinflammation and neurodegeneration supports the notion that it is a distinct aspect of LongCOVID syndrome with specific underlying biology. Accounting for the latter, translational studies on SARS-CoV-2's interactions with its hosts have provided evidence on type I interferon dysregulation, which is seen in neuroinflammatory and neurodegenerative diseases. To date, studies attempting to describe this overlap have only described common mechanisms. In this manuscript, we attempt to propose a mechanistic model based on the host-virus interaction hypothesis. We discuss the molecular basis for a SARS-CoV-2-associated neurocognitive disorder (SAND) focusing on specific genes and pathways with potential mechanistic implications, several of which have been predicted by Vavougios and their research group. Furthermore, our hypothesis links translational evidence on interferon-responsive gene perturbations introduced by SARS-CoV-2 and known dysregulated pathways in dementia. Discussion emphasizes the crosstalk between central and peripheral immunity via danger-associated molecular patterns in inducing SAND's emergence in the absence of neuroinfection. Finally, we outline approaches to identifying targets that are both testable and druggable, and could serve in the design of future clinical and translational studies.

Tele-Exercise in Non-Hospitalized versus Hospitalized Post-COVID-19 Patients.

The purpose of our study was to investigate the effect of tele-exercise (TE) performed for 4 consecutive weeks on fitness indicators in hospitalized post-COVID-19 patients versus non-hospitalized patients. Forty COVID-19 survivors were included, and divided into two groups: non-hospitalized versus hospitalized. Body composition, anthropometric characteristics, pulmonary function tests, single-breath diffusing capacity for carbon monoxide, 6-min walk tests (6MWT) and handgrip strength tests were recorded before and after a TE regimen (3 sessions per week, 60 min each session, warm-up and cool-down with mobility exercises, aerobic exercise such as walking outdoors, and multi-joint strength exercises). Following TE, the 6-min walk distance and handgrip were increased in both groups, with a greater observed response in the non-hospitalized group (6MWT: 32.9 ± 46.6% vs. 18.5 ± 14.3%, p < 0.001; handgrip: 15.9 ± 12.3% vs. 8.9 ± 7.6%, p < 0.001). Self-assessed dyspnea and leg fatigue were reduced in both groups, while a higher percentage of reduction was observed in the non-hospitalized group (dyspnea: 62.9 ± 42.5% vs. 37.5 ± 49.0%, p < 0.05; leg fatigue: 50.4 ± 42.2% vs. 31.7 ± 45.1%, p < 0.05). Post- vs. pre-TE arterial blood pressure decreased significantly in both groups, with the hospitalized group exhibiting more prominent reduction (p < 0.001). Both groups benefited from the TE program, and regardless of the severity of the disease the non-hospitalized group exhibited a potentially diminished adaptative response to exercise, compared to the hospitalized group.

The Comparative Superiority of SARS-CoV-2 Antibody Response in Different Immunization Scenarios.

Background: Both SARS-CoV-2 infection and/or vaccination result in the production of SARS-CoV-2 antibodies. We aimed to compare the antibody titers against SARS-CoV-2 in different scenarios for antibody production. Methods: A surveillance program was conducted in the municipality of Deskati in January 2022. Antibody titers were obtained from 145 participants while parallel recording their infection and/or vaccination history. The SARS-CoV-2 IgG II Quant method (Architect, Abbott, IL, USA) was used for antibody testing. Results: Advanced age (>56 years old) was associated with higher antibody titers. No significant differences were detected in antibody titers among genders, BMI, smoking status, comorbidities, vaccine brands, and months after the last dose. Hospitalization length and re-infection were predictors of antibody titers. The individuals who were fully or partially vaccinated and were also double infected had the highest antibody levels (25,017 ± 1500 AU/mL), followed by people who were fully vaccinated (20,647 ± 500 AU/mL) or/partially (15,808 ± 1800 AU/mL) vaccinated and were infected once. People who were only vaccinated had lower levels of antibodies (9946 ± 300 AU/mL), while the lowest levels among all groups were found in individuals who had only been infected (1124 ± 200 AU/mL). Conclusions: Every hit (infection or vaccination) gives an additional boost to immunization status.

Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium.

Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term. Methods: This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Results: Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. Discussion: The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection. Key Points: The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease.We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic.The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.

Post-COVID-19 Parkinsonism and Parkinson's Disease Pathogenesis: The Exosomal Cargo Hypothesis.

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.

Trained immunity in viral infections, Alzheimer's disease and multiple sclerosis: A convergence in type I interferon signalling and IFNß-1a.

Type I interferon (IFN-I) signalling represents a major target for modulation in a virus' bid for latency. IFN-I perturbations are also present in such as Alzheimer's disease (AD) and multiple sclerosis (MS), where viral infections are known to increase symptomatic burden. IFN-I modulation such as via IFNß-1a, an established MS treatment, has been researched to a limited extent to both AD and COVID-19. In this mini review, we present emerging research on trained immunity as a pathogenetic basis for Alzheimer's disease and the emerging context for IFNß-1a repositioning, via mechanisms shared with multiple sclerosis and induced by viral infections.

Lessons We Have Learned Regarding Seroprevalence in High and Low SARS-CoV-2 Contexts in Greece before the Omicron Pandemic Wave.

BACKGROUND: Antibody seroprevalence in rural communities remains poorly investigated. We compared the SARS-CoV-2 seroprevalence in two Greek communities in June and July 2021 after the end of the Delta-driven pandemic wave that started in November 2020. One community was affected worse than the other. METHODS: The SARS-CoV-2 IgG II Quant method (Architect, Abbott, IL, USA) was used for antibody testing. RESULTS: We found a high rate of SARS-CoV-2 seropositivity in both communities, approaching 77.5%. In the area with a higher burden of COVID-19, Malesina, seropositivity was achieved with vaccine-acquired and naturally acquired immunity, whereas in the low-burden context of Domokos, the high rates of seropositivity were achieved mainly with vaccination. Previously infected individuals were less likely to be vaccinated than previously uninfected adults. The antibody titers were significantly higher in previously infected, vaccinated participants than in unvaccinated ones. In total, 4% and 10% of the unvaccinated population were diagnosed seropositive for the first time while not knowing about the previous infection. Age and gender did not impact antibody titers in high- or low-burden contexts. CONCLUSIONS: Before the Omicron pandemic wave, herd immunity was reached in different contexts in Greece. Higher antibody titers were measured in infected vaccinated individuals than in infected unvaccinated ones.

COVID-19 Phenotypes and Comorbidity: A Data-Driven, Pattern Recognition Approach Using National Representative Data from the United States.

The aim of our study was to determine COVID-19 syndromic phenotypes in a data-driven manner using the survey results based on survey results from Carnegie Mellon University's Delphi Group. Monthly survey results (>1 million responders per month; 320,326 responders with a certain COVID-19 test status and disease duration <30 days were included in this study) were used sequentially in identifying and validating COVID-19 syndromic phenotypes. Logistic Regression-weighted multiple correspondence analysis (LRW-MCA) was used as a preprocessing procedure, in order to weigh and transform symptoms recorded by the survey to eigenspace coordinates, capturing a total variance of >75%. These scores, along with symptom duration, were subsequently used by the Two Step Clustering algorithm to produce symptom clusters. Post-hoc logistic regression models adjusting for age, gender, and comorbidities and confirmatory linear principal components analyses were used to further explore the data. Model creation, based on August's 66,165 included responders, was subsequently validated in data from March-December 2020. Five validated COVID-19 syndromes were identified in August: 1. Afebrile (0%), Non-Coughing (0%), Oligosymptomatic (ANCOS); 2. Febrile (100%) Multisymptomatic (FMS); 3. Afebrile (0%) Coughing (100%) Oligosymptomatic (ACOS); 4. Oligosymptomatic with additional self-described symptoms (100%; OSDS); 5. Olfaction/Gustatory Impairment Predominant (100%; OGIP). Our findings indicate that the COVID-19 spectrum may be undetectable when applying current disease definitions focusing on respiratory symptoms alone.

Physical Fitness Differences, Amenable to Hypoxia-Driven and Sarcopenia Pathophysiology, between Sleep Apnea and COVID-19.

Handgrip strength is an indirect indicator of physical fitness that is used in medical rehabilitation for its potential prognostic value. An increasing number of studies indicate that COVID-19 survivors experience impaired physical fitness for months following hospitalization. The aim of our study was to assess physical fitness indicator differences with another prevalent and hypoxia-driven disease, Obstructive Sleep Apnea Syndrome (OSAS). Our findings showed differences between post-COVID-19 and OSAS groups in cardiovascular responses, with post-COVID-19 patients exhibiting higher values for heart rate and in mean arterial blood pressure. Oxygen saturation (SpO2) was lower in post-COVID-19 patients during a six-minute walking test (6MWT), whereas the ΔSpO2 (the difference between the baseline to end of the 6MWT) was higher compared to OSAS patients. In patients of both groups, statistically significant correlations were detected between handgrip strength and distance during the 6MWT, anthropometric characteristics, and body composition parameters. In our study, COVID-19 survivors demonstrated a long-term reduction in muscle strength compared to OSAS patients. Lower handgrip strength has been independently associated with a prior COVID-19 hospitalization. The differences in muscle strength and oxygenation could be attributed to the abrupt onset of the disorder, which does not allow compensatory mechanisms to act effectively. Targeted rehabilitation focusing on such residual impairments may thus be indispensable within the setting of post-COVID-19 syndrome.

Defining Antibody Seroprevalence and Duration of Humoral Responses to SARS-CoV-2 Infection and/or Vaccination in a Greek Community.

BACKGROUND: In this work, we aimed to evaluate antibody-response longevity to SARS-CoV-2 infection and/or vaccination in one of the Greek communities that was worst hit by the pandemic, Deskati, five months after a previous serosurveillance and nine months after the pandemic wave initiation (October 2020). METHODS: The SARS-CoV-2 IgG II Quant method (Architect, Abbott, IL, USA) was used for antibody testing. RESULTS: A total of 69 subjects, who previously tested positive or negative for COVID-19 antibodies, participated in the study. We found that 48% of participants turned positive due to vaccination. 27% of participants were both previously infected and vaccinated. However, all previously infected participants retained antibodies to the virus, irrespective of their vaccination status. The antibody titers were significantly higher in previously infected participants that had been vaccinated than those who were unvaccinated and in those that had been previously hospitalized for COVID-19 than those with mild disease. CONCLUSIONS: Antibody responses to SARS-CoV-2 infection were maintained nine months after the pandemic. Vaccination alone had generated an immune response in almost half of the population. Higher antibody titers were found in the case of vaccination in previously infected subjects and especially in those with severe disease leading to hospitalization.

Investigating the prevalence of cognitive impairment in mild and moderate COVID-19 patients two months post-discharge: Associations with physical fitness and respiratory function

Background The aim of our study was to investigate the prevalence and associations of cognitive impairment in previously COVID-19 patients 2 months after discharge. Method Our study included previously hospitalized, consecutive COVID-19 patients with mild to moderate disease, followed up 2 months post discharge at a tertiary hospital?s outpatient clinic during May 2021. Exclusion criteria included intensive care unit admission, intubation, or a history of neurodegenerative disease and stroke prior to COVID-19. Prior to inclusion, eligible patients had provided written informed consent. The full battery of measurements in our study included demographics, medical and family history, anthropometrics, the 6-minute walk test (6MWT), the Borg Dyspnea Scale, spirometry, the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Short Form 36 health Survey (SF-36), the Montreal Cognitive Assessment (MoCA) and the Symptom Checklist 90-R (SLC90-R), reactive oxygen metabolites (dROMs) and plasma antioxidant capacity (PAT test;FRAS5, Parma, Italy). Cognitive impairment was considered on a MoCA cutoff ≤24. Data are presented as mean ±SD or Frequencies (%). Correlations between continuous data were assessed via the Spearman?s Rho correlation coefficient, whereas associations were assessed via multiple linear regression (MLR) models. For all tests, a p-value <0.05 was considered statistically significant. Results A total of 32 subjects were included in the study (35 Male, 17 Female;Mean age of 61.6±9.4). A total of 56.2% presented with cognitive decline (CD) as indicated by a MoCA score <24. Principal component analysis revealed that short-term memory impairments and multidomain impairment without short-term memory deficits were the predominant patterns of cognitive impairment. MoCA score correlated with age (?=-0.513, p=0.003), waist circumference (?=-0.388, p=0.028) waist to hip ratio (?=-0.361, p=0.042) and SpO2 during 6MWT (1st, 4th and 6th minute;p<0.05). MLR indicated that after adjusting for age and gender, SpO2 at the 6th minute of the 6MWT was independently associated with MoCA score (Beta=0.579, p-value=0.001). Conclusion Our findings indicated that among 32 outpatient clinic subjects, 56.2% presented with cognitive decline. The associations with oxygen saturation and physical condition as detected by the 6MWT may indicate overlap with post-COVID-19 fatigue and warrants further investigation.

Supervised Versus Unsupervised Pulmonary Rehabilitation in Patients with Pulmonary Embolism: A Valuable Alternative in COVID Era.

The aim of our study was to assess the effect of 8 weeks of pulmonary rehabilitation (PR) in patients with pulmonary embolism (PE) during unsupervised PR (unSPRgroup) versus supervised PR (SPRgroup) on cardiopulmonary exercise testing (CPET) parameters, sleep quality, quality of life and cardiac biomarkers (NT-pro-BNP). Fourteen patients with PE (unSPRgroup, n = 7, vs. SPRgroup, n = 7) were included in our study (age, 50.7 ± 15.1 years; BMI, 30.0 ± 3.3 kg/m2). We recorded anthropometric characteristics and questionnaires (Quality of life (SF-36) and Pittsburg sleep quality index (PSQI)), we performed blood sampling for NT-pro-BNP measurement and underwent CPET until exhausting before and after the PR program. All patients were subjected to transthoracic echocardiography prior to PR. The SPRgroup differed in mean arterial pressure at rest before and after the PR program (87.6 ± 3.3 vs. 95.0 ± 5.5, respectively, p = 0.010). Patients showed increased levels of leg fatigue (rated after CPET) before and after PR (p = 0.043 for SPRgroup, p = 0.047 for unSPRgroup) while the two groups differed between each other (p = 0.006 for post PR score). Both groups showed increased levels in SF-36 scores (general health; p = 0.032 for SPRgroup, p = 0.010 for unSPRgroup; physical health; p = 0.009 for SPRgroup, p = 0.022 for unSPRgroup) and reduced levels in PSQI (cannot get to sleep within 30-min; p = 0.046 for SPRgroup, p = 0.007 for unSPRgroup; keep up enough enthusiasm to get things done; p = 0.005 for SPRgroup, p = 0.010 for unSPRgroup) following the PR program. The ΝT-pro-BNP was not significantly different before and after PR or between groups. PR may present a safe intervention in patients with PE. The PR results are similar in SPRgroup and unSPRgroup.

Characterizing Long COVID: Deep Phenotype of a Complex Condition.

BACKGROUND: 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. METHODS: 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. FUNDING: 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. INTERPRETATION: 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. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411.

Human coronaviruses in idiopathic Parkinson's disease: Implications of SARS-CoV-2's modulation of the host's transcriptome.

OBJECTIVE: A recent study on the effects of SARS-CoV-2 infection on the host's transcriptome indicated the perturbation of several pathways associated with neurodegeneration, including but not limited to Parkinson's and Huntington's diseases. The purpose of this study was to determine overlapping pathways between iPD vs. Controls and those associated with SARS-CoV-2 infection. METHODS: Gene set enrichment analyses (GSEA) were performed on gene expression data from tissues donated by idiopathic Parkinson's disease patients (iPD). These included dorsal motor nucleus of the vagus (DMNV), substantia nigra (SN), whole blood (WB) and peripheral blood mononuclear cell samples (PBMC). Enriched pathways detected by GSEA results were subsequently compared to (a) those retrieved by two independently constructed SARS-CoV-2 - host interactomes, as well as (b) previously published pathway data. For all analyses, a false discovery rate (FDR) <0.05 was considered statistically significant. RESULTS: Analysis of iPD data revealed multiple immune response and viral parasitism -related pathways (FDR < 0.05). Head-to-head comparisons as well as confirmatory analyses revealed several pathways and gene ontology (GO) terms overlapping between iPD tissues and SARS-CoV-2 induced transcriptomic changes: "Parkinson's Disease" and "Huntington's Disease" (overlapping in DMNV, ION, SN, and WB; FDR < 0.05), "NAFLD" (overlapping in DMNV, SN, PBMC and WB; FDR < 0.05), mRNA surveillance and proteostasis pathways (All datasets; FDR < 0.5), among others. CONCLUSION: The overlap noted in this comparative transcriptomic study outlines the potential contribution of human coronaviruses in the pathogenesis of iPD. Furthermore, given SARS-CoV-2's neuroinvasive potential, closer scrutiny is warranted towards its contribution in the long-term development of neurodegenerative disease.