Tag: long Covid

Illness presentation and quality of life in myalgic encephalomyelitis/chronic fatigue syndrome and post COVID-19 condition: a pilot Australian cross-sectional study

Abstract:

Purpose: Post COVID-19 Condition (PCC), being persistent COVID-19 symptoms, is reminiscent of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-a chronic multi-systemic illness characterised by neurocognitive, autonomic, endocrinological and immunological disturbances. This novel cross-sectional investigation aims to: (1) compare symptoms among people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) to inform developing PCC diagnostic criteria; and (2) compare health outcomes between patients and people without acute or chronic illness (controls) to highlight the illness burdens of ME/CFS and PCC.

Methods: Sociodemographic and health outcome data were collected from n = 61 pwME/CFS, n = 31 pwPCC and n = 54 controls via validated, self-administered questionnaires, including the 36-Item Short-Form Health Survey version 2 (SF-36v2) and World Health Organization Disability Assessment Schedule version 2.0 (WHODAS 2.0). PwME/CFS and pwPCC also provided self-reported severity and frequency of symptoms derived from the Canadian and International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC.

Results: Both illness cohorts similarly experienced key ME/CFS symptoms. Few differences in symptoms were observed, with memory disturbances, muscle weakness, lymphadenopathy and nausea more prevalent, light-headedness more severe, unrefreshed sleep more frequent, and heart palpitations less frequent among pwME/CFS (all p < 0.05). The ME/CFS and PCC participants’ SF-36v2 or WHODAS 2.0 scores were comparable (all p > 0.05); however, both cohorts returned significantly lower scores in all SF-36v2 and WHODAS 2.0 domains when compared with controls (all p < 0.001).

Conclusion: This Australian-first investigation demonstrates the congruent and debilitating nature of ME/CFS and PCC, thereby emphasising the need for multidisciplinary care to maximise patient health outcomes.

Source: Weigel B, Eaton-Fitch N, Thapaliya K, Marshall-Gradisnik S. Illness presentation and quality of life in myalgic encephalomyelitis/chronic fatigue syndrome and post COVID-19 condition: a pilot Australian cross-sectional study. Qual Life Res. 2024 Jul 3. doi: 10.1007/s11136-024-03710-3. Epub ahead of print. PMID: 38961009. https://link.springer.com/article/10.1007/s11136-024-03710-3 (Full text)

Flow Clotometry: Measuring Amyloid Microclots in ME/CFS, Long COVID, and Healthy Samples with Imaging Flow Cytometry

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has received more attention since the characterization of Long COVID (LC), a condition somewhat similar in symptom presentation and, to some extent, pathophysiological mechanisms. A prominent feature of LC pathology is amyloid, fibrinolysis-resistant fibrin(ogen) fragments, termed microclots. Despite prior identification of microclots in ME/CFS, quantitative analysis has remained challenging due to the reliance on representative micrographs and software processing for estimations.

Addressing this gap, the present study uses a cell-free imaging flow cytometry approach, optimized for the quantitative analysis of Thioflavin T-stained microclots, to precisely measure microclot concentration and size distribution across ME/CFS, LC, and healthy cohorts. We refer to our cell-free flow cytometry technique for detecting microclots as ‘flow clotometry’.

We demonstrate significant microclot prevalence in ME/CFS and LC, with LC patients exhibiting the highest concentration (18- and 3-fold greater than the healthy and ME/CFS groups, respectively). This finding underscores a common pathology across both conditions, emphasizing a dysregulated coagulation system. Moreover, relating to microclot size distribution, the ME/CFS group exhibited a significantly higher prevalence across all area ranges when compared to the controls, but demonstrated a significant difference for only a single area range when compared to the LC group.

This suggests a partially overlapping microclot profile in ME/CFS relative to LC, despite the overall higher concentration in the latter. The present study paves the way for prospective clinical application that aims to efficiently detect, measure and treat microclots.

Source: Etheresia Pretorius, Massimo Nunes, Jan pretorius et al. Flow Clotometry: Measuring Amyloid Microclots in ME/CFS, Long COVID, and Healthy Samples with Imaging Flow Cytometry, 24 June 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-4507472/v1] https://www.researchsquare.com/article/rs-4507472/v1 (Full text)

Reduction of long COVID symptoms after stellate ganglion block: A retrospective chart review study

Abstract:

The SARS-CoV-2 pandemic has left millions of individuals with a host of post-viral symptoms that can be debilitating and persist indefinitely. To date there are no definitive tests or treatments for the collection of symptoms known as “Long COVID” or Post-acute sequelae of COVID-19 (PASC). Following our initial case report detailing improvement of Long COVID symptoms after sequential bilateral stellate ganglion blockade (SGB), we performed a retrospective chart analysis study on individuals treated with the same protocol over the course of six months (2021-2022) in our clinic.

Patients self-reported symptoms on a 10-point scale as part of optional patient follow-up using an online survey. After one month or more following treatment, patients reported striking reductions in Fatigue, Worsening of Symptoms following Mental and Physical Activity, Memory Problems, Problems Concentrating, Sleep Problems, Anxiety, and Depression. Loss of Taste and Loss of Smell in some individuals did not respond to treatment, likely indicating structural damage following infection.

This study suggests that neuromodulation may provide relief of Long COVID symptoms for at least a subset of individuals, and provides support for prospective studies of this potential treatment.

Source: Duricka D, Liu L. Reduction of long COVID symptoms after stellate ganglion block: A retrospective chart review study. Auton Neurosci. 2024 Jun 13;254:103195. doi: 10.1016/j.autneu.2024.103195. Epub ahead of print. PMID: 38901177. https://www.autonomicneuroscience.com/article/S1566-0702(24)00049-3/fulltext (Full text)

Systems Modeling Reveals Shared Metabolic Dysregulation and Novel Therapeutic Treatments in ME/CFS and Long COVID

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID are complex, multisystemic conditions that pose ongoing challenges to healthcare professionals. Emerging research suggests that ME/CFS and Long COVID exhibit overlapping metabolic symptoms, indicating possible shared metabolic dysfunctions. This study aims to systematically explore these shared metabolic disturbances and their potential treatments.

Utilizing our novel metabolic modeling method, GPMM, we identified the key metabolic irregularities in patients with ME/CFS and Long COVID, notably the downregulation of the alanine and aspartate metabolism pathway, and the arginine and proline metabolism pathway.

Genome-wide knockout analyses indicated that supplementation with aspartate (ASP) or asparagine (ASN) could potentially ameliorate these metabolic deficiencies. Further metabolic assessments in Long COVID patients highlighted the significant downregulation of ASP in both blood and muscle, supporting our predictions.

Consequently, we propose that the combination of l-ornithine and l-aspartate (LOLA) offers a promising approach to alleviate metabolic symptoms in both ME/CFS and Long COVID patients. This study not only elucidates the shared metabolic pathways in ME/CFS and Long COVID but also positions LOLA as a viable candidate for future clinical trials.

Source: Gong-Hua Li, Feifei Han, Qing-Peng Kong, Wenzhong Xiao. Systems Modeling Reveals Shared Metabolic Dysregulation and Novel Therapeutic Treatments in ME/CFS and Long COVID. bioRxiv 2024.06.17.599450; doi: https://doi.org/10.1101/2024.06.17.599450 https://www.biorxiv.org/content/10.1101/2024.06.17.599450v1.full (Full text)

Transfer of IgG from Long COVID patients induces symptomology in mice

Abstract:

SARS-CoV-2 infections worldwide led to a surge in cases of Long COVID, a post-infectious syndrome. It has been hypothesized that autoantibodies play a crucial role in the development of Long COVID and other syndromes, such as fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, we tested this hypothesis by passively transferring total IgG from Long COVID patients to mice.

Using Glial Fibrillary Acidic Protein (GFAP) and type-I interferon expression, we stratified patients into three Long COVID subgroups, each with unique plasma proteome signatures. Remarkably, IgG transfer from the two subgroups, which are characterized by higher plasma levels of neuronal proteins and leukocyte activation markers, induced pronounced and persistent sensory hypersensitivity with distinct kinetics. Conversely, IgG transfer from the third subgroup, which are characterized by enriched skeletal and cardiac muscle proteome profiles, reduced locomotor activity in mice without affecting their motor coordination.

These findings demonstrate that transfer of IgG from Long COVID patients to mice replicates disease symptoms, underscoring IgG’s causative role in Long COVID pathogenesis. This work proposes a murine model that mirrors Long COVID’s pathophysiological mechanisms, which may be used as a tool for screening and developing targeted therapeutics.

Source: Hung-Jen Chen, Brent Appelman, Hanneke Willemen, Amelie Bos, Judith Prado, Chiara. E. Geyer, Patrícia Silva Santos Ribeiro, Sabine Versteeg, Mads Larsen, Eline Schüchner, Marije K. Bomers, Ayesha H.A. Lavell, Amsterdam UMC COVID-19 biobank, Braeden Charlton, Rob Wüst, W. Joost Wiersinga, Michèle van Vugt, Gestur Vidarsson, Niels Eijkelkamp, Jeroen den Dunnen. Transfer of IgG from Long COVID patients induces symptomology in mice. bioRxiv 2024.05.30.596590; doi: https://doi.org/10.1101/2024.05.30.596590 https://www.biorxiv.org/content/10.1101/2024.05.30.596590v1.full (Full text)

Psychological outcomes of COVID-19 survivors at sixth months after diagnose: the role of kynurenine pathway metabolites in depression, anxiety, and stress

Abstract:

Coronavirus disease 2019 (COVID-19) has resulted in long-term psychiatric symptoms because of the immunologic response to the virus itself as well as fundamental life changes related to the pandemic. This immune response leads to altered tryptophan (TRP)-kynurenine (KYN) pathway (TKP) metabolism, which plays an essential role in the pathophysiology of mental illnesses. We aimed to define TKP changes as a potential underlying mechanism of psychiatric disorders in post-COVID-19 patients.

We measured plasma levels of several TKP markers, including KYN, TRP, kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN), as well as the TRP/KYN, KYNA/3-HK, and KYNA/QUIN ratios, in 90 post-COVID-19 patients (on the first day of hospitalization) and 59 healthy controls (on the first admission to the Check-Up Center). An online questionnaire that included the Depression, Anxiety and Stress Scale-21 (DASS-21) was used 6 months after the initial assessment in both groups.

A total of 32.2% of participants with COVID-19 showed depressive symptoms, 21.1% exhibited anxiety, and 33.3% had signs of stress at follow-up, while 6.6% of healthy controls exhibited depressive and anxiety symptoms and 18.6% had signs of stress. TRP and 3-HK were negative predictors of anxiety and stress, but KYN positively predicted anxiety and stress. Moreover, TRP negatively predicted depression, while KYNA/3-HK was a negative predictor of anxiety.

The correlation between depression, anxiety, and stress and TKP activation in COVID-19 could provide prospective biomarkers, especially the reduction in TRP and 3HK levels and the increase in KYN. Our results suggest that the alteration of TKP is not only a potential biomarker of viral infection-related long-term psychiatric disorders but also that the therapy targets future viral infections related to depression and anxiety.

Source: Kucukkarapinar M, Yay-Pence A, Yildiz Y, Buyukkoruk M, Yaz-Aydin G, Deveci-Bulut TS, Gulbahar O, Senol E, Candansayar S. Psychological outcomes of COVID-19 survivors at sixth months after diagnose: the role of kynurenine pathway metabolites in depression, anxiety, and stress. J Neural Transm (Vienna). 2022 Aug;129(8):1077-1089. doi: 10.1007/s00702-022-02525-1. Epub 2022 Jul 7. PMID: 35796878; PMCID: PMC9261222. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261222/ (Full text)

Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue

Abstract:

After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition, marked by neurologic symptoms such as cognitive deficits, olfactory dysfunction, and fatigue. Despite this, biomarkers and pathophysiological understandings of this condition remain limited. Employing magnetic resonance imaging, we conduct a comparative analysis of cerebral microstructure among patients with Post-COVID-Condition, healthy controls, and individuals that contracted COVID-19 without long-term symptoms.

We reveal widespread alterations in cerebral microstructure, attributed to a shift in volume from neuronal compartments to free fluid, associated with the severity of the initial infection. Correlating these alterations with cognition, olfaction, and fatigue unveils distinct affected networks, which are in close anatomical-functional relationship with the respective symptoms.

Source: Hosp JA, Reisert M, Dressing A, Götz V, Kellner E, Mast H, Arndt S, Waller CF, Wagner D, Rieg S, Urbach H, Weiller C, Schröter N, Rau A. Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue. Nat Commun. 2024 May 18;15(1):4256. doi: 10.1038/s41467-024-48651-0. PMID: 38762609; PMCID: PMC11102465. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11102465/ (Full text)

Long-COVID autonomic syndrome in working age and work ability impairment

Abstract:

Long-COVID19 has been recently associated with long-sick leave and unemployment. The autonomic nervous system functioning may be also affected by SARS-CoV-2, leading to a chronic autonomic syndrome. This latter remains widely unrecognized in clinical practice. In the present study, we assessed the occurrence of Long-COVID19 Autonomic Syndrome in a group of active workers as well as the relationships between their autonomic dysfunction and work ability.

This prospective observational study was conducted during the 2nd wave of the pandemic in Italy. Forty-five patients (53.6 ± 8.4 years; 32 M) hospitalized for COVID19, were consecutively enrolled at the time of their hospital discharge (T0) and followed-up for 6 months. Autonomic symptoms and work ability were assessed by COMPASS31 and Work Ability Index questionnaires at T0, one (T1), three and six (T6) months after hospital discharge and compared to those retrospectively collected for a period preceding SARS-CoV-2 infection. Clinical examination and standing test were also performed at T1 and T6.

One in three working-age people developed a new autonomic syndrome that was still evident 6 months after the acute infection resolution. This was associated with a significant reduction in the work ability. Recognition of Long-COVID19 Autonomic Syndrome may promote early intervention to facilitate return to work and prevent unemployment.

Source: Rinaldi L, Rigo S, Pani M, Bisoglio A, Khalaf K, Minonzio M, Shiffer D, Romeo MA, Verzeletti P, Ciccarelli M, Bordoni MG, Stranges S, Riboli E, Furlan R, Barbic F. Long-COVID autonomic syndrome in working age and work ability impairment. Sci Rep. 2024 May 23;14(1):11835. doi: 10.1038/s41598-024-61455-y. PMID: 38782998; PMCID: PMC11116376. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116376/ (Full text)

The risks of autoimmune- and inflammatory post-acute COVID-19 conditions: a network cohort study in six European countries, the US, and Korea

ABSTRACT

Objectives We aimed to assess the risk of autoimmune- and inflammatory post-acute COVID-19 conditions.

Design Descriptive network cohort study.

Setting Electronic health records from UK and Dutch primary care, Norwegian linked health registry, hospital records of specialist centres in Spain, France, and Korea, and healthcare claims from Estonia and the US.

Participants We followed individuals between September 2020 and the latest available data from the day they fulfilled at least 365 days of prior observation (general population), additionally from day 91 after a SARS-Cov-2 negative test (comparator) or a COVID-19 record (exposed patients).

Main outcome measures We assessed postural orthostatic tachycardia syndrome (POTS) diagnoses/symptoms, myalgic encephalomyelitis / chronic fatigues syndrome (ME/CFS) diagnoses/symptoms, multi-inflammatory syndrome (MIS), and several autoimmune diseases. For contextualisation, we assessed any diabetes mellitus (DM).

Meta-analysed crude incidence rate ratios (IRR) of outcomes measures after COVID-19 versus negative testing yield the ratios of absolute risks. Furthermore, incidence rates (IR) of the outcomes in the general population describe the total disease burden.

Results We included 34’549’575 individuals of whom 2’521’812 had COVID-19, and 4’233’145 a first negative test. After COVID-19 compared to test negative patients, we observed IRRs of 1.24 (1.23-1.25), 1.22 (1.21-1.23), and 1.12 (1.04-1.21) for POTS symptoms, ME/CFS symptoms and diagnoses, respectively. In contrast, autoimmune diseases and DM did not yield higher rates after COVID-19. In individual general database populations, IRs of POTS and ME/CFS diagnoses were 17-1’477/100’000 person-years (pys) and 2-473/100’000 pys, respectively. IRs of MIS were lowest with IRs 0.4-16/100’000 pys, those of DM as a benchmark 8-86/100’000 pys. IRs largely depended on the care setting.

Conclusion In our unmatched comparison, we observed that, following COVID-19, POTS and ME/CFS yielded higher rates than after negative testing. In absolute terms, we observed POTS and ME/CFS diagnoses to have a similar disease burden as DM.

WHAT IS ALREADY KNOWN ON THIS TOPIC

  • Observational research suggested positive associations between COVID-19 and so called post-acute COVID-19 conditions, whose spectrum is yet to be established

  • Basic research suggested pathways that link COVID-19 with autoimmune- and inflammatory diseases such as postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis / chronic fatigues syndrome (ME/CFS), multiple inflammatory syndrome (MIS), and autoimmune diseases

WHAT THIS STUDY ADDS

  • After COVID-19, the rates of POTS symptoms and ME/CFS symptoms/diagnoses was higher than those after negative testing

  • After COVID-19 versus negative testing, rates of ME/CFS diagnoses were increased in the working age group and rates of symptoms of POTS and ME/CFS were increased in children and elderly

  • Disease burdens of POTS and ME/CFS diagnoses in the general population were higher among women than among men and overall similar to that of diabetes mellitus

Source: Theresa Burkard, Kim López-Güell, Martí Català, Edward Burn, Antonella Delmestri, Sara Khalid, Annika M Joedicke, Daniel Dedman, Jessie O Oyinlola, Alicia Abellan, Laura Pérez-Crespo, Núria Mercadé-Besora, Talita Duarte-Salles, Daniel Prieto-Alhambra, Johnmary T Arinze, Mees Mosseveld, Raivo Kolde, Jaime Meléndez-Cardiel, Raúl López-Blasco, Álvaro Martínez, Bernardo Valdivieso, Dominique Delseny, Gregoire Mercier, Chungsoo Kim, Ji-woo Kim, Kristin Kostka, Juan Manuel Ramírez-Anguita, Miguel A Mayer, Nhung TH Trinh, Hedvig ME Nordeng, Roger Paredes, Anneli Uusküla, Akihiko Nishimura, Cora Loste, Lourdes Mateu, Junqing Xie. The risks of autoimmune- and inflammatory post-acute COVID-19 conditions: a network cohort study in six European countries, the US, and Korea. medRxiv 2024.05.15.24307344; doi: https://doi.org/10.1101/2024.05.15.24307344 https://www.medrxiv.org/content/10.1101/2024.05.15.24307344v1.full-text (Full text)

Impact of inflammatory response in the acute phase of COVID-19 on predicting objective and subjective post-COVID fatigue

Abstract:

The biological predictors of objective and subjective fatigue in individuals with post-COVID syndrome remains unclear. This study aims to ascertain the predictive significance of the immune response measured during the acute phase of SARS-CoV-2 infection on various dimensions of fatigue 6–9 months post-infection.

We examined the association between immune markers obtained from the serum of 54 patients (mean age: 58.69 ± 10.90; female: 31%) and objective and subjective chronic fatigue using general linear mixed models. Level of IL-1RA, IFNγ and TNFα in plasma and the percentage of monocytes measured in the acute phase of COVID-19 predicted physical and total fatigue.

Moreover, the higher the concentration of TNFα (r=-0.40 ; p = .019) in the acute phase, the greater the lack of awareness of cognitive fatigue 6–9 months post-infection. These findings shed light on the relationship between acute inflammatory response and the persistence of both objective and subjective fatigue.

Source: Julie Péron, Anthony Nuber-Champier, Gautier Breville et al. Impact of inflammatory response in the acute phase of COVID-19 on predicting objective and subjective post-COVID fatigue, 28 May 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-4374986/v1] https://www.researchsquare.com/article/rs-4374986/v1 (Full text)