Tag: long covid vs fibromyalgia

Metabolomics-Based Machine Learning Diagnostics of Post-Acute Sequelae of SARS-CoV-2 Infection

Abstract:

Background: COVID-19 has taken millions of lives and continues to affect people worldwide. Post-Acute Sequelae of SARS-CoV-2 Infection (also known as Post-Acute Sequelae of COVID-19 (PASC) or more commonly, Long COVID) occurs in the aftermath of COVID-19 and is poorly understood despite its widespread effects.

Methods: We created a machine-learning model that distinguishes PASC from PASC-similar diseases. The model was trained to recognize PASC-dysregulated metabolites (p ≤ 0.05) using molecular descriptors.

Results: Our multi-layer perceptron model accurately recognizes PASC-dysregulated metabolites in the independent testing set, with an AUC-ROC of 0.8991, and differentiates PASC from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Lyme disease, postural orthostatic tachycardia syndrome (POTS), and irritable bowel syndrome (IBS). However, it was unable to differentiate fibromyalgia (FM) from PASC.

Conclusions: By creating and testing models pairwise on each of these diseases, we elucidated the unique strength of the similarity between FM and PASC relative to other PASC-similar diseases. Our approach is unique to PASC diagnosis, and our use of molecular descriptors enables our model to work with any metabolite where molecular descriptors can be identified, as these descriptors can be generated and compared for any metabolite. Our study presents a novel approach to PASC diagnosis that partially circumvents the lengthy process of exclusion, potentially facilitating faster interventions and improved patient outcomes.

Source: Cai E, Kouznetsova VL, Tsigelny IF. Metabolomics-Based Machine Learning Diagnostics of Post-Acute Sequelae of SARS-CoV-2 Infection. Metabolites. 2025 Dec 17;15(12):801. doi: 10.3390/metabo15120801. PMID: 41441042; PMCID: PMC12734907. https://pmc.ncbi.nlm.nih.gov/articles/PMC12734907/ (Full text)

Blood parameters differentiate post COVID-19 condition from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia

Abstract:

Post-COVID-19 condition, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM), are characterized by fatigue, pain, shortness of breath, sleep disturbances, cognitive dysfunction and other symptoms, heavily impacting on patients daily functioning. Moreover, over half of patients end up fulfilling ME/CFS and/or FM clinical criteria after a few months of SARS-CoV-2 infection.

Expression of the toxic human endogenous retrovirus (HERV)-W ENV protein can be induced by viral infection and HERV-W detection was correlated with acute COVID-19 severity and found significantly expressed in post-COVID-19 condition. This study shows that HERV-W ENV may also be present in prepandemic cases of ME/CFS, FM or co-diagnosed with both clinical criteria, suggesting viral participation in these chronic diseases.

To learn whether associated antiviral mechanisms may also show differing patterns of immunological responses, we measured IgM, IgG, IgA and IgE antibody isotypes against SARS-CoV-2 spike and nucleocapsid antigens, the levels of IL-6, IL-8, IL-10, IFNγ and TNFα cytokines, the level of NfL, a neural damage biomarker, as well as some blood cell markers potentially related with fatigue.

Importantly, some of the measured variables showed a capacity to discriminate post-COVID-19 condition cases from all other participants, with 100 % sensitivity and up to 71.9 % specificity providing a new tool for a differential diagnosis between diseases or syndromes with so many overlapping clinical symptoms. Interestingly, the detected markers showed moderate-to-strong correlations with patient symptoms pointing at novel therapeutic opportunities.

Source: Giménez-Orenga K, Pierquin J, Brunel J, Charvet B, Martín-Martínez E, Lemarinier M, Fried S, Lucas A, Perron H, Oltra E. Blood parameters differentiate post COVID-19 condition from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia. Brain Behav Immun Health. 2025 Jul 4;48:101058. doi: 10.1016/j.bbih.2025.101058. PMID: 40726775; PMCID: PMC12302357. https://pmc.ncbi.nlm.nih.gov/articles/PMC12302357/ (Full text)

Prevalence and severity of neurologic symptoms in Long-COVID and the role of pre-existing conditions, hospitalization, and mental health

Abstract:

Background: Long-COVID refers to ongoing, relapsing, or new symptoms present 30 or more days after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This study examined the prevalence and severity of neurologic symptoms at greater than 1 month following acute SARS-CoV-2 infection and the influence of pre-existing neurologic and psychiatric conditions, current depression and anxiety status, and hospitalization on the presence and severity of these symptoms.

Methods: This prospective cohort study recruited primarily self-referred Long-COVID participants with confirmed SARS-CoV-2 infection. Online questionnaires inquiring about pre-existing conditions, neurologic symptoms and their severity pre, during and post COVID-19, and current anxiety and depression screening were completed by 213 participants at a median time of 8 months after infection. Descriptive analyses and prevalence modeling were performed.

Results: The most frequent neurologic symptoms post COVID-19 were fatigue, concentration/memory difficulties, unrefreshed sleep, and dysarthria/word finding difficulties (73.2–86.4%). Neurologic symptoms were highly prevalent with significantly greater odds post COVID-19 compared to pre for all symptoms and higher prevalence at time periods farther from infection, including those implicit in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. Several severe neurologic symptoms were significantly more prevalent post COVID-19. Moderate to severe anxiety (34%) and depression (27%) were observed post COVID-19. Preexisting neurologic or psychiatric conditions did not demonstrate any significant difference in neurologic symptom prevalence post COVID-19. Those who met criteria for moderate or severe anxiety post COVID-19 had a significant difference in prevalence of fatigue, sensitivity to touch and unrefreshed sleep. Similarly, fatigue, concentration/memory difficulty and unrefreshed sleep were more prevalent in moderate to severe depression. There were no significant differences in neurologic symptom prevalence in a hospitalized group when compared to non- hospitalized.

Conclusion: Long-COVID has a high burden of long lasting and severe neurological sequelae. These sequelae are independent of pre-existing self-reported neurologic and psychiatric conditions, as well as previous hospitalization. Current moderate to severe anxiety and depression status can impact fatigue, cognition, and sleep post COVID-19. Focus on the biological impact of SARS-CoV-2 on the nervous system will be essential in ameliorating the tremendous symptom burden left in the wake of the COVID-19 pandemic.

Source: Huff Hanalise V. , Roberts Henry , Bartrum Elizabeth , Norato Gina , Grayson Nicholas , Fleig Katherine , Wilkerson Miciah J. , Stussman Barbara J. , Nath Avindra , Walitt Brian. Prevalence and severity of neurologic symptoms in Long-COVID and the role of pre-existing conditions, hospitalization, and mental health. Frontiers in Neurology, Volume 16 – 2025 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1562084 10.3389/fneur.2025.1562084 ISSN:1664-2295 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1562084/full (Full text)

Metabolic Fingerprinting for the Diagnosis of Clinically Similar Long COVID and Fibromyalgia Using a Portable FT-MIR Spectroscopic Combined with Chemometrics

Abstract:

Post Acute Sequelae of SARS-CoV-2 infection (PASC or Long COVID) is characterized by lingering symptomatology post-initial COVID-19 illness that is often debilitating. It is seen in up to 30–40% of individuals post-infection. Patients with Long COVID (LC) suffer from dysautonomia, malaise, fatigue, and pain, amongst a multitude of other symptoms.
Fibromyalgia (FM) is a chronic musculoskeletal pain disorder that often leads to functional disability and severe impairment of quality of life. LC and FM share several clinical features, including pain that often makes them indistinguishable. The aim of this study is to develop a metabolic fingerprinting approach using portable Fourier-transform mid-infrared (FT-MIR) spectroscopic techniques to diagnose clinically similar LC and FM.
Blood samples were obtained from LC (n = 50) and FM (n = 50) patients and stored on conventional bloodspot protein saver cards. A semi-permeable membrane filtration approach was used to extract the blood samples, and spectral data were collected using a portable FT-MIR spectrometer. Through the deconvolution analysis of the spectral data, a distinct spectral marker at 1565 cm−1 was identified based on a statistically significant analysis, only present in FM patients. This IR band has been linked to the presence of side chains of glutamate.
An OPLS-DA algorithm created using the spectral region 1500 to 1700 cm−1 enabled the classification of the spectra into their corresponding classes (Rcv > 0.96) with 100% accuracy and specificity. This high-throughput approach allows unique metabolic signatures associated with LC and FM to be identified, allowing these conditions to be distinguished and implemented for in-clinic diagnostics, which is crucial to guide future therapeutic approaches.
Source: Hackshaw KV, Yao S, Bao H, de Lamo Castellvi S, Aziz R, Nuguri SM, Yu L, Osuna-Diaz MM, Brode WM, Sebastian KR, et al. Metabolic Fingerprinting for the Diagnosis of Clinically Similar Long COVID and Fibromyalgia Using a Portable FT-MIR Spectroscopic Combined with Chemometrics. Biomedicines. 2023; 11(10):2704. https://doi.org/10.3390/biomedicines11102704 https://www.mdpi.com/2227-9059/11/10/2704 (Full text)

A comparison of pain, fatigue, and function between post–COVID-19 condition, fibromyalgia, and chronic fatigue syndrome: a survey study

Abstract

A growing number of individuals report prolonged symptoms following acute COVID-19 infection, known as post-COVID-19 condition (post-COVID-19).

While studies have emerged investigating the symptom sequelae of post-COVID-19, there has been limited investigation into the characterization of pain, fatigue, and function in these individuals, despite initial reports of a clinical phenotype similar to fibromyalgia (FMS) and chronic fatigue syndrome/myalgic encephalomyelitis (CFS).

This study aimed to characterize multiple symptom domains in individuals reporting post-COVID-19 and compare its clinical phenotype to those with FMS and CFS.

A total of 707 individuals with a single or comorbid diagnosis of post-COVID-19, FMS, and/or CFS completed multiple surveys assessing self-reported pain, fatigue, physical and cognitive function, catastrophizing, kinesiophobia, anxiety, depression, dyspnea, and sleep quality. In all three diagnoses, elevated pain, fatigue, anxiety, depression, catastrophizing, and kinesiophobia were reported.

Physical and cognitive function were similarly impacted among individuals with post-COVID-19, FMS, and CFS; however, individuals with post-COVID-19 reported lower pain and fatigue than FMS and CFS.

The comorbid diagnosis of post-COVID-19 with FMS and/or CFS further exacerbated pain, fatigue, and psychological domains when compared to post-COVID-19 alone.

In summary, individuals with post-COVID-19 report a symptom phenotype similar to FMS and CFS, negatively impacting cognitive and physical function, but with less severe pain and fatigue overall. These findings may help direct future investigations of the benefit of a biopsychosocial approach to the clinical management of post-COVID-19.

Source: Haider S, Janowski AJ, Lesnak JB, Hayashi K, Dailey DL, Chimenti R, Frey-Law LA, Sluka KA, Berardi G. A comparison of pain, fatigue, and function between post-COVID-19 condition, fibromyalgia, and chronic fatigue syndrome: a survey study. Pain. 2023 Feb 1;164(2):385-401. doi: 10.1097/j.pain.0000000000002711. Epub 2022 Jun 29. PMID: 36006296; PMCID: PMC9797623.  https://pubmed.ncbi.nlm.nih.gov/36006296/

Rheumatology and Long COVID: lessons from the study of fibromyalgia

Abstract:

Rheumatology, such as other subspecialties, has both a unique perspective to offer as well as an evolving role to play in the global COVID-19 pandemic. Our field has already contributed meaningfully to the development and repurposing of many of the immune-based therapeutics which are now standard treatments for severe forms of the disease as well as to the understanding of the epidemiology, risk factors and natural history of COVID-19 in immune-mediated inflammatory diseases. Still in evolution is our potential to contribute to burgeoning research efforts in the next phase of the pandemic: the syndrome of postacute sequelae of COVID-19 or Long COVID. While our field brings many assets to the study of Long COVID including our expertise in the investigation of chronic inflammation and autoimmunity, our Viewpoint focuses on the strong similarities between fibromyalgia (FM) and Long COVID. While one can speculate on how embracing and confident practising rheumatologists already are regarding these interrelationships, we assert that in the emerging field of Long COVID the potential lessons from the field of fibromyalgia care and research have been underappreciated and marginalised and most importantly now deserve a critical appraisal.

Source: Clauw DJ, Calabrese L. Rheumatology and Long COVID: lessons from the study of fibromyalgia. Ann Rheum Dis. 2023 May 25:ard-2023-224250. doi: 10.1136/ard-2023-224250. Epub ahead of print. PMID: 37230736. https://ard.bmj.com/content/early/2023/05/24/ard-2023-224250 (Full text)