Improvement of Long COVID symptoms over one year

Abstract:

Importance: Early and accurate diagnosis and treatment of Long COVID, clinically known as post-acute sequelae of COVID-19 (PASC), may mitigate progression to chronic diseases such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our objective was to determine the utility of the DePaul Symptom Questionnaire (DSQ) to assess the frequency and severity of common symptoms of ME/CFS, to diagnose and monitor symptoms in patients with PASC.

Methods: This prospective, observational cohort study enrolled 185 people that included 34 patients with PASC that had positive COVID-19 test and persistent symptoms of >3 months and 151 patients diagnosed with ME/CFS. PASC patients were followed over 1 year and responded to the DSQ at baseline and 12 months. ME/CFS patients responded to the DSQ at baseline and 1 year later. Changes in symptoms over time were analyzed using a fixed-effects model to compute difference-in-differences estimates between baseline and 1-year follow-up assessments.

Participants: Patients were defined as having PASC if they had a previous positive COVID-19 test, were experiencing symptoms of fatigue, post-exertional malaise, or other unwellness for at least 3 months, were not hospitalized for COVID-19, had no documented major medical or psychiatric diseases prior to COVID-19, and had no other active and untreated disease processes that could explain their symptoms. PASC patients were recruited in 2021. ME/CFS patients were recruited in 2017.

Results: At baseline, patients with PASC had similar symptom severity and frequency as patients with ME/CFS and satisfied ME/CFS diagnostic criteria. ME/CFS patients experienced significantly more severe unrefreshing sleep and flu-like symptoms. Five symptoms improved significantly over the course of 1 year for PASC patients including fatigue, post-exertional malaise, brain fog, irritable bowel symptoms and feeling unsteady. In contrast, there were no significant symptom improvements for ME/CFS patients.

Conclusion and relevance: There were considerable similarities between patients with PASC and ME/CFS at baseline. However, symptoms improved for PASC patients over the course of a year but not for ME/CFS patients. PASC patients with significant symptom improvement no longer met ME/CFS clinical diagnostic criteria. These findings indicate that the DSQ can be used to reliably assess and monitor PASC symptoms.

Source: Oliveira CR, Jason LA, Unutmaz D, Bateman L, Vernon SD. Improvement of Long COVID symptoms over one year. Front Med (Lausanne). 2023 Jan 9;9:1065620. doi: 10.3389/fmed.2022.1065620. PMID: 36698810; PMCID: PMC9868805. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868805/ (Full text)

Converging Evidence of Similar Symptomatology of ME/CFS and PASC Indicating Multisystemic Dyshomeostasis

Abstract:

The purpose of this article is to review the evidence of similar symptomatology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-acute sequelae of SARS-CoV-2 infection (PASC).
Reanalysis of data from a study by Jason comparing symptom reports from two groups of ME/CFS and PASC patients shows a notably similar symptomatology. Symptom scores of the PASC group and the ME/CFS group correlated 0.902 (p < 0.0001) across items. The hypothesis is presented that ME/CFS and PASC are caused by a chronic state of multisystemic disequilibrium including endocrinological, immunological, and/or metabolic changes.
The hypothesis holds that a changed set point persistently pushes the organism towards a pathological dysfunctional state which fails to reset. To use an analogy of a thermostat, if the ‘off switch’ of a thermostat intermittently stops working, for periods the house would become warmer and warmer without limit. The hypothesis draws on recent investigations of the Central Homeostasis Network showing multiple interconnections between the autonomic system, central nervous system, and brain stem.
The hypothesis helps to explain the shared symptomatology of ME/CFS and PASC and the unpredictable, intermittent, and fluctuating pattern of symptoms of ME/CFS and PASC. The current theoretical approach remains speculative and requires in-depth investigation before any definite conclusions can be drawn.
Source: Marks DF. Converging Evidence of Similar Symptomatology of ME/CFS and PASC Indicating Multisystemic Dyshomeostasis. Biomedicines. 2023; 11(1):180. https://doi.org/10.3390/biomedicines11010180 https://www.mdpi.com/2227-9059/11/1/180 (Full text)

Pediatric Post-Acute Sequelae of SARS-CoV-2 infection

Abstract:

Aim: Youth who have not recovered from COVID-19 have been referred to as having Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The goal of this study was to better understand which symptoms persisted since onset of infection and how these symptoms compare to symptoms experienced by those with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Method: A sample of 19 parents who had a child with PASC were recruited using social media to fill out a questionnaire detailing symptoms at two time points. The first time point included their child’s current symptoms and the second captured symptoms at initial infection. These participants were compared to a sample of 19 youth with ME/CFS.

Results: Findings indicated significant decreases among several immune, neuroendocrine, pain, post-exertional malaise (PEM), and COVID-19 Centers for Disease Control and Prevention (CDC) domain symptoms from time of acute infection to time of current reporting. Fatigue remained at a high level as did several symptoms within the sleep and PEM domains. Participants with ME/CFS had overall worse symptomatology when compared to participants with PASC, especially in the neurocognitive domain.

Conclusion: Most symptoms of those with PASC decline over time, but several remain at high levels, including fatigue. These findings are helpful in better understanding common symptom presentation profiles for youth with PASC and can be used to more adequately tailor diagnostic criteria and treatment strategies for youth.

Source: Leonard A. Jason, Madeline Johnson & Chelsea Torres (2023) Pediatric Post-Acute Sequelae of SARS-CoV-2 infection, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2162764 https://www.tandfonline.com/doi/abs/10.1080/21641846.2022.2162764

ME/CFS and Post-Exertional Malaise among Patients with Long COVID

Abstract:

This study sought to ascertain the prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) among a sample of 465 patients with Long COVID. The participants completed three questionnaires: (1) a new questionnaire measuring both the frequency and severity of 38 common symptoms of COVID and Long COVID, (2) a validated short form questionnaire assessing ME/CFS, and (3) a validated questionnaire measuring post-exertional malaise.
The population was predominantly white, female, and living in North America. The mean duration since the onset of COVID-19 symptoms was 70.5 weeks. Among the 465 participants, 58% met a ME/CFS case definition. Of respondents who reported that they had ME/CFS only 70.57% met criteria for ME/CFS and of those who did not report they had ME/CFS, 29.43% nevertheless did meet criteria for the disease: both over-diagnosis and under-diagnosis were evident on self-report. This study supports prior findings that ME/CFS occurs with high prevalence among those who have persistent COVID-19 symptoms.
Source: Jason LA, Dorri JA. ME/CFS and Post-Exertional Malaise among Patients with Long COVID. Neurology International. 2023; 15(1):1-11. https://doi.org/10.3390/neurolint15010001 https://www.mdpi.com/2035-8377/15/1/1 (Full text)

Differences in Symptoms among Black and White Patients with ME/CFS

Abstract:

Study samples of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have primarily involved White subjects, so the literature on ethnic differences is sparse. The current study identified a sample of 19 Black patients diagnosed with ME/CFS and compared them with White patients with ME/CFS, as well as with healthy controls. The studies used a similar psychometrically sound assessment tool to assess symptoms in all subjects.

Findings indicated there were significant differences between patients with ME/CFS versus controls, but few differences between patients who identified as Black or White. The results suggest there might be few symptom differences between patients with ME/CFS in these two ethnic groups. The implications of these findings are discussed.

Source: Jason LA, Torres C. Differences in Symptoms among Black and White Patients with ME/CFS. J Clin Med. 2022 Nov 12;11(22):6708. doi: 10.3390/jcm11226708. PMID: 36431185. https://www.mdpi.com/2077-0383/11/22/6708 (Full text)

Orthostatic intolerance and neurocognitive impairment in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Objectives: The Institute of Medicine (IOM 2015. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington: The National Academies Press) suggested new criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), which requires an endorsement of either neurocognitive impairment or orthostatic intolerance (OI) in addition to other core symptoms. While some research supports the inclusion of OI as a core symptom, others argue that overlap with neurocognitive impairment does not justify the either/or option. The current study assessed methods of operationalizing OI using items from the DePaul Symptom Questionnaire (DSQ-1 and -2) as a part of the IOM criteria. Evaluating the relationship between OI and neurocognitive symptoms may lead to a better understanding of diagnostic criteria for ME/CFS.

Methods: Two-hundred and forty-two participants completed the DSQ. We examined how many participants met the IOM criteria while endorsing different frequencies and severities of various OI symptoms.

Results: Neurocognitive impairment was reported by 93.4% of respondents. OI without concurrent neurocognitive symptoms only allowed for an additional 1.7–4.5% of participants to meet IOM criteria.

Conclusions: Neurocognitive symptoms and OI overlap in ME/CFS, and our results do not support the IOM’s inclusion of neurocognitive impairment and OI as interchangeable symptoms. Furthermore, our findings highlight the need for a uniform method of defining and measuring OI via self-report in order to accurately study OI as a symptom of ME/CFS.

Source: Gaglio, Caroline L., Islam, Mohammed F., Cotler, Joseph and Jason, Leonard A.. “Orthostatic intolerance and neurocognitive impairment in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)” Epidemiologic Methods, vol. 11, no. 1, 2022, pp. 20210033. https://doi.org/10.1515/em-2021-0033

A new clinical challenge: Supporting patients coping with the long-term effects of COVID-19

Abstract:

Mental Health Practitioners (MHPs) have a unique opportunity to provide resources and support to those suffering from Long COVID (LC), the post infectious illness that often follows an acute SARS-CoV-2 infection. In working with these individuals, MHPs can learn from the experiences of patients with another post-infectious disease known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS was once thought to be a psychologically mediated disorder caused by deconditioning and the fear of exertion following a precipitating event such as a viral infection. Research now shows that LC and ME/CFS are biomedical, multisystem, complex physiologic diseases. This article provides a framework to MHPs for the treatment of LC patients using knowledge derived from three decades of research on ME/CFS.

Source: Neal C. Goldberg, Sabrina Poirier, Allison Kanas, Lisa McCorkell, Carrie Anna McGinn, Yochai Re’em, Kathi Kuehnel, Nina Muirhead, Tahlia Ruschioni, Susan Taylor-Brown & Leonard A. Jason (2022) A new clinical challenge: supporting patients coping with the long-term effects of COVID-19, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2128576 (Full text)

Comparing Operationalized Approaches for Substantial Reduction of Functioning in Chronic Fatigue Syndrome and Myalgic Encephalomyelitis

Abstract:

A core criterion for Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME) is a substantial reduction in functioning from pre-illness levels. Despite its ubiquity in diagnostic criteria, there is considerable debate regarding how to measure this domain. The current study assesses five distinct methods for measuring substantial reductions. The analysis used an international, aggregated dataset of patients (N = 2,368) and controls (N=359) to compare the effectiveness of each method.

Four methods involved sophisticated analytic approaches using the Medical Outcomes Survey Short Form-36; the fifth method included a single self-report item on the DePaul Symptom Questionnaire (DSQ). Our main finding was that all methods produced comparable results, though the DSQ item was the most valid in differentiating patients from controls. Having a simple, reliable method to capture a substantial reduction in functioning has considerable advantages for patients and health care workers.

Source: Wiedbusch E, Jason LA. Comparing Operationalized Approaches for Substantial Reduction of Functioning in Chronic Fatigue Syndrome and Myalgic Encephalomyelitis. Arch Community Med. 2022;4(1):59-63. doi: 10.36959/547/653. Epub 2022 Apr 21. PMID: 35673386; PMCID: PMC9168545. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168545/ (Full text)

Pre-illness data reveals differences in multiple metabolites and metabolic pathways in those who do and do not recover from infectious mononucleosis

Abstract:

Metabolic pathways related to energy production, amino acids, nucleotides, nitrogen, lipids, and neurotransmitters in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may contribute to the pathophysiology of ME/CFS. 4501 Northwestern University college students were enrolled in a prospective, longitudinal study.

We collected data before illness, during infectious mononucleosis (IM), and at a 6 month follow-up for those who recovered (N = 18) versus those who went on to develop ME/CFS 6 months later (N = 18). Examining pre-illness blood samples, we found significant detectable metabolite differences between participants fated to develop severe ME/CFS following IM versus recovered controls. We identified glutathione metabolism, nucleotide metabolism, and the TCA cycle (among others) as potentially dysregulated pathways.

The pathways that differed between cases and controls are essential for proliferating cells, particularly during a pro-inflammatory immune response. Performing a series of binary logistic regressions using a leave-one-out cross-validation (LOOCV), our models correctly classified the severe ME/CFS group and recovered controls with an accuracy of 97.2%, sensitivity of 94.4%, and specificity of 100.0%. These changes are consistent with the elevations in pro-inflammatory cytokines that we have reported for patients fated to develop severe ME/CFS 6 months after IM.

Source: Jason LA, Conroy KE, Furst J, Vasan K, Katz BZ. Pre-illness data reveals differences in multiple metabolites and metabolic pathways in those who do and do not recover from infectious mononucleosis. Mol Omics. 2022 May 31. doi: 10.1039/d2mo00124a. Epub ahead of print. PMID: 35640165. https://pubmed.ncbi.nlm.nih.gov/35640165/

Cytokine network analysis in a community-based pediatric sample of patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Objectives: Studies have demonstrated immune dysfunction in adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); however, evidence is varied. The current study used network analysis to examine relationships between cytokines among a sample of pediatric participants with ME/CFS.

Methods: 10,119 youth aged 5-17 in the Chicagoland area were screened for ME/CFS; 111 subjects and controls were brought in for a physician examination and completed a blood draw. Youth were classified as controls (Cs, N = 43), ME/CFS (N = 23) or severe (S-ME/CFS, N = 45). Patterns of plasma cytokine networks were analyzed.

Results: All participant groups displayed a primary network of interconnected cytokines. In the ME/CFS group, inflammatory cytokines IL-12p70, IL-17A, and IFN-γ were connected and included in the primary membership, suggesting activation of inflammatory mechanisms. The S-ME/CFS group demonstrated a strong relationship between IL-17A and IL-23, a connection associated with chronic inflammation. The relationships of IL-6 and IL-8 in ME/CFS and S-ME/CFS participants also differed from Cs. Together, these results indicate pro-inflammatory responses in our illness populations.

Discussion: Our data imply biological differences between our three participant groups, with ME/CFS and S-ME/CFS participants demonstrating an inflammatory profile. Examining co-expression of cytokines may aid in the identification of a biomarker for pediatric ME/CFS.

Source: Jason LA, Gaglio CL, Furst J, Islam M, Sorenson M, Conroy KE, Katz BZ. Cytokine network analysis in a community-based pediatric sample of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Chronic Illn. 2022 May 16:17423953221101606. doi: 10.1177/17423953221101606. Epub ahead of print. PMID: 35570777.  https://pubmed.ncbi.nlm.nih.gov/35570777/