Tag: 2023

Serum ferritin level during hospitalization is associated with Brain Fog after COVID-19

Abstract:

The coronavirus disease 2019 (COVID-19) remains an epidemic worldwide. Most patients suffer residual symptoms, the so-called “Long COVID,” which includes respiratory and neuropsychiatric symptoms. Brain Fog, one of the symptoms of Long COVID, is a major public health issue because it can impair patients’ quality of life even after recovery from the disease. However, neither the pathogenesis nor the treatment of this condition remains unknown.

We focused on serum ferritin levels in this study and collected information on the onset of Brain Fog through questionnaires and found that high ferritin levels during hospitalization were associated with the occurrence of Brain Fog. In addition, we excluded confounders as far as possible using propensity score analyses and found that ferritin was independently associated with Brain Fog in most of the models. We conducted phase analysis and evaluated the interaction of each phase with ferritin levels and Brain Fog.

We found a positive correlation between serum ferritin levels during hospitalization and Brain Fog after COVID-19. High ferritin levels in patients with Brain Fog may reflect the contribution of chronic inflammation in the development of Brain Fog. This study provides a novel insight into the pathogenic mechanism of Brain Fog after COVID-19.

Source: Ishikura T, Nakano T, Kitano T, Tokuda T, Sumi-Akamaru H, Naka T. Serum ferritin level during hospitalization is associated with Brain Fog after COVID-19. Sci Rep. 2023 Aug 11;13(1):13095. doi: 10.1038/s41598-023-40011-0. PMID: 37567939; PMCID: PMC10421912. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421912/ (Full text)

Long-term symptom severity and clinical biomarkers in post-COVID-19/chronic fatigue syndrome: results from a prospective observational cohort

Summary:

Background: Post-COVID-19 syndrome (PCS) is characterised by a wide range of symptoms, primarily fatigue and exertion intolerance. While disease courses in the early months post-infection have been well-described, the long-term health consequences for patients with PCS with disabling fatigue remain unclear.

Methods: In this prospective observational cohort study, we evaluated symptom severity and various biomarkers, including hand grip strength (HGS), cardiovascular function, and laboratory parameters, in 106 patients with PCS with moderate to severe fatigue and exertion intolerance at three time points after infection (3–8, 9–16, and 17–20 months). The study was conducted at the Charité’s Fatigue Centre and the Charité’s outpatient clinic for neuroimmunology at Berlin, Germany from July 16, 2020, to February 18, 2022. A subset of patients (PCS-ME/CFS) met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome according to the Canadian Consensus Criteria (CCC). The aim was to determine differences in the disease course between the two patient groups (i.e., PCS vs PCS-ME/CFS) and identify correlating biomarkers.

Findings: Patients with PCS-ME/CFS reported persistently high severity of most symptoms up to 20 months after infection, while patients with PCS showed overall health improvement. Although fatigue and post-exertional malaise (PEM), hallmarks of post-infectious fatigue syndromes, were still evident in both groups, they remained more pronounced in PCS-ME/CFS. Inflammatory biomarkers decreased in both groups, but not antinuclear antibodies. Lower HGS at onset correlated with symptom persistence, particularly in patients with PCS-ME/CFS.

Interpretation: Our findings suggest that PCS can persist beyond 20 months post-infection and encompass the full scope of post-infectious ME/CFS as defined by the CCC. Sub-classifying patients with PCS based on the CCC can assist in the management and monitoring of patients with PCS-ME/CFS due to their persistently higher symptom severity.

Source: Franziska Legler, Lil Meyer-Arndt, Lukas Mödl, Claudia Kedor, Helma Freitag, Elisa Stein, Uta Hoppmann, Rebekka Rust, Kirsten Wittke, Nadja Siebert, Janina Behrens, Andreas Thiel, Frank Konietschke, Friedemann Paul, Carmen Scheibenbogen, Judith Bellmann-Strobl,
Long-term symptom severity and clinical biomarkers in post-COVID-19/chronic fatigue syndrome: results from a prospective observational cohort, eClinicalMedicine, Volume 63, 2023, 102146, ISSN 2589-5370, https://doi.org/10.1016/j.eclinm.2023.102146. https://www.sciencedirect.com/science/article/pii/S2589537023003231 (Full text)

The microbiome in post-acute infection syndrome (PAIS)

Abstract:

Post-Acute Infection Syndrome (PAIS) is a relatively new medical terminology that represents prolonged sequelae symptoms after acute infection by numerous pathogenic agents. Imposing a substantial public health burden worldwide, PASC (post-acute sequelae of COVID-19 infection) and ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) are two of the most recognized and prevalent PAIS conditions. The presences of prior infections and similar symptom profiles in PAIS reflect a plausible common etiopathogenesis. The human microbiome is known to play an essential role in health and disease.

In this review, we reviewed and summarized available research on oral and gut microbiota alterations in patients with different infections or PAIS conditions. We discussed key theories about the associations between microbiome dysbiosis and PAIS disease development, aiming to explore the mechanistic roles and potential functions the microbiome may have in the process. Additionally, we discuss the areas of knowledge gaps and propose the potential clinical applications of the microbiome for prevention and treatment of PAIS conditions.

Source: Guo C, Yi B, Wu J, Lu J. The microbiome in post-acute infection syndrome (PAIS). Comput Struct Biotechnol J. 2023 Aug 5;21:3904-3911. doi: 10.1016/j.csbj.2023.08.002. PMID: 37602232; PMCID: PMC10432703. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432703/ (Full text)

The viral origin of myalgic encephalomyelitis/chronic fatigue syndrome

ME/CFS is a disabling and often severe disease, so-far incurable, that has long been associated with discrete outbreaks and sporadic incidents of viral-like illness. First, a word about the controversial name. The designation “Myalgic Encephalomyelitis” (abbreviated ME) originated following an outbreak at London’s Royal Free Hospital in 1955. More than 200 members of the hospital staff became disabled [1]. Melvin Ramsay, MD, eventually published important case descriptions in Lancet [2]. He coined “ME” based on predominant symptoms of muscle pain (myalgia) and effects on the brain (encephalo), spinal cord (myel), and inflammation (itis). For 32 years, “ME” was deemed acceptable until, in 1987, the Centers for Disease Control (CDC) convened an extramural committee to change the name. CDC did so in response to a series of outbreaks of a similar, if not identical, illness in the United States, introducing “chronic fatigue syndrome” in 1988 [3].

Because the CDC name trivializes the serious nature of the disease, the patient community and many medical professionals prefer ME, which continues to be widely used in the United Kingdom and Europe. In 2015, a US Institute of Medicine (IOM) committee recommended yet another name, Systemic Exertion Intolerance Disease [4], which has been largely ignored. Should inflammation of the brain and spinal cord be definitively shown with modern methods, the name Myalgic Encephalomyelitis will finally be vindicated. The compromise name ME/CFS is now used most frequently and will be used here despite its faults.

Source: Hanson MR (2023) The viral origin of myalgic encephalomyelitis/chronic fatigue syndrome. PLoS Pathog 19(8): e1011523. https://doi.org/10.1371/journal.ppat.1011523 https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011523 (Full text)

 

Home-based testing protocol to measure physiological responses to everyday activities in ME: a feasibility study

Abstract:

Background and objectives: Individuals with Myalgic Encephalomyelitis (ME) have shown altered physiological responses during maximum cardiopulmonary exercise testing. However, maximal testing is not representative of the everyday activities reported to cause or increase symptoms in ME, and is not accessible for those with severe or very severe illness. The aim of this study was to assess the feasibility and acceptability of a home-based testing protocol to measure physiological responses in ME to everyday activity.

Methods: Researchers attended participants’ homes to collect data and provide equipment for independent testing. Adults with ME who met the International Consensus Criteria wore a portable metabolic assessment system and a physiological stress monitor. Blood pressure, heart rate, oxygen saturation and lactic acid were assessed during a range of everyday positions and activities in their own homes.

Results: Online recruitment yielded 70 volunteers in 24 h. 17 eligible individuals reflecting a range of illness severities were enrolled. All participants found the procedures acceptable with 12 (70%) subjects completing every listed activity. Apparent physiological abnormalities were identified in all participants.

Conclusion: Physiological measurement during everyday activities was feasible for our participants who represented a range of ME severities. Activities must be adapted for different levels of severity to avoid significant symptom exacerbation. Further research is needed to develop home-based assessment protocols to advance the biobehavioral understanding of ME.

Trial registration number: ISRCTN78379409

Source: Nicola Clague-Baker, Sarah Tyson, Karen Leslie, Helen Dawes, Michelle Bull & Natalie Hilliard (2023) Home-based testing protocol to measure physiological responses to everyday activities in ME: a feasibility study, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2023.2245584 https://www.tandfonline.com/doi/full/10.1080/21641846.2023.2245584 (Full text)

Risk of autoimmune diseases following COVID-19 and the potential protective effect from vaccination: a population-based cohort study

Summary:

Background: Case reports suggest that SARS-CoV-2 infection could lead to immune dysregulation and trigger autoimmunity while COVID-19 vaccination is effective against severe COVID-19 outcomes. We aim to examine the association between COVID-19 and development of autoimmune diseases (ADs), and the potential protective effect of COVID-19 vaccination on such an association.

Methods: A retrospective cohort study was conducted in Hong Kong between 1 April 2020 and 15 November 2022. COVID-19 was confirmed by positive polymerase chain reaction or rapid antigen test. Cox proportional hazard regression with inverse probability of treatment weighting was applied to estimate the risk of incident ADs following COVID-19. COVID-19 vaccinated population was compared against COVID-19 unvaccinated population to examine the protective effect of COVID-19 vaccination on new ADs.

Findings: The study included 1,028,721 COVID-19 and 3,168,467 non-COVID individuals. Compared with non-COVID controls, patients with COVID-19 presented an increased risk of developing pernicious anaemia [adjusted Hazard Ratio (aHR): 1.72; 95% Confidence Interval (CI): 1.12–2.64]; spondyloarthritis [aHR: 1.32 (95% CI: 1.03–1.69)]; rheumatoid arthritis [aHR: 1.29 (95% CI: 1.09–1.54)]; other autoimmune arthritis [aHR: 1.43 (95% CI: 1.33–1.54)]; psoriasis [aHR: 1.42 (95% CI: 1.13–1.78)]; pemphigoid [aHR: 2.39 (95% CI: 1.83–3.11)]; Graves’ disease [aHR: 1.30 (95% CI: 1.10–1.54)]; anti-phospholipid antibody syndrome [aHR: 2.12 (95% CI: 1.47–3.05)]; immune mediated thrombocytopenia [aHR: 2.1 (95% CI: 1.82–2.43)]; multiple sclerosis [aHR: 2.66 (95% CI: 1.17–6.05)]; vasculitis [aHR: 1.46 (95% CI: 1.04–2.04)]. Among COVID-19 patients, completion of two doses of COVID-19 vaccine shows a decreased risk of pemphigoid, Graves’ disease, anti-phospholipid antibody syndrome, immune-mediated thrombocytopenia, systemic lupus erythematosus and other autoimmune arthritis.

Interpretation: Our findings suggested that COVID-19 is associated with an increased risk of developing various ADs and the risk could be attenuated by COVID-19 vaccination. Future studies investigating pathology and mechanisms would be valuable to interpreting our findings.

Source: Kuan Peng, Xue Li, Deliang Yang, Shirley C.W. Chan, Jiayi Zhou, Eric Y.F. Wan, et al. Risk of autoimmune diseases following COVID-19 and the potential protective effect from vaccination: a population-based cohort study. The Lancet, VOLUME 63, 102154, SEPTEMBER 2023 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00331-0/fulltext (Full text)

Influence of Prior SARS-CoV-2 Infection on COVID-19 Severity: Evidence from the National COVID Cohort Collaborative

Abstract:

Background As SARS-CoV-2 has transitioned from a pandemic to endemic disease, the majority of new infections have been among previously infected individuals. To manage the risks and benefits of ongoing COVID-19 policies, it is important to understand whether prior infection modifies the severity of subsequent infections.

Methods We used data from first and second COVID-19 episodes in the National COVID Cohort Collaborative (N3C), a collection of health systems who provide de-identified electronic health records for research purposes. Our analysis was a sequential series of nested trial emulations. In the first of two analytic stages, we created a month-specific model of the probability of prior infection for each individual. In the second stage, we used an ordinal logistic regression with inverse probability weights calculated in the first stage to simulate a series of monthly trials comparing severity between the cohorts of first and second infections. In addition to cohort-wide effect estimates, we also conducted analyses among race/ethnicity, sex, and age subgroups.

Results From an initial cohort of 7,446,481 combined first and second infections, we identified a cohort of 2,227,484 infections, among which 7.6% were second infections. Ninety-four percent of patients with two recorded infections experienced mild disease for both. The overall odds ratio (OR) for more severe disease with prior infection was 1.06 (95% confidence interval [CI]: 1.03 – 1.10). Monthly point estimates of the OR ranged from 0.56 (95% CI: 0.37 – 0.84) in October 2020 to 1.64 (95% CI: 1.33 – 2.00) in February 2023. In most subgroups, the effect of prior infection was significant. In 8 out of 10 subgroups, the maximum monthly OR occurred after the minimum monthly OR, suggesting that protection has waned throughout the pandemic.

Conclusion Overall, prior infection was associated with a significant slightly elevated risk of severe disease. This effect varied month to month. As the pandemic proceeded, the effect of prior infection tended to evolve from generally protective during the pre-Omicron era to unprotective during the Omicron era. This points to the need for continued strategies to avert and minimize the harms of COVID-19, rather than relying upon immunity acquired through previous infection.

Question Does prior infection with SARS-CoV-2 affect the severity of subsequent COVID-19 episodes?

Findings We observed a mild protective effect of prior infection during the early and mid-stages of the pandemic that waned after the rise of the Omicron variants, ultimately resulting in loss of protection or a tendency toward more severe second infections.

Meaning Prior infection alone is likely not enough to avert the worst public health harms of endemic SARS-CoV-2. Interventions to avoid infection and reduce the severity of COVID-19 will still be important in the post-pandemic era.

Source: Nathaniel Hendrix, Hythem Sidky, David K. Sahner, The N3C Consortium. Influence of Prior SARS-CoV-2 Infection on COVID-19 Severity: Evidence from the National COVID Cohort Collaborative. medRxiv 2023.08.03.23293612; doi: https://doi.org/10.1101/2023.08.03.23293612 https://www.medrxiv.org/content/10.1101/2023.08.03.23293612v1.full-text (Full text)

Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study

Abstract:

A significant proportion of patients after SARS-CoV-2 infection suffer from long-lasting symptoms. Although many different symptoms are described, the majority of patients complains about neuropsychological symptoms. Additionally, a subgroup of patients fulfills diagnostic criteria for ME/CFS. We analyzed a registry of all patients presenting in the out-patients clinic at a German university center. For patients with more than one visit, changes in reported symptoms from first to second visit were analyzed.

A total of 1022 patients were included in the study, 411 of them had more than one visit. 95.5% of the patients reported a polysymptomatic disease. At the first visit 31.3% of the patients fulfilled ME/CFS criteria after a median time of 255 days post infection and and at the second visit after a median of 402 days, 19.4% still suffered from ME/CFS. Self-reported fatigue (83.7-72.7%) and concentration impairment (66.2-57.9%) decreased from first to second visit contrasting non-significant changes in the structured screening.

A significant proportion of SARS-CoV-2 survivors presenting with ongoing symptoms present with ME/CFS. Although the proportion of subjective reported symptoms and their severity reduce over time, a significant proportion of patients suffer from long-lasting symptoms necessitating new therapeutic concepts.

Source: Reuken PA, Besteher B, Finke K, Fischer A, Holl A, Katzer K, Lehmann-Pohl K, Lemhöfer C, Nowka M, Puta C, Walter M, Weißenborn C, Stallmach A. Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study. Eur Arch Psychiatry Clin Neurosci. 2023 Aug 16. doi: 10.1007/s00406-023-01661-3. Epub ahead of print. PMID: 37587244. https://link.springer.com/article/10.1007/s00406-023-01661-3 (Full text)

Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases?

Abstract:

It is now well established that the blood-clotting protein fibrinogen can polymerise into an anomalous form of fibrin that is amyloid in character; the resultant clots and microclots entrap many other molecules, stain with fluorogenic amyloid stains, are rather resistant to fibrinolysis, can block up microcapillaries, are implicated in a variety of diseases including Long COVID, and have been referred to as fibrinaloids. A necessary corollary of this anomalous polymerisation is the generation of novel epitopes in proteins that would normally be seen as ‘self’, and otherwise immunologically silent.

The precise conformation of the resulting fibrinaloid clots (that, as with prions and classical amyloid proteins, can adopt multiple, stable conformations) must depend on the existing small molecules and metal ions that the fibrinogen may (and is some cases is known to) have bound before polymerisation. Any such novel epitopes, however, are likely to lead to the generation of autoantibodies.

A convergent phenomenology, including distinct conformations and seeding of the anomalous form for initiation and propagation, is emerging to link knowledge in prions, prionoids, amyloids and now fibrinaloids. We here summarise the evidence for the above reasoning, which has substantial implications for our understanding of the genesis of autoimmunity (and the possible prevention thereof) based on the primary process of fibrinaloid formation.

Source: Kell DB, Pretorius E. Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases? Biochem J. 2023 Aug 16;480(15):1217-1240. doi: 10.1042/BCJ20230241. PMID: 37584410. https://portlandpress.com/biochemj/article/480/15/1217/233389/Are-fibrinaloid-microclots-a-cause-of-autoimmunity (Full text)

A Scoping Review of Pacing for Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Lessons Learned for the Long COVID Pandemic

Abstract:

Background: Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing is a prominent coping strategy for people with ME/CFS that involves regulating activity to avoid post exertional malaise (PEM), the worsening of symptoms after an activity. Until now, characteristics of pacing, and the effects on patients’ symptoms had not been systematically reviewed. This is problematic as the most common approach to pacing, pacing prescription, and the pooled efficacy of pacing was unknown. Collating evidence may help advise those suffering with similar symptoms, including long COVID, as practitioners would be better informed on methodological approaches to adopt, pacing implementation, and expected outcomes.

Objectives: In this scoping review of the literature, we aggregated type of, and outcomes of, pacing in people with ME/CFS. Eligibility criteria: Original investigations concerning pacing were considered in participants with ME/CFS. Sources of evidence: Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature.

Methods: A scoping review was conducted. Review selection and characterisation was performed by two independent reviewers using pretested forms.

Results: Authors reviewed 177 titles and abstracts, resulting in included 17 studies: three randomised control trials (RCTs); one uncontrolled trial; one interventional case series; one retrospective observational study; two prospective observational studies; four cross-sectional observational studies; and five cross-sectional analytical studies. Studies included variable designs, durations, and outcome measures. In terms of pacing administration, studies used educational sessions and diaries for activity monitoring. Eleven studies reported benefits of pacing, four studies reported no effect, and two studies reported a detrimental effect in comparison to the control group.

Conclusions: Highly variable study designs and outcome measures, allied to poor to fair methodological quality resulted in heterogenous findings and highlights the requirement for more research examining pacing. Looking to the long COVID pandemic, future studies should be RCTs utilising objectively quantified digitised pacing, over a longer duration of examination, using the core outcome set for patient reported outcome measures.

Source: Nilihan Sanal-Hayes, Marie Mclaughlin, Lawrence D D Hayes, Jacqueline Mair, Jane Ormerod, David Carless, Natalie Hilliard, Rachel Meach, Joanne Ingram, Nicholas Sculthorpe. A Scoping Review of Pacing for Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Lessons Learned for the Long COVID Pandemic. medRxiv 2023.08.10.23293935; doi: https://doi.org/10.1101/2023.08.10.23293935 https://www.medrxiv.org/content/10.1101/2023.08.10.23293935v1 (Full text available as PDF file)