Tag: 2022

Post-Acute Sequelae of SARS-CoV-2 infection (PASC) – Lessons Learned From a Coordinated Health Systems Response

Abstract:

Objective: To outline a consensus designed process for triaging and managing patients with Post COVID syndrome at the Mayo Clinic.

Patients and methods: We convened a central multidisciplinary team including members from General Internal Medicine, Occupational Medicine, Physical Medicine & Rehabilitation, Psychology, Allergy and Immunology, Infectious Disease, Pulmonology, Neurology, Cardiology, Pediatrics and Otorhinolaryngology, with membership from all the Mayo Clinic sites in Arizona, Florida, Iowa, Minnesota, and Wisconsin.

Results: Consensus recommendations were made for best practice guidelines on triaging and managing patients. Several innovations were agreed upon including a PASC specific appointment request form for data collection, a bio-registry, a bio-repository, and a PASC specific treatment program.

Conclusions: Given that each clinical site had individual clinical practices, these recommendations were implemented using different models, which may provide broad applicability to other clinical settings.

Source: Ganesh R, Vanichkachorn GS, Munipalli B, Hanson SN, Abu Dabrh AM, Croghan IT, Dawson NL, Hurt RT. Post-Acute Sequelae of SARS-CoV-2 infection (PASC) – Lessons Learned From a Coordinated Health Systems Response. Mayo Clin Proc Innov Qual Outcomes. 2022 Jun 1. doi: 10.1016/j.mayocpiqo.2022.05.007. Epub ahead of print. PMID: 35669936; PMCID: PMC9156955. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156955/ (Full text)

AMMES WANTS YOU!

AMMES needs volunteers! AMMES is actively recruiting volunteers to help AMMES grow and prosper.

Fundraising coordinator –  should have experience fundraising for non-profits (We usually run fundraisers once or twice a year.)

IT Person – keeps website  up to date – experience with WordPress a must! (Time commitment: 1 hour a month)

Patient Advocate – ideally someone with Social Work background. Occasionally we get requests from patients who need help finding housing programs or other types of government assistance. (Time commitment:1 hour a month)

We are also looking for board members. Board members do not need to have ME/CFS, but must demonstrate knowledge about the disease and share a commitment to serve the community. Because we are a nationally-focused nonprofit, board members must be US citizens or residents.

Read more about what we do on our website HERE.

Please contact us at admin@ammes.org if you are interested in being a part of this wonderful organization.

AMMES is a 501(c)(3) national nonprofit. Your donations are tax deductible.

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Long COVID in children and young people: uncertainty and contradictions

AN EVOLVING PICTURE:

‘Long COVID’ describes both ongoing symptomatic COVID-19 (5–12 weeks after onset) and post-COVID-19 syndrome (≥12 weeks after onset).1 Long COVID is also a patient-preferred term2 so will be used throughout this editorial to describe symptoms lasting ≥4 weeks after an acute episode of COVID-19.

As the phenomenon of long COVID emerged and came to be recognised, including with the publication of the guideline by the National Institute for Health and Care Excellence, Scottish Intercollegiate Guideline Network, and the Royal College of General Practitioners,1 there was still limited evidence about whether children and young people could suffer with prolonged symptoms following an acute COVID-19 infection. The general opinion was still that SARS-CoV-2 was a mild infection in the young.3

Narratives emerged, however, from parents describing prolonged problems in their children, following an acute COVID- 19 infection,4 and this was borne out in the scientific literature.5

Jasmin (young person with long COVID) describes her situation: ‘I’m Jasmin. I am 11 years old and I have suffered from long COVID for over a year. I was perfectly fit and happy, and enjoyed doing sports. Having long COVID has really changed my life in many different ways. I can’t go to school much anymore, I don’t see my friends, I can’t exercise, I can’t even walk far without a wheelchair. I think that a lot of people don’t understand what the illness is and how difficult it is for me.’

The prevalence of long COVID in children is disputed. Evidence from the CLoCK study,6 which recruited a cohort of 11–17- year- olds from the general UK population between January and March 2021, gives a broad estimate. The study reported 66.5% of children had symptoms 3 months after a positive polymerase chain reaction (PCR) test, compared with 53.3% who had a negative test; 30.3% versus 16.2% had ≥3 symptoms at 3 months. The big limitation of this study was the response rate of only 13.4%. The researchers say that if this 13.4% is representative of all 11–17 year olds who have tested positive for COVID-19, over 32 000 (one in seven) young people throughout England would still have ≥3 physical symptoms 3 months later. However, if only teenagers who responded to the survey had any persisting problems and those who chose not to respond had completely recovered, this would mean a best-case scenario of 4000 cases of long COVID in children and young people.

The Office for National Statistics prevalence estimates indicate that 149 000 children and young people (aged 5–16 years) had symptoms lasting for ≥4 weeks after infection, 31 000 of whom have had symptoms for over a year.7 The impact of the Delta and Omicron waves on these figures is yet to be determined.

Read the rest of this article HERE.

Source: Carolyn A Chew-Graham, Tracy A Briggs and Binita Kane. Long COVID in children and young people: uncertainty and contradictions. British Journal of General Practice 2022; 72 (719): 253-254. DOI: https://doi.org/10.3399/bjgp22X719501  https://bjgp.org/content/72/719/253 (Full text)

Cytokine Hub Classification of PASC, ME-CFS and other PASC-like Conditions

Abstract:

Background: Post-acute sequelae of COVID-19 (PASC) is a growing healthcare and economic concern affecting as many as 10%-30% of those infected with COVID-19. Though the symptoms have been well-documented, they significantly overlap with other common chronic inflammatory conditions which could confound treatment and therapeutic trials.

Methods: A total of 236 patients including 64 with post-acute sequelae of COVID-19 (PASC), 50 with myalgic encephalomyelitis-chronic fatigue syndrome (ME-CFS), 29 with post-treatment Lyme disease (PTLD), and 42 post-vaccine individuals with PASC-like symptoms (POVIP) were enrolled in the study. We performed a 14-plex cytokine/chemokine panel previously described to generate raw data that was normalized and run in a decision tree model using a Classification and Regression Tree (CART) algorithm. The algorithm was used to classify these conditions in distinct groups despite their similar symptoms.

Results: PASC, ME-CSF, POVIP, and Acute COVID-19 disease categories were able to be classified by our cytokine hub based CART algorithm with an average F1 score of 0.61 and high specificity (94%).

Conclusions: Proper classification of these inflammatory conditions with very similar symptoms is critical for proper diagnosis and treatment.

Source: Bruce K. Patterson, Jose Guevara-Coto, Edgar B. Francisco et al. Cytokine Hub Classification of PASC, ME-CFS and other PASC-like Conditions, 27 April 2022, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-1598634/v1]  https://www.researchsquare.com/article/rs-1598634/v1 (Full text)

The Role of Kynurenine Pathway and NAD + Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, complex, and highly debilitating long-term illness. People with ME/CFS are typically unable to carry out their routine activities. Key hallmarks of the disease are neurological and gastrointestinal impairments accompanied by pervasive malaise that is exacerbated after physical and/or mental activity. Currently, there is no validated cure of biomarker signature for this illness. Impaired tryptophan (TRYP) metabolism is thought to play significant role in the pathobiology of ME/CFS.

TRYP is an important precursor for serotonin and the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+). TRYP has been associated with the development of some parts of the brain responsible for behavioural functions. The main catabolic route for TRYP is the kynurenine pathway (KP). The KP produces NAD+ and several neuroactive metabolites with neuroprotective (i.e., kynurenic acid (KYNA)) and neurotoxic (i.e., quinolinic acid (QUIN)) activities. Hyperactivation of the KP, whether compensatory or a driving mechanism of degeneration can limit the availability of NAD+ and exacerbate the symptoms of ME/CFS.

This review discusses the potential association of altered KP metabolism in ME/CFS. The review also evaluates the role of the patient’s gut microbiota on TRYP availability and KP activation. We propose that strategies aimed at raising the levels of NAD+ (e.g., using nicotinamide mononucleotide and nicotinamide riboside) may be a promising intervention to overcome symptoms of fatigue and to improve the quality of life in patients with ME/CFS. Future clinical trials should further assess the potential benefits of NAD+ supplements for reducing some of the clinical features of ME/CFS.

Source: Dehhaghi M, Panahi HKS, Kavyani B, Heng B, Tan V, Braidy N, Guillemin GJ. The Role of Kynurenine Pathway and NAD+ Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Aging Dis. 2022 Jun 1;13(3):698-711. doi: 10.14336/AD.2021.0824. PMID: 35656104; PMCID: PMC9116917. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116917/ (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/

Systemic exertion intolerance disease associated to neuroendocrine dysfunction and cortical atrophy: a case report

Abstract:

Background: Scarce evidence about the organic and functional abnormalities of systemic exertion intolerance disease (SEID) is found in literature and the pathophysiology is still unclear.

Methods: Following the CARE Guidelines, this case report describes a patient with a 5-year history of nonspecific symptoms, lately recognized as SEID.

Results: Low serum thyroid- and adrenocorticotropic stimulating hormone levels, and 24-h urinary cortisol excretion almost twice the upper limit were detected. Computed tomography scan found significant cortical atrophy. Low-dose modafinil improved the clinical outcome, added to nonpharmacologic approach.

Conclusion: To ascertain an accurate SEID diagnosis and treatment are a challenge in daily clinical practice, that must be engaged based in clear methods and good practice recommendations. Thus, family practitioners should be aware of this diagnosis.

Source: López-Amador N. Systemic exertion intolerance disease associated to neuroendocrine dysfunction and cortical atrophy: a case report. Fam Pract. 2022 May 28:cmac060. doi: 10.1093/fampra/cmac060. Epub ahead of print. PMID: 35640045. https://pubmed.ncbi.nlm.nih.gov/35640045/

Recommendation for standardized medical care for children and adolescents with long COVID

Abstract:

in English, German

This current consensus paper for long COVID complements the existing AWMF S1 guidelines for long COVID with a detailed overview on the various clinical aspects of long COVID in children and adolescents. Members of 19 different pediatric societies of the DGKJ convent and collaborating societies together provide expert-based recommendations for the clinical management of long COVID based on the currently available but limited academic evidence for long COVID in children and adolescents. It contains screening questions for long COVID and suggestions for a structured, standardized pediatric medical history and diagnostic evaluation for patients with suspected long COVID. A time and resource-saving questionnaire, which takes the clinical complexity of long COVID into account, is offered via the DGKJ and DGPI websites as well as additional questionnaires suggested for an advanced screening of specific neurocognitive and/or psychiatric symptoms including post-exertional malaise (PEM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). According to the individual medical history as well as clinical signs and symptoms a step by step diagnostic procedure and a multidisciplinary therapeutic approach are recommended.

Source: Töpfner N; Deutsche Gesellschaft für Pädiatrische Infektiologie e. V. (DGPI), Alberer M, Ankermann T; Gesellschaft für Pädiatrische Pneumologie e. V. (GPP), Bender S; Deutsche Gesellschaft für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie e. V. (DGKJP), Berner R, de Laffolie J; Gesellschaft für Pädiatrische Gastroenterologie und Ernährung e. V. (GPGE), Dingemann J; Deutsche Gesellschaft für Kinderchirurgie e. V. (DGKCH), Heinicke D; Bündnis Kinder- und Jugendreha e. V. (BKJR), Haas JP; Gesellschaft für Kinder- und Jugendrheumatologie (GKJR), Hufnagel M, Hummel T; Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V. (DGHNO-KHC), Huppertz HI; Deutsche Akademie für Kinder- und Jugendmedizin (DAKJ), Knuf M, Kobbe R, Lücke T; Gesellschaft für Neuropädiatrie e. V. (GNP), Riedel J; Deutsche Gesellschaft für Sozialpädiatrie und Jugendmedizin (DGSPJ), Rosenecker J; Deutsche Gesellschaft für Pädiatrische Rehabilitation und Prävention e. V. (DGpRP), Wölfle J; Deutsche Gesellschaft für Kinderendokrinologie und -diabetologie e. V. (DGKED), Schneider B; Deutsche Gesellschaft für Schlafforschung und Schlafmedizin e. V. (DGSM), Schneider D; Deutsche Gesellschaft für Kinder- und Jugendmedizin e. V. (DGKJ), Schriever V; Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V. (DGHNO-KHC), Schroeder A; Gesellschaft für Neuropsychologie (GNP), Stojanov S, Tenenbaum T, Trapp S; Berufsverband der Kinder- und Jugendärzte e. V. (BVKJ), Vilser D; Deutsche Gesellschaft für Pädiatrische Kardiologie und Angeborene Herzfehler e. V. (DGPK), Brinkmann F, Behrends U. Einheitliche Basisversorgung von Kindern und Jugendlichen mit Long COVID: Stellungnahme einer multidisziplinären Arbeitsgruppe der DGKJ-Konvent-Gesellschaften (Stand: Februar 2022) [Recommendation for standardized medical care for children and adolescents with long COVID]. Monatsschr Kinderheilkd. 2022 May 25;170(6):1-9. German. doi: 10.1007/s00112-021-01408-1. Epub ahead of print. PMID: 35637934; PMCID: PMC9131710. https://pubmed.ncbi.nlm.nih.gov/35637934/ (Full article available in German)

Association of Congenital and Acquired Cardiovascular Conditions With COVID-19 Severity Among Pediatric Patients in the US

Abstract:

Importance: Identifying the associations between severe COVID-19 and individual cardiovascular conditions in pediatric patients may inform treatment.

Objective: To assess the association between previous or preexisting cardiovascular conditions and severity of COVID-19 in pediatric patients.

Design, setting, and participants: This retrospective cohort study used data from a large, multicenter, electronic health records database in the US. The cohort included patients aged 2 months to 17 years with a laboratory-confirmed diagnosis of COVID-19 or a diagnosis code indicating infection or exposure to SARS-CoV-2 at 85 health systems between March 1, 2020, and January 31, 2021.

Exposures: Diagnoses for 26 cardiovascular conditions between January 1, 2015, and December 31, 2019 (before infection with SARS-CoV-2).

Main outcomes and measures: The main outcome was severe COVID-19, defined as need for supplemental oxygen or in-hospital death. Mixed-effects, random intercept logistic regression modeling assessed the significance and magnitude of associations between 26 cardiovascular conditions and COVID-19 severity. Multiple comparison adjustment was performed using the Benjamini-Hochberg false discovery rate procedure.

Results: The study comprised 171 416 pediatric patients; the median age was 8 years (IQR, 2-14 years), and 50.28% were male. Of these patients, 17 065 (9.96%) had severe COVID-19. The random intercept model showed that the following cardiovascular conditions were associated with severe COVID-19: cardiac arrest (odds ratio [OR], 9.92; 95% CI, 6.93-14.20), cardiogenic shock (OR, 3.07; 95% CI, 1.90-4.96), heart surgery (OR, 3.04; 95% CI, 2.26-4.08), cardiopulmonary disease (OR, 1.91; 95% CI, 1.56-2.34), heart failure (OR, 1.82; 95% CI, 1.46-2.26), hypotension (OR, 1.57; 95% CI, 1.38-1.79), nontraumatic cerebral hemorrhage (OR, 1.54; 95% CI, 1.24-1.91), pericarditis (OR, 1.50; 95% CI, 1.17-1.94), simple biventricular defects (OR, 1.45; 95% CI, 1.29-1.62), venous embolism and thrombosis (OR, 1.39; 95% CI, 1.11-1.73), other hypertensive disorders (OR, 1.34; 95% CI, 1.09-1.63), complex biventricular defects (OR, 1.33; 95% CI, 1.14-1.54), and essential primary hypertension (OR, 1.22; 95% CI, 1.08-1.38). Furthermore, 194 of 258 patients (75.19%) with a history of cardiac arrest were younger than 12 years.

Conclusions and relevance: The findings suggest that some previous or preexisting cardiovascular conditions are associated with increased severity of COVID-19 among pediatric patients in the US and that morbidity may be increased among individuals children younger than 12 years with previous cardiac arrest.

Source: Ehwerhemuepha L, Roth B, Patel AK, Heutlinger O, Heffernan C, Arrieta AC, Sanger T, Cooper DM, Shahbaba B, Chang AC, Feaster W, Taraman S, Morizono H, Marano R. Association of Congenital and Acquired Cardiovascular Conditions With COVID-19 Severity Among Pediatric Patients in the US. JAMA Netw Open. 2022 May 2;5(5):e2211967. doi: 10.1001/jamanetworkopen.2022.11967. PMID: 35579899. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2792374 (Full text)

Persistent COVID-19 symptoms in a community study of 606,434 people in England

Abstract:

Long COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3-5 of the REACT-2 study (n = 508,707; September 2020 – February 2021), a representative community survey of adults in England, and replication data from round 6 (n = 97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms.

At 12 weeks in rounds 3-5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3-5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.

Source: Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, Ward H, Elliott P. Persistent COVID-19 symptoms in a community study of 606,434 people in England. Nat Commun. 2022 Apr 12;13(1):1957. doi: 10.1038/s41467-022-29521-z. PMID: 35413949; PMCID: PMC9005552. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005552/ (Full text)