Orthostatic Intolerance in Long-Haul COVID after SARS-CoV-2: A Case-Control Comparison with Post-EBV and Insidious-Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Background: As complaints of long-haul COVID patients are similar to those of ME/CFS patients and as orthostatic intolerance (OI) plays an important role in the COVID infection symptomatology, we compared 14 long-haul COVID patients with 14 ME/CFS patients with a post-viral Ebstein-Barr (EBV) onset and 14 ME/CFS patients with an insidious onset of the disease.
Methods: In all patients, OI analysis by history taking and OI assessed during a tilt test, as well as cerebral blood flow measurements by extracranial Doppler, and cardiac index measurements by suprasternal Doppler during the tilt test were obtained in all patients.
Results: Except for disease duration no differences were found in clinical characteristics. The prevalence of POTS was higher in the long-haul patients (100%) than in post-EBV (43%) and in insidious-onset (50%) patients (p = 0.0002). No differences between the three groups were present in the prevalence of OI, heart rate and blood pressure changes, changes in cerebral blood flow or in cardiac index during the tilt test.
Conclusion: OI symptomatology and objective abnormalities of OI (abnormal cerebral blood flow and cardiac index reduction during tilt testing) are comparable to those in ME/CFS patients. It indicates that long-haul COVID is essentially the same disease as ME/CFS.
Source: van Campen CMC, Visser FC. Orthostatic Intolerance in Long-Haul COVID after SARS-CoV-2: A Case-Control Comparison with Post-EBV and Insidious-Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Healthcare. 2022; 10(10):2058. https://doi.org/10.3390/healthcare10102058 (Full text)

Experiences of carers of youth, adult children and spouses with ME/CFS

Abstract:

Objectives: The debilitating nature of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) means that family members often take on a caring role. This study compared the experiences of people caring for three groups: youth, young adults, spouses.

Methods: An opportunistic sample of 36 carers completed an online survey of open-ended questions asking about their experiences. Thematic analysis was used to consider the three sets of responses separately and Thematic Comparison was used to identify points of connection and disconnection across the sets.

Results: The themes identified were very similar to those identified in past studies. Two super-ordinate themes were identified: “Lack of knowledge and understanding” and “Holistic Impact”. Though most sub-ordinate themes were evident across all three groups, important differences were found. The sub-ordinate themes “Caring Blindly”, “Emotional and physical health cost”, and “Impact on the whole family” were more evident amongst carers of youth while the theme “Worry for the future” was more evident from carers of young adults and spouses.

Discussion: Differences seemed to be related to both the time since diagnosis and the life stage. A longitudinal study would help to understand how carer experiences change over the life course of caring for someone with ME/CFS.

Source: Baken DM, Ross KJ, Hodges LD, Batten L. Experiences of carers of youth, adult children and spouses with ME/CFS. Chronic Illn. 2022 Oct 18:17423953221121696. doi: 10.1177/17423953221121696. Epub ahead of print. PMID: 36259126. https://pubmed.ncbi.nlm.nih.gov/36259126/

The Hindi Version of International Consensus Criteria: A Cross-cultural Adaptation and Validation Study for Myalgic Encephalomyelitis in Post-COVID Patients

Abstract: 

Context: Fatigue is the most prominent feature of long COVID. With the increasing burden of long COVID cases post-acute phase of illness after recurrent waves of the pandemic, understanding its pathophysiology is of paramount importance.

Such fatigue and post-viral illness could be associated with features of neuroimmune exhaustion and thus be a part of a larger syndrome such as myalgic encephalomyelitis (ME).

Identifying the proportion of patients having ME from those experiencing fatigue would bring us one step closer to understanding the pathophysiology. International consensus criteria (ICC) originally published in English (ICC-E) is a valid and reliable tool for identifying cases of ME. However, a validated Hindi version of ICC-E is not available.

Aims: To develop and validate an equivalent version of ICC-E in the native Hindi language (ICC-H) to suit Indian patients and health care workers even at peripheries and to make conducting large scales surveys more feasible.

Subjects and methods: Once permission from the ethics board was granted, guidelines given by MAPI Research Trust were followed and ICC-H was developed from ICC-E, in the following steps: (a) translation to Hindi, (b) back translation, (c) comparison between the translated and back-translated version performed by experts, and (d) pre-pilot test in the intended population. The ICC-H was applied to 53 bilingual individuals knowing both Hindi and English.

Statistical analysis used: The distribution of Hindi and English questionnaires was analyzed using the Chi-square test and Spearman’s correlation coefficient was used for correlation between answers of each question.

Results: The score of individual items and its global score was highly correlated with each other (p<0.001). The scores of individual components and global scores of ICC-H at baseline and original ICC-E after 4 weeks did not differ significantly.

Conclusion: This study shows that the ICC-H is a valid and reliable instrument for the assessment of ME. ICC-H can be used for Hindi speaking population for identifying cases of ME.

Source: Shah M, Kakar A, Gogia A. The Hindi Version of International Consensus Criteria: A Cross-cultural Adaptation and Validation Study for Myalgic Encephalomyelitis in Post-COVID Patients. J Assoc Physicians India 2022;70(10):59–63. https://www.japi.org/x2d4b494/the-hindi-version-of-international-consensus-criteria-a-cross-cultural-adaptation-and-validation-study-for-myalgic-encephalomyelitis-in-post-covid-patients  https://www.researchgate.net/profile/Atul-Gogia/publication/364241915_Postgraduate_Student_2_Vice_Chairman_and_Senior_Consultant_The_Hindi_Version_of_International_Consensus_Criteria_A_Cross-cultural_Adaptation_and_Validation_Study_for_Myalgic_Encephalomyelitis_in_Post-/links/63405e8aff870c55ce0adebf/Postgraduate-Student-2-Vice-Chairman-and-Senior-Consultant-The-Hindi-Version-of-International-Consensus-Criteria-A-Cross-cultural-Adaptation-and-Validation-Study-for-Myalgic-Encephalomyelitis-in-Post.pdf (Full text available as PDF file)

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

Preliminary Guidelines for the Clinical Evaluation and Management of Long COVID

Abstract:

Long-lasting coronavirus disease 2019 (COVID-19) symptoms beyond 12 weeks, the so-called ‘long COVID’ have been increasingly reported worldwide. Long COVID can be manifested in various forms, and there is an increasing demand for proper assessment and management. However, it is challenging when trying to determine the best-practice standards of care based on the current evidence because there is no internationally agreed clinical definition or clear treatment pathway. Therefore, the present guidelines have been drafted to provide advice on diagnosis and management based on the latest updated available evidence and the consensus of expert opinion. So far, no standard test and drug treatment can be strongly recommended for patients with long COVID because of a lack of evidence. The present guidelines provide advice based on 12 key questions, including appropriate interventions for long COVID that can be used in clinical practice. Continuous careful observation and studies related to long COVID are needed for the long-term impact of COVID-19 and proper management for long COVID to be determined.

Source: Kim Y, Kim SE, Kim T, Yun KW, Lee SH, Lee E, Seo JW, Jung YH, Chong YP. Preliminary Guidelines for the Clinical Evaluation and Management of Long COVID. Infect Chemother. 2022 Sep;54(3):566-597. doi: 10.3947/ic.2022.0141. PMID: 36196612; PMCID: PMC9533168. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533168/ (Full text)

Long COVID: defining the role of rheumatology in care and research

The global pandemic of COVID-19 has had an impact on the profession of rheumatology from many perspectives, including its effects on our patients with immune-mediated conditions and immunocompromised states, the disruption of care pathways, and beyond. There also are lingering questions about how the next phase of the pandemic will evolve, with the continuing emergence of new viral variants posing a continuing threat to our patients. Beyond these formidable challenges is the uncertainty around the long-term effects of COVID-19—referred to as long COVID among other names—in the rheumatology patient population, and the role of the rheumatology practitioner in care of and research among this population. Given the current global impact of long COVID and our early stages of understanding of the condition, we pose a series of questions for the rheumatology profession, to stimulate reflection and discussion around how to address long COVID.

Read the rest of this article HERE.

Source: Calabrese LH, Calabrese CM. Long COVID: defining the role of rheumatology in care and research. Lancet Rheumatol. 2022 Oct 3. doi: 10.1016/S2665-9913(22)00266-1. Epub ahead of print. PMID: 36211989; PMCID: PMC9529216. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529216/ (Full text)

Antioxidants and Long Covid

Abstract:

Long Covid has many symptoms that overlap with ME(myalgic encephalomyelitis)/CFS(chronic fatigue syndrome), FM(fibromyalgia), EBV(Epstein-Barr virus), CMV(cytomegalovirus), CIRS (chronic inflammatory response syndrome), MCAS(mast cell activation syndrome), POTS(postural orthostatic tachycardia syndrome), and post viral fatigue syndrome. They all portend a “long haul” with an antioxidant shortfall and elevated Ca:Mg. Oxidative stress is the root cause.

Linkage between TGF(transforming growth factor)-β, IFN(interferon)-γ, the RAS(renin angiotensin system), and the KKS(kallikrein kinin system) is discussed. Technical explanations for the renin aldosterone paradox in POTS, the betrayal of TGF-β, and the commonality of markers for the Warburg effect are offered. The etiology of the common Long Covid symptoms of post exertional malaise, fatigue, and brain fog as well as anosmia, hair loss, and GI symptoms is technically discussed. Ca:Mg is critical to the glutamate/GABA balance. The role of GABA and butyrates from the “good” intestinal bacteria in the gut-brain axis and its correlation with chronic fatigue diseases are explored.

The crosstalk between the ENS(enteric nervous system) and the ANS(autonomic nervous system) and the role of the vagus in both are emphasized. HRV(heart rate variability), the fifth vital sign, points to an expanded gut-brain-heart/lung axis. A suggested approach to all of these – Long Covid, chronic fatigue diseases, post viral fatigue syndrome, and general health – is presented.

Source: Chambers, P. Antioxidants and Long Covid. Preprints 2022, 2022100195 (doi: 10.20944/preprints202210.0195.v1).  https://www.preprints.org/manuscript/202210.0195/v1 (Full text available as PDF file)

Support amid uncertainty: Long COVID illness experiences and the role of online communities

Abstract:

Long COVID is characterized by persistent and debilitating long-term symptoms from COVID-19. Many persons with Long COVID began gathering in online communities during the early phases of the pandemic to share their illness experiences. This qualitative interview study explored the subjective experiences of 20 persons with Long COVID recruited from five online communities. Their understandings of illness and associated implications for social relationships with family and friends, healthcare professionals, and online community members were explored.

Three themes were identified from our analysis, including (1) complex and unpredictable illness experienced amid an evolving understanding of the pandemic; (2) frustration, dismissal, and gaslighting in healthcare interactions; and (3) validation and support from online communities. These findings highlight the significant uncertainty that persons with Long COVID navigated, the features of their often dismaying healthcare experiences, and the ways in which online communities aided them in understanding their illness.

Source: Russell D, Spence NJ, Chase JD, Schwartz T, Tumminello CM, Bouldin E. Support amid uncertainty: Long COVID illness experiences and the role of online communities. SSM Qual Res Health. 2022 Dec;2:100177. doi: 10.1016/j.ssmqr.2022.100177. Epub 2022 Oct 4. PMID: 36212783; PMCID: PMC9531408. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531408/ (Full text)

Acute COVID-19 Syndrome Predicts Severe Long COVID-19: An Observational Study

Abstract:

Introduction Tissue damage, chronic dysfunction, and symptoms that last more than 12 weeks are hallmarks of long-term chronic opportunistic viral infection (COVID-19), and the disease may have a permanent, relapsing/remitting, or gradually improving course. This study aimed to determine the risk factors of severe long COVID-19.

Methods In October 2021, primary care clinics enrolled consenting 18- to 89-year-olds to complete an online questionnaire on self-diagnosis, clinician diagnosis, testing, symptom presence, and duration of COVID-19. Long COVID-19 was identified if symptoms were beyond 12 weeks. Patients with long-lasting COVID-19 symptoms were assessed using multivariable regression to identify potential predictors of severe long COVID-19.

Results Of the 220 respondents, 108 (49%) patients were self- or clinician-diagnosed with COVID-19 or had a confirmed positive laboratory test result. Patients aged >45 years and with at least 15 COVID-19 symptoms were 5.55 and 6.02 times, respectively, more likely to acquire severe long COVID-19. Most patients with severe and moderate post-acute COVID-19 syndrome had no relevant comorbidities (p=0.0402; odds ratio [OR]=0.4; 95% confidence interval [CI]=0.18-0.98). Obesity was a significant predictor (p=0.0307; OR=6.2; 95% CI=1.1-33.2).

Conclusion The simultaneous presence of 15 or more COVID-19 symptoms, age >45 years, and obesity were related to a higher probability of severe long COVID-19.

Source: Menezes AS Jr, Botelho SM, Santos LR, Rezende AL. Acute COVID-19 Syndrome Predicts Severe Long COVID-19: An Observational Study. Cureus. 2022 Oct 2;14(10):e29826. doi: 10.7759/cureus.29826. PMID: 36204261; PMCID: PMC9527039.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527039/ (Full text)

Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics

Abstract:

Introduction: In patients with SARS-CoV-2, innate immunity is playing a central role, depicted by hyperinflammation and longer lasting inflammatory response. Reliable inflammatory markers that cover both acute and long-lasting COVID-19 monitoring are still lacking. Thus, we investigated one specific inflammatory marker involved as one key player of the immune system, kynurenine (Kyn), and its use for diagnosis/detection of the Long-/Post-COVID syndrome in comparison to currently used markers in both serum and saliva samples.

Material and methods: The study compromised in total 151 inpatients with a SARS-CoV-2 infection hospitalized between 03/2020 and 09/2021. The group NC (normal controls) included blood bank donors (n=302, 144f/158m, mean age 47.1 ± 18.3 years (range 18-75)). Two further groups were generated based on Group A (n=85, 27f/58m, mean age 63.1 ± 18.3 years (range 19-90), acute admission to the hospital) and Group B (n=66, 22f/44m, mean age 66.6 ± 17.6 years (range 17-90), admitted either for weaning or for rehabilitation period due to Long-COVID symptoms/syndrome). Plasma concentrations of Kyn, C-Reactive Protein (CRP) and interleukin-6 (IL-6) were measured on admission. In Group B we determined Kyn 4 weeks after the negative PCR-test. In a subset of patients (n=11) concentrations of Kyn and CRP were measured in sera and saliva two, three and four months after dismission. We identified 12 patients with Post-COVID symptoms >20 weeks with still significant elevated Kyn-levels.

Results: Mean values for NC used as reference were 2.79 ± 0.61 µM, range 1.2-4.1 µM. On admission, patients showed significantly higher concentrations of Kyn compared to NC (p-values < 0.001). Kyn significantly correlated with IL-6 peak-values (r=0.411; p-values <0.001) and CRP (r=0.488, p-values<0.001). Kyn values in Group B (Long-/Post-COVID) showed still significant higher values (8.77 ± 1.72 µM, range 5.5-16.6 µM), whereas CRP values in Group B were in the normal range.

Conclusion: Serum and saliva Kyn are reflecting the acute and long-term pathophysiology of the SARS-CoV-2 disease concerning the innate immune response and thus may serve a useful biomarker for diagnosis and monitoring both Long- and Post-COVID syndrome and its therapy.

Source: Bizjak DA, Stangl M, Börner N, Bösch F, Durner J, Drunin G, Buhl JL, Abendroth D. Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics. Front Immunol. 2022 Sep 23;13:1004545. doi: 10.3389/fimmu.2022.1004545. PMID: 36211365; PMCID: PMC9537769. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537769/ (Full text)