Tag: 2021

Assessment of Prolonged Physiological and Behavioral Changes Associated With COVID-19 Infection

Introduction: Long-term COVID symptoms marked by autonomic dysfunction1 and cardiac damage2 following COVID-19 infection have been noted for up to 6 months after symptom onset,3 but to date have not been quantified, to our knowledge. Previous studies have found that wearable data can improve real-time detection of viral illness4 or discrimination of individuals with COVID-19 vs other viral infections.5 Wearable devices provide a way to continuously track an individual’s physiological and behavioral metrics beginning when healthy (ie, before infection), during the course of infection, and recovery back to baseline. In this cohort study, we aimed to examine the duration and variation of recovery among COVID-19–positive vs COVID-19–negative participants.
Methods: DETECT (Digital Engagement and Tracking for Early Control and Treatment) is a remote, app-based, longitudinal research study enrolling adult participants from all over the US and collecting their wearable data to better understand individual changes associated with viral illness, including COVID-19. All participants provided informed consent electronically. The protocol for this study was reviewed and approved by the Scripps Office for the Protection of Research Subjects. This study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

From March 25, 2020, through January 24, 2021, 37 146 participants were enrolled. This analysis focuses on 875 individuals who reported symptoms of an acute respiratory illness and underwent swab testing for COVID-19 and were found to be either positive (234 individuals) or negative (641 individuals) (eFigure in the Supplement).

The following calculation was used for resting heart rate (RHR): deviation from baseline = daily RHR − baseline RHR mean. Individuals with COVID-19 were also grouped by their mean RHR deviation from baseline 28 to 56 days after symptom onset (<1, 1-5, or >5 beats per minute).

Data analysis was conducted in SAS statistical software version 9.4 (SAS Institute). Significance was set at P < .05. P values were calculated with 1-way ANOVA (for mean age) or χ2 tests. Additional details about our methods can be found in the eAppendix in the Supplement.

Results: For this analysis, our study population consisted of 234 COVID-19–positive individuals (mean [range] age, 45.3 [18-76] years; 164 women [70.9%]) and 641 COVID-19–negative symptomatic individuals (mean [range] age, 44.7 [19-75] years; 455 women [71.1%]). Individuals with COVID-19 took longer to return to their RHR (Figure, A and B), sleep (Figure, C and D), and activity (Figure, E and F) baselines compared with symptomatic individuals who were COVID-19 negative. This difference was most marked for RHR, with COVID-19–positive individuals initially experiencing a transient bradycardia followed by a prolonged relative tachycardia that did not return to baseline, on average, until 79 days after symptom onset. Step count and sleep quantity returned to baseline sooner than RHR at 32 and 24 days, respectively. During recovery, individuals with COVID-19 experienced different trajectories in the return of their RHR to their normal compared with COVID-19–negative individuals (Figure, B). A small subset of COVID-19–positive participants (32 participants [13.7%]) maintained an RHR more than 5 beats per minute greater than their baseline RHR that did not return to their normal for more than 133 days. During the acute phase of COVID-19, individuals in this group reported higher frequencies of cough (27 participants [84.4%] vs 57 participants [55.3%] in the <1 beat per minute group and 57 participants [57.6%] in the 1-5 beats per minute group), body ache (20 participants [62.5%] vs 42 participants [40.8%] in the <1 beat per minute group and 35 participants [35.4%] in the 1-5 beats per minute group), and shortness of breath (9 participants [28.1%] vs 9 participants [8.7%] in the <1 beat per minute group and 6 participants [6.1%] in the 1-5 beats per minute group) compared with the other groups (Table).
Discussion: To our knowledge, this is the first study to examine longer duration wearable sensor data. We found a prolonged physiological impact of COVID-19 infection, lasting approximately 2 to 3 months, on average, but with substantial intraindividual variability, which may reflect various levels of autonomic nervous system dysfunction or potentially ongoing inflammation. Transient bradycardia has been noted in a case study6 approximately 9 to 15 days after symptom onset, which was also seen in our population. Our data suggest that early symptoms and larger initial RHR response to COVID-19 infection may be associated with the physiological length of recovery from this virus.

Symptom data were collected only during the acute phase of infection, which limited our ability to compare long-term physiological and behavioral changes with long-term symptoms. In the future, with larger sample sizes and more comprehensive participant-reported outcomes, it will be possible to better understand factors associated with interindividualized variability in COVID-19 recovery.

Source: Radin JM, Quer G, Ramos E, et al. Assessment of Prolonged Physiological and Behavioral Changes Associated With COVID-19 Infection. JAMA Netw Open. 2021;4(7):e2115959. doi:10.1001/jamanetworkopen.2021.15959 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781687 (Full article)

Functional somatic syndromes and joint hypermobility: A systematic review and meta-analysis

Abstract:

Objective: There have been multiple reports of increased joint hypermobility (JH) in functional somatic syndromes (FSS). We sought to evaluate the evidence for an association.

Methods: A systematic search of the databases Medline and PsycINFO was conducted to identify all controlled studies from inception to February 2020 measuring the association of an FSS and JH. Records were identified and screened, and full-text articles assessed for eligibility by two independent authors. Meta-analysis was performed using random-effects modelling with the DerSimonian and Laird method.

Results: We found 220 studies initially, which yielded 11 studies for inclusion in the qualitative review and 10 in the quantitative analysis – 5 studies on fibromyalgia, 3 on chronic fatigue syndrome and 3 on functional gastrointestinal disorder. Nine of the 11 studies found increased rates of JH in FSS compared to controls, though most studies were fair to poor in quality. Meta-analysis showed a weighted summary effect odds ratio of 3.27 (95% CI: 1.83, 5.84; p < 0.001) of JH in FSS, suggesting greater odds of FSS in individuals with JH than in those without.

Conclusions: There is some evidence for an association between FSS and JH, but this is limited by the generally poor quality of studies and the narrow range of FSS studied. Better research is needed to confirm these findings as well as evaluate causation using prospective cohort studies.

Source: Chen G, Olver JS, Kanaan RA. Functional somatic syndromes and joint hypermobility: A systematic review and meta-analysis. J Psychosom Res. 2021 Jun 24;148:110556. doi: 10.1016/j.jpsychores.2021.110556. Epub ahead of print. PMID: 34237584. https://pubmed.ncbi.nlm.nih.gov/34237584/

Incidence of chronic Q fever and chronic fatigue syndrome: a six year follow-up of a large Q fever outbreak

Abstract:

Objectives: Acute Q fever is a generally self-limiting infection caused by the intracellular gram-negative bacterium Coxiella (C.) burnetii. For yet unknown reasons, a subset of patients develops chronic a infection. Furthermore, a Chronic Fatigue Syndrome (CFS) as post-acute Q fever sequelae has been described. We here investigated the rates of chronic Q fever and incidences of CFS six years after one of the largest European Q fever outbreaks that occurred in Jena, Germany in 2005 with 331 reported cases, who lived in proximity of a grazing sheep herd.

Methods: A total of 80 patients and 52 non-diseased household members from the former outbreak, were enrolled six years after the outbreak, blood samples collected and tested for a chronic Q fever were determined by seroprevalence using referenced immunofluorescence tests. Also, the presence of a CFS was assessed using the Short Form Symptom Inventory developed by the Centers (United States) for Disease Control and Prevention (SF CDC- SI).

Results: In 80 out of 132 (60.6%) study participants, previous Q fever infection was confirmed serologically, while no previous infection was detected in the 52 household members. None of the participants fulfilled the serological criteria of chronic Q fever. The evaluation of the CDC-SI did not show any differences between the two groups. Also, there was no difference between both groups regarding fulfillment of CFS-defining criteria (n = 3 (3.8 %; sero-positive) vs. n = 2 (3.8 %; sero-negative), p = 0.655).

Conclusion: Our six-year follow-up study of a large Q fever outbreak did not find evidence for chronic Q fever or post Q fever CFS. There was no asymptomatic sero-positivity in household members of Q fever patients.

Source: Ankert J, Frosinski J, Weis S, Boden K, Pletz MW. Incidence of chronic Q fever and chronic fatigue syndrome: a six year follow-up of a large Q fever outbreak. Transbound Emerg Dis. 2021 Jul 9. doi: 10.1111/tbed.14224. Epub ahead of print. PMID: 34240822. https://pubmed.ncbi.nlm.nih.gov/34240822/

Efficacy of Qigong Exercise for Treatment of Fatigue: A Systematic Review and Meta-Analysis

Abstract:

Objective: Several studies suggested that Qigong exercise (QE) can relieve fatigue in patients diagnosed with various diseases. Our review aimed to evaluate the efficacy of QE for alleviating fatigue.

Methods: A related literature search was performed in the PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang, and VIP data bases from inception to November 2020. Information on fatigue, malaise, tiredness, and Qigong research data was collected.

Results: Sixteen randomized controlled trials (RCTs) were reported in patients with cancer (n = 4), chronic fatigue syndrome (n = 2), and other diseases (n = 10). The QE groups showed significant improvements in total fatigue intensity [15 RCTs, p < 0.00001; standard mean difference (SMD) -0.69 (-0.95 to -0.44)]. The QE groups did not show significant improvement in quality of life [4 RCTs, p = 0.08; SMD 0.53 (-0.07 to 1.14)]. The statistically significant difference of the subgroup analyses (different primary diseases, QE types, and study quality) also remained unchanged.

Conclusion: The findings of this meta-analysis indicate that QE may be beneficial for improving fatigue in patients diagnosed with various diseases. Considering the limitations of the study, we draw a very cautious conclusion regarding the resulting estimate of the effect. Further studies are warranted to better understand the benefits of QE in primary medical care.

Source: Wang R, Huang X, Wu Y, Sun D. Efficacy of Qigong Exercise for Treatment of Fatigue: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2021 Jun 22;8:684058. doi: 10.3389/fmed.2021.684058. PMID: 34239889; PMCID: PMC8257957. https://pubmed.ncbi.nlm.nih.gov/34239889/

Causal attributions and perceived stigma for myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease with the hallmark symptom of post-exertional malaise. Evidence for physiological causes is converging, however, currently no diagnostic test or biomarker is available. People with ME/CFS experience stigmatization, including the perception that the disease is psychosomatic.

In a sample of 499 participants with self-diagnosed ME/CFS, we investigated perceived stigma as a pathway through which perceived others’ causal attributions relate to lower satisfaction with social roles and activities and functional status. Higher perceived attributions by others to controllable and unstable causes predicted lower health-related and social outcomes via higher perceived stigma.

Source: Froehlich L, Hattesohl DB, Cotler J, Jason LA, Scheibenbogen C, Behrends U. Causal attributions and perceived stigma for myalgic encephalomyelitis/chronic fatigue syndrome. J Health Psychol. 2021 Jul 9:13591053211027631. doi: 10.1177/13591053211027631. Epub ahead of print. PMID: 34240650. https://journals.sagepub.com/doi/10.1177/13591053211027631#  (Full text)

Post COVID syndrome: a new challenge for medicine

Abstract:

The huge concern raised by SARS-CoV2 pandemic about public health management and social impact is still under debate, particularly because COVID-19 may affect infected people much longer than expected from a typical air-borne viral disease. The scientific community is actually wondering about the etiopathogenesis and clinical development of this “post-COVID” complex symptomatology, very close to symptoms typically observed in chronic fatigue syndrome, so recently named as “post-acute sequelae of COVID-19 (PASC)”. This commentary tries to focus on the most recent news about this issue.

Source: Tirelli U, Taibi R, Chirumbolo S. Post COVID syndrome: a new challenge for medicine. Eur Rev Med Pharmacol Sci. 2021 Jun;25(12):4422-4425. doi: 10.26355/eurrev_202106_26154. PMID: 34227079. https://pubmed.ncbi.nlm.nih.gov/34227079/

The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-system disease whose etiological basis has not been established. Enteroviruses (EVs) as a cause of ME/CFS have sometimes been proposed, as they are known agents of acute respiratory and gastrointestinal infections that may persist in secondary infection sites, including the central nervous system, muscle, and heart. To date, the body of research that has investigated enterovirus infections in relation to ME/CFS supports an increased prevalence of chronic or persistent enteroviral infections in ME/CFS patient cohorts than in healthy individuals. Nevertheless, inconsistent results have fueled a decline in related studies over the past two decades.

This review covers the aspects of ME/CFS pathophysiology that are consistent with a chronic enterovirus infection and critically reviews methodologies and approaches used in past EV-related ME/CFS studies. We describe the prior sample types that were interrogated, the methods used and the limitations to the approaches that were chosen. We conclude that there is considerable evidence that prior outbreaks of ME/CFS were caused by one or more enterovirus groups. Furthermore, we find that the methods used in prior studies were inadequate to rule out the presence of chronic enteroviral infections in individuals with ME/CFS. Given the possibility that such infections could be contributing to morbidity and preventing recovery, further studies of appropriate biological samples with the latest molecular methods are urgently needed.

Source: O’Neal AJ, Hanson MR. The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review. Front Med (Lausanne). 2021 Jun 18;8:688486. doi: 10.3389/fmed.2021.688486. PMID: 34222292; PMCID: PMC8253308. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253308/  (Full text)

Subcortical brain segment volumes in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Aims: There is controversy about brain volumes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS) and Gulf War Illness (GWI). Subcortical regions were assessed because of significant differences in blood oxygenation level dependent signals in the midbrain between these diseases.

Materials and method: Magnetization-prepared rapid acquisition with gradient echo (MPRAGE) images from 3 Tesla structural magnetic resonance imaging scans from sedentary control (n = 34), CFS (n = 38) and GWI (n = 90) subjects were segmented in FreeSurfer. Segmented subcortical volumes were regressed against intracranial volume and age, then iteratively analyzed by multivariate general linear modeling with disease status, gender and demographics as independent co-variates.

Key findings: The optimal model for all subjects used disease status and gender as fixed factors with independent variables eliminated after iteration. Volumes of anterior and midanterior corpus callosum were significantly larger in GWI than CFS. Gender was a significant variable for many segment volumes, and so female and male subjects were analyzed separately. CFS females had smaller left putamen, right caudate and left cerebellum white matter than control women. CFS males had larger left hippocampus than GWI males. Orthostatic status and posttraumatic distress syndrome were not significant covariates.

Significance: CFS and GWI were appropriate “illness controls” for each other. The different patterns of adjusted segment volumes suggested that sexual dimorphisms contributed to pathological changes. Previous volumetric studies may need to be reevaluated to account for gender differences. The findings are framed by comparison to the spectrum of magnetic resonance imaging outcomes in the literature.

Source: Addiego FM, Zajur K, Knack S, Jamieson J, Rayhan RU, Baraniuk JN. Subcortical brain segment volumes in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Life Sci. 2021 Jun 29:119749. doi: 10.1016/j.lfs.2021.119749. Epub ahead of print. PMID: 34214570. https://pubmed.ncbi.nlm.nih.gov/34214570/

Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous, debilitating, and complex disease. Along with disabling fatigue, ME/CFS presents an array of other core symptoms, including autonomic nervous system (ANS) dysfunction, sustained inflammation, altered energy metabolism, and mitochondrial dysfunction. Here, we evaluated patients’ symptomatology and the mitochondrial metabolic parameters in peripheral blood mononuclear cells (PBMCs) and plasma from a clinically well-characterised cohort of six ME/CFS patients compared to age- and gender-matched controls.

We performed a comprehensive cellular assessment using bioenergetics (extracellular flux analysis) and protein profiles (quantitative mass spectrometry-based proteomics) together with self-reported symptom measures of fatigue, ANS dysfunction, and overall physical and mental well-being. This ME/CFS cohort presented with severe fatigue, which correlated with the severity of ANS dysfunction and overall physical well-being.

PBMCs from ME/CFS patients showed significantly lower mitochondrial coupling efficiency. They exhibited proteome alterations, including altered mitochondrial metabolism, centred on pyruvate dehydrogenase and coenzyme A metabolism, leading to a decreased capacity to provide adequate intracellular ATP levels. Overall, these results indicate that PBMCs from ME/CFS patients have a decreased ability to fulfill their cellular energy demands.

Source: Fernandez-Guerra P, Gonzalez-Ebsen AC, Boonen SE, Courraud J, Gregersen N, Mehlsen J, Palmfeldt J, Olsen RKJ, Brinth LS. Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study. Biomolecules. 2021 Jun 29;11(7):961. doi: 10.3390/biom11070961. PMID: 34209852. https://pubmed.ncbi.nlm.nih.gov/34209852/

Systematic Review of Mind-Body Interventions to Treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background and Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic condition distinguished by disabling fatigue associated with post-exertional malaise, as well as changes to sleep, autonomic functioning, and cognition. Mind-body interventions (MBIs) utilize the ongoing interaction between the mind and body to improve health and wellbeing. Purpose: To systematically review studies using MBIs for the treatment of ME/CFS symptoms.

Materials and Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane CENTRAL were searched (inception to September 2020). Interventional studies on adults diagnosed with ME/CFS, using one of the MBIs in comparison with any placebo, standard of care treatment or waitlist control, and measuring outcomes relevant to the signs and symptoms of ME/CFS and quality of life were assessed for inclusion. Characteristics and findings of the included studies were summarized using a descriptive approach.

Results: 12 out of 382 retrieved references were included. Seven studies were randomized controlled trials (RCTs) with one including three reports (1 RCT, 2 single-arms); others were single-arm trials. Interventions included mindfulness-based stress reduction, mindfulness-based cognitive therapy, relaxation, Qigong, cognitive-behavioral stress management, acceptance and commitment therapy and isometric yoga. The outcomes measured most often were fatigue severity, anxiety/depression, and quality of life. Fatigue severity and symptoms of anxiety/depression were improved in nine and eight studies respectively, and three studies found that MBIs improved quality of life.

Conclusions: Fatigue severity, anxiety/depression and physical and mental functioning were shown to be improved in patients receiving MBIs. However, small sample sizes, heterogeneous diagnostic criteria, and a high risk of bias may challenge this result. Further research using standardized outcomes would help advance the field.

Source: Khanpour Ardestani S, Karkhaneh M, Stein E, Punja S, Junqueira DR, Kuzmyn T, Pearson M, Smith L, Olson K, Vohra S. Systematic Review of Mind-Body Interventions to Treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Medicina (Kaunas). 2021 Jun 24;57(7):652. doi: 10.3390/medicina57070652. PMID: 34202826. https://pubmed.ncbi.nlm.nih.gov/34202826/