Category: Overlapping Illnesses

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)

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/

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/

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/

Post-Acute COVID-19 Symptoms, a Potential Link with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A 6-Month Survey in a Mexican Cohort

Abstract:

The aim of this study was to describe the clinical evolution during 6 months of follow-up of adults recovered from COVID-19. We tried to determine how many met the definition of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A total of 130 patients (51.0 ± 14 years, 34.6% female) were enrolled. Symptoms were common, participants reported a median number of 9 (IQR 5-14) symptoms. Fatigue was the most common symptom (61/130; 46.9%). Patients with fatigue were older 53.9 ± 13.5 years compared with 48.5 ± 13.3 years in those without fatigue (p = 0.02) and had a longer length of hospital stay, 17 ± 14 days vs. 13 ± 10 days (p = 0.04). There was no difference in other comorbidities between patients with fatigue and those without it, and no association between COVID-19 severity and fatigue.

After multivariate adjustment of all baseline clinical features, only age 40 to 50 years old was positively associated with fatigue, OR 2.5 (95% CI 1.05-6.05) p = 0.03. In our survey, only 17 (13%) patients met the Institute of Medicine’s criteria for “systemic exertion intolerance disease,” the new name of ME/CFS. In conclusion, in some patients, the features of post-acute COVID-19 syndrome overlap with the clinical features of ME/CFS.

Source: González-Hermosillo JA, Martínez-López JP, Carrillo-Lampón SA, Ruiz-Ojeda D, Herrera-Ramírez S, Amezcua-Guerra LM, Martínez-Alvarado MDR. Post-Acute COVID-19 Symptoms, a Potential Link with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A 6-Month Survey in a Mexican Cohort. Brain Sci. 2021 Jun 8;11(6):760. doi: 10.3390/brainsci11060760. PMID: 34201087. https://pubmed.ncbi.nlm.nih.gov/34201087/

Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known?

Abstract:

Post-Acute COVID-19 Syndrome (PACS) is defined by persistent symptoms >3-4 weeks after onset of COVID-19. The mechanism of these persistent symptoms is distinct from acute COVID-19 although not completely understood despite the high incidence of PACS. Cardiovascular symptoms such as chest pain and palpitations commonly occur in PACS, but the underlying cause of symptoms is infrequently known. While autopsy studies have shown that the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rarely causes direct myocardial injury, several syndromes such as myocarditis, pericarditis, and Postural Orthostatic Tachycardia Syndrome have been implicated in PACS. Additionally, patients hospitalized with acute COVID-19 who display biomarker evidence of myocardial injury may have underlying coronary artery disease revealed by the physiological stress of SARS-CoV-2 infection and may benefit from medical optimization. We review what is known about PACS and the cardiovascular system and propose a framework for evaluation and management of related symptoms.

Source: Dixit NM, Churchill A, Nsair A, Hsu JJ. Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known? Am Heart J Plus. 2021 May;5:100025. doi: 10.1016/j.ahjo.2021.100025. Epub 2021 Jun 24. PMID: 34192289; PMCID: PMC8223036. https://pubmed.ncbi.nlm.nih.gov/34192289/

Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause chronic and acute disease. Postacute sequelae of SARS-CoV-2 infection (PASC) include injury to the lungs, heart, kidneys, and brain that may produce a variety of symptoms. PASC also includes a post-coronavirus disease 2019 (COVID-19) syndrome (‘long COVID’) with features that can follow other acute infectious diseases and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Here we summarize what is known about the pathogenesis of ME/CFS and of ‘acute’ COVID-19, and we speculate that the pathogenesis of post-COVID-19 syndrome in some people may be similar to that of ME/CFS. We propose molecular mechanisms that might explain the fatigue and related symptoms in both illnesses, and we suggest a research agenda for both ME/CFS and post-COVID-19 syndrome.

Source: Komaroff AL, Lipkin WI. Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome. Trends Mol Med. 2021 Jun 7:S1471-4914(21)00134-9. doi: 10.1016/j.molmed.2021.06.002. Epub ahead of print. PMID: 34175230. https://pubmed.ncbi.nlm.nih.gov/34175230/

Physical and Mental Fatigue in Subjects Recovered from COVID-19 Infection: A Case–Control Study

Abstract:

Purpose: Much effort has been directed toward studying COVID-19 symptoms; however, the post–COVID-19 phase remains mysterious. The aim of this work was to conduct a clinical and neurophysiological evaluation of physical and mental fatigue in COVID-19 long-haulers and to study whether markers of COVID-19 severity are able to predict the likelihood of developing postinfectious fatigue syndrome (PIFS) in such patients.

Patients and Methods: This case–control study was conducted on 46 COVID-19 long-haulers who met the criteria for PIFS and 46 recovered COVID-19 subjects without any residuals. Clinical assessment of fatigue was done using a fatigue questionnaire. Repetitive nerve stimulation and single-fiber electromyography were done after excluding neuropathy and myopathy.

Results: The median value for physical fatigue was 4 (IQR 2– 7), while that for mental fatigue was 2 (IQR 0– 3). Each day’s increase in the period of COVID-19 illness increased the odds of PIFS in COVID-19 long-haulers 1.104-fold, and each unit increase in ferritin increased the odds of PIFS 1.006-fold. A significant decrement in at least one muscle was observed in 50% of patients. Patients with PIFS had significantly higher mean consecutive difference (MCD) in the extensor digitorum communis than the control group. There were statistically significant positive correlations between MCD values and physical, mental, and total fatigue scores.

Conclusion: Higher ferritin levels and prolonged COVID-19 infection were independent predictors of PIFS in COVID-19 long-haulers. There was electrophysiological evidence of abnormalities in the peripheral portion of the motor unit in COVID-19 long-haulers with PIFS.

Source: Elanwar R, Hussein M, Magdy R, Eid RA, Yassien A, Abdelsattar AS, Alsharaway LA, Fathy W, Hassan A, Kamal YS. Physical and Mental Fatigue in Subjects Recovered from COVID-19 Infection: A Case–Control Study. Neuropsychiatr Dis Treat. 2021;17:2063-2071 https://doi.org/10.2147/NDT.S317027 https://www.dovepress.com/physical-and-mental-fatigue-in-subjects-recovered-from-covid-19-infect-peer-reviewed-fulltext-article-NDT (Full text)

Migraine Is More Than Just Headache: Is the Link to Chronic Fatigue and Mood Disorders Simply Due to Shared Biological Systems?

Abstract:

Migraine is a symptomatically heterogeneous condition, of which headache is just one manifestation. Migraine is a disorder of altered sensory thresholding, with hypersensitivity among sufferers to sensory input. Advances in functional neuroimaging have highlighted that several brain areas are involved even prior to pain onset. Clinically, patients can experience symptoms hours to days prior to migraine pain, which can warn of impending headache. These symptoms can include mood and cognitive change, fatigue, and neck discomfort. Some epidemiological studies have suggested that migraine is associated in a bidirectional fashion with other disorders, such as mood disorders and chronic fatigue, as well as with other pain conditions such as fibromyalgia. This review will focus on the literature surrounding alterations in fatigue, mood, and cognition in particular, in association with migraine, and the suggested links to disorders such as chronic fatigue syndrome and depression.

We hypothesize that migraine should be considered a neural disorder of brain function, in which alterations in aminergic networks integrating the limbic system with the sensory and homeostatic systems occur early and persist after headache resolution and perhaps interictally. The associations with some of these other disorders may allude to the inherent sensory sensitivity of the migraine brain and shared neurobiology and neurotransmitter systems rather than true co-morbidity.

Source: Karsan N, Goadsby PJ. Migraine Is More Than Just Headache: Is the Link to Chronic Fatigue and Mood Disorders Simply Due to Shared Biological Systems? Front Hum Neurosci. 2021 Jun 3;15:646692. doi: 10.3389/fnhum.2021.646692. PMID: 34149377; PMCID: PMC8209296. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209296/ (Full text)

Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis?

Abstract:

As millions of patients have been infected by SARS-CoV-2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called “post-COVID syndrome” or “long-COVID” [1]. There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups.

Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.

Source: Bornstein SR, Voit-Bak K, Donate T, Rodionov RN, Gainetdinov RR, Tselmin S, Kanczkowski W, Müller GM, Achleitner M, Wang J, Licinio J, Bauer M, Young AH, Thuret S, Bechmann N, Straube R. Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis? Mol Psychiatry. 2021 Jun 17. doi: 10.1038/s41380-021-01148-4. Epub ahead of print. PMID: 34140635. https://pubmed.ncbi.nlm.nih.gov/34140635/