Post-COVID-19 syndrome: Something to think about

The disease caused by the new coronavirus detected in 2019 (COVID-19), which arose in the Asian continent and later spread worldwide, has generated more than 3.5 million deaths, in America, 1.6 million have been registered, and in Mexico, around 223,000 , in the latter, it is equivalent to 10% of the population that suffered from COVID-19.

With the above, we must take the next step and ask ourselves: do we have to worry about the 90% who survived the acute infection? The answer is yes. The symptoms caused by COVID-19 can continue more than 4 weeks after the onset of the disease and are known as a post-COVID-19 syndrome.

The syndrome has a persistent cough, dyspnea, chest pain, and fatigue, and it may be present in one-third of survivors regardless of the severity of the initial infection 1 . The cause has not yet been founded; however, we know that the transforming growth factor-beta is involved. This cytokine promotes cell repair through fibrosis, which may explain the persistence of the symptoms 2 . It can also present with neurological disorders characterized by post-traumatic stress syndrome, neuropathy, and critically ill myopathy, especially in patients who required invasive mechanical ventilation support in intensive care units and general care wards 3 .

Regarding treatment, there is nothing specific but general recommendations such as identifying the syndrome and documentation of the present symptoms, leaving as a cornerstone the follow-up of patients after hospital discharge without forgetting those who kept at home.

Who can follow up? It can be done by family or general practitioner, with interventions of a pulmonary rehabilitator, and last the pulmonologist and cardiologist if there is an exacerbation of the symptoms 4 . It should be noted that people who have post-COVID-19 syndrome are predisposed to develop depression, anxiety, and obsessive-compulsive disorder 5 . Therefore, the purposeful search and evaluation by psychology and psychiatry are essential.

Finally, the post-COVID-19 syndrome can be considered as a chronic disease, which generates the need to implement strategies that include continuing education for health personnel and, above all, the dissemination of information to the general public. It is probably not enough in the months to follow, but no strategy has better results than the one that does not start with a vision for the future since this will be a large percentage of the consultation in general for a long time.

Source: Moral OR. Post-COVID-19 syndrome: Something to think about. Cir Cir. 2021;89(6):848-849. English. doi: 10.24875/CIRU.21000510. PMID: 34851597. https://www.cirugiaycirujanos.com/frame_esp.php?id=593

Comparison of assessment scores for fatigue between multidimensional fatigue inventory (MFI-K) and modified chalder fatigue scale (mKCFQ)

Abstract:

Background: Because of the absence of biological parameters for fatigue, appropriate instruments for assessing the degree of fatigue are important in the diagnosis and management of people complaining of fatigue-like symptoms. This study statistically analyzed the fatigue scores from two typical questionnaire-based instruments: the Korean version of the Multidimensional Fatigue Inventory (MFI-K) and the modified Chalder Fatigue Scale (mKCFQ).

Methods: Seventy participants (males n = 40, females n = 30, median age 48 years old, range of 25-67) were grouped into three groups (‘mild’ = 20, ‘moderate’ = 42, and ‘severe’ = 8) according to self-reported fatigue levels using a 7-point Likert scale. The similarities and differences between two instrument-derived scores were analyzed using correlations (r) and multidimensional scaling (MDS).

Results: The total scores of the two assessments were significantly correlated (r = 75%, p < 0.001), as were the subscores (‘Total Physical fatigue’: r = 76%, p < 0.001, ‘Total Mental fatigue’: r = 56%, p < 0.001). Relative overestimation of the MFI-K (45.8 ± 11.3) compared to the mKCFQ (36.1 ± 16.2) was observed, which was especially prominent in the ‘mild’ group. The scores of the three groups were more easily distinguished by the mKCFQ than by the MFI-K. In terms of the five dimension scores, we found a higher correlation of the two assessments for ‘general fatigue’ (r = 79%, p < 0.001) and ‘physical fatigue’ (r = 66%, p < 0.001) than for the reductions in ‘motivation’ (r = 41%, p < 0.01) and ‘activity’ (r = 26%, p > 0.05).

Conclusions: Our results may indicate the usefulness of the two instruments, especially for the physical symptoms of fatigue (‘general’ and ‘physical’ fatigue). Furthermore, the MFI-K may be useful for conditions of moderate-to-severe fatigue, such as chronic fatigue syndrome, but the mKCFQ may be useful for all spectra of fatigue, including in subhealthy people.

Source: Lim EJ, Son CG. Comparison of assessment scores for fatigue between multidimensional fatigue inventory (MFI-K) and modified chalder fatigue scale (mKCFQ). J Transl Med. 2022 Jan 3;20(1):8. doi: 10.1186/s12967-021-03219-0. PMID: 34980164. https://pubmed.ncbi.nlm.nih.gov/34980164/

Brainstem Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multisystem medical condition with heterogeneous symptom expression. Currently, there is no effective cure or treatment for the standard care of patients. A variety of ME/CFS symptoms can be linked to the vital life functions of the brainstem, the lower extension of the brain best known as the hub relaying information back and forth between the cerebral cortex and various parts of the body.

Objective/Methods: Over the past decade, Magnetic Resonance Imaging (MRI) studies have emerged to understand ME/CFS with interesting findings, but there has lacked a synthesized evaluation of what has been found thus far regarding the involvement of the brainstem. We conducted this study to review and evaluate the recent MRI findings via a literature search of the MEDLINE database, from which 11 studies met the eligibility criteria.

Findings: Data showed that MRI studies frequently reported structural changes in the white and gray matter. Abnormalities of the functional connectivity within the brainstem and with other brain regions have also been found. The studies have suggested possible mechanisms including astrocyte dysfunction, cerebral perfusion impairment, impaired nerve conduction, and neuroinflammation involving the brainstem, which may at least partially explain a substantial portion of the ME/CFS symptoms and their heterogeneous presentations in individual patients.

Conclusions: This review draws research attention to the role of the brainstem in ME/CFS, helping enlighten future work to uncover the pathologies and mechanisms of this complex medical condition, for improved management and patient care.

Source: Nelson T, Zhang LX, Guo H, Nacul L, Song X. Brainstem Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings. Front Neurol. 2021 Dec 17;12:769511. doi: 10.3389/fneur.2021.769511. PMID: 34975729; PMCID: PMC8718708. https://www.frontiersin.org/articles/10.3389/fneur.2021.769511/full (Full text)

Submaximal Exercise Provokes Increased Activation of the Anterior Default Mode Network During the Resting State as a Biomarker of Postexertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by disabling fatigue and postexertional malaise. We developed a provocation paradigm with two submaximal bicycle exercise stress tests on consecutive days bracketed by magnetic resonance imaging, orthostatic intolerance, and symptom assessments before and after exercise in order to induce objective changes of exercise induced symptom exacerbation and cognitive dysfunction.

Method: Blood oxygenation level dependent (BOLD) scans were performed while at rest on the preexercise and postexercise days in 34 ME/CFS and 24 control subjects. Seed regions from the FSL data library with significant BOLD signals were nodes that clustered into networks using independent component analysis. Differences in signal amplitudes between groups on pre- and post-exercise days were determined by general linear model and ANOVA.

Results: The most striking exercise-induced effect in ME/CFS was the increased spontaneous activity in the medial prefrontal cortex that is the anterior node of the Default Mode Network (DMN). In contrast, this region had decreased activation for controls. Overall, controls had higher BOLD signals suggesting reduced global cerebral blood flow in ME/CFS.

Conclusion: The dynamic increase in activation of the anterior DMN node after exercise may be a biomarker of postexertional malaise and symptom exacerbation in CFS. The specificity of this postexertional finding in ME/CFS can now be assessed by comparison to post-COVID fatigue, Gulf War Illness, fibromyalgia, chronic idiopathic fatigue, and fatigue in systemic medical and psychiatric diseases.

Source: Rayhan RU, Baraniuk JN. Submaximal Exercise Provokes Increased Activation of the Anterior Default Mode Network During the Resting State as a Biomarker of Postexertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Neurosci. 2021 Dec 15;15:748426. doi: 10.3389/fnins.2021.748426. PMID: 34975370; PMCID: PMC8714840. https://www.frontiersin.org/articles/10.3389/fnins.2021.748426/full  (Full text)

Controlling the Burden of COVID-19 by Manipulating Host Metabolism

Abstract:

The coronavirus disease 2019 (COVID-19) pandemic caused by the coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause global health problems, but its impact would be minimized if the many effective vaccines that have been developed were available and in widespread use by all societies. This ideal situation is not occurring so other means of controlling COVID-19 are needed. In this short review, we make the case that manipulating host metabolic pathways could be a therapeutic approach worth exploring. The rationale for such an approach comes from the fact that viruses cause metabolic changes in cells they infect, effective host defense mechanisms against viruses requires the activity of one or more metabolic pathways, and that hosts with metabolic defects such as diabetes are more susceptible to severe consequences after COVID-19.

We describe the types of approaches that could be used to redirect various aspects of host metabolism and the success that some of these maneuvers have had at controlling other virus infections. Manipulating metabolic activities to control the outcome of COVID-19 has to date received minimal attention. Manipulating host metabolism will never replace vaccines to control COVID-19 but could be used as an adjunct therapy to the extent of ongoing infection.

Source: Miller L, Berber E, Sumbria D, Rouse BT. Controlling the Burden of COVID-19 by Manipulating Host Metabolism. Viral Immunol. 2021 Dec 13. doi: 10.1089/vim.2021.0150. Epub ahead of print. PMID: 34905407. https://pubmed.ncbi.nlm.nih.gov/34905407/

Compression Stockings Improve Cardiac Output and Cerebral Blood Flow during Tilt Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients: A Randomized Crossover Trial

Abstract:

Background and Objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Limited data are available to guide the treatment of OI in ME/CFS patients. We and others have previously described patient-reported subjective improvement in symptoms using compression stockings. We hypothesized that these subjective reports would be accompanied by objective hemodynamic improvements.
Materials and Methods: We performed a randomized crossover trial in 16 ME/CFS patients. Each underwent two 15-min head-up tilt table tests, one with and one without wearing knee-high compression stockings that provided 20–25 mm Hg compression. The order of the tests was randomized. We measured heart rate and blood pressure as well as cardiac output and cerebral blood flow (CBF) using extracranial Doppler of the internal carotid and vertebral arteries.
Results: There were no differences in supine measurements between the 2 baseline measurements. There were no differences in heart rate and blood pressure at either end-tilt testing period. Compared to the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 15 (4)% versus 27 (6)% (p < 0.0001), as was the mean percentage CBF reduction, 14 (4)% versus 25 (5)% (p < 0.0001).
Conclusion: In ME/CFS patients with orthostatic intolerance symptoms, cardiac output and CBF are significantly reduced during a tilt test. These abnormalities were present without demonstrable heart rate and blood pressure changes and were ameliorated by the use of compression stockings.
Source: van Campen CMC, Rowe PC, Visser FC. Compression Stockings Improve Cardiac Output and Cerebral Blood Flow during Tilt Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients: A Randomized Crossover Trial. Medicina. 2022; 58(1):51. https://doi.org/10.3390/medicina58010051 https://www.mdpi.com/1648-9144/58/1/51/htm  (Full text)

Polio Vaccination and Chronic Fatigue Syndrome

Abstract:

Background: Previous research has suggested that enteroviruses may be implicated in the development and persistence of Chronic Fatigue Syndrome (CFS). One method of investigating this topic has been to use a polio vaccination challenge, and a previous study showed that CFS patients had more shedding than healthy controls. There was no effect of the vaccination on the clinical condition or wellbeing of the CFS patients.

Methods: In the previous study, the control group were more likely to have had a recent booster vaccination. This was controlled in the present study, where 18 CFS patients were randomly assigned to vaccination or placebo conditions. Nine healthy volunteers were also given the polio vaccination.

Results: The results confirmed that vaccination had no negative effects on the CFS group. Although there was more virus shedding in the CFS polio group than in the control polio group, this difference was not significant.

Conclusion: This study confirms that polio vaccination is not contraindicated in CFS patients but could not confirm that they are more susceptible to enterovirus infection.

Source: Smith AP and Thomas M. Polio Vaccination and Chronic Fatigue Syndrome. Asian Journal of Research in Infectious Diseases 8(4): 43-49. https://orca.cardiff.ac.uk/146095/1/poliocfs.pdf (Full text)

Severity of COVID-19: Causes and Consequences — From Obesity to Chronic Fatigue Syndrome

Introduction:

In circumstances of COVID-19 epidemiological uncertainty, the causes and consequences of the disease remain important issues.

The aim of this study was to investigate obesity as a potential predisposition and chronic fatigue syndrome (CFS) as a possible consequence of COVID-19.

The study was conducted in two parts: a theoretical part, in which a literature review was performed, and an empirical part, in which COVID-19 patient survey data were analysed. To identify the main findings regarding the relationship between obesity and COVID-19, the literature review was focused on the investigation of systematic reviews and meta-analyses by three databases – Medline(via  PubMed),  Cochrane  COVID-19  Study  Register,  and  PROSPERO  (International prospective register of systematic reviews).

The patient survey was performed to investigate the relationship between obesity and severity of the disease, as well as the presence of CFS symptoms in COVID-19 patients in Latvia.

The main findings of the literature review showed that obesity increases the risk of hospitalisation, disease severity, clinical complications, poor outcomes, and mortality. The results of the patient survey showed that overweight and obesity were more critical factors for men (males) suffering with COVID-19 than for women (females) in Latvia.

The patient group with obesity caused almost half of all hospitalisations. The research data assumed that CFS  patients  were  not  a  high-risk  group  for  COVID-19,  but  COVID-19  caused  CFS-like symptoms in patients and potentially increased the number of undiagnosed patients.

In the context of further epidemiological uncertainty and the possibility of severe post-viral consequences, preventive measures are becoming increasingly important.

Source: Arāja, Diāna, Rovīte, Vita, Murovska, Modra, Terentjeva, Anna, Vaidere, Diāna, Vecvagare, Katrīne and Vīksna, Ludmila. Severity of COVID-19: Causes and Consequences — From Obesity to Chronic Fatigue Syndrome. Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences., vol.75, no.6, 2021, pp.411-416. https://sciendo.com/article/10.2478/prolas-2021-0061 (Full text)

What treatments work for anxiety and depression in children and adolescents with Chronic Fatigue Syndrome? An updated systematic review

Abstract:

Objectives: Children with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) experience a higher prevalence of depression and anxiety compared to age-matched controls. Our previous systematic reviews in 2015/16 found little evidence for effective treatment for children with CFS/ME with comorbid depression and/or anxiety. This review updates these findings.

Design: A systematic review. We searched Cochrane library, Medline, Embase and PsychINFO databases from 2015-2020. We combined the updated results with our previous reviews in a narrative synthesis.

Participants: Inclusion criteria: <18 years old; diagnosed with CFS/ME (using Centre for Disease Control, National Institute for Health and Care Excellence, or Oxford criteria); validated measures of depression and/or anxiety.

Interventions: Observational studies or randomised controlled trials.

Comparison: Any or none.

Outcomes: Studies with outcome measures of anxiety, depression, or fatigue.

Results: The updated review identified two studies. This brings the total number of paediatric CFS/ME studies with a measure of anxiety and/or depression since 1991 to 16. None of the studies specifically targeted depression, nor anxiety. One new study showed the Lightning Process (in addition to specialist care) was more effective at reducing depressive and anxiety symptoms compared to specialist care alone. Previous studies evaluated cognitive behavioural therapy (CBT); pharmacological interventions; and behavioural approaches. CBT-type interventions had most evidence for improving comorbid anxiety and/or depressive symptoms but varied in delivery and modality. Other interventions showed promise but studies were small and have not been replicated.

Conclusion: Very few paediatric CFS/ME intervention studies have been conducted. This review update does not significantly add to what is known from previous reviews. The evidence is of poor quality and insufficient to conclude which interventions are effective at treating comorbid anxiety and/or depression in paediatric CFS/ME.

Source:Clery, P., Royston , A., Driver, K., Bailey, J., Crawley, E. M., & Loades, M. (Accepted/In press). What treatments work for anxiety and depression in children and adolescents with Chronic Fatigue Syndrome? An updated systematic review. BMJ Open. https://research-information.bris.ac.uk/en/publications/what-treatments-work-for-anxiety-and-depression-in-children-and-a

Markers of Cardiac Autonomic Function During Consecutive Day Peak Exercise Tests in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have been shown to exhibit altered ventilatory characteristics on the second of two progressive maximal cardiopulmonary exercise tests (CPET) performed on consecutive days. However, maximal exercise can exacerbate symptoms for ME/CFS patients and cause significant post-exertional malaise. Assessment of heart rate (HR) parameters known to track post-exertional fatigue may represent more effective physiological markers of the condition and could potentially negate the need for maximal exercise testing.

Sixteen ME/CFS patients and 10 healthy controls underwent a sub-maximal warm-up followed by CPET on two consecutive days. Ventilation, ratings of perceived exertion, work rate (WR) and HR parameters were assessed throughout on both days. During sub-maximal warm-up, a time effect was identified for the ratio of low frequency to high frequency power of HR variability (p=0.02) during sub-maximal warm-up, and for HR at ventilatory threshold (p=0.03), with both being higher on Day Two of testing. A significant group (p<0.01) effect was identified for a lower post-exercise HR recovery (HRR) in ME/CFS patients. Receiver operator characteristic curve analysis of HRR revealed an area under the curve of 74.8% (p=0.02) on Day One of testing, with a HRR of 34.5bpm maximising sensitivity (63%) and specificity (40%) suggesting while HRR values are altered in ME/CFS patients, low sensitivity and specificity limit its potential usefulness as a biomarker of the condition.

Source: Nelson MJ, Buckley JD, Thomson RL, Bellenger CR, Davison K. Markers of Cardiac Autonomic Function During Consecutive Day Peak Exercise Tests in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Physiol. 2021 Dec 14;12:771899. doi: 10.3389/fphys.2021.771899. PMID: 34970156; PMCID: PMC8713453.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8713453/ (Full text)