The incidence and characteristics of chronic pain and fatigue after 12 months later admitting with COVID-19; The Post- COVID 19 syndrome

Abstract:

Introduction: This study aimed to evaluate chronic pain and fatigue in patients 12 months after hospitalization for Covid-19.

Methods: We studied the COVID-19 patients discharged from Hospital, March 10 and April 20, 2020.

Results: A total of 157 patients were included in this study. Forty-three patients (27.4%) complained of chronic fatigue and muscle weakness in the last six months. The visual analog fatigue scale (VAFS) score of 3.84 ± 1.48 was obtained. Forty patients (25.5%) were suspected of Chronic Fatigue Syndrome (CFS).Twenty-four patients (15.3%) had severe chronic pain or exacerbation of previous chronic pain, most of which were reported in the lower back (70.8%) and lower extremities (66.7%). Pain intensity had a mean score of 2.33 ± 0.87 and was mainly described as “muscle cramps,” “persistent dull pain,” and “boring and numbing.” In women, chronic pain and fatigue, extended hospital stays, ICU admission, and depressed mood were common than in men.For these pain and fatigue, 37% used nonsteroidal anti-inflammatory drugs, and 16.3% used antidepressants. Only one person had applied for physiotherapy, and none of the patients had received psychotherapy.

Conclusion: Fatigue and chronic pain in patients recovering from COVID-19 are common complications, even after 12 months of illness.

Source: Janbazi L, Kazemian A, Mansouri K, Madani SP, Yousefi N, Vahedifard F, Raissi G. The incidence and characteristics of chronic pain and fatigue after 12 months later admitting with COVID-19; The Post- COVID 19 syndrome. Am J Phys Med Rehabil. 2022 Apr 13. doi: 10.1097/PHM.0000000000002030. Epub ahead of print. PMID: 35473921.  https://pubmed.ncbi.nlm.nih.gov/35473921/

Ginger-indirect moxibustion plus acupuncture versus acupuncture alone for chronic fatigue syndrome: a randomized controlled trial

Abstract:

Objective: To assess the efficacy and safety of ginger-indirect moxibustion for chronic fatigue syndrome (CFS).

Methods: In this central randomized, controlled trial, 290 CFS participants were recruited and randomly allocated to group A (ginger-indirect moxibustion plus acupuncture) or group B (acupuncture alone). The study consisted of a treatment period of 8 weeks with a total of 24 treatments (3 sessions per week, every other day), and a follow-up period of 12 weeks. The outcome was measured by Fatigue Severity Scale (FSS), Psychological Health Report (SPHERE), the Self-rating depression scale (SDS) and the Hamilton anxiety scale (HAMA) at baseline, 2, 4, 6, 8, 12 and 20 weeks.

Results: With the treatment undergoing, the changes of FSS, SPHERE, SDS and HAMA scores in both groups increased gradually, and the effect maintained at the 12th week. Between groups, significantly higher score changes were seen in group A in FSS after 4 weeks treatment (11.94 9.12, 95%: 0.94, 4.7) and in SPHERE after 2 weeks treatment (3.7 2.27, 95%: 0.56, 2.31). But for SDS and HAMA, the improvement did not differ significantly between groups. No severe adverse events were reported.

Conclusion: Ginger-indirect moxibustion is a safe and effective intervention to relieve fatigue and accompanying physical symptoms of CFS.

Source: Tingting MA, Jie WU, Lijie Y, Fen F, Huilin Y, Jinhua Z, Yanjin Z, Qing N, Lirong H, Youbing L, Jue Y, Guiquan C, Tianshu H, Li W, Yuanfang R, Jing T. Ginger-indirect moxibustion plus acupuncture versus acupuncture alone for chronic fatigue syndrome: a randomized controlled trial. J Tradit Chin Med. 2022 Apr;42(2):242-249. doi: 10.19852/j.cnki.jtcm.20211214.003. PMID: 35473345. https://pubmed.ncbi.nlm.nih.gov/35473345/

Frailty assessment for COVID-19 follow-up: a prospective cohort study

Abstract:

Background: The Clinical Frailty Scale (CFS) is increasingly used for clinical decision making in acute care but little is known about frailty after COVID-19.

Objectives: To investigate frailty and the CFS for post-COVID-19 follow-up.

Methods: This prospective multicentre cohort study included COVID-19 survivors aged ≥50 years presenting for a follow-up visit ≥3 months after the acute illness. Nine centres retrospectively collected pre-COVID-19 CFS and prospectively CFS at follow-up. Three centres completed the Frailty Index (FI), the short physical performance battery (SPPB), 30 s sit-to-stand test and handgrip strength measurements. Mixed effect logistic regression models accounting for repeated measurements and potential confounders were used to investigate factors associated with post-COVID-19 CFS. Criterion and construct validity were determined by correlating the CFS to other concurrently assessed frailty measurements and measures of respiratory impairment, respectively.

Results: Of the 288 participants 65% were men, mean (SD) age was 65.1 (9) years. Median (IQR) CFS at follow-up was 3 (2-3), 21% were vulnerable or frail (CFS ≥4). The CFS was responsive to change, correlated with the FI (r=0.69, p<0.001), the SPPB score (r=-0.48, p<0.001) (criterion validity) and with the St George’s Respiratory Questionnaire score (r=0.59, p<0.001), forced vital capacity %-predicted (r=-0.25, p<0.001), 6 min walk distance (r=-0.39, p<0.001) and modified Medical Research Council (mMRC) (r=0.59, p<0.001). Dyspnoea was significantly associated with a higher odds for vulnerability/frailty (per one mMRC adjusted OR 2.01 (95% CI 1.13 to 3.58), p=0.02).

Conclusions: The CFS significantly increases with COVID-19, and dyspnoea is an important risk factor for post-COVID-19 frailty and should be addressed thoroughly.

Source: Müller I, Mancinetti M, Renner A, Bridevaux PO, Brutsche MH, Clarenbach C, Garzoni C, Lenoir A, Naccini B, Ott S, Piquilloud L, Prella M, Que YA, Soccal PM, von Garnier C, Geiser TK, Funke-Chambour M, Guler S. Frailty assessment for COVID-19 follow-up: a prospective cohort study. BMJ Open Respir Res. 2022 Apr;9(1):e001227. doi: 10.1136/bmjresp-2022-001227. PMID: 35459694. https://bmjopenrespres.bmj.com/content/9/1/e001227.long (Full text)

Global Prevalence of Post COVID-19 Condition or Long COVID: A Meta-Analysis and Systematic Review

Abstract:

Introduction: This study aims to examine the worldwide prevalence of post COVID-19 condition, through a systematic review and meta-analysis.

Methods: PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random effects framework with DerSimonian-Laird estimator, we meta-analyzed post COVID-19 condition prevalence at 28+ days from infection.

Results: 50 studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post COVID-19 condition was 0.43 (95% CI: 0.39,0.46). Hospitalized and non-hospitalized patients have estimates of 0.54 (95% CI: 0.44,0.63) and 0.34 (95% CI: 0.25,0.46), respectively. Regional prevalence estimates were Asia- 0.51 (95% CI: 0.37,0.65), Europe- 0.44 (95% CI: 0.32,0.56), and North America- 0.31 (95% CI: 0.21,0.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI: 0.26,0.49), 0.25 (95% CI: 0.15,0.38), 0.32 (95% CI: 0.14,0.57) and 0.49 (95% CI: 0.40,0.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI: 0.17,0.30), followed by memory problems (0.14 [95% CI: 0.10,0.19]).

Discussion: This study finds post COVID-19 condition prevalence is substantial; the health effects of COVID-19 appear to be prolonged and can exert stress on the healthcare system.

Source: Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B. Global Prevalence of Post COVID-19 Condition or Long COVID: A Meta-Analysis and Systematic Review. J Infect Dis. 2022 Apr 16:jiac136. doi: 10.1093/infdis/jiac136. Epub ahead of print. PMID: 35429399. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiac136/6569364?login=false (Full text available as PDF file)

Health-related quality of life in Young People with Chronic fatigue syndrome/ Myalgic encephalomyelitis

Abstract

Background: Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) is a disease that affects people of all ages. CFS/ME significantly limits the activity level of those affected, including in relation to physical activity, schooling, occupational life and social life.

High levels of school absence among young people with CFS/ME result in loss of important learning and social development among peers. As such, there is increasing uncertainty about their future, and personal and socio-economic consequences could put them at risk of becoming disabled at a young age. Measurements of health-related quality of life (HRQoL), including being able to function in school, have shown that young people with CFS/ME score lower than their counterparts without CFS/ME.

Aims: The overall aim of this project was to explore HRQoL among young people with CFS/ME, including the factors associated with HRQoL in relation to school and everyday life.

More specifically, the aim was to firstly (Study1) examine HRQoL, including factors that are positively or negatively associated with HRQoL, in a cohort of young people with CFS/ME.

Study 1, along with the previous literature, provided the basis for an in-depth study (Study 2) to investigate the positive and negative factors that young people with CFS/ME experience in school and everyday life.

Based on the findings from Study 1 and Study 2, a third study (Study 3) was planned to explore teachers’, counsellors’ and school nurses’ experiences with educational and social adaptation at school for young people with CFS/ME.

Method: To explore HRQoL and the factors associated with HRQoL among young people with CFS/ME (Studies 1 & 2), a cross-sectional survey- and interview-based study was conducted. The participants of the cross-sectional study were recruited to participate in the interview study.

To explore the experiences of teachers, counsellors and school nurses with education and social adaptions at school for young people with CFS/ME (Study 3), an interview study was conducted with participants recruited among school personnel and school nurses in secondary school (educating students aged 13-16), high school (educating students aged 16-19) and educational psychological services (EPS).

Results: A total of 63 participants were included in the cross-sectional study, 18 of whom participated in the interview study. A total of 12 participants were included in the interview study with the teachers, counsellors and school nurses. In the cross-sectional study (Study 1), young people with CFS/ME scored lower on HRQoL than their counterparts who were healthy or had other chronic diseases. Contact with school and teachers was associated with a higher HRQoL among young people with CFS/ME.

This association could be due to that more contact resulted from adaptations of education and social life at school, or that fewer health problems due to CFS/ME had abled the young people to maintain the contact with school and teachers.

In Study 2, it was found that an adapted plan for education and social life at school for young people with CFS/ME could increase the possibility of continuing schooling with peers. The lack of an adapted plan for education and social life at school could lead to increased school absence as well as loss of education, social contact and development among peers. Subsequently, this could lead to depressive thoughts and worry about the future.

The school personnel and school nurses in Study 3 experienced that young people with CFS/ME lost confidence in school. The challenges experienced by school personnel included (1) understanding students’ needs before they received a diagnosis and before school personnel received information from healthcare providers and (2) maintaining the teacher–student relationship and (3) the continuity of teaching.

In terms of measures for better management, early problematization of school absence, interdisciplinary collaboration on early measures, ensuring the maintenance of the teacher–student relationship and increasing CFS/ME-related competence in schools were proposed. These measures could contribute to prevent loss of function and school absence among young people with CFS/ME.

Conclusion: HRQoL among young people with CFS/ME was associated with contact with school and teachers, but a causal relationship could not be proven.

Interviews with young people with CFS/ME and school personnel suggested that interdisciplinary strategies for early adaptations to education and social life at school for young people with CFS/ME may benefit education and social development among peers for young people with CFS/ME. Lack of educational and social adaptations at school might lead to loss of education, social life and development among peers.

Source: Similä, Wenche Ann. Health-related quality of life in Young People with Chronic fatigue syndrome/ Myalgic encephalomyelitis. Doctoral thesis. https://ntnuopen.ntnu.no/ntnu-xmlui/handle/11250/2991015

Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disorder that is characterized by fatigue that persists for more than 6 months, weakness, sleep disturbances, and cognitive dysfunction.

There are multiple possible etiologies for ME/CFS, among which mitochondrial dysfunction plays a major role in abnormal energy metabolism.

The potential of many substances for the treatment of ME/CFS has been examined; however, satisfactory outcomes have not yet been achieved. The development of new substances for curative, not symptomatic, treatments is desired.

Molecular hydrogen (H2) ameliorates mitochondrial dysfunction by scavenging hydroxyl radicals, the most potent oxidant among reactive oxygen species.

Animal experiments and clinical trials reported that H2 exerted ameliorative effects on acute and chronic fatigue. Therefore, we conducted a literature review on the mechanism by which H2 improves acute and chronic fatigue in animals and healthy people and showed that the attenuation of mitochondrial dysfunction by H2 may be involved in the ameliorative effects.

Although further clinical trials are needed to determine the efficacy and mechanism of H2 gas in ME/CFS, our literature review suggested that H2 gas may be an effective medical gas for the treatment of ME/CFS.

Source: Shin-ichi Hirano, Yusuke Ichikawa, Bunpei Sato, Yoshiyasu Takefuji and Fumitake Satoh. Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review. Front. Neurol., 11 April 2022  https://doi.org/10.3389/fneur.2022.841310 (Full text)

Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features

Abstract:

Many of the survivors of the novel coronavirus disease (COVID-19) are suffering from persistent symptoms, causing significant morbidity and decreasing their quality of life, termed “post-COVID-19 syndrome” or “long COVID”. Understanding the mechanisms surrounding PCS is vital to developing the diagnosis, biomarkers, and possible treatments.

Here, we describe the prevalence and manifestations of PCS, and similarities with previous SARS epidemics. Furthermore, we look at the molecular mechanisms behind the neurological features of PCS, where we highlight important neural mechanisms that may potentially be involved and pharmacologically targeted, such as glutamate reuptake in astrocytes, the role of NMDA receptors and transporters (EAAT2), ROS signaling, astrogliosis triggered by NF-κB signaling, KNDy neurons, and hypothalamic networks involving Kiss1 (a ligand for the G-protein-coupled receptor 54 (GPR54)), among others. We highlight the possible role of reactive gliosis following SARS-CoV-2 CNS injury, as well as the potential role of the hypothalamus network in PCS manifestations.

Source: Mohamed MS, Johansson A, Jonsson J, Schiöth HB. Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features. Int J Mol Sci. 2022 Apr 12;23(8):4275. doi: 10.3390/ijms23084275. PMID: 35457093. https://www.mdpi.com/1422-0067/23/8/4275/htm (Full text)

The Relationship between Physical Activity and Long COVID: A Cross-Sectional Study

Abstract:

The relationship between Long Covid (LC) symptoms and physical activity (PA) levels are unclear. In this cross-sectional study, we examined this association, and the advice that individuals with LC received on PA. Adults with LC were recruited via social media. The New Zealand physical activity questionnaire short form (NZPAQ-SF) was adapted to capture current and pre-COVID-19 PA levels and activities of daily living (ADLs).
Participants reported how PA affected their symptoms, and what PA recommendations they had received from healthcare professionals and other resources; 477 participants completed the survey. Mean age (SD) was 45.69 (10.02) years, 89.1% female, 92.7% white, and median LC duration was 383.5 days (IQR: 168.25,427). Participants were less active than pre-COVID-19 (26.88 ± 74.85 vs. 361.68 ± 396.29 min per week, p < 0.001) and required more assistance with ADLs in a 7-day period compared to pre-COVID-19 (2.23 ± 2.83 vs. 0.11 ± 0.74 days requiring assistance, p < 0.001). No differences were found between the number of days of assistance required with ADLs, or the amount of PA, and the different durations of LC illness (p > 0.05).
Participants reported the effect of PA on LC symptoms as: worsened (74.84%), improved (0.84%), mixed effect (20.96%), or no effect (28.72%). Participants received contradictory advice on whether to be physically active in LC. LC is associated with a reduction in PA and a loss of independence, with most participants reporting PA worsened LC symptoms. PA level reduction is independent of duration of LC. Research is needed to understand how to safely return to PA without worsening LC symptoms.
Source: Wright J, Astill SL, Sivan M. The Relationship between Physical Activity and Long COVID: A Cross-Sectional Study. International Journal of Environmental Research and Public Health. 2022; 19(9):5093. https://doi.org/10.3390/ijerph19095093  https://www.mdpi.com/1660-4601/19/9/5093/htm (Full text)

A systematic review on physical function, activities of daily living and health-related quality of life in COVID-19 survivors

Abstract:

Objective: To analyze the published studies that investigated the physical function, activities of daily living and health-related quality of life in COVID-19 survivors.

Design: Systematic review.

Methods: We searched MEDLINE/PubMed, Scopus, SciELO, and Cochrane Library for studies that evaluated the physical function, activities of daily living and health-related quality of life after COVID-19 from the earliest date available to July 2021. Two independent reviewers screened and selected the studies. The Newcastle Ottawa Scale was used to evaluate methodological quality.

Results: We included 35 studies in this systematic review. Of the 35 studies included, 28 were cohort, and 7 cross-sectional studies The studies demonstrated that COVID-19 survivors had reduced levels of physical function, activities of daily living, and health-related quality of life. Furthermore, incomplete recovery of physical function, and performance in activities of daily living were observed 1 to 6 months post-infection.

Discussion: Physical disability and reduction in health-related quality of life is a common condition in post-COVID-19 and impairments may persist up to 1 to 6 months. Researchers and clinicians can use these findings to understand the potential disabilities and rehabilitation needs of people recovering from the COVID-19.

Source: de Oliveira Almeida K, Nogueira Alves IG, de Queiroz RS, de Castro MR, Gomes VA, Santos Fontoura FC, Brites C, Neto MG. A systematic review on physical function, activities of daily living and health-related quality of life in COVID-19 survivors. Chronic Illn. 2022 Apr 11:17423953221089309. doi: 10.1177/17423953221089309. Epub ahead of print. PMID: 35404175; PMCID: PMC9006095. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006095/ (Full text)

Risk factors and multidimensional assessment of long COVID fatigue: a nested case-control study

Abstract:

Background: Fatigue is the most prevalent and debilitating long COVID symptom, however risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long COVID fatigue and explored its possible pathophysiology.

Methods: Nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long COVID fatigue.

Results: Total of 141 individuals were included. Mean age was 47 (SD 13) years; 115 (82%) were recovering from mild COVID-19. Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long COVID fatigue. They had significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness and long COVID symptoms, and of physical limitation in daily activities. Individuals with fatigue had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53), p=0.038] and oxygen consumption per Kg [27.69 (7.52) vs 30.71 (7.52), p=0.036] at peak exercise. The two independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (odds ratio [OR] 0.79 per 10 beats/minute, 95% confidence interval [CI] 0.65-0.96, p=0.019); and long COVID memory impairment (OR 3.76, 95% CI 1.57-9.01, p=0.003).

Conclusions: Long COVID fatigue may be related to autonomic dysfunction, impaired cognition and decreased mood. This may suggest a limbic-vagal pathophysiology. Clinical Trial registration: NCT04851561.

Source: Margalit I, Yelin D, Sagi M, Rahat MM, Sheena L, Mizrahi N, Gordin Y, Agmon H, Epstein NK, Atamna A, Tishler O, Daitch V, Babich T, Abecasis D, Yarom Y, Kazum S, Shitenberg D, Baltaxe E, Elkana O, Shapira-Lichter I, Leibovici L, Yahav D. Risk factors and multidimensional assessment of long COVID fatigue: a nested case-control study. Clin Infect Dis. 2022 Apr 11:ciac283. doi: 10.1093/cid/ciac283. Epub ahead of print. PMID: 35403679.  https://pubmed.ncbi.nlm.nih.gov/35403679/