Tag: 2023

A 2-day cardiopulmonary exercise test in chronic fatigue syndrome patients who were exposed to humidifier disinfectants

Abstract:

Some survivors of humidifier disinfectants (HDs) complain of chronic, inexplicable fatigue, and post-exertional malaise (PEM). Two-day cardiopulmonary exercise tests (CPETs) performed 24 hours apart (2-day CPET protocol) are increasingly employed to evaluate PEM and related disabilities among individuals with chronic fatigue syndrome (CFS). The purpose of this study was to assess the reproducibility of CPET variables in individuals who had been exposed to HD and to show that 2-day CPET is an objective means of differentiating between fatigue conditions in people with CFS symptoms who have been exposed to HDs.

Twenty-nine HD survivors with CFS symptoms were enrolled in this study. To document and assess PEM in CFS, a 2-day CPET was conducted to measure baseline functional capacity (CPET1) and provoke PEM. Twenty-four hours later, a second CPET assessed changes in related variables, focusing on PEM effects on functional capacity. This CPET also measured changes in energy production and physiological function, objectively documenting PEM effects.

In the 2-day CPET, the peak oxygen consumption (VO2peak), VO2 at ventilatory threshold (VO2@VT), time to reach VO2peak, and time to reach VO2@VT were significantly decreased (p<0.001). The peak O2 pulse and O2 pulse at VT also decreased significantly (p<0.001). A 6-minute walk test revealed significantly decreased distance (p<0.01). This is the first study to conduct a 2-day consecutive CPET in previously exposed HD participants with CFS symptoms.

Our results confirm previous work that demonstrated abnormal responses to PEM in CFS patients. Therefore, a 2-day CPET is an objective measure to differentiate fatigue conditions in people with CFS symptoms who have been exposed to HDs.

Source: Leem JH, Jeon HE, Nam H, Kim HC, Joa KL. A 2-day cardiopulmonary exercise test in chronic fatigue syndrome patients who were exposed to humidifier disinfectants. Environ Anal Health Toxicol. 2022 Dec;37(4):e2022033-0. doi: 10.5620/eaht.2022033. Epub 2022 Nov 3. PMID: 36916046; PMCID: PMC10014750. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014750/ (Full text)

Post-exertional malaise among people with long COVID compared to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Abstract:

Background: Long COVID describes a condition with symptoms that linger for months to years following acute COVID-19. Many of these Long COVID symptoms are like those experienced by patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Objective: We wanted to determine if people with Long COVID experienced post-exertional malaise (PEM), the hallmark symptom of ME/CFS, and if so, how it compared to PEM experienced by patients with ME/CFS.

Methods: A questionnaire that asked about the domains of PEM including triggers, experience, recovery, and prevention was administered to 80 people seeking care for Long COVID at Bateman Horne Center. Their responses were compared to responses about PEM given by 151 patients with ME/CFS using chi-square tests of independence.

Results: All but one Long COVID respondent reported having PEM. There were many significant differences in the types of PEM triggers, symptoms experienced during PEM, and ways to recover and prevent PEM between Long COVID and ME/CFS. Similarities between Long COVID and ME/CFS included low and medium physical and cognitive exertion to trigger PEM, symptoms of fatigue, pain, immune reaction, neurologic, orthostatic intolerance, and gastrointestinal symptoms during PEM, rest to recover from PEM, and pacing to prevent PEM.

Conclusion: People with Long COVID experience PEM. There were significant differences in PEM experienced by people with Long COVID compared to patients with ME/CFS. This may be due to the newness of Long COVID, not knowing what exertional intolerance is or how to manage it.

Source: Vernon SD, Hartle M, Sullivan K, Bell J, Abbaszadeh S, Unutmaz D, Bateman L. Post-exertional malaise among people with long COVID compared to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Work. 2023 Mar 7. doi: 10.3233/WOR-220581. Epub ahead of print. PMID: 36911963. https://content.iospress.com/articles/work/wor220581 (Full text)

Predictors of impaired functioning among long COVID patients

Abstract:

Background: There is limited information on what acute factors predict more long-term symptoms from COVID-19.

Objective: Our objective was to conduct an exploratory factor analysis of self-reported symptoms at two time points of Long COVID-19.

Methods: Data from patients with Long COVID-19 were collected at the initial two weeks of contracting SARS CoV-2 and the most recent two weeks, with a mean duration of 21.7 weeks between the two-time points. At time point 2, participants also complete the Coronavirus Impact Scale (CIS), measuring how the COVID-19 pandemic affected various dimensions of their lives (e.g., routine, access to medical care, social/family support, etc.).

Results: At time 1, a three-factor model emerged consisting of Cognitive Dysfunction, Autonomic Dysfunction and Gastrointestinal Dysfunction. The analysis of time 2 resulted in a three-factor model consisting of cognitive dysfunction, autonomic dysfunction, and post-exertional malaise. Using factor scores from time 1, the Autonomic Dysfunction and the Gastrointestinal Dysfunction factor scores significantly predicted the CIS summary score at time two. In addition, the same two factor scores at time 1 predicted the occurrence of myalgic encephalomyelitis/chronic fatigue syndrome at time 2.

Conclusion: As Cognitive and Autonomic Dysfunction emerged as factors for both time points, suggesting health care workers might want to pay particular attention to these factors that might be related to later symptoms and difficulties with returning to pre-illness family life and work functioning.

Source: Jason LA, Dorri JA. Predictors of impaired functioning among long COVID patients. Work. 2023 Mar 8. doi: 10.3233/WOR-220428. Epub ahead of print. PMID: 36911958. https://content.iospress.com/articles/work/wor220428 (Full text)

Adults with ME/CFS report surprisingly high rates of youth symptoms: A qualitative analysis of patient blog commentary

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness that impacts pediatric populations.

Objective: The current study aimed to better understand adult perceptions of their experiences leading up to their diagnosis of ME/CFS.

Method: Patients provided data regarding symptoms of ME/CFS they may have experienced during childhood through a popular community blog forum, with participants interacting via blog comments in real-time and across various geographical locations.

Results: Descriptive analyses indicated that roughly 43% of adult survey participants reported having developed ME/CFS prior to age 18. A standard content analysis of patient blog commentary revealed several themes, such as poor mental health, family pattern/history, healthy childhood preceding sick adulthood, feeling misunderstood, lack of clarity until adulthood, sharing of resources, poor school functioning, isolation/poor social supports, and coping mechanisms.

Conclusion: There are unique benefits and insights that can be used by investigators who collaborate with patient organizations as a means of better understanding ME/CFS illness severity, presentation, and lived experiences.

Source: Johnson M, Torres C, Watts-Rich H, Jason L. Adults with ME/CFS report surprisingly high rates of youth symptoms: A qualitative analysis of patient blog commentary. Work. 2023 Mar 9. doi: 10.3233/WOR-220484. Epub ahead of print. PMID: 36911960. https://content.iospress.com/articles/work/wor220484 (Full text)

My experience with ME/CFS and implications: A personal narrative

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating health condition characterized by overwhelming fatigue and post-exertional malaise, or exacerbation of symptoms following physical, mental, or emotional exertion. ME/CFS often impacts every aspect of an individual’s life, and one’s new reality may be much different from the daily life experienced before the onset of the condition. Though the long-term effects of COVID-19 have brought increased attention to chronic fatigue and related disorders, ME/CFS is still vastly understudied and frequently misunderstood.

People with ME/CFS are often passed between various healthcare providers as evidence-based treatments remain scarce. These patients are sometimes sent to rehabilitation professionals, who often lack appropriate education and experience with this patient population. This article describes the experience of a young woman and physical therapist with ME/CFS following COVID-19 infection, as well as potential implications for rehabilitation professionals and those who care for those with this condition.

Source: Sirotiak Z. My experience with ME/CFS and implications: A personal narrative. Work. 2023 Mar 9. doi: 10.3233/WOR-220487. Epub ahead of print. PMID: 36911961. https://content.iospress.com/articles/work/wor220487 (Full text)

Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review

Abstract:

Background: Millions of COVID-19 pediatric survivors are facing the risk of long COVID after recovery from acute COVID-19. The primary objective of this study was to systematically review the available literature and determine the pooled prevalence of, and risk factors for long COVID among the pediatric survivors.

Methods: Studies that assessed the prevalence of, or risk factors associated with long COVID among pediatric COVID-19 survivors were systematically searched in PubMed, Embase, Cochrane Library, medRxiv and bioRxiv up to December 11th, 2022. Random effects model was performed to estimate the pooled prevalence of long COVID among pediatric COVID-19 patients. Subgroup analyses and meta-regression on the estimated prevalence of long COVID were performed by stratification with follow-up duration, mean age, sex ratio, percentage of multisystem inflammatory syndrome, hospitalization rate at baseline, and percentage of severe illness.

Results: Based on 40 studies with 12,424 individuals, the pooled prevalence of any long COVID was 23.36% ([95% CI 15.27-32.53]). The generalized symptom (19.57%, [95% CI 9.85-31.52]) was reported most commonly, followed by respiratory (14.76%, [95% CI 7.22-24.27]), neurologic (13.51%, [95% CI 6.52-22.40]), and psychiatric (12.30%, [95% CI 5.38-21.37]). Dyspnoea (22.75%, [95% CI 9.38-39.54]), fatigue (20.22%, [95% CI 9.19-34.09]), and headache (15.88%, [95% CI 6.85-27.57]) were most widely reported specific symptoms. The prevalence of any symptom during 3-6, 6-12, and >12 months were 26.41% ([95% CI 14.33-40.59]), 20.64% ([95% CI 17.06-24.46]), and 14.89% ([95% CI 6.09-26.51]), respectively. Individuals with aged over ten years, multisystem inflammatory syndrome, or had severe clinical symptoms exhibited higher prevalence of long COVID in multi-systems. Factors such as older age, female, poor physical or mental health, or had severe infection or more symptoms were more likely to have long COVID in pediatric survivors.

Conclusions: Nearly one quarter of pediatric survivors suffered multisystem long COVID, even at 1 year after infection. Ongoing monitoring, comprehensive prevention and intervention is warranted for pediatric survivors, especially for individuals with high risk factors.

Source: Zheng YB, Zeng N, Yuan K, Tian SS, Yang YB, Gao N, Chen X, Zhang AY, Kondratiuk AL, Shi PP, Zhang F, Sun J, Yue JL, Lin X, Shi L, Lalvani A, Shi J, Bao YP, Lu L. Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review. J Infect Public Health. 2023 Mar 7. doi: 10.1016/j.jiph.2023.03.005. Epub ahead of print. PMCID: PMC9990879. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990879/ (Full text)

Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics

Abstract:

The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed “long COVID” or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, “brain fog”, headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy.
Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood–brain barrier dysfunction, respectively.
Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.
Source: Leng A, Shah M, Ahmad SA, Premraj L, Wildi K, Li Bassi G, Pardo CA, Choi A, Cho S-M. Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics. Cells. 2023; 12(5):816. https://doi.org/10.3390/cells12050816 (Full text)

“Long COVID”: the current state of the problem. Review of foreign scientific and medical publications

Abstract:

Not all the patients who are diagnosed with COVID-19 can completely recover; some of them experience miscellaneous persistent symptoms that subsequently wax or wane.  As the COVID-19 pandemic continues, the number of people with long-term symptoms is rapidly increasing, adding to the burden on healthcare and society. The prevalence of the consequences of COVID-19 varies between studies, with some reporting that more than half of hospitalized patients have prolonged symptoms for at least 6 months after acute SARS-CoV-2 infection, and others for more than 12 months. The overall prevalence of residual symptoms in patients infected with SARS-CoV-2 is currently estimated to be 10–30%.

This clinical syndrome is commonly referred to as post-acute COVID syndrome (PACS) or long COVID. This multifactorial syndrome is characterised by a variety of debilitating symptoms, including fatigue, brain fog, postural hypotension with tachycardia, and post-exertional malaise. Many of the observations of post COVID-19 condition, including changes in immune, cardiovascular, gastrointestinal, nervous and autonomic systems, are shared with the symptoms described in myalgic encephalitis/chronic fatigue syndrome (ME/CFS) patients.

Comprehensive longitudinal symptom monitoring is required to confirm of diagnosis, uncover the mechanisms of post-COVID-19-associated ME/CFS, and develop prevention and treatment measures. Current absence of the effective treatment reflects the unclear causes of the post COVID-19 conditions which cannot be targeted properly until the mechanism is established and confirmed.

The multisystem aspects of long COVID remain poorly understood. The COVID-19 pandemic has exposed a significant gap in knowledge about the post-acute consequences of infectious diseases and the need for a unified nomenclature and classification of post-COVID conditions, diagnostic criteria, and reliable assessments of these disorders. Unraveling the complex biology of PACS relies on the identification of biomarkers in plasma and tissue samples taken from individuals infected with SARS-CoV-2 that will allow classification of the phenotypes of patients who develop PACS.

For the full treatment of patients with post-COVID syndrome, multidisciplinary therapy and rehabilitation are required. Understanding the physiological mechanisms underlying the long-term clinical manifestations of COVID-19 and the post-COVID-19 state is vital to the development of appropriate effective therapies.

Source: Golota A.S., Vologzhanin D.A., Kamilova T.A., Sсherbak S.G., Makarenko S.V. “Long COVID”: the current state of the problem. Review of foreign scientific and medical publications // Physical and rehabilitation medicine, medical rehabilitation. – 2023. – Vol. 5. – N. 1. doi: 10.36425/rehab121733 (Full text available in Russian)

Symptomatic Characteristics of Hypozincemia Detected in Long COVID Patients

Abstract:

Objectives: The aim of this study was to determine the characteristics of hypozincemia in long COVID patients.
Methods: This study was a single-center retrospective observational study for outpatients who visited the long COVID clinic established in a university hospital during the period from 15 February 2021 to 28 February 2022. Characteristics of patients with a serum zinc concentration lower than 70 μg/dL (10.7 μmol/L) were compared with characteristics of patients with normozincemia.
Results: In a total of 194 patients with long COVID after excluding 32 patients, hypozincemia was detected in 43 patients (22.2%) including 16 male patients (37.2%) and 27 female patients (62.8%). Among various parameters including the background characteristics of the patients and medical histories, the patients with hypozincemia were significantly older than the patients with normozincemia (median age: 50 vs. 39 years). A significant negative correlation was found between serum zinc concentrations and age in male patients (R = −0.39; p < 0.01) but not in female patients. In addition, there was no significant correlation between serum zinc levels and inflammatory markers. General fatigue was the most frequent symptom in both male patients with hypozincemia (9 out of 16: 56.3%) and female patients with hypozincemia (8 out of 27: 29.6%). Patients with severe hypozincemia (serum zinc level lower than 60 μg/dL) had major complaints of dysosmia and dysgeusia, which were more frequent complaints than general fatigue.
Conclusions: The most frequent symptom in long COVID patients with hypozincemia was general fatigue. Serum zinc levels should be measured in long COVID patients with general fatigue, particularly in male patients.
Source: Matsuda Y, Tokumasu K, Otsuka Y, Sunada N, Honda H, Sakurada Y, Nakano Y, Hasegawa T, Obika M, Ueda K, Otsuka F. Symptomatic Characteristics of Hypozincemia Detected in Long COVID Patients. Journal of Clinical Medicine. 2023; 12(5):2062. https://doi.org/10.3390/jcm12052062 https://www.mdpi.com/2077-0383/12/5/2062 (Full text)

The role of immune activation and antigen persistence in acute and long COVID

Abstract:

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the global coronavirus disease 2019 (COVID-19) pandemic. Although most infections cause a self-limited syndrome comparable to other upper respiratory viral pathogens, a portion of individuals develop severe illness leading to substantial morbidity and mortality. Furthermore, an estimated 10%-20% of SARS-CoV-2 infections are followed by post-acute sequelae of COVID-19 (PASC), or long COVID.

Long COVID is associated with a wide variety of clinical manifestations including cardiopulmonary complications, persistent fatigue, and neurocognitive dysfunction. Severe acute COVID-19 is associated with hyperactivation and increased inflammation, which may be an underlying cause of long COVID in a subset of individuals. However, the immunologic mechanisms driving long COVID development are still under investigation.

Early in the pandemic, our group and others observed immune dysregulation persisted into convalescence after acute COVID-19. We subsequently observed persistent immune dysregulation in a cohort of individuals experiencing long COVID. We demonstrated increased SARS-CoV-2-specific CD4+ and CD8+ T-cell responses and antibody affinity in patients experiencing long COVID symptoms. These data suggest a portion of long COVID symptoms may be due to chronic immune activation and the presence of persistent SARS-CoV-2 antigen.

This review summarizes the COVID-19 literature to date detailing acute COVID-19 and convalescence and how these observations relate to the development of long COVID. In addition, we discuss recent findings in support of persistent antigen and the evidence that this phenomenon contributes to local and systemic inflammation and the heterogeneous nature of clinical manifestations seen in long COVID.

Source: Opsteen S, Files JK, Fram T, Erdmann N. The role of immune activation and antigen persistence in acute and long COVID. J Investig Med. 2023 Mar 6:10815589231158041. doi: 10.1177/10815589231158041. Epub ahead of print. PMID: 36879504; PMCID: PMC9996119. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996119/ (Full text)