RESUMO
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), long COVID (LC) and post-COVID-19 vaccine syndrome show similarities in their pathophysiology and clinical manifestations. These disorders are related to viral or adjuvant persistence, immunological alterations, autoimmune diseases and hormonal imbalances. A developmental model is postulated that involves the interaction between immune hyperactivation, autoimmune hypophysitis or pituitary hypophysitis, and immune depletion. This process might begin with a deficient CD4 T-cell response to viral infections in genetically predisposed individuals (HLA-DRB1), followed by an uncontrolled immune response with CD8 T-cell hyperactivation and elevated antibody production, some of which may be directed against autoantigens, which can trigger autoimmune hypophysitis or direct damage to the pituitary, resulting in decreased production of pituitary hormones, such as ACTH. As the disease progresses, prolonged exposure to viral antigens can lead to exhaustion of the immune system, exacerbating symptoms and pathology. It is suggested that these disorders could be included in the autoimmune/adjuvant-induced inflammatory syndrome (ASIA) because of their similar clinical manifestations and possible relationship to genetic factors, such as polymorphisms in the HLA-DRB1 gene. In addition, it is proposed that treatment with antivirals, corticosteroids/ginseng, antioxidants, and metabolic precursors could improve symptoms by modulating the immune response, pituitary function, inflammation and oxidative stress. Therefore, the purpose of this review is to suggest a possible autoimmune origin against the adenohypophysis and a possible improvement of symptoms after treatment with corticosteroid replacement therapy.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Síndrome de Fadiga Crônica , SARS-CoV-2 , Humanos , COVID-19/imunologia , Síndrome de Fadiga Crônica/imunologia , Síndrome de Fadiga Crônica/etiologia , Síndrome de Fadiga Crônica/virologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , SARS-CoV-2/imunologia , Síndrome de COVID-19 Pós-Aguda , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologiaRESUMO
Long COVID should be limited to patients with multiple, persistent symptoms not related to well-defined organ damage. Once redefined, a focused review of long COVID demonstrates striking similarity to chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), fibromyalgia (FM) and irritable bowel syndrome (IBS). Research in long COVID has revealed similar findings to those noted in CFS/ME and FM, characterized by central nervous system organ dysfunction. Long COVID, like CFS/ME, FM and IBS, is best understood as a bidirectional mind-body, neuroimmune illness.
Assuntos
COVID-19 , Síndrome de Fadiga Crônica , Fibromialgia , Síndrome do Intestino Irritável , Síndrome de COVID-19 Pós-Aguda , Humanos , Síndrome do Intestino Irritável/fisiopatologia , Fibromialgia/fisiopatologia , Síndrome de Fadiga Crônica/virologia , Síndrome de Fadiga Crônica/fisiopatologia , COVID-19/complicações , SARS-CoV-2RESUMO
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease presenting with severe fatigue, post-exertional malaise, and cognitive disturbances-among a spectrum of symptoms-that collectively render the patient housebound or bedbound. Epigenetic studies in ME/CFS collectively confirm alterations and/or malfunctions in cellular and organismal physiology associated with immune responses, cellular metabolism, cell death and proliferation, and neuronal and endothelial cell function. The sudden onset of ME/CFS follows a major stress factor that, in approximately 70% of cases, involves viral infection, and ME/CFS symptoms overlap with those of long COVID. Viruses primarily linked to ME/CFS pathology are the symbiotic herpesviruses, which follow a bivalent latent-lytic lifecycle. The complex interaction between viruses and hosts involves strategies from both sides: immune evasion and persistence by the viruses, and immune activation and viral clearance by the host. This dynamic interaction is imperative for herpesviruses that facilitate their persistence through epigenetic regulation of their own and the host genome. In the current article, we provide an overview of the epigenetic signatures demonstrated in ME/CFS and focus on the potential strategies that latent viruses-particularly Epstein-Barr virus-may employ in long-term epigenetic reprograming in ME/CFS. Epigenetic studies could aid in elucidating relevant biological pathways impacted in ME/CFS and reflect the physiological variations among the patients that stem from environmental triggers, including exogenous viruses and/or altered viral activity.
Assuntos
Epigênese Genética , Síndrome de Fadiga Crônica , Humanos , Síndrome de Fadiga Crônica/virologia , Síndrome de Fadiga Crônica/genética , Latência Viral/genética , Herpesvirus Humano 4RESUMO
More than 800 million individuals have contracted SARSCOV2 infection worldwide. It was estimated that almost 10-20% of these might suffer from Long COVID. It is a multisystemic syndrome, which negatively affects the quality of life with a significant burden of health loss compared to COVID negative individuals. Moreover, the risk of sequelae still remains high at 2 years in both nonhospitalized and hospitalized individuals. This review summarizes studies regarding long COVID and clarifies the definitions, the risk factors and the management of this syndrome. Finally, it delves into the most frequent long-term outcomes, especially postural orthostatic tachycardia syndrome" (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), brain fog, and their therapeutical possibilities.
Assuntos
COVID-19 , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/virologia , Síndrome de Fadiga Crônica/virologia , Fatores de Risco , Qualidade de Vida , Síndrome da Taquicardia Postural Ortostática/fisiopatologiaRESUMO
Understanding the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is critical for advancing treatment options. This review explores the novel hypothesis that a herpesvirus infection of endothelial cells (ECs) may underlie ME/CFS symptomatology. We review evidence linking herpesviruses to persistent EC infection and the implications for endothelial dysfunction, encompassing blood flow regulation, coagulation, and cognitive impairment-symptoms consistent with ME/CFS and Long COVID. This paper provides a synthesis of current research on herpesvirus latency and reactivation, detailing the impact on ECs and subsequent systemic complications, including latent modulation and long-term maladaptation. We suggest that the chronicity of ME/CFS symptoms and the multisystemic nature of the disease may be partly attributable to herpesvirus-induced endothelial maladaptation. Our conclusions underscore the necessity for further investigation into the prevalence and load of herpesvirus infection within the ECs of ME/CFS patients. This review offers conceptual advances by proposing an endothelial infection model as a systemic mechanism contributing to ME/CFS, steering future research toward potentially unexplored avenues in understanding and treating this complex syndrome.
Assuntos
Células Endoteliais , Síndrome de Fadiga Crônica , Infecções por Herpesviridae , Humanos , Células Endoteliais/virologia , Síndrome de Fadiga Crônica/virologia , Síndrome de Fadiga Crônica/fisiopatologia , Herpesviridae/fisiologia , Infecções por Herpesviridae/virologia , Latência Viral , Síndrome de COVID-19 Pós-Aguda/patologia , Síndrome de COVID-19 Pós-Aguda/fisiopatologiaRESUMO
BACKGROUND: Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID. OBJECTIVES: To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers. METHODS: We examined 90 long COVID patients and ninety healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5'-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR). RESULTS: Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6, and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve = 0.876); the topmost predictors were as follows: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top 5 predictors of affective symptoms due to long COVID were IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r = 0.636). The top 5 predictors of CFS due to long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r = 0.709). CONCLUSION: Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of long COVID as well as the severity of its affective symptoms and CFS.
Assuntos
Ativinas , COVID-19 , Síndrome de Fadiga Crônica , Herpesvirus Humano 6 , Imunoglobulina A , Imunoglobulina M , SARS-CoV-2 , Humanos , Herpesvirus Humano 6/imunologia , Síndrome de Fadiga Crônica/sangue , Síndrome de Fadiga Crônica/imunologia , Síndrome de Fadiga Crônica/virologia , Masculino , Feminino , Imunoglobulina A/sangue , Imunoglobulina M/sangue , COVID-19/imunologia , COVID-19/sangue , Adulto , Ativinas/sangue , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Síndrome de COVID-19 Pós-Aguda , Anticorpos Antivirais/sangue , Herpesvirus Humano 4/imunologia , Biomarcadores/sangue , Infecções por Roseolovirus/sangue , Infecções por Roseolovirus/imunologiaRESUMO
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness often triggered by an initiating acute event, mainly viral infections. The transition from acute to chronic disease remains unknown, but interest in this phenomenon has escalated since the COVID-19 pandemic and the post-COVID-19 illness, termed 'long COVID' (LC). Both ME/CFS and LC share many clinical similarities. Here, we present recent findings in ME/CFS research focussing on proposed disease pathologies shared with LC. Understanding these disease pathologies and how they influence each other is key to developing effective therapeutics and diagnostic tests. Given that ME/CFS typically has a longer disease duration compared with LC, with symptoms and pathologies evolving over time, ME/CFS may provide insights into the future progression of LC.
Assuntos
COVID-19 , Síndrome de Fadiga Crônica , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/virologia , Síndrome de Fadiga Crônica/virologiaRESUMO
BACKGROUND: Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients. METHODS: We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections' contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased). RESULTS: Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a "moderate association" by Cohen's d test) compared to both healthy and diseased controls. CONCLUSION: This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.
Assuntos
Encefalite , Síndrome de Fadiga Crônica , Viroses , Humanos , Encefalite/virologia , Síndrome de Fadiga Crônica/virologia , Fibromialgia/virologia , Viroses/complicaçõesRESUMO
Myalgic encephalomyelitis and Long Covid have overlapping presentation.
Assuntos
COVID-19 , Síndrome de Fadiga Crônica , COVID-19/complicações , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/virologia , Humanos , Síndrome de COVID-19 Pós-AgudaRESUMO
Despite recovering from the acute phase of coronavirus disease (COVID-19), many patients report continuing symptoms that most commonly include fatigue, cough, neurologic problems, hair loss, headache, and musculoskeletal pain, a condition termed long-COVID syndrome. Neither its etiopathogenesis, nor its clinical presentation or risk factors are fully understood. Therefore, the purpose of this study was to retrospectively evaluate the most common symptoms of long-COVID among patients from the STOP COVID registry of the PoLoCOV study, and to search for risk factors for development of the syndrome. The registry includes patients who presented to the medical center for persistent clinical symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The analysis included data from initial presentation and at three-month follow-up. Of the 2218 patients, 1569 (70.7%) reported having at least one symptom classified as long-COVID syndrome three months after recovery from the initial SARS-CoV-2 infection. The most common symptoms included chronic fatigue (35.6%\), cough (23.0%), and a set of neurological symptoms referred to as brain fog (12.1%). Risk factors for developing long-COVID syndrome included female gender (odds ratio [OR]: 1.48, 95% confidence intervals [CI] [1.19-1.84]), severe COVID-19 (OR: 1.56, CI: 1.00-2.42), dyspnea (OR: 1.31, CI: 1.02-1.69), and chest pain (OR: 1.48, CI: 1.14-1.92). Long-COVID syndrome represents a significant clinical and social problem. The most common clinical manifestations are chronic fatigue, cough, and brain fog. Given the still-limited knowledge of long-COVID syndrome, further research and observation are needed to better understand the mechanisms and risk factors of the disease.
Assuntos
COVID-19 , Síndrome de Fadiga Crônica , COVID-19/complicações , COVID-19/epidemiologia , Tosse/epidemiologia , Tosse/virologia , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/virologia , Feminino , Humanos , Fadiga Mental/epidemiologia , Fadiga Mental/virologia , Sistema de Registros , Estudos Retrospectivos , SARS-CoV-2 , Síndrome de COVID-19 Pós-AgudaRESUMO
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, multisystem illness of unknown etiology for which no cure and no diagnostic tests are available. Despite increasing evidence implicating EBV and human herpesvirus 6A (HHV-6A) as potential causative infectious agents in a subset of patients with ME/CFS, few mechanistic studies address a causal relationship. In this study we examined a large ME/CFS cohort and controls and demonstrated a significant increase in activin A and IL-21 serum levels, which correlated with seropositivity for antibodies against the EBV and HHV-6 protein deoxyuridine triphosphate nucleotidohydrolase (dUTPases) but no increase in CXCL13. These cytokines are critical for T follicular helper (TFH) cell differentiation and for the generation of high-affinity antibodies and long-lived plasma cells. Notably, ME/CFS serum was sufficient to drive TFH cell differentiation via an activin A-dependent mechanism. The lack of simultaneous CXCL13 increase with IL-21 indicates impaired TFH function in ME/CFS. In vitro studies revealed that virus dUTPases strongly induced activin A secretion while in vivo, EBV dUTPase induced the formation of splenic marginal zone B and invariant NKTFH cells. Together, our data indicate abnormal germinal center (GC) activity in participants with ME/CFS and highlight a mechanism by which EBV and HHV6 dUTPases may alter GC and extrafollicular antibody responses.
Assuntos
Síndrome de Fadiga Crônica , Herpesvirus Humano 4 , Herpesvirus Humano 6 , Pirofosfatases , Linfócitos T Auxiliares-Indutores , Diferenciação Celular , Infecções por Vírus Epstein-Barr/enzimologia , Infecções por Vírus Epstein-Barr/virologia , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/enzimologia , Síndrome de Fadiga Crônica/virologia , Herpesvirus Humano 4/enzimologia , Herpesvirus Humano 6/enzimologia , Humanos , Pirofosfatases/metabolismo , Infecções por Roseolovirus/enzimologia , Infecções por Roseolovirus/virologia , Linfócitos T Auxiliares-Indutores/enzimologia , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Auxiliares-Indutores/virologiaRESUMO
BACKGROUND: Post-acute COVID-19 syndrome (PACS) is an emerging healthcare burden. We therefore aimed to determine predictors of different functional outcomes after hospital discharge in patients with COVID-19. METHODS: An ambidirectional cohort study was conducted between May and July 2020, in which PCR-confirmed COVID-19 patients underwent a standardized telephone assessment between 6 weeks and 6 months post discharge. We excluded patients who died, had a mental illness or failed to respond to two follow-up phone calls. The medical research council (MRC) dyspnea scale, metabolic equivalent of task (MET) score for exercise tolerance, chronic fatigability syndrome (CFS) scale and World Health Organization-five well-being index (WHO-5) for mental health were used to evaluate symptoms at follow-up. RESULTS: 375 patients were contacted and 153 failed to respond. The median timing for the follow-up assessment was 122 days (IQR, 109-158). On multivariate analyses, female gender, pre-existing lung disease, headache at presentation, intensive care unit (ICU) admission, critical COVID-19 and post-discharge ER visit were predictors of higher MRC scores at follow-up. Female gender, older age >67 years, arterial hypertension and emergency room (ER) visit were associated with lower MET exercise tolerance scores. Female gender, pre-existing lung disease, and ER visit were associated with higher risk of CFS. Age, dyslipidemia, hypertension, pre-existing lung disease and duration of symptoms were negatively associated with WHO-5 score. CONCLUSIONS: Several risk factors were associated with an increased risk of PACS. Hospitalized patients with COVID-19 who are at risk for PACS may benefit from a targeted pre-emptive follow-up and rehabilitation programs.
Assuntos
COVID-19 , Dispneia , Tolerância ao Exercício , Síndrome de Fadiga Crônica , Adolescente , Adulto , Assistência ao Convalescente , Idoso , COVID-19/complicações , Estudos de Coortes , Dispneia/epidemiologia , Dispneia/virologia , Síndrome de Fadiga Crônica/virologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Adulto Jovem , Síndrome de COVID-19 Pós-AgudaRESUMO
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) affects approximately 1% of the general population. It is a chronic, disabling, multi-system disease for which there is no effective treatment. This is probably related to the limited knowledge about its origin. Here, we summarized the current knowledge about the pathogenesis of ME/CFS and revisit the immunopathobiology of Epstein-Barr virus (EBV) infection. Given the similarities between EBV-associated autoimmune diseases and cancer in terms of poor T cell surveillance of cells with EBV latency, expanded EBV-infected cells in peripheral blood and increased antibodies against EBV, we hypothesize that there could be a common etiology generated by cells with EBV latency that escape immune surveillance. Albeit inconclusive, multiple studies in patients with ME/CFS have suggested an altered cellular immunity and augmented Th2 response that could result from mechanisms of evasion to some pathogens such as EBV, which has been identified as a risk factor in a subset of ME/CFS patients. Namely, cells with latency may evade the immune system in individuals with genetic predisposition to develop ME/CFS and in consequence, there could be poor CD4 T cell immunity to mitogens and other specific antigens, as it has been described in some individuals. Ultimately, we hypothesize that within ME/CFS there is a subgroup of patients with DRB1 and DQB1 alleles that could confer greater susceptibility to EBV, where immune evasion mechanisms generated by cells with latency induce immunodeficiency. Accordingly, we propose new endeavors to investigate if anti-EBV therapies could be effective in selected ME/CFS patients.
Assuntos
Infecções por Vírus Epstein-Barr/etiologia , Síndrome de Fadiga Crônica/etiologia , Herpesvirus Humano 4/patogenicidade , Antígenos Virais/imunologia , Linfócitos B/imunologia , Linfócitos B/virologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Síndrome de Fadiga Crônica/imunologia , Síndrome de Fadiga Crônica/virologia , Predisposição Genética para Doença , Antígenos HLA-D/imunologia , Herpesvirus Humano 4/imunologia , Humanos , Imunidade Celular , Ativação Linfocitária , Modelos ImunológicosRESUMO
OBJECTIVES: This study aimed to investigate post-COVID-19 symptoms amongst elderly females and whether they could be a risk factor for developing chronic fatigue syndrome (CFS) later on. METHODS: This was a retrospective cross-sectional study, in the form of an online survey. A total of 115 responses were finally included. RESULTS: The mean age was 73.18 ± 6.42. Eighty-nine reported symptoms in the post-recovery period; of these 54 had no symptoms of CFS, 60 were possible, and only 1 was probable. Fatigue was reported by 66, musculoskeletal symptoms by 56, and sleep problems by 73. Twenty-nine patients visited a doctor's office as a result. Post-recovery symptoms were significantly related to stress, sadness and sleep disturbances. Also, stress, sadness, sleep disturbances, fatigue, cognitive impairment, and recurrent falls were all significantly associated with CFS-like symptoms. CONCLUSIONS: From our findings, the presence of fatigue, cognitive impairment, stress, sadness, sleep disturbances and recurrent falls in the post-recovery period were all significantly associated with CFS-like symptoms. To conclude it would be reasonable to screen for long COVID and consider the potential for developing CFS later on. Whether it can be a risk factor for developing CFS-like other viral infections will need more larger scale studies to confirm this.
Assuntos
COVID-19 , Síndrome de Fadiga Crônica , Idoso , COVID-19/complicações , Estudos Transversais , Egito , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/virologia , Feminino , Humanos , Estudos Retrospectivos , Sobreviventes , Síndrome de COVID-19 Pós-AgudaRESUMO
SARS-CoV-2 survivors may report persistent symptoms that resemble myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We explored (a) ME/CFS-like symptom prevalence and (b) whether axonal, inflammatory, and/or lung changes may contribute to ME/CFS-like symptoms in SARS-CoV-2 survivors through clinical, neuropsychiatric, neuropsychological, lung function assessment, and serum neurofilament light chain, an axonal damage biomarker. ME/CFS-like features were found in 27% of our sample. ME/CFS-like group showed worse sleep quality, fatigue, pain, depressive symptoms, subjective cognitive complaints, Borg baseline dyspnea of the 6-min walking test vs. those without ME/CFS-like symptoms. These preliminary findings raise concern on a possible future ME/CFS-like pandemic in SARS-CoV-2 survivors.
Assuntos
COVID-19/complicações , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/virologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , SARS-CoV-2RESUMO
The potential benefits of the scientific insights gleaned from years of treating ME/CFS for the emerging symptoms of COVID-19, and in particular Longhaul- or Longhauler-COVID-19 are discussed in this opinion article. Longhaul COVID-19 is the current name being given to the long-term sequelae (symptoms lasting beyond 6 weeks) of SARS-CoV-2 infection. Multiple case definitions for ME/CFS exist, but post-exertional malaise (PEM) is currently emerging as the 'hallmark' symptom. The inability to identify a unique trigger of ME/CFS, as well as the inability to identify a specific, diagnostic laboratory test, led many physicians to conclude that the illness was psychosomatic or non-existent. However, recent research in the US and the UK, championed by patient organizations and their use of the internet and social media, suggest underlying pathophysiologies, e.g., oxidative stress and mitochondrial dysfunction. The similarity and overlap of ME/CFS and Longhaul COVID-19 symptoms suggest to us similar pathological processes. We put forward a unifying hypothesis that explains the precipitating events such as viral triggers and other documented exposures: For their overlap in symptoms, ME/CFS and Longhaul COVID-19 should be described as Post Active Phase of Infection Syndromes (PAPIS). We further propose that the underlying biochemical pathways and pathophysiological processes of similar symptoms are similar regardless of the initiating trigger. Exploration of the biochemical pathways and pathophysiological processes should yield effective therapies for these conditions and others that may exhibit these symptoms. ME/CFS patients have suffered far too long. Longhaul COVD-19 patients should not be subject to a similar fate. We caution that failure to meet the now combined challenges of ME/CFS and Longhaul COVID-19 will impose serious socioeconomic as well as clinical consequences for patients, the families of patients, and society as a whole.
Assuntos
COVID-19/complicações , Síndrome de Fadiga Crônica/virologia , SARS-CoV-2 , Humanos , TempoRESUMO
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease characterized by severe and disabling fatigue that fails to improve with rest; it is commonly accompanied by multifocal pain, as well as sleep disruption, and cognitive dysfunction. Even mild exertion can exacerbate symptoms. The prevalence of ME/CFS in the U.S. is estimated to be 0.5-1.5 % and is higher among females. Viral infection is an established trigger for the onset of ME/CFS symptoms, raising the possibility of an increase in ME/CFS prevalence resulting from the ongoing COVID-19 pandemic. Current treatments are largely palliative and limited to alleviating symptoms and addressing the psychological sequelae associated with long-term disability. While ME/CFS is characterized by broad heterogeneity, common features include immune dysregulation and mitochondrial dysfunction. However, the underlying mechanistic basis of the disease remains poorly understood. Herein, we review the current understanding, diagnosis and treatment of ME/CFS and summarize past clinical studies aimed at identifying effective therapies. We describe the current status of mechanistic studies, including the identification of multiple targets for potential pharmacological intervention, and ongoing efforts towards the discovery of new medicines for ME/CFS treatment.
Assuntos
Descoberta de Drogas , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/complicações , Descoberta de Drogas/métodos , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/virologia , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêuticoRESUMO
As the SARS-COV-2 becomes a global pandemic, many researchers have a concern about the long COVID-19 complications. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a persistent, debilitating, and unexplained fatigue disorder. We investigated psychological morbidities such as CFS and post-traumatic stress disorder (PTSD) among survivors of COVID-19 over 6 months. All COVID-19 survivors from the university-affiliated hospital of Tehran, Iran, were assessed 6 months after infection onset by a previously validated questionnaire based on the Fukuda guidelines for CFS/EM and DSM-5 Checklist for PTSD (The Post-traumatic Stress Disorder Checklist for DSM-5 or PCL-5) to determine the presence of stress disorder and chronic fatigue problems. A total of 120 patients were enrolled. The prevalence rate of fatigue symptoms was 17.5%. Twelve (10%) screened positive for chronic idiopathic fatigue (CIF), 6 (5%) for CFS-like with insufficient fatigue syndrome (CFSWIFS), and 3 (2.5%) for CFS. The mean total scores in PCL-5 were 9.27 ± 10.76 (range:0-44), and the prevalence rate of PTSD was 5.8%. There was no significant association after adjusting between CFS and PTSD, gender, comorbidities, and chloroquine phosphate administration. The obtained data revealed the prevalence of CFS among patients with COVID-19, which is almost similar to CFS prevalence in the general population. Moreover, PTSD in patients with COVID-19 is not associated with the increased risk of CFS. Our study suggested that medical institutions should pay attention to the psychological consequences of the COVID-19 outbreak.