Myalgic encephalomyelitis/chronic fatigue syndrome post coronavirus disease 2019

Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been the most impactful infectious disease in the 21st century. The SARS-CoV-2 pandemic significantly increased the number of patients and deaths worldwide. Long-course diseases related to COVID-19, which present with persistent reparatory distress or fatigue (so-called long COVID) have been reported in adult and pediatric patients since the latter half of 2020. Long-COVID is observed as a persistent symptom after the acute phase of the disease.1 Recent research suggested that it can present with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).2 We report a case of long COVID to contribute to the body of knowledge regarding this disease, which has not been well investigated in children.

A 14-year-old boy with well controlled asthma, controlled by a long-acting muscarinic antagonist, long-acting beta-agonist, and corticosteroid inhaler, was admitted to our hospital for severe fatigue and appetite loss. He suffered from COVID-19 diagnosed using reverse transcription polymerase chain reaction 90 days prior to hospitalization. He presented with a low-grade fever, mild cough, dysgeusia, and dysosmia. He was placed under quarantine in a hotel room for 6 days. His low-grade fever and mild cough resolved after 10 days, while the dysgeusia and dysosmia disappeared within a month. He presented with gradually progressive upper limb muscle weakness, severe fatigue, and difficulty concentrating (so-called “brain fog”) 20 days before hospitalization (70 days after the onset of COVID-19). He was unable to commute to attend junior high school. Three days before hospitalization, the patient did not eat due to appetite loss. He received oral prednisolone (20 mg/day) and Kanpō medicine (Rikkun-shito and Hotyu-ekkito). However, his symptoms were not relieved, and the patient was hospitalized. At the time of hospitalization, he did not present with fever, dyspnea, or desaturation. Physical examination revealed an upper limb strength of grade 4 on manual muscle testing, but the tendon reflexes or sensory/motor nerve abnormalities were not noted in the extremities. Blood tests revealed normal white blood cell and C-reactive protein levels. Epstein–Barr virus and human immunodeficiency virus antibodies and antinuclear antibodies were not detected. The 10 min standing test revealed an increase of 52 heartbeats after standing at an upright position (from 81 to 133 beats/min). The patient was diagnosed with postural orthostatic tachycardia syndrome (POTS). After the test, the patient complained of worsening fatigue, suggesting post-exertional malaise (PEM), a specific characteristic of ME/CFS. Based on the clinical course and physical examination, the patient was diagnosed with ME/CFS due to long-COVID. Oral prednisolone was discontinued, while the Kanpō medicine was continued. The patient then developed alopecia. Meanwhile, his muscle weakness and fatigue were alleviated by activity restriction due to hospitalization. On the 14th day of admission, he was discharged because his appetite improved, and he was referred to a hospital that specifically tended to chronic fatigue syndrome patients. Neither brain imaging nor electroencephalography were performed throughout the patient’s hospitalization.

The National Institute for Health Research in England classified long-COVID into four categories, namely, post-ICU syndrome, long-term organ damage, post-viral syndrome, and an entirely novel syndrome.3 Myalgic encephalomyelitis/chronic fatigue syndrome is typical of post-viral syndromes in adults, and similar cases have also been reported in children.4 Females are more likely to suffer from the disease, but males could also be affected. The exacerbation of symptoms upon exertion is known as PEM; avoiding extensive work is the essential aspect of ME/CFS management.5 In this case, the patient’s muscle fatigue and weakness dramatically improved with activity restriction due to hospitalization. This strategy may be useful for treating the severe exacerbation of ME/CFS. Chronic fatigue syndrome is diagnosed based on the persistence of symptoms for more than 6 months.2 This implies that patients have to wait for 6 months to be diagnosed with ME/CFS. Thus, new diagnostic criteria, specifically for ME/CFS due to COVID, are required to allow early intervention. Petracek et al. reported that POTS might be an early sign of COVID-induced ME/CFS,4 POTS is considered to be a viable diagnostic criterion. To prepare for a surge of pediatric ME/CFS, the diagnostic and treatment algorithm for the disease should be standardized, and physicians need to know about or recognize the disease.

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Source: Kusama Y, Fukui S, Maruyama M, Kamimura K, Maihara T. Myalgic encephalomyelitis/chronic fatigue syndrome post coronavirus disease 2019. Pediatr Int. 2022 Jan;64(1):e14976. doi: 10.1111/ped.14976. PMID: 35143110. https://onlinelibrary.wiley.com/doi/10.1111/ped.14976 (Full text)

Pediatric Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Overlaps and Opportunities

David Spodick once wrote: “We must view published material critically (if not biblically), for too often the ‘Conclusions’ giveth, but the ‘Materials and Methods’ taketh away.” In the December 2021 issue of the Pediatric Infectious Diseases Journal, Zimmermann et al provide a masterful application of Spodick’s exhortation. Their review of the existing evidence regarding long COVID in children enumerates important methodologic challenges in interpreting this literature, including the heterogeneity of available case definitions for long COVID, differences in the time intervals in which symptoms are ascertained, variability regarding which symptoms are included under the rubric of long COVID, and whether laboratory confirmation of the initial COVID infection is required. Additionally, the authors emphasize that without control groups in many of these studies, and in light of the overlap of some long COVID symptoms with symptoms of prolonged social isolation, it is difficult to discern which symptoms are attributable to the general pandemic circumstances rather than the COVID-19 infection itself. Despite such limitations, it is clear that pediatric patients are at risk for prolonged symptoms following acute SARS-CoV-2 infection. Although many persistent symptoms, such as anosmia, dysgeusia and shortness of breath are unique to the post-COVID state, many other symptoms such as fatigue, cognitive dysfunction, lightheadedness and postexertional malaise overlap with symptoms found in myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). In this commentary, we review case definitions for long COVID and ME/CFS, emphasize recent research findings on the biologic basis of ME/CFS, discuss the overlap with long COVID, and consider opportunities posed by the pandemic to improve the understanding of both conditions

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Source: Siberry VGR, Rowe PC. Pediatric Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Overlaps and Opportunities. Pediatr Infect Dis J. 2022 Feb 4. doi: 10.1097/INF.0000000000003477. Epub ahead of print. PMID: 35121715. https://journals.lww.com/pidj/Citation/9000/Pediatric_Long_COVID_and_Myalgic.95546.aspx (Full text)

Long COVID: to investigate immunological mechanisms and sex/gender related aspects as fundamental steps for tailored therapy

Introduction:

Around a quarter of people who have had coronavirus disease 2019 (COVID-19) experience symptoms that continue for at least 1 month, but one in ten are still unwell after 12 weeks. This very debilitating condition has been defined by patient groups as “long COVID”, elsewhere called post-COVID, whereas the patients are frequently called COVID-19 long-haulers [1]. Long COVID has a serious impact on patient ability to go back to work or school, to have a social life and may have significant economic consequences for patients, their families and for society.

The condition is characterised by long-term sequelae and can involve a range of about 200 different and overlapping symptoms, such as persistent fatigue, chest and muscle pain, headache, shortness of breath, anosmia, muscle weakness, fever, cognitive dysfunction (brain fog), tachycardia, intestinal disorders and skin manifestations. It can affect anyone, but women appear to be twice as likely to develop long COVID as men, but only until around age 60 years, when the risk level becomes similar [2–4]. Long COVID has also been described in paediatric patients [5]. An Italian study reported that at least one symptom persisted 4 months after COVID-19 infection [6] whereas an Australian analysis suggested that only 8% of children had ongoing symptoms 3–6 months after mild SARS-CoV-2 infection [7]. No gender difference was observed in the prevalence of long COVID in this population [5].

Source: Elena Ortona, Walter Malorni. Long COVID: to investigate immunological mechanisms and sex/gender related aspects as fundamental steps for tailored therapy. European Respiratory Journal Feb 2022, 59 (2) 2102245; DOI: 10.1183/13993003.02245-2021. https://erj.ersjournals.com/content/59/2/2102245?rss=1  (Full text)

Long covid in children and adolescents

Editorial:

Risk appears low, but many questions remain

Symptoms involving almost every organ system have been reported after SARS-CoV-2 infection.123 Estimates of the prevalence of long covid (also called post-covid-19 condition, post-acute sequelae of covid-19, or chronic covid syndrome) vary considerably, partly because of confusion around the definition. The term long covid encompasses a broad range of symptoms, including objective complications of covid-19 (pulmonary fibrosis, myocardial dysfunction), mental health conditions, and more subjective, non-specific symptoms resembling those seen in post-viral chronic fatigue syndrome (myalgic encephalomyelitis). Most studies to date have substantial limitations, including small cohorts, absence of control groups, non-standardised capture of symptoms, lack of correction for pre-existing medical conditions, participant reported infection, and variation in follow-up, as well as selection, non-response, misclassification, and recall biases.4

In children and adolescents, acute covid-19 is less severe than in adults.56 Concern among many parents has therefore focused more on the potential long term effects of SARS-CoV-2 infection. Unfortunately, fewer data are available on long covid in young people compared with adults.7 The widely quoted one in seven frequency in children is based on a study with a 13% response rate.78

The linked study by Magnusson and colleagues (doi:10.1136/bmj-2021-066809) used nationwide register data from Norway to estimate the impact of covid-19 on long term healthcare use among 1.3 million children and adolescents.9 The authors identified a short term increase in primary (but not specialist) care use after covid-19 in all the studied age groups. This increase was related to respiratory and general or non-specific conditions, mostly in the four weeks after infection. The increase in primary care use persisted for up to six months among children aged 1-5 years. Notably, covid-19 in children had limited overall impact on healthcare services.

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Source: Petra Zimmermann. Long covid in children and adolescents. BMJ 2022; 376 doi: https://doi.org/10.1136/bmj.o143 (Published 20 January 2022) https://www.bmj.com/content/376/bmj.o143.full (Full article)

Long COVID symptoms and duration in SARS-CoV-2 positive children – a nationwide cohort study

Abstract:

Most children have a mild course of acute COVID-19. Only few mainly non-controlled studies with small sample size have evaluated long-term recovery from SARS-CoV-2 infection in children. The aim of this study was to evaluate symptoms and duration of ‘long COVID’ in children. A nationwide cohort study of 37,522 children aged 0-17 years with RT-PCR verified SARS-CoV-2 infection (response rate 44.9%) and a control group of 78,037 children (response rate 21.3%).

An electronic questionnaire was sent to all children from March 24th until May 9th, 2021. Symptoms lasting > 4 weeks were common among both SARS-CoV-2 children and controls. However, SARS-CoV-2 children aged 6-17 years reported symptoms more frequently than the control group (percent difference 0.8%). The most reported symptoms among pre-school children were fatigue Risk Difference (RD) 0.05 (CI 0.04-0.06), loss of smell RD 0.01 (CI 0.01-0.01), loss of taste RD 0.01 (CI 0.01-0.02) and muscle weakness RD 0.01 (CI 0.00-0.01). Among school children the most significant symptoms were loss of smell RD 0.12 (CI 0.12-0.13), loss of taste RD 0.10 (CI 0.09-0.10), fatigue RD 0.05 (CI 0.05-0.06), respiratory problems RD 0.03 (CI 0.03-0.04), dizziness RD 0.02 (CI 0.02-0.03), muscle weakness RD 0.02 (CI 0.01-0.02) and chest pain RD 0.01 (CI 0.01-0.01). Children in the control group experienced significantly more concentration difficulties, headache, muscle and joint pain, cough, nausea, diarrhea and fever than SARS-CoV-2 infected. In most children ‘long COVID’ symptoms resolved within 1-5 months.

Conclusions: Long COVID in children is rare and mainly of short duration.

What is Known:

• There are increasing reports on ‘long COVID’ in adults.

• Only few studies have evaluated the long-term recovery from COVID-19 in children, and common for all studies is a small sample size (median number of children included 330), and most lack a control group.

What is New:

• 0.8% of SARS-CoV-2 positive children reported symptoms lasting >4 weeks (‘long COVID’), when compared to a control group.

• The most common ‘long COVID’ symptoms were fatigue, loss of smell and loss of taste, dizziness, muscle weakness, chest pain and respiratory problems.

• These ‘long COVID’ symptoms cannot be assigned to psychological sequelae of social restrictions.

• Symptoms such as concentration difficulties, headache, muscle- and joint pain as well as nausea are not ‘long COVID’ symptoms.

• In most cases ‘long COVID’ symptoms resolve within 1-5 months.

Source: Borch L, Holm M, Knudsen M, Ellermann-Eriksen S, Hagstroem S. Long COVID symptoms and duration in SARS-CoV-2 positive children – a nationwide cohort study. Eur J Pediatr. 2022 Jan 9:1–11. doi: 10.1007/s00431-021-04345-z. Epub ahead of print. PMID: 35000003; PMCID: PMC8742700. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742700/ (Full text)

Long COVID-The New “Invisible” Illness: How School Nurses Can Support the Nursing and Educational Teams for Student Success

Abstract:

School-age children are not immune to COVID-19 or the pronounced and persistent symptoms associated with a long-COVID diagnosis. Students may present with a variety of symptoms affecting their physical, cognitive, and mental health. The school community should be educated on the school-based interventions and recommendations for creating an individualized safe and successful return to school plan. As we await approval for vaccinations in school-age children younger than 12 years and continue to reposition ourselves to the waves of this pandemic and new variants of the virus, understanding the medical and educational long-term effects on our students may be a long-term need.

Source: Roesler M, Fato P, Obst B. Long COVID-The New “Invisible” Illness: How School Nurses Can Support the Nursing and Educational Teams for Student Success. NASN Sch Nurse. 2021 Dec 10:1942602X211059427. doi: 10.1177/1942602X211059427. Epub ahead of print. PMID: 34889154. https://pubmed.ncbi.nlm.nih.gov/34889154/

Spectrum of SARS-CoV-2-Related Clinical Syndromes in Children: A Year in the Life

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a wide pediatric clinical spectrum. Initial reports suggested that children had milder symptoms compared with adults; then diagnosis of multisystem inflammatory syndrome in children (MIS-C) emerged. We performed a retrospective cohort study of hospitalized patients at a children’s hospital over 1 year. Our objectives were to study the demographic and clinical profile of pediatric SARS-CoV-2-associated diagnoses.

Based on the clinical syndrome, patients were classified into coronavirus disease 2019 (COVID-19; non-MIS-C) and MIS-C cohorts. Among those who tested positive, 67% were symptomatic. MIS-C was diagnosed in 24 patients. Both diagnoses were more frequent in Caucasians. Both cohorts had different symptom profiles.

Inflammatory markers were several-fold higher in MIS-C patients. These patients had critical care needs and longer hospital stays. More COVID-19 patients had respiratory complications, while MIS-C cohort saw cardiovascular involvement. Health care awareness of both syndromes is important for early recognition, diagnosis, and prompt treatment.

Source: Khan M, Dang L, Singh H, Dalrymple A, Miller A, Tanios A. Spectrum of SARS-CoV-2-Related Clinical Syndromes in Children: A Year in the Life. Clin Pediatr (Phila). 2021 Dec 3:99228211064655. doi: 10.1177/00099228211064655. Epub ahead of print. PMID: 34859714. https://pubmed.ncbi.nlm.nih.gov/34859714/