Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people

Abstract:

Objectives: To describe the physical and mental health of children and young people (CYP) 6 months after infection with SARS-CoV-2 and explore whether this varies by COVID-19 vaccination.

Design: A non-hospitalised, national cohort of people aged 11-17 years old with PCR-confirmed SARS-CoV-2 infection and PCR negatives matched at study invitation, by age, sex, region and date of testing who completed questionnaires 6 months after PCR testing. The questionnaire included 21 symptoms and standardised scales (eg, EQ-5D-Y and Chalder Fatigue Scale).

Results: 6407 test-positive and 6542 test-negative CYP completed the 6-month questionnaire: 60.9% of test-positive vs 43.2% of test-negative CYP reported at least one symptom 6 months post-test; 27.6% of test-positive vs 15.9% of test-negative CYP reported 3+ symptoms. Common symptoms at 6 months were tiredness and shortness of breath among both test-positive and test-negative CYP; however, the prevalence of both was higher in test-positive (38.4% and 22.8%, respectively) compared with test-negative CYP (26.7% and 10.9%, respectively). 24.5% test-positive vs 17.8% test-negative CYP met the Delphi research definition of long COVID. Mental health, well-being, fatigue and health-related quality of life scores were similar among test-positive and test-negative CYP 6 months post-test. Similarly, symptomatology was similar among COVID-19-vaccinated and COVID-19-unvaccinated test-positive and test-negative CYP.

Conclusions: Six-months post-PCR testing, CYP who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but test-positive CYP had higher symptom prevalence. Mental health, well-being, fatigue and health-related quality of life were similar among test-positive and test-negative CYP, and symptoms at 6 months were similar in COVID-19 vaccinated and unvaccinated.

Source: Pinto Pereira SM, Nugawela MD, Rojas NK, Shafran R, McOwat K, Simmons R, Ford T, Heyman I, Ladhani SN, Cheung EY, Fox-Smith L, Dalrymple E, Stephenson T. Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people. Arch Dis Child. 2023 Apr;108(4):289-295. doi: 10.1136/archdischild-2022-324656. Epub 2023 Jan 4. PMID: 36599625. https://adc.bmj.com/content/108/4/289.long (Full text)

Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis

Abstract:

Current data suggests that coronavirus disease 2019 (COVID-19) survivors experience long-lasting problems. It is not yet understood how long these symptoms last. The goal of this study was to compile all the data that was currently available to evaluate COVID-19’s long-term effects at 12 months and above.

We looked for studies published by December 15, 2022, in PubMed and Embase that discussed follow-up findings for COVID-19 survivors who had been alive for at least a year. A random-effect model was carried out to determine the combined prevalence of different long-COVID symptoms. The Joanna Briggs Institute tool was used to assess the risk of bias for the included studies, and the I2 statistics were used to evaluate the heterogeneity. After reviewing 3,209 studies, 46 were deemed admissible, with an aggregate COVID-19 population of 17976.

At 12 months and above, 57% of patients reported a minimum of one symptom, and the five most prevalent symptoms were: dyspnea on exertion (34%, 95% CI 0.2; 0.94); difficulty in concentration (32%, 95% CI 0.16; 0.52); fatigue (31%, 95% CI 0.22; 0.40); frailty (31%, 95% CI 0.06; 0.78); and arthromyalgia (28%, 95% CI 0.09; 0.6). The findings of the present study showed that at 12 months and beyond, a sizable fraction of COVID-19 survivors still have lasting symptoms that impair several body systems. Long-COVID patients require an urgent understanding of pathophysiological processes and the development of tailored treatments.

Source: Mudgal S K, Gaur R, Rulaniya S, et al. (March 18, 2023) Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis. Cureus 15(3): e36325. doi:10.7759/cureus.36325 https://www.cureus.com/articles/143288-pooled-prevalence-of-long-covid-19-symptoms-at-12-months-and-above-follow-up-period-a-systematic-review-and-meta-analysis#!/ (Full text)

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series

Abstract:

Introduction: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG).

Materials and methods: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20-30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers.

Results: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%).

Conclusion: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.

Source: Bocci T, Bertini A, Campiglio L, Botta S, Libelli G, Guidetti M, Priori A. Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series. Neurol Sci. 2023 Apr;44(4):1147-1153. doi: 10.1007/s10072-023-06637-8. Epub 2023 Feb 3. PMID: 36735149; PMCID: PMC9896447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896447/ (Full study)

Understanding pediatric long COVID using a tree-based scan statistic approach: an EHR-based cohort study from the RECOVER Program

Abstract:

Objectives: Post-acute sequalae of SARS-CoV-2 infection (PASC) is not well defined in pediatrics given its heterogeneity of presentation and severity in this population. The aim of this study is to use novel methods that rely on data mining approaches rather than clinical experience to detect conditions and symptoms associated with pediatric PASC.

Materials and methods: We used a propensity-matched cohort design comparing children identified using the new PASC ICD10CM diagnosis code (U09.9) (N = 1309) to children with (N = 6545) and without (N = 6545) SARS-CoV-2 infection. We used a tree-based scan statistic to identify potential condition clusters co-occurring more frequently in cases than controls.

Results: We found significant enrichment among children with PASC in cardiac, respiratory, neurologic, psychological, endocrine, gastrointestinal, and musculoskeletal systems, the most significant related to circulatory and respiratory such as dyspnea, difficulty breathing, and fatigue and malaise.

Discussion: Our study addresses methodological limitations of prior studies that rely on prespecified clusters of potential PASC-associated diagnoses driven by clinician experience. Future studies are needed to identify patterns of diagnoses and their associations to derive clinical phenotypes.

Conclusion: We identified multiple conditions and body systems associated with pediatric PASC. Because we rely on a data-driven approach, several new or under-reported conditions and symptoms were detected that warrant further investigation.

Source: Lorman V, Rao S, Jhaveri R, Case A, Mejias A, Pajor NM, Patel P, Thacker D, Bose-Brill S, Block J, Hanley PC, Prahalad P, Chen Y, Forrest CB, Bailey LC, Lee GM, Razzaghi H. Understanding pediatric long COVID using a tree-based scan statistic approach: an EHR-based cohort study from the RECOVER Program. JAMIA Open. 2023 Mar 14;6(1):ooad016. doi: 10.1093/jamiaopen/ooad016. PMID: 36926600; PMCID: PMC10013630. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10013630/ (Full text)

Pain Management in the Post-COVID Era-An Update: A Narrative Review

Abstract:

An extensive computer search (from January 2020 to January 2023) was conducted including literature from the PubMed, Scopus, MEDLINE, Web of Science, and EMBASE databases. According to preset criteria, a total of 58 articles were included in this review article. Generally, any patient who becomes infected with COVID-19 can develop post-COVID-19 conditions. The course of COVID-19 is divided into three main stages: acute COVID-19 (up to 4 weeks), post-acute COVID-19 (from 4 to 12 weeks), and post-COVID (from 12 weeks to 6 months). If a more protracted course of COVID (over 6 months) is demonstrated, the term “long-COVID” is used.

Although the acute stage of COVID-19 infection most commonly manifests with acute respiratory symptoms, one very common symptom of the disease is pain, while the most common symptoms of post-COVID syndrome are shortness of breath, dry cough, fatigue, loss of olfactory and gustatory function, tightness and chest pain, sleep and mood disturbances, body aches, muscle and joint pain, sore throat, fever, and persistent headaches.

All observations demonstrated a high incidence of chronic pain syndromes of various localization in the post- and long-COVID period. Post-COVID chronic pain might include a newly developed chronic pain as a part of post-viral syndrome; worsening of preexisting chronic pain due to the associated changes in the medical services, or a de novo chronic pain in healthy individuals who are not infected with COVID.

Chronic pain during and post-COVID-19 pandemic is an important health issue due to the significant impacts of pain on the patients, health care systems, and society as well. Therefore, it is important that patients with chronic pain receive effective treatment according to their specific needs. Accordingly, the main goal of this review article is to provide a broad description about the post-COVID pain and to explore the impact of long COVID-19 on chronic pain patients, and also to give brief reports about the prevalence, risk factors, possible mechanisms, different presentations, and the management tools through a systematic approach.

Source: El-Tallawy SN, Perglozzi JV, Ahmed RS, Kaki AM, Nagiub MS, LeQuang JK, Hadarah MM. Pain Management in the Post-COVID Era-An Update: A Narrative Review. Pain Ther. 2023 Apr;12(2):423-448. doi: 10.1007/s40122-023-00486-1. Epub 2023 Feb 28. PMID: 36853484; PMCID: PMC9971680. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971680/ (Full text)

Epidemiological and clinical perspectives of long COVID syndrome

Abstract:

Long COVID, or post-acute COVID-19 syndrome, is characterized by multi-organ symptoms lasting 2+ months after initial COVID-19 virus infection. This review presents the current state of evidence for long COVID syndrome, including the global public health context, incidence, prevalence, cardiopulmonary sequelae, physical and mental symptoms, recovery time, prognosis, risk factors, rehospitalization rates, and the impact of vaccination on long COVID outcomes. Results are presented by clinically relevant subgroups.

Overall, 10-35% of COVID survivors develop long COVID, with common symptoms including fatigue, dyspnea, chest pain, cough, depression, anxiety, post-traumatic stress disorder, memory loss, and difficulty concentrating. Delineating these issues will be crucial to inform appropriate post-pandemic health policy and protect the health of COVID-19 survivors, including potentially vulnerable or underrepresented groups. Directed to policymakers, health practitioners, and the general public, we provide recommendations and suggest avenues for future research with the larger goal of reducing harms associated with long COVID syndrome.

Source: Huerne K, Filion KB, Grad R, Ernst P, Gershon AS, Eisenberg MJ. Epidemiological and clinical perspectives of long COVID syndrome. Am J Med Open. 2023 Jun;9:100033. doi: 10.1016/j.ajmo.2023.100033. Epub 2023 Jan 18. PMID: 36685609; PMCID: PMC9846887. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846887/ (Full text)

Is Central Sensitisation the Missing Link of Persisting Symptoms after COVID-19 Infection?

Abstract:

Patients recovered from a COVID-19 infection often report vague symptoms of fatigue or dyspnoea, comparable to the manifestations in patients with central sensitisation. The hypothesis was that central sensitisation could be the underlying common aetiology in both patient populations. This study explored the presence of symptoms of central sensitisation, and the association with functional status and health-related quality of life, in patients post COVID-19 infection.

Patients who were previously infected with COVID-19 filled out the Central Sensitisation Inventory (CSI), the Post-COVID-19 Functional Status (PCFS) Scale and the EuroQol with five dimensions, through an online survey. Eventually, 567 persons completed the survey. In total, 29.73% of the persons had a score of <40/100 on the CSI and 70.26% had a score of ≥40/100. Regarding functional status, 7.34% had no functional limitations, 9.13% had negligible functional limitations, 37.30% reported slight functional limitations, 42.86% indicated moderate functional limitations and 3.37% reported severe functional limitations.

Based on a one-way ANOVA test, there was a significant effect of PCFS Scale group level on the total CSI score (F(4,486) = 46.17, p < 0.001). This survey indicated the presence of symptoms of central sensitisation in more than 70% of patients post COVID-19 infection, suggesting towards the need for patient education and multimodal rehabilitation, to target nociplastic pain.

Source: Goudman L, De Smedt A, Noppen M, Moens M. Is Central Sensitisation the Missing Link of Persisting Symptoms after COVID-19 Infection? J Clin Med. 2021 Nov 28;10(23):5594. doi: 10.3390/jcm10235594. PMID: 34884296; PMCID: PMC8658135. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658135/ (Full text)

Neuropathology and Neurological Manifestations in ME/CFS and Long COVID with focus on Post-Exertional Symptom Exacerbation: a Literature Review

Summary:

Many of the people that get infected with the Coronavirus develop long-lasting complaints and are diagnosed with Long COVID after the acute infection is gone. These complains can last several months or years and include fatigue, cognitive impairment, sleeping problems and post-exertional symptom exacerbation (PESE). Research shows that COVID-19 patients with an acute infection have abnormalities in their brain, which could potentially lead to long-lasting neurological problems and symptoms. However, although many researchers are trying to uncover the underlying mechanisms, Long COVID is still very new.
The underlying mechanisms causing and maintaining the disease are therefore unclear. A large group of Long COVID patients resembles patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in terms of symptoms and, in many cases, the viral trigger of the disease. A core symptom of ME/CFS is PESE, which is uncommon in other fatiguing illnesses, but frequently seen in Long COVID patients. PESE involves an abnormal worsening of symptoms and cognitive and physical functions after any type of normal activity. Because of the large symptom overlap and lack of knowledge regarding PESE, underlying brain-mechanisms associated with Long COVID and ME/CFS in general as well as after physical exertion were investigated.
The findings of this review indicate that ME/CFS is associated with several abnormalities in the brain which are also proposed to be present in Long COVID patients. Such abnormalities include inflammation of the brain, shrinkage of the brain and less blood flow to the brain. After physical exertion, these abnormalities might be exacerbated in ME/CFS patients. This results in a brain that needs to work harder than the healthy brain to complete a task. It is demonstrated by increased brain activity in several brain regions after physical exertion and general symptom exacerbation. Since the two diseases seem to have a large overlap in symptoms and underlying brain-mechanisms, this finding might apply to patients with long COVID as well. Importantly, Long COVID seems to consist of different subgroups of which a large part fulfills the criteria for ME/CFS.
Treatment and therapy for ME/CFS patients is therefore likely transferable to this subgroup of Long COVID patients, with explicit attention towards the PESE phenomenon. More research is needed to uncover the underlying mechanisms as well as correct treatment approach of these diseases. Future research should take subgroups of Long COVID into account.
Source: Rodenburg, Sanne. Neuropathology and Neurological Manifestations in ME/CFS and Long COVID with focus on Post-Exertional Symptom Exacerbation: a Literature Review. Master Thesis, Utrecht University. March 14, 2023. https://studenttheses.uu.nl/bitstream/handle/20.500.12932/43647/Rodenburg_7433050_Neuropathology%20and%20neurological%20manifestations%20in%20MECFS%20and%20Long%20COVID%20with%20focus%20on%20PESE.pdf (Full text)

Clinical and radiological outcomes of longCOVID: Is the post-COVID fibrosis common?

Abstract:

Introduction: COVID-19 survivors may take longer to regain full well-being. This study aimed to investigate clinical and functional evaluation and radiologic changes in the third month after COVID-19.

Materials and methods: A total of 126 patients were assessed in the third month for symptoms, pulmonary function, exercise capacity, radiologic imaging, and quality of life after being discharged following COVID-19 treatment. Two radiologists evaluated the initial and follow-up images.

Result: At the third month follow-up visit, the most common persisting symptoms were shortness of breath (32.5%), cough (12.7%), and muscle pain (12.7%). At the follow-up visit, oxygen saturations at rest and after a six min walking test were lower in patients with prior intensive care hospitalization compared to those without (p<0.001, p= 0.004). Computed tomography (CT) scans revealed persisting pulmonary pathologies in 64.6% of patients at the third month follow-up. The most common pathologies on follow-up thoracic CT were fibrotic-like changes in 44.2% and ground-glass opacities (GGO) in 33.3%. Regression analysis unveiled that age [95% confidence interval (CI), 1.01 to 1.15; p= 0.020], male sex (95% CI, 4.06 to 95.3, p<0.001), first CT severity score (95% CI, 1.02 to 1.41, p= 0.028), duration of hospitalization (95% CI, 1.02 to 1.18, p= 0.012), oxygen saturation (95% CI, 0.86 to 0.96, p<0.001) were independent predictors of fibrotic-like changes.

Conclusions: In the third month following COVID-19, the most common symptom was dyspnea, and the most common radiological findings were fibrotic-like changes and GGO. Longer follow-up studies of COVID-19 survivors are needed to observe lasting changes.

Source: Sarıoğlu N, Aksu GD, Çoban H, Bülbül E, Demirpolat G, Arslan AT, Erel F. Clinical and radiological outcomes of longCOVID: Is the post-COVID fibrosis common? Tuberk Toraks. 2023 Mar;71(1):48-57. English. doi: 10.5578/tt.20239907. PMID: 36912409. http://tuberktoraks.org/managete/fu_folder/2023-01/2023-71-1-48-57.pdf (Full text)

The Prevalence of Psychiatric Symptoms and their correlates as part of the Long-Covid Syndrome.

Abstract:

The Long COVID syndrome has now been documented clearly in the literature, but whether or not psychiatric symptoms are prominent is unclear. We performed a retrospective chart review of all patients receiving medical care during the pandemic in an outpatient Long-COVID specialty clinic that serves a large racial and ethnic minority population. As many as 44% of patients had symptoms that necessitated referrals to psychiatrists, predominantly depression or anxiety. Spanish speaking patients had greater COVID severity (48%) than did predominantly English speakers (15%). We conclude that the long COVID syndrome is predominantly a cluster of physical symptoms that are sequelae of the viral infection.

Source: Clifton Chow, Will Schleyer, Lynn E DeLisi. The Prevalence of Psychiatric Symptoms and their correlates as part of the Long-Covid Syndrome. Psychiatry Research, 2023, 115166, ISSN 0165-1781, https://doi.org/10.1016/j.psychres.2023.115166. https://www.sciencedirect.com/science/article/pii/S0165178123001178