Tag: pediatric long covid

Orbito-Frontal Cortex Hypometabolism in Children With Post-COVID Condition (Long COVID): A Preliminary Experience

Abstract:

We describe 3 children with new-onset neurocognitive problems after coronavirus disease 2019 (COVID-19), that showed, at the brain [18F]-fluorodeoxyglucose positron emission tomography/computed tomography, hypometabolism in the left orbito-frontal region. The voxel-wise analysis confirmed a cluster of hypometabolic voxels in this region with a peak at -18/46/-4mm (179 voxels, T-Score 8.1). These findings may explain neurocognitive symptoms that some children develop after COVID-19 and require further investigations.

Source: Cocciolillo F, Di Giuda D, Morello R, De Rose C, Valentini P, Buonsenso D. Orbito-Frontal Cortex Hypometabolism in Children With Post-COVID Condition (Long COVID): A Preliminary Experience. Pediatr Infect Dis J. 2022 Aug 1;41(8):663-665. doi: 10.1097/INF.0000000000003578. Epub 2022 Jul 13. PMID: 35839175.  https://pubmed.ncbi.nlm.nih.gov/35839175/

Long COVID in children and young people: uncertainty and contradictions

AN EVOLVING PICTURE:

‘Long COVID’ describes both ongoing symptomatic COVID-19 (5–12 weeks after onset) and post-COVID-19 syndrome (≥12 weeks after onset).1 Long COVID is also a patient-preferred term2 so will be used throughout this editorial to describe symptoms lasting ≥4 weeks after an acute episode of COVID-19.

As the phenomenon of long COVID emerged and came to be recognised, including with the publication of the guideline by the National Institute for Health and Care Excellence, Scottish Intercollegiate Guideline Network, and the Royal College of General Practitioners,1 there was still limited evidence about whether children and young people could suffer with prolonged symptoms following an acute COVID-19 infection. The general opinion was still that SARS-CoV-2 was a mild infection in the young.3

Narratives emerged, however, from parents describing prolonged problems in their children, following an acute COVID- 19 infection,4 and this was borne out in the scientific literature.5

Jasmin (young person with long COVID) describes her situation: ‘I’m Jasmin. I am 11 years old and I have suffered from long COVID for over a year. I was perfectly fit and happy, and enjoyed doing sports. Having long COVID has really changed my life in many different ways. I can’t go to school much anymore, I don’t see my friends, I can’t exercise, I can’t even walk far without a wheelchair. I think that a lot of people don’t understand what the illness is and how difficult it is for me.’

The prevalence of long COVID in children is disputed. Evidence from the CLoCK study,6 which recruited a cohort of 11–17- year- olds from the general UK population between January and March 2021, gives a broad estimate. The study reported 66.5% of children had symptoms 3 months after a positive polymerase chain reaction (PCR) test, compared with 53.3% who had a negative test; 30.3% versus 16.2% had ≥3 symptoms at 3 months. The big limitation of this study was the response rate of only 13.4%. The researchers say that if this 13.4% is representative of all 11–17 year olds who have tested positive for COVID-19, over 32 000 (one in seven) young people throughout England would still have ≥3 physical symptoms 3 months later. However, if only teenagers who responded to the survey had any persisting problems and those who chose not to respond had completely recovered, this would mean a best-case scenario of 4000 cases of long COVID in children and young people.

The Office for National Statistics prevalence estimates indicate that 149 000 children and young people (aged 5–16 years) had symptoms lasting for ≥4 weeks after infection, 31 000 of whom have had symptoms for over a year.7 The impact of the Delta and Omicron waves on these figures is yet to be determined.

Read the rest of this article HERE.

Source: Carolyn A Chew-Graham, Tracy A Briggs and Binita Kane. Long COVID in children and young people: uncertainty and contradictions. British Journal of General Practice 2022; 72 (719): 253-254. DOI: https://doi.org/10.3399/bjgp22X719501  https://bjgp.org/content/72/719/253 (Full text)

Recommendation for standardized medical care for children and adolescents with long COVID

Abstract:

in English, German

This current consensus paper for long COVID complements the existing AWMF S1 guidelines for long COVID with a detailed overview on the various clinical aspects of long COVID in children and adolescents. Members of 19 different pediatric societies of the DGKJ convent and collaborating societies together provide expert-based recommendations for the clinical management of long COVID based on the currently available but limited academic evidence for long COVID in children and adolescents. It contains screening questions for long COVID and suggestions for a structured, standardized pediatric medical history and diagnostic evaluation for patients with suspected long COVID. A time and resource-saving questionnaire, which takes the clinical complexity of long COVID into account, is offered via the DGKJ and DGPI websites as well as additional questionnaires suggested for an advanced screening of specific neurocognitive and/or psychiatric symptoms including post-exertional malaise (PEM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). According to the individual medical history as well as clinical signs and symptoms a step by step diagnostic procedure and a multidisciplinary therapeutic approach are recommended.

Source: Töpfner N; Deutsche Gesellschaft für Pädiatrische Infektiologie e. V. (DGPI), Alberer M, Ankermann T; Gesellschaft für Pädiatrische Pneumologie e. V. (GPP), Bender S; Deutsche Gesellschaft für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie e. V. (DGKJP), Berner R, de Laffolie J; Gesellschaft für Pädiatrische Gastroenterologie und Ernährung e. V. (GPGE), Dingemann J; Deutsche Gesellschaft für Kinderchirurgie e. V. (DGKCH), Heinicke D; Bündnis Kinder- und Jugendreha e. V. (BKJR), Haas JP; Gesellschaft für Kinder- und Jugendrheumatologie (GKJR), Hufnagel M, Hummel T; Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V. (DGHNO-KHC), Huppertz HI; Deutsche Akademie für Kinder- und Jugendmedizin (DAKJ), Knuf M, Kobbe R, Lücke T; Gesellschaft für Neuropädiatrie e. V. (GNP), Riedel J; Deutsche Gesellschaft für Sozialpädiatrie und Jugendmedizin (DGSPJ), Rosenecker J; Deutsche Gesellschaft für Pädiatrische Rehabilitation und Prävention e. V. (DGpRP), Wölfle J; Deutsche Gesellschaft für Kinderendokrinologie und -diabetologie e. V. (DGKED), Schneider B; Deutsche Gesellschaft für Schlafforschung und Schlafmedizin e. V. (DGSM), Schneider D; Deutsche Gesellschaft für Kinder- und Jugendmedizin e. V. (DGKJ), Schriever V; Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V. (DGHNO-KHC), Schroeder A; Gesellschaft für Neuropsychologie (GNP), Stojanov S, Tenenbaum T, Trapp S; Berufsverband der Kinder- und Jugendärzte e. V. (BVKJ), Vilser D; Deutsche Gesellschaft für Pädiatrische Kardiologie und Angeborene Herzfehler e. V. (DGPK), Brinkmann F, Behrends U. Einheitliche Basisversorgung von Kindern und Jugendlichen mit Long COVID: Stellungnahme einer multidisziplinären Arbeitsgruppe der DGKJ-Konvent-Gesellschaften (Stand: Februar 2022) [Recommendation for standardized medical care for children and adolescents with long COVID]. Monatsschr Kinderheilkd. 2022 May 25;170(6):1-9. German. doi: 10.1007/s00112-021-01408-1. Epub ahead of print. PMID: 35637934; PMCID: PMC9131710. https://pubmed.ncbi.nlm.nih.gov/35637934/ (Full article available in German)

Association of Congenital and Acquired Cardiovascular Conditions With COVID-19 Severity Among Pediatric Patients in the US

Abstract:

Importance: Identifying the associations between severe COVID-19 and individual cardiovascular conditions in pediatric patients may inform treatment.

Objective: To assess the association between previous or preexisting cardiovascular conditions and severity of COVID-19 in pediatric patients.

Design, setting, and participants: This retrospective cohort study used data from a large, multicenter, electronic health records database in the US. The cohort included patients aged 2 months to 17 years with a laboratory-confirmed diagnosis of COVID-19 or a diagnosis code indicating infection or exposure to SARS-CoV-2 at 85 health systems between March 1, 2020, and January 31, 2021.

Exposures: Diagnoses for 26 cardiovascular conditions between January 1, 2015, and December 31, 2019 (before infection with SARS-CoV-2).

Main outcomes and measures: The main outcome was severe COVID-19, defined as need for supplemental oxygen or in-hospital death. Mixed-effects, random intercept logistic regression modeling assessed the significance and magnitude of associations between 26 cardiovascular conditions and COVID-19 severity. Multiple comparison adjustment was performed using the Benjamini-Hochberg false discovery rate procedure.

Results: The study comprised 171 416 pediatric patients; the median age was 8 years (IQR, 2-14 years), and 50.28% were male. Of these patients, 17 065 (9.96%) had severe COVID-19. The random intercept model showed that the following cardiovascular conditions were associated with severe COVID-19: cardiac arrest (odds ratio [OR], 9.92; 95% CI, 6.93-14.20), cardiogenic shock (OR, 3.07; 95% CI, 1.90-4.96), heart surgery (OR, 3.04; 95% CI, 2.26-4.08), cardiopulmonary disease (OR, 1.91; 95% CI, 1.56-2.34), heart failure (OR, 1.82; 95% CI, 1.46-2.26), hypotension (OR, 1.57; 95% CI, 1.38-1.79), nontraumatic cerebral hemorrhage (OR, 1.54; 95% CI, 1.24-1.91), pericarditis (OR, 1.50; 95% CI, 1.17-1.94), simple biventricular defects (OR, 1.45; 95% CI, 1.29-1.62), venous embolism and thrombosis (OR, 1.39; 95% CI, 1.11-1.73), other hypertensive disorders (OR, 1.34; 95% CI, 1.09-1.63), complex biventricular defects (OR, 1.33; 95% CI, 1.14-1.54), and essential primary hypertension (OR, 1.22; 95% CI, 1.08-1.38). Furthermore, 194 of 258 patients (75.19%) with a history of cardiac arrest were younger than 12 years.

Conclusions and relevance: The findings suggest that some previous or preexisting cardiovascular conditions are associated with increased severity of COVID-19 among pediatric patients in the US and that morbidity may be increased among individuals children younger than 12 years with previous cardiac arrest.

Source: Ehwerhemuepha L, Roth B, Patel AK, Heutlinger O, Heffernan C, Arrieta AC, Sanger T, Cooper DM, Shahbaba B, Chang AC, Feaster W, Taraman S, Morizono H, Marano R. Association of Congenital and Acquired Cardiovascular Conditions With COVID-19 Severity Among Pediatric Patients in the US. JAMA Netw Open. 2022 May 2;5(5):e2211967. doi: 10.1001/jamanetworkopen.2022.11967. PMID: 35579899. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2792374 (Full text)

Serum NGF and BDNF in Long-COVID-19 Adolescents: A Pilot Study

Abstract:

COVID-19 (COronaVIrus Disease 19) is an infectious disease also known as an acute respiratory syndrome caused by the SARS-CoV-2. Although in children and adolescents SARS-CoV-2 infection produces mostly mild or moderate symptoms, in a certain percentage of recovered young people a condition of malaise, defined as long-COVID-19, remains. To date, the risk factors for the development of long-COVID-19 are not completely elucidated. Neurotrophins such as NGF (Nerve Growth Factor) and BDNF (Brain-Derived Neurotrophic Factor) are known to regulate not only neuronal growth, survival and plasticity, but also to influence cardiovascular, immune, and endocrine systems in physiological and/or pathological conditions; to date only a few papers have discussed their potential role in COVID-19.

In the present pilot study, we aimed to identify NGF and BDNF changes in the serum of a small cohort of male and female adolescents that contracted the infection during the second wave of the pandemic (between September and October 2020), notably in the absence of available vaccines. Blood withdrawal was carried out when the recruited adolescents tested negative for the SARS-CoV-2 (“post-infected COVID-19”), 30 to 35 days after the last molecular test. According to their COVID-19 related outcomes, the recruited individuals were divided into three groups: asymptomatics, acute symptomatics and symptomatics that over time developed long-COVID-19 symptoms (“future long-COVID-19”). As a control group, we analyzed the serum of age-matched healthy controls that did not contract the infection. Inflammatory biomarkers (TNF-α, TGF-β), MCP-1, IL-1α, IL-2, IL-6, IL-10, IL-12) were also analyzed with the free oxygen radicals’ presence as an oxidative stress index.

We showed that NGF serum content was lower in post-infected-COVID-19 individuals when compared to healthy controls; BDNF levels were found to be higher compared to healthy individuals only in post-infected-COVID-19 symptomatic and future long-COVID-19 girls, leaving the BDNF levels unchanged in asymptomatic individuals if compared to controls. Oxidative stress and inflammatory biomarkers were unchanged in male and female adolescents, except for TGF-β that, similarly to BDNF, was higher in post-infected-COVID-19 symptomatic and future long-COVID-19 girls. We predicted that NGF and/or BDNF could be used as early biomarkers of COVID-19 morbidity in adolescents.

Source: Petrella C, Nenna R, Petrarca L, Tarani F, Paparella R, Mancino E, Di Mattia G, Conti MG, Matera L, Bonci E, Ceci FM, Ferraguti G, Gabanella F, Barbato C, Di Certo MG, Cavalcanti L, Minni A, Midulla F, Tarani L, Fiore M. Serum NGF and BDNF in Long-COVID-19 Adolescents: A Pilot Study. Diagnostics (Basel). 2022 May 7;12(5):1162. doi: 10.3390/diagnostics12051162. PMID: 35626317. https://www.mdpi.com/2075-4418/12/5/1162/htm (Full text)

Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol

Abstract:

Background: Emerging evidence shows that both adults and children may develop post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this study is to characterise and compare long-term post-SARS-CoV-2 infection outcomes in adults and children in a defined region in Italy.

Methods: A prospective cohort study including children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection and their household members. Participants were assessed via telephone and face-to-face visits up to 12 months post-SARS-CoV-2 diagnosis of household index case, using the ISARIC COVID-19 follow-up survey.

Results: Of 507 participants from 201 households, 56.4% (286/507) were children, 43.6% (221/507) adults. SARS-CoV-2 positivity was 87% (249/286) in children, and 78% (172/221) in adults. The mean age of PCR positive children was 10.4 (SD = 4.5) and of PCR positive adults was 44.5 years (SD = 9.5), similar to the PCR negative control groups [children 10.5 years (SD = 3.24), adults 42.3 years (SD = 9.06)]. Median follow-up post-SARS-CoV-2 diagnosis was 77 days (IQR 47-169). A significantly higher proportion of adults compared to children reported at least one persistent symptom (67%, 68/101 vs. 32%, 57/179, p < 0.001) at the first follow up. Adults had more frequently coexistence of several symptom categories at both follow-up time-points. Female gender was identified as a risk factor for PASC in adults (p 0.02 at 1-3 months and p 0.01 at 6-9 months follow up), but not in children. We found no significant correlation between adults and children symptoms. In the paediatric group, there was a significant difference in persisting symptoms between those with confirmed SARS-CoV-2 infection compared to controls at 1-3 months follow up, but not at 6-9 months. Conversely, positive adults had a higher frequency of persisting symptoms at both follow-up assessments.

Conclusion: Our data highlights that children can experience persistent multisystemic symptoms months after diagnosis of mild acute SARS-CoV-2 infection, although less frequently and less severely than co-habitant adults. There was no correlation between symptoms experienced by adults and children living in the same household. Our data highlights an urgent need for studies to characterise PASC in whole populations and the wider impact on families.

Source: Buonsenso D, Munblit D, Pazukhina E, Ricchiuto A, Sinatti D, Zona M, De Matteis A, D’Ilario F, Gentili C, Lanni R, Rongai T, Del Balzo P, Fonte MT, Valente M, Zampino G, De Rose C, Sigfrid L, Valentini P; FIMP-Roma. Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol. Front Pediatr. 2022 Apr 21;10:834875. doi: 10.3389/fped.2022.834875. PMID: 35529336; PMCID: PMC9070551.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070551/ (Full text)

Long COVID (post-COVID-19 condition) in children: a modified Delphi process

Abstract:

Objective: The aim of this study was to derive a research definition for ‘Long COVID (post-COVID-19 condition)’ in children and young people (CYP) to allow comparisons between research studies.

Design: A three-phase online Delphi process was used, followed by a consensus meeting. Participants were presented with 49 statements in each phase and scored them from 1 to 9 based on how important they were for inclusion in the research definition of Long COVID in CYP. The consensus meeting was held to achieve representation across the stakeholder groups. Statements agreed at the consensus meeting were reviewed by participants in the Patient and Public Involvement (PPI) Research Advisory Group.

Setting: The study was conducted remotely using online surveys and a virtual consensus meeting.

Participants: 120 people with relevant expertise were divided into three panels according to their area of expertise: Service Delivery, Research (or combination of research and service delivery) and Lived Experience. The PPI Research Advisory group consisted of CYP aged 11-17 years.

Main outcome measures: Consensus was defined using existing guidelines. If consensus was achieved in two or more panels or was on the border between one and two panels, those statements were discussed and voted on at the consensus meeting.

Results: Ten statements were taken forward for discussion in the consensus meeting and five statements met threshold to be included in the research definition of Long COVID among CYP. The research definition, aligned to the clinical case definition of the WHO, is proposed as follows: Post-COVID-19 condition occurs in young people with a history of confirmed SARS-CoV-2 infection, with at least one persisting physical symptom for a minimum duration of 12 weeks after initial testing that cannot be explained by an alternative diagnosis. The symptoms have an impact on everyday functioning, may continue or develop after COVID infection, and may fluctuate or relapse over time. The positive COVID-19 test referred to in this definition can be a lateral flow antigen test, a PCR test or an antibody test.

Conclusions: This is the first research definition of Long COVID (post-COVID-19 condition) in CYP and complements the clinical case definition in adults proposed by the WHO.

Source: Stephenson T, Allin B, Nugawela MD, Rojas N, Dalrymple E, Pinto Pereira S, Soni M, Knight M, Cheung EY, Heyman I; CLoCk Consortium, Shafran R. Long COVID (post-COVID-19 condition) in children: a modified Delphi process. Arch Dis Child. 2022 Apr 1:archdischild-2021-323624. doi: 10.1136/archdischild-2021-323624. Epub ahead of print. PMID: 35365499; PMCID: PMC8983414. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983414/ (Full text)

Long-term outcomes of pediatric infections: from traditional infectious diseases to long covid

Abstract:

There is limited evidence available on the long-term impact of SARS-CoV-2 infection in children. In this article, the authors analyze the recent evidence on pediatric long covid and lessons learnt from a pediatric post-covid unit in Rome, Italy. To gain a better understanding of the concerns raised by parents and physicians in relation to the potential long-term consequences of this novel infection, it is important to recognize that long-term effect of a post-infectious disease is not a new phenomenon.

Source: Buonsenso D, Di Gennaro L, Rose C, Morello R, D’Ilario F, Zampino G, Piazza M, Boner AL, Iraci C, O’Connell S, Cohen VB, Esposito S, Munblit D, Reena J, Sigfrid L, Valentini P. Long-term outcomes of pediatric infections: from traditional infectious diseases to long covid. Future Microbiol. 2022 Mar 10:10.2217/fmb-2022-0031. doi: 10.2217/fmb-2022-0031. Epub ahead of print. PMID: 35264003; PMCID: PMC8910780.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910780/ (Full text)

Long-Term COVID 19 Sequelae in Adolescents: the Overlap with Orthostatic Intolerance and ME/CFS

Abstract

Purpose of Review: To discuss emerging understandings of adolescent long COVID or post-COVID-19 conditions, including proposed clinical definitions, common symptoms, epidemiology, overlaps with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and orthostatic intolerance, and preliminary guidance on management.

Recent Findings: The recent World Health Organization clinical case definition of post-COVID-19 condition requires a history of probable or confirmed SARS-CoV-2 infection, with symptoms starting within 3 months of the onset of COVID-19. Symptoms must last for at least 2 months and cannot be explained by an alternative diagnosis.

Common symptoms of the post-COVID-19 condition include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction. These symptoms generally have an impact on everyday functioning.

The incidence of prolonged symptoms following SARS-CoV-2 infection has proven challenging to define, but it is now clear that those with relatively mild initial infections, without severe initial respiratory disease or end-organ injury, can still develop chronic impairments, with symptoms that overlap with conditions like ME/CFS (profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance).

Summary: We do not yet have a clear understanding of the mechanisms by which individuals develop post-COVID-19 conditions. There may be several distinct types of long COVID that require different treatments.

At this point, there is no single pharmacologic agent to effectively treat all symptoms. Because some presentations of post-COVID-19 conditions mimic disorders such as ME/CFS, treatment guidelines for this and related conditions can be helpful for managing post-COVID-19 symptoms.

Source: Morrow, A.K., Malone, L.A., Kokorelis, C. et al. Long-Term COVID 19 Sequelae in Adolescents: the Overlap with Orthostatic Intolerance and ME/CFS. Curr Pediatr Rep (2022). https://doi.org/10.1007/s40124-022-00261-4  (Full text)

Long-Term COVID 19 Sequelae in Adolescents: the Overlap with Orthostatic Intolerance and ME/CFS

Abstract:

Purpose of review: To discuss emerging understandings of adolescent long COVID or post-COVID-19 conditions, including proposed clinical definitions, common symptoms, epidemiology, overlaps with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and orthostatic intolerance, and preliminary guidance on management.

Recent findings: The recent World Health Organization clinical case definition of post-COVID-19 condition requires a history of probable or confirmed SARS-CoV-2 infection, with symptoms starting within 3 months of the onset of COVID-19. Symptoms must last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms of the post-COVID-19 condition include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction. These symptoms generally have an impact on everyday functioning. The incidence of prolonged symptoms following SARS-CoV-2 infection has proven challenging to define, but it is now clear that those with relatively mild initial infections, without severe initial respiratory disease or end-organ injury, can still develop chronic impairments, with symptoms that overlap with conditions like ME/CFS (profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance).

Summary: We do not yet have a clear understanding of the mechanisms by which individuals develop post-COVID-19 conditions. There may be several distinct types of long COVID that require different treatments. At this point, there is no single pharmacologic agent to effectively treat all symptoms. Because some presentations of post-COVID-19 conditions mimic disorders such as ME/CFS, treatment guidelines for this and related conditions can be helpful for managing post-COVID-19 symptoms.

Supplementary information: The online version contains supplementary material available at 10.1007/s40124-022-00261-4.

Source: Morrow AK, Malone LA, Kokorelis C, Petracek LS, Eastin EF, Lobner KL, Neuendorff L, Rowe PC. Long-Term COVID 19 Sequelae in Adolescents: the Overlap with Orthostatic Intolerance and ME/CFS. Curr Pediatr Rep. 2022 Mar 9:1-14. doi: 10.1007/s40124-022-00261-4. Epub ahead of print. PMID: 35287333; PMCID: PMC8906524. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906524/ (Full text)