Tag: pediatric long covid

Bulk RNA sequencing for analysis of post COVID-19 condition in adolescents and young adults

Abstract:

Background: Post COVID-19 condition (PCC) is a complication of SARS-COV-2 infection and can lead to long-term disability.

Methods: The present study was designed to analyse the gene expression patterns of PCC through bulk RNA sequencing of whole blood and to explore the potential molecular mechanisms of PCC. Whole blood was collected from 80 participants enrolled in a prospective cohort study following SARS-CoV-2 infected and non-infected individuals for 6 months after recruitment and was used for bulk RNA sequencing. Identification of differentially expressed genes (DEG), pathway enrichment and immune cell deconvolution was performed to explore potential biological pathways involved in PCC.

Results: We have found 13 differentially expressed genes associated with PCC. Enriched pathways were related to interferon-signalling and anti-viral immune processes.

Conclusion: The PCC transcriptome is characterized by a modest overexpression of interferon-stimulated genes, pointing to a subtle ongoing inflammatory response.

Source: Sommen SL, Zhao Z, Segtnan S, Stiansen-Sonerud T, Selvakumar J, Beier Havdal L, Gjerstad J, Wyller VBB, Lund Berven L. Bulk RNA sequencing for analysis of post COVID-19 condition in adolescents and young adults. J Transl Med. 2024 Mar 26;22(1):312. doi: 10.1186/s12967-024-05117-7. PMID: 38532465. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05117-7 (Full text)

Navigating the Spectrum of Two Pediatric COVID-19 Complications: Multi-System Inflammatory Syndrome in Children and Post-Acute Sequelae of SARS-CoV-2 Infection

Abstract:

Purpose: This review summarizes the current scope of understanding associated with two common post-infectious complications associated with COVID-19 infection: Multi-System Inflammatory Syndrome in Children (MIS-C) and Post-Acute Sequelae of SARS-CoV-2 infection (PASC). It identifies current gaps in the knowledge and issues that may limit the ability to fill these gaps. This review provides a framework to drive continued research.

Methods: A comprehensive review of the current literature was performed, identifying seminal articles describing the emergence of MIS-C and PASC, and works from the literature focused on the clinical implications and pathophysiologic understanding of these disorders.

Findings: Although pediatric patients experienced few severe cases of acute COVID-19 infection, the burden of disease from post-infectious sequelae is substantial. Mortality is low, but morbidity is significant. There are still numerous unknowns about the pathophysiology of both MIS-C and PASC; however, with widespread immunity developing after increased vaccination and prior infection, it may be difficult to perform adequate prospective studies to answer pathophysiologic questions. Long-term sequalae of MIS-C seem to be minimal whereas, by definition, PASC is an ongoing problem and may be severe.

Implications: The rapid sharing of information regarding novel conditions such as MIS-C and PASC are key to interventions related to future post-infectious sequelae outside of those stemming from COVID-19. Although MIS-C seems unlikely to return as a clinical condition in substantial numbers, there is still significant learning that can be gleaned from existing patients about general aspects of epidemiology, equity, and pathophysiology. There is significant morbidity associated with PASC and additional resources need to be dedicated to determining appropriate and effective therapies moving forward.

Source: Parzen-Johnson S, Katz BZ. Navigating the Spectrum of Two Pediatric COVID-19 Complications: Multi-System Inflammatory Syndrome in Children and Post-Acute Sequelae of SARS-CoV-2 Infection. J Clin Med. 2024 Feb 18;13(4):1147. doi: 10.3390/jcm13041147. PMID: 38398460. https://www.mdpi.com/2077-0383/13/4/1147 (Full text)

How does post COVID differ from other post-viral conditions in childhood and adolescence (0-20 years old)? A systematic review

Abstract:

Background: Post Coronavirus disease (COVID) and other post-viral infection syndromes present an overlap of pathogenesis, onset, progression, and symptom profile. We aimed to systematically describe studies on post-viral conditions and determine the entity of post COVID compared to other post-viral conditions in children.

Methods: We conducted a systematic search of the Embase, MEDLINE, Cochrane Library, and GoogleScholar databases (January 1946-3 November 2023), according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The main outcomes were differences in condition duration, symptom type, and development of chronic symptoms. This systematic review was registered on PROSPERO (CRD42023401789).

Findings: 35/5051 studies were included, with 42,934 children, adolescents and young adults (0-20 years old) overall. Twenty-eight studies focused on post COVID symptoms, followed by five papers on Respiratory Syncytial Virus (RSV) and Rhinovirus, one study on Epstein-Barr Virus (EBV), and one on gastrointestinal viruses. Studies on post COVID mainly reported data on older children/adolescents, describing long-lasting symptoms, including fatigue, neurologic, cardiorespiratory, musculoskeletal, mental health, and gastrointestinal symptoms. The maximum described symptoms duration was eighteen months, with an average follow-up of seven months. The development of chronic symptoms was reported by 30 studies (93.8%) for 10,473/28,474 patients (36.8%). Recovery was achieved in 18,001/28,474 cases (63.2%). The study on EBV reported persistent fatigue in adolescents for a similar duration (6 months, 46% chronic). Studies on RSV and Rhinovirus were mainly done in children under three years, with development of recurrent wheezing (up to 3 years).

Interpretation: Post-viral fatigue was a shared feature between post COVID and post EBV conditions. A better understanding of post COVID as a unique condition, sharing features with other post-viral syndromes, is needed. The healthcare burden and socio-economic consequences for children and their families warrant further investigation and development of appropriate healthcare management plans. The foremost requirement is the establishment of consistent and shareable definitions, as well as a consensus on outcomes, to effectively evaluate follow-up and quantify the burden of different viral infections.

Source: Minotti C, McKenzie C, Dewandel I, Bekker C, Sturniolo G, Doni D, Giaquinto C, Van Der Zalm MM, Donà D. How does post COVID differ from other post-viral conditions in childhood and adolescence (0-20 years old)? A systematic review. EClinicalMedicine. 2024 Feb 2;68:102436. doi: 10.1016/j.eclinm.2024.102436. PMID: 38333536; PMCID: PMC10850405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10850405/ (Full text)

Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID)

Abstract:

Background: Long-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections.

Methods: A prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the ‘exposed cohorts’ and ‘reference cohort’ was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC.

Results: Of 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final ‘matched’ analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3-120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9-21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts.

Conclusions: Wuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.

Source: Pazukhina E, Rumyantsev M, Baimukhambetova D, Bondarenko E, Markina N, El-Taravi Y, Petrova P, Ezhova A, Andreeva M, Iakovleva E, Bobkova P, Pikuza M, Trefilova A, Abdeeva E, Galiautdinova A, Filippova Y, Bairashevskaia A, Zolotarev A, Bulanov N, DunnGalvin A, Chernyavskaya A, Kondrikova E, Kolotilina A, Gadetskaya S, Ivanova YV, Turina I, Eremeeva A, Fedorova LA, Comberiati P, Peroni DG, Nekliudov N, Genuneit J, Reyes LF, Brackel CLH, Mazankova L, Miroshina A, Samitova E, Borzakova S, Carson G, Sigfrid L, Scott JT, McFarland S, Greenhawt M, Buonsenso D, Semple MG, Warner JO, Olliaro P, Osmanov IM, Korsunskiy AA, Munblit D; Sechenov StopCOVID Research Team. Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID). BMC Med. 2024 Feb 1;22(1):48. doi: 10.1186/s12916-023-03221-x. PMID: 38302974; PMCID: PMC10835884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835884/ (Full text)

Postacute Sequelae of SARS-CoV-2 in Children

Abstract:

The coronavirus disease 2019 (COVID-19) pandemic has caused significant medical, social, and economic impacts globally, both in the short and long term. Although most individuals recover within a few days or weeks from an acute infection, some experience longer lasting effects. Data regarding the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) in children, or long COVID, are only just emerging in the literature. These symptoms and conditions may reflect persistent symptoms from acute infection (eg, cough, headaches, fatigue, and loss of taste and smell), new symptoms like dizziness, or exacerbation of underlying conditions. Children may develop conditions de novo, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune conditions and multisystem inflammatory syndrome in children.

This state-of-the-art narrative review provides a summary of our current knowledge about PASC in children, including prevalence, epidemiology, risk factors, clinical characteristics, underlying mechanisms, and functional outcomes, as well as a conceptual framework for PASC based on the current National Institutes of Health definition. We highlight the pediatric components of the National Institutes of Health-funded Researching COVID to Enhance Recovery Initiative, which seeks to characterize the natural history, mechanisms, and long-term health effects of PASC in children and young adults to inform future treatment and prevention efforts. These initiatives include electronic health record cohorts, which offer rapid assessments at scale with geographical and demographic diversity, as well as longitudinal prospective observational cohorts, to estimate disease burden, illness trajectory, pathobiology, and clinical manifestations and outcomes.

Source: Suchitra Rao, MBBS, MSCS; Rachel S. Gross, MD, MS; Sindhu Mohandas, MD; Cheryl R. Stein, PhD; Abigail Case, MD; Benard Dreyer, MD; Nathan M. Pajor, MD; H. Timothy Bunnell, PhD; David Warburton, MD; Elizabeth Berg, MD; Jonathan B. Overdevest, MD; Mark Gorelik, MD; Joshua Milner, MD; Sejal Saxena, BA; Ravi Jhaveri, MD; John C. Wood, MD, PhD; Kyung E. Rhee, MD, MSc, MA; Rebecca Letts, BA; Christine Maughan, BS; Nick Guthe, BA; Leah Castro-Baucom, MA; Melissa S. Stockwell, MD, MPH. Postacute Sequelae of SARS-CoV-2 in Children. Pediatrics e2023062570. https://doi.org/10.1542/peds.2023-062570 https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2023-062570/196606/Postacute-Sequelae-of-SARS-CoV-2-in-Children (Full text)

Post-COVID Postural Orthostatic Tachycardia Syndrome and Inappropriate Sinus Tachycardia in the Pediatric Population

Abstract:

Purpose of Review: Long COVID, or post-COVID Condition, is increasingly recognized in children and adolescents, despite being less studied compared with the adult population. Recent studies are documenting that inappropriate sinus tachycardia (IST) or postural orthostatic tachycardia syndrome (POTS) may be key clinical problems in patients with long COVID, and preliminary findings have shown that these may be important features also in children. However, POTS and IST are poorly known among non-specialized pediatricians, and this gap may limit access to appropriate care for children and adolescents with long COVID or other post-viral fatigue syndromes. In this review, we critically evaluate the available literature investigating the burden of post-COVID-19 IST and POTS in children and young people, their pathogenesis, and available evidence for their management in the pediatric population.

Recent Findings: In line with adult studies, there is increasing evidence that also children with long COVID may suffer from IST and POTS. Case reports and case series, as well as pediatric experience from other conditions, suggest that IST and POTS can be treated also in the pediatric population

Summary: IST and POTS are under-recognized conditions in children. Clinical findings as well as diagnostics like 24-h ECG and heart rate variability are non-invasive tests to diagnose IST and POTS. If properly recognized, these conditions are treatable.

Source: Spera, F.R., Mistrulli, R., Salerno, L. et al. Post-COVID Postural Orthostatic Tachycardia Syndrome and Inappropriate Sinus Tachycardia in the Pediatric Population. Curr Clin Micro Rpt (2024). https://doi.org/10.1007/s40588-024-00217-w (Full text available as PDF file)

COVID-19 Pediatric Follow-Up: Respiratory Long COVID-Associated Comorbidities and Lung Ultrasound Alterations in a Cohort of Italian Children

Abstract:

In children, the factors that influence COVID-19 disease and its medium- and long-term effects are little known. Our investigation sought to evaluate the presence of comorbidity factors associated with respiratory long COVID manifestations in children and to study ultrasound abnormalities following SARS-CoV-2 infection. Children, who arrived at the ‘Respiratory Diseases of Pediatric Interest Unit’ at the Department of Woman, Child, and General and Specialized Surgery of the University of Campania ‘Luigi Vanvitelli’, were selected during the timeframe from September 2021 to October 2022.
The children were diagnosed with a SARS-CoV-2 infection that occurred at least one month before the visit. All patients followed a COVID-19 follow-up protocol, developed by the Italian Society of Pediatric Respiratory Diseases (SIMRI), which included: collection of data regarding SARS-CoV-2 illness and history of known respiratory and allergic diseases; physical examination; BMI assessment; baseline spirometry and after bronchodilation test; six-minute walking test; and lung ultrasound (LUS).
In a cohort of 104 participants with respiratory long COVID symptoms (64.7% male, average age 8.92 years), 46.1% had fever with other symptoms, and 1% required hospitalization. BMI analysis showed 58.4% of the cohort was overweight. The LUS was positive in 27.0% of cases. A significant BMI association was observed with COVID-19 symptoms and LUS score (p-value < 0.05). No associations were found with asthma or atopy.
Source: Indolfi C, Klain A, Dinardo G, D’Addio E, Ferrara S, Decimo F, Ciprandi G, Tosca MA, Miraglia del Giudice M. COVID-19 Pediatric Follow-Up: Respiratory Long COVID-Associated Comorbidities and Lung Ultrasound Alterations in a Cohort of Italian Children. Children. 2024; 11(2):166. https://doi.org/10.3390/children11020166 https://www.mdpi.com/2227-9067/11/2/166 (Full text)

Long Covid

Abstract:

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), refers to a constellation of persistent symptoms and health issues that continue beyond the acute phase of COVID-19. This chapter provides an overview of the pathogenesis, risk factors, manifestations, major findings, and diagnosis and treatment strategies associated with Long COVID.

Hypotheses regarding the pathogenesis of Long COVID are discussed, encompassing various factors such as persistent viral reservoirs, immune dysregulation with or without reactivation of herpesviruses (e.g., Epstein-Barr Virus and human herpesvirus), dysbiosis, autoimmunity triggered by infection, endothelial dysfunction, microvessel blood clotting, and dysfunctional brainstem and/or vagal signaling. The chapter also highlights the risk factors associated with Long COVID and its occurrence in children.

The major findings of Long COVID, including immune dysregulation, vessel and tissue damage, neurological and cognitive pathology, eye symptoms, endocrinal issues, myalgic encephalomyelitis and chronic fatigue syndrome, reproductive system involvement, respiratory and gastrointestinal symptoms, and the chronology of symptoms, are thoroughly explored.

Lastly, the chapter discusses the challenges and current approaches in the diagnosis and treatment of Long COVID, emphasizing the need for multidisciplinary care and individualized management strategies.

Source: Asiya Kamber Zaidi and Puya Dehgani-Mobaraki. Long Covid. Progress in Molecular Biology and Translational Science, Volume 202, 2024, Pages 113-125 https://www.sciencedirect.com/science/article/abs/pii/S1877117323001771

Long COVID in pediatrics-epidemiology, diagnosis, and management

Abstract:

This review summarizes current knowledge on post-acute sequelae of COVID-19 (PASC) and post-COVID-19 condition (PCC) in children and adolescents. A literature review was performed to synthesize information from clinical studies, expert opinions, and guidelines. PASC also termed Long COVID — at any age comprise a plethora of unspecific symptoms present later than 4 weeks after confirmed or probable infection with severe respiratory syndrome corona virus type 2 (SARS-CoV-2), without another medical explanation. PCC in children and adolescents was defined by the WHO as PASC occurring within 3 months of acute coronavirus disease 2019 (COVID-19), lasting at least 2 months, and limiting daily activities.

Pediatric PASC mostly manifest after mild courses of COVID-19 and in the majority of cases remit after few months. However, symptoms can last for more than 1 year and may result in significant disability. Frequent symptoms include fatigue, exertion intolerance, and anxiety. Some patients present with postural tachycardia syndrome (PoTS), and a small number of cases fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To date, no diagnostic marker has been established, and differential diagnostics remains challenging. Therapeutic approaches include appropriate self-management as well as the palliation of symptoms by non-pharmaceutical and pharmaceutical strategies.

Conclusion: PASC in pediatrics present with heterogenous severity and duration. A stepped, interdisciplinary, and individualized approach is essential for appropriate clinical management. Current health care structures have to be adapted, and research was extended to meet the medical and psychosocial needs of young people with PASC or similar conditions.

Source: Toepfner N, Brinkmann F, Augustin S, Stojanov S, Behrends U. Long COVID in pediatrics-epidemiology, diagnosis, and management. Eur J Pediatr. 2024 Jan 27. doi: 10.1007/s00431-023-05360-y. Epub ahead of print. PMID: 38279014. https://link.springer.com/article/10.1007/s00431-023-05360-y (Full text available as PDF file)

Vaccine Effectiveness Against Long COVID in Children

Abstract:

Objective: Vaccination reduces the risk of acute COVID-19 in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5-17 years.

Methods: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record (EHR) Program for visits after vaccine availability. Conditional logistic regression was used to estimate VE against long COVID with matching on age group (5-11, 12-17) and time period and adjustment for sex, ethnicity, health system, comorbidity burden, and pre-exposure health care utilization. We examined both probable (symptom-based) and diagnosed long COVID in the year following vaccination.

Results: The vaccination rate was 56% in the cohort of 1,037,936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, while diagnosed long COVID was 0.7%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5 – 44.5) against probable long COVID and 41.7% (15.0 – 60.0) against diagnosed long COVID. VE was higher for adolescents 50.3% [36.3 – 61.0]) than children aged 5-11 (23.8% [4.9 – 39.0]). VE was higher at 6 months (61.4% [51.0 – 69.6]) but decreased to 10.6% (-26.8 – 37.0%) at 18-months.

Discussion: This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data.

Source: Razzaghi H, Forrest CB, Hirabayashi K, Wu Q, Allen A, Rao S, Chen Y, Bunnell HT, Chrischilles EA, Cowell LG, Cummins MR, Hanauer DA, Higginbotham M, Horne BD, Horowitz CR, Jhaveri R, Kim S, Mishkin A, Muszynski JA, Naggie S, Pajor NM, Paranjape A, Schwenk HT, Sills MR, Tedla YG, Williams DA, Bailey C. Vaccine Effectiveness Against Long COVID in Children. Pediatrics. 2024 Jan 16. doi: 10.1542/peds.2023-064446. Epub ahead of print. PMID: 38225804. https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2023-064446/196419 (Full text available as PDF file)