Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children".

The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice via a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.

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).

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.

Post-COVID-19 condition in children: epidemiological evidence stratified by acute disease severity.

BACKGROUND: To determine the prevalence of pediatric Post-COVID-19 condition (PPCC), identify risk factors, and assess the quality of life in children with differing severities of acute COVID-19. METHODS: During a prospective longitudinal study with a 1-year follow-up, we compared non-hospitalized (mild) and hospitalized (severe) COVID-19 cases to a negatively tested control group. RESULTS: 579 children were included in this study. Of these, 260 had mild acute disease (median age:8, IQR:6-10), 60 had severe acute disease (median age:1, IQR:0.1-4.0), and 259 tested negative for SARS-CoV-2 (NT) (median age:8, IQR:5-10). At three months, 14.6% of the SARS-CoV-2 positive mild group (RR:6.31 (CI 95%: 2.71-14.67)) and 29.2% of the severe group (RR:12.95 (CI 95%: 5.37-31.23)) reported sequelae, versus 2.3% of the NT group. PPCC prevalence in the mild group decreased from 16.1% at one month to 4.4% at one year. Children with PPCC exhibited lower physical health-related quality of life scores and higher fatigue scores than the NT children. CONCLUSIONS: Severe acute COVID-19 in children leads to a higher PPCC prevalence than in mild cases. PPCC prevalence decreases over time. Risk factors at three months include prior medical history, hospital admission, and persistent fatigue one month after a positive test. IMPACT: We demonstrate children with severe COVID-19 are more likely to develop Post-COVID-19 condition than those with mild or no infections, and highlights the risk factors. Here we have stratified by acute disease severity, prospectively included a negative control group, and have demonstrated the heterogeneity in prevalence when utilizing various recent definitions of post-COVID. Identifying risk factors for pediatric post-COVID and highlighting the heterogeneity in prevalence based on various current definitions for post-COVID should aid in correctly identifying potential pediatric post-COVID cases, aiding in early intervention.

International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

Prevalence and risk factors of post-COVID-19 condition in adults and children at 6 and 12 months after hospital discharge: a prospective, cohort study in Moscow (StopCOVID).

BACKGROUND: Previous studies assessing the prevalence of COVID-19 sequelae in adults and children were performed in the absence of an agreed definition. We investigated prevalence of post-COVID-19 condition (PCC) (WHO definition), at 6- and 12-months follow-up, amongst previously hospitalised adults and children and assessed risk factors. METHODS: Prospective cohort study of children and adults with confirmed COVID-19 in Moscow, hospitalised between April and August, 2020. Two follow-up telephone interviews, using the International Severe Acute Respiratory and Emerging Infection Consortium survey, were performed at 6 and 12 months after discharge. RESULTS: One thousand thirteen of 2509 (40%) of adults and 360 of 849 (42%) of children discharged participated in both the 6- and 12-month follow-ups. PCC prevalence was 50% (95% CI 47-53) in adults and 20% (95% CI 16-24) in children at 6 months, with decline to 34% (95% CI 31-37) and 11% (95% CI 8-14), respectively, at 12 months. In adults, female sex was associated with PCC at 6- and 12-month follow-up (OR 2.04, 95% CI 1.57 to 2.65) and (OR 2.04, 1.54 to 2.69), respectively. Pre-existing hypertension (OR 1.42, 1.04 to 1.94) was associated with post-COVID-19 condition at 12 months. In children, neurological comorbidities were associated with PCC both at 6 months (OR 4.38, 1.36 to 15.67) and 12 months (OR 8.96, 2.55 to 34.82) while allergic respiratory diseases were associated at 12 months (OR 2.66, 1.04 to 6.47). CONCLUSIONS: Although prevalence of PCC declined one year after discharge, one in three adults and one in ten children experienced ongoing sequelae. In adults, females and persons with pre-existing hypertension, and in children, persons with neurological comorbidities or allergic respiratory diseases are at higher risk of PCC.

A Multidisciplinary Approach: Management and Rehabilitation of Children With Pediatric Post-COVID-19 Condition.

Post-COVID-19 condition in children is a still largely unknown syndrome with a diverse pattern of symptoms, which can have a major impact on daily life. Currently, there are no evidence-based proven treatments, and the focus is on symptom management and recovery of daily functioning. A multidisciplinary, tailored approach is recommended, with attention to energy management and activity building, where the main goal should be a return to baseline levels of cognitive, physical and social activity.

Clinical-based phenotypes in children with pediatric post-COVID-19 condition.

BACKGROUND: Pediatric post coronavirus disease 2019 (COVID-19) condition (PPCC) is a heterogeneous syndrome, which can significantly affect the daily lives of children. This study aimed to identify clinically meaningful phenotypes in children with PPCC, to better characterize and treat this condition. METHODS: Participants were children with physician-diagnosed PPCC, referred to the academic hospital Amsterdam UMC in the Netherlands between November 2021 and March 2023. Demographic factors and information on post-COVID symptoms, comorbidities, and impact on daily life were collected. Clinical clusters were identified using an unsupervised and unbiased approach for mixed data types. RESULTS: Analysis of 111 patients (aged 3-18 years) revealed three distinct clusters within PPCC. Cluster 1 (n = 62, median age = 15 years) predominantly consisted of girls (74.2%). These patients suffered relatively more from exercise intolerance, dyspnea, and smell disorders. Cluster 2 (n = 33, median age = 13 years) contained patients with an even gender distribution (51.5% girls). They suffered from relatively more sleep problems, memory loss, gastrointestinal symptoms, and arthralgia. Cluster 3 (n = 16, median age = 11 years) had a higher proportion of boys (75.0%), suffered relatively more from fever, had significantly fewer symptoms (median of 5 symptoms compared to 8 and 10 for clusters 1 and 2 respectively), and experienced a lower impact on daily life. CONCLUSIONS: This study identified three distinct clinical PPCC phenotypes, with variations in sex, age, symptom patterns, and impact on daily life. These findings highlight the need for further research to understand the potentially diverse underlying mechanisms contributing to post-COVID symptoms in children.

Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children From Wild-type to Population Immunity: A Prospective Multicenter Cohort Study With Real-time Reporting.

BACKGROUND: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data. METHODS: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity. RESULTS: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies. CONCLUSIONS: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections.

Pediatric long-COVID: An overlooked phenomenon?

BACKGROUND: Long-COVID is a well-documented multisystem disease in adults. Far less is known about long-term sequelae of COVID in children. Here, we report on the occurrence of long-COVID in Dutch children. PATIENTS AND METHODS: We conducted a national survey asking Dutch pediatricians to share their experiences on long-COVID in children. We furthermore describe a case series of six children with long-COVID to explore the clinical features in greater detail. RESULTS: With a response rate of 78% of Dutch pediatric departments, we identified 89 children, aged 2-18 years, suspected of long-COVID with various complaints. Of these children, 36% experienced severe limitations in daily function. The most common complaints were fatigue, dyspnea, and concentration difficulties with 87%, 55%, and 45% respectively. Our case series emphasizes the nonspecific and broad clinical manifestations seen in post-COVID complaints. CONCLUSION: Our study shows that long-COVID is also present in the pediatric population. The main symptoms resemble those previously described in adults. This novel condition demands a multidisciplinary approach with international awareness and consensus to aid early detection and effective management.

[Group A streptococcal-associated arthritis in children]. / Artritis door groep A-streptokokken bij kinderen.

Group A streptococcal (GAS) infection can cause septic arthritis (SA), acute rheumatic fever (ARF) and post-streptococcal reactive arthritis (PSRA). Differentiating between these three entities can have important consequences for both therapy and prognosis. SA is diagnosed by means of clinical, biochemical and microbiological parameters. With respect to ARF and PSRA, evidence of a recent GAS infection should be established, in combination with several other major or minor criteria. Currently there is ongoing scientific debate as to whether PSRA and ARF are two different disease entities or belong to the same spectrum. PSRA presents earlier after GAS pharyngitis than ARF, is normally less responsive to NSAIDs, has a longer duration and is often accompanied by skin abnormalities. However, there are also many similarities. In this report we describe three children suffering from GAS-associated arthritis and discuss the symptoms, diagnosis and therapy.