Tag: pediatric long covid

Computable Clinical Phenotyping of Postacute Sequelae of COVID-19 in Pediatrics Using Real-World Data

INTRODUCTION:

Since the SARS-CoV-2 pandemic began in late 2019, over 13 million children in the United States have been infected with the virus [1]. Although many of these acute infections have not resulted in severe morbidity or mortality, a subset of children and adolescents have experienced recurrent or persistent symptoms beyond the typical recovery period [2]. The constellation of findings that occur postinfection is known as postacute sequelae of SARS-CoV-2 (PASC), or colloquially as “long-Covid.” The U.S. Centers for Disease Control and Prevention (CDC) defines PASC as a wide range of health problems that linger for more than 4 weeks following an acute COVID-19 infection [3]. Although this is an area of active research, relatively little is currently known about its clinical epidemiology in the pediatric population.

Considering the large number of children who have been affected by COVID-19, it is critical that we monitor the rates, trends, and outcomes of PASC in this population. An important first step toward these efforts is the development of a tool that can quickly and easily identify cases in large clinical populations. With the widespread adoption of electronic health records (EHR), it is now possible to develop computable phenotypes using data that are collected for clinical care, which can be used for population-level analysis to inform the public health response [4, 5]. In this report, we describe a novel phenotyping algorithm to define the burden, clinical spectrum, and outcomes of pediatric PASC using real-world data.

Source: Tomini A Fashina, Christine M Miller, Elijah Paintsil, Linda M Niccolai, Cynthia Brandt, Carlos R Oliveira, Computable Clinical Phenotyping of Postacute Sequelae of COVID-19 in Pediatrics Using Real-World Data, Journal of the Pediatric Infectious Diseases Society, 2022;, piac132, https://doi.org/10.1093/jpids/piac132 https://academic.oup.com/jpids/advance-article/doi/10.1093/jpids/piac132/6957369 (Full text)

Pediatric Post-Acute Sequelae of SARS-CoV-2 infection

Abstract:

Aim: Youth who have not recovered from COVID-19 have been referred to as having Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The goal of this study was to better understand which symptoms persisted since onset of infection and how these symptoms compare to symptoms experienced by those with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Method: A sample of 19 parents who had a child with PASC were recruited using social media to fill out a questionnaire detailing symptoms at two time points. The first time point included their child’s current symptoms and the second captured symptoms at initial infection. These participants were compared to a sample of 19 youth with ME/CFS.

Results: Findings indicated significant decreases among several immune, neuroendocrine, pain, post-exertional malaise (PEM), and COVID-19 Centers for Disease Control and Prevention (CDC) domain symptoms from time of acute infection to time of current reporting. Fatigue remained at a high level as did several symptoms within the sleep and PEM domains. Participants with ME/CFS had overall worse symptomatology when compared to participants with PASC, especially in the neurocognitive domain.

Conclusion: Most symptoms of those with PASC decline over time, but several remain at high levels, including fatigue. These findings are helpful in better understanding common symptom presentation profiles for youth with PASC and can be used to more adequately tailor diagnostic criteria and treatment strategies for youth.

Source: Leonard A. Jason, Madeline Johnson & Chelsea Torres (2023) Pediatric Post-Acute Sequelae of SARS-CoV-2 infection, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2162764 https://www.tandfonline.com/doi/abs/10.1080/21641846.2022.2162764

Mid- and Long-Term Atrio-Ventricular Functional Changes in Children after Recovery from COVID-19

Abstract:

Background: Although most children may experience mild to moderate symptoms and do not require hospitalization, there are little data on cardiac involvement in COVID-19. However, cardiac involvement is accurately demonstrated in children with MISC. The objective of this study was to evaluate cardiac mechanics in previously healthy children who recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a long-term follow-up by means of two-dimensional speckle-tracking echocardiography (STE).
Methods: We analyzed a cohort of 157 paediatric patients, mean age 7.7 ± 4.5 years (age range 0.3–18 years), who had a laboratory-confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent a standard transthoracic echocardiogram and STE at an average time of 148 ± 68 days after diagnosis and were divided in three follow-up groups (<180 days, 180–240 days, >240 days). Patients were compared with 107 (41 females—38%) age- and BSA-comparable healthy controls (CTRL).
Results: Left ventricular (LV) global longitudinal strain (post-COVID-19: −20.5 ± 2.9%; CTRL: −21.8 ± 1.7%; p < 0.001) was significantly reduced in cases compared with CTRLs. No significant differences were seen among the three follow-up groups (p = NS). Moreover, regional longitudinal strain was significantly reduced in LV apical-wall segments of children with disease onset during the second wave of the COVID-19 pandemic compared to the first wave (second wave: −20.2 ± 2.6%; first wave: −21.2 ± 3.4%; p = 0.048). Finally, peak left atrial systolic strain was within the normal range in the post-COVID-19 group with no significant differences compared to CTRLs.
Conclusions: Our study demonstrated for the first time the persistence of LV myocardial deformation abnormalities in previously healthy children with an asymptomatic or mildly symptomatic (WHO stages 0 or 1) COVID-19 course after an average follow-up of 148 ± 68 days. A more significant involvement was found in children affected during the second wave. These findings imply that subclinical LV dysfunction may also be a typical characteristic of COVID-19 infection in children and are concerning given the predictive value of LV longitudinal strain in the general population.
Source: Sabatino J, Di Chiara C, Di Candia A, Sirico D, Donà D, Fumanelli J, Basso A, Pogacnik P, Cuppini E, Romano LR, Castaldi B, Reffo E, Cerutti A, Biffanti R, Cozzani S, Giaquinto C, Di Salvo G. Mid- and Long-Term Atrio-Ventricular Functional Changes in Children after Recovery from COVID-19. Journal of Clinical Medicine. 2023; 12(1):186. https://doi.org/10.3390/jcm12010186 https://www.mdpi.com/2077-0383/12/1/186 (Full text)

Feasibility Assessment of a School Nurse-Led Approach Using Chronic Absenteeism to Establish the School-Based Active Surveillance Process

Abstract:

This article shares what was learned from the feasibility assessment of a nurse-led school-based active surveillance (SBAS) pilot to track chronic absenteeism using myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as an exemplar. This pilot encompassed a 3-year period with training and feedback from school nurses (SNs) on data collection and ME/CFS. SNs found that the SBAS process helped them effectively identifying undiagnosed conditions.

The assessment revealed the importance of focusing outreach efforts and establishing relationships with the school leadership in developing health policies and programs in the school setting. The pilot data were used to develop a manual to guide SNs for the SBAS process. This can be viewed as a model for SNs in establishing a surveillance to identify and track conditions like ME/CFS. With overlapping symptoms of Long COVID to ME/CFS, this assessment may provide insights for additional efforts to understand the impact of Long COVID on students’ education.

Source: Maughan ED, Thompson ME, Walsh CA, Issa A, Lin JS. Feasibility Assessment of a School Nurse-Led Approach Using Chronic Absenteeism to Establish the School-Based Active Surveillance Process. J Sch Nurs. 2022 Dec 20:10598405221144259. doi: 10.1177/10598405221144259. Epub ahead of print. PMID: 36540020. https://pubmed.ncbi.nlm.nih.gov/36540020/

Clinical assessment of children with long COVID syndrome

Abstract:

Background: There is a need for further understanding pediatric long COVID syndrome (LCS) to be able to create specific case definitions and guidelines for providing good clinical care.

Methods: Medical records of all LCS patients who presented at our designated LC clinic were collected. We carried out descriptive analyses summarizing the history, clinical presentation, and findings of children, while doing a diagnosis of exclusion with multi-disciplinary medical examinations (physical, laboratory, and radiological examinations, specialist consultations, etc.) without a control group.

Results: Most children reported at least minor impairment to their quality of life, of which 17 (23%) had moderate or severe difficulties. Findings that could be directly connected to the linked complaint category were observed in an average of 18%, respiratory symptoms with objective alterations being the most frequent (37%). Despite our detecting mostly non-specific conditions, in a smaller number we identified well-described causes such as autoimmune thyroiditis (7%).

Conclusions: The majority of children stated an impairment in their quality of life, while symptom-related conditions were detected only in a minority. Controlled studies are needed to separate the effect of the pandemic era from the infection itself. Evidence-based pediatric guidelines could aid to rationalize the list of recommended examinations.

Impact: Long COVID syndrome is a complex entity with a great impact on children’s everyday lives. Still, there is no clear guidance for pediatric clinical management. Systematic, detailed studies with medical assessment findings could aid the process of creating evidence-based guidelines. We present validated systematic information collected during in-person medical assessments with detailed medical findings and quality of life changes. While making a diagnosis of exclusion, we could confirm symptom-related conditions only in a minority of children; however, the majority reported at least minor impairment to their quality of life.

Source: Garai R, Krivácsy P, Herczeg V, Kovács F, Tél B, Kelemen J, Máthé A, Zsáry E, Takács J, Veres DS, Szabó AJ. Clinical assessment of children with long COVID syndrome. Pediatr Res. 2022 Dec 7. doi: 10.1038/s41390-022-02378-0. Epub ahead of print. PMID: 36474113. https://www.nature.com/articles/s41390-022-02378-0 (Full text)

Clinical and laboratory predictors of long-COVID in children: a single center retrospective study

Abstract:

Objective: The majority of children experience a mild course of acute Coronavirus Disease 2019 (COVID-19). Only few studies have looked at long-term recovery from COVID-19 infection in children. The purpose of this study was to identify the predictors of long-COVID by performing a thorough analysis of the clinical, laboratory, and demographic characteristics of children with COVID-19.

Patients and methods: Between August and October 2021, data were obtained retrospectively from the medical records of 251 children diagnosed with COVID-19 at a tertiary single-center hospital. The prognostic effects of admission-related factors were compared between patients who experienced long-lasting symptoms and those who did not.

Results: Long-COVID symptoms were noted in 12.4% of patients. Joint pain (7.6%), lumbago (4.8%), and headache (3.2%) were the most common symptoms. The mean onset of long-COVID symptoms was 1.35±0.49 months. The onset of long-COVID symptoms was 4 weeks after initial diagnosis in 64.5% of patients and 4-8 weeks later in 35.5% of the patients. The mean duration of long-COVID symptoms was 5.32±2.51 months. Children with long-COVID had higher leukocytes, neutrophils, monocytes, basophils, platelets, and D-dimer when compared with patients without long-COVID (p < 0.001). Leukocytes, neutrophils, monocytes, platelets, and D-dimer had the highest AUC in the ROC analysis (0.694, 0.658, 0.681, 0.667, and 0.612, respectively) and were statistically significant.

Conclusions: Despite the majority of children with COVID-19 having mild or asymptomatic acute disease, the majority of long-COVID symptoms were associated with functional impairment between 1 and 9 months after the start of the infection. Increased leukocytes, monocytes, neutrophils, platelets, and D-dimer appear to be the most powerful laboratory predictors for long-COVID and monitoring these predictors may assist clinicians to identify and follow-up patients with higher risk for long-COVID.

Source: Güven D, Buluş AD. Clinical and laboratory predictors of long-COVID in children: a single center retrospective study. Eur Rev Med Pharmacol Sci. 2022 Oct;26(20):7695-7704. doi: 10.26355/eurrev_202210_30046. PMID: 36314341.  https://www.europeanreview.org/article/30046 (Full text)

Dysautonomia in Children with Post-Acute Sequelae of Coronavirus 2019 Disease and/or Vaccination

Abstract:

Long-term health problems such as fatigue, palpitations, syncope, and dizziness are well-known in patients after COVID-19 (post-acute sequelae of coronavirus (PASC)). More recently, comparable problems have been noticed after the SARS-CoV-2 vaccination (post-VAC). The pathophysiology of these problems is not well-understood.

Methods: In 38 children and young adults, we tested if these health problems were related to dysautonomia in an active standing test (Group 1: 19 patients after COVID-19; Group 2: 12 patients with a breakthrough infection despite a vaccination; and Group 3: 7 patients after a vaccination without COVID-19). The data were compared with a control group of 47 healthy age-matched patients, as recently published.

Results: All patients had a normal left ventricular function as measured by echocardiography. Significantly elevated diastolic blood pressure in all patient groups indicated a regulatory cardiovascular problem. Compared with the healthy control group, the patient groups showed significantly elevated heart rates whilst lying and standing, with significantly higher heart rate increases. The stress index was significantly enhanced in all patient groups whilst lying and standing. Significantly decreased pNN20 values, mostly whilst standing, indicated a lower vagus activity in all patient groups. The respiratory rates were significantly elevated in Groups 1 and 2.

Conclusion: The uniform increase in the heart rates and stress indices, together with low pNN20 values, indicated dysautonomia in children with health problems after COVID-19 disease and/or vaccination. A total of 8 patients fulfilled the criteria of postural orthostatic tachycardia syndrome and 9 patients of an inappropriate sinus tachycardia, who were successfully treated with omega-3 fatty acid supplementation and pharmacotherapy.

Source: Buchhorn R. Dysautonomia in Children with Post-Acute Sequelae of Coronavirus 2019 Disease and/or Vaccination. Vaccines (Basel). 2022 Oct 9;10(10):1686. doi: 10.3390/vaccines10101686. PMID: 36298551; PMCID: PMC9607162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607162/ (Full text)

Association of SARS-CoV-2 Seropositivity With Myalgic Encephalomyelitis and/or Chronic Fatigue Syndrome Among Children and Adolescents in Germany

Abstract:

Importance: During the COVID-19 pandemic, a reduction in quality of life and physical and mental health among children and adolescents has been reported that may be associated with SARS-CoV-2 infection and/or containment measures.

Objective: To assess the association of SARS-CoV-2 seropositivity with symptoms that may be related to myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS) among children and adolescents.

Design, setting, and participants: This substudy of the cross-sectional SARS-CoV-2 seroprevalence surveys in Germany (SARS-CoV-2 KIDS) was performed in 9 pediatric hospitals from May 1 to October 31, 2021. Pediatric patients were recruited during an inpatient or outpatient visit regardless of the purpose of the visit. Parental questionnaires and serum samples were collected during clinically indicated blood draws. The parental questionnaire on demographic and clinical information was extended by items according to the DePaul Symptom Questionnaire, a pediatric screening tool for ME/CFS in epidemiological studies in patients aged 5 to 17 years.

Exposures: Seropositivity was determined by SARS-CoV-2 IgG antibodies in serum samples using enzyme-linked immunosorbent assays.

Main outcomes and measures: Key symptoms of ME/CFS were evaluated separately or as clustered ME/CFS symptoms according to the DePaul Symptom Questionnaire, including fatigue.

Results: Among 634 participants (294 male [46.4%] and 340 female [53.6%]; median age, 11.5 [IQR, 8-14] years), 198 (31.2%) reported clustered ME/CFS symptoms, including 40 of 100 SARS-CoV-2-seropositive (40.0%) and 158 of 534 SARS-CoV-2-seronegative (29.6%) children and adolescents. After adjustment for sex, age group, and preexisting disease, the risk ratio for reporting clustered ME/CFS symptoms decreased from 1.35 (95% CI, 1.03-1.78) to 1.18 (95% CI, 0.90-1.53) and for substantial fatigue from 2.45 (95% CI, 1.24-4.84) to 2.08 (95% CI, 1.05-4.13). Confinement to children and adolescents with unknown previous SARS-CoV-2 infection status (n = 610) yielded lower adjusted risks for all symptoms except joint pain ME/CFS-related symptoms. The adjusted risk ratio was 1.08 (95% CI, 0.80-1.46) for reporting clustered ME/CFS symptoms and 1.43 (95% CI, 0.63-3.23) for fatigue.

Conclusions and relevance: These findings suggest that the risk of ME/CFS in children and adolescents owing to SARS-CoV-2 infection may be very small. Recall bias may contribute to risk estimates of long COVID-19 symptoms in children. Extensive lockdowns must be considered as an alternative explanation for complex unspecific symptoms during the COVID-19 pandemic.

Source: Sorg AL, Becht S, Jank M, Armann J, von Both U, Hufnagel M, Lander F, Liese JG, Niehues T, Verjans E, Wetzke M, Stojanov S, Behrends U, Drosten C, Schroten H, von Kries R. Association of SARS-CoV-2 Seropositivity With Myalgic Encephalomyelitis and/or Chronic Fatigue Syndrome Among Children and Adolescents in Germany. JAMA Netw Open. 2022 Sep 1;5(9):e2233454. doi: 10.1001/jamanetworkopen.2022.33454. PMID: 36166227.  https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2796733 (Full text)

Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review

Abstract:

Long COVID is an emergent, heterogeneous, and multisystemic condition with an increasingly important impact also on the pediatric population. Among long COVID symptoms, patients can experience chronic gastrointestinal symptoms such as abdominal pain, constipation, diarrhea, vomiting, nausea, and dysphagia.
Although there is no standard, agreed, and optimal diagnostic approach or treatment of long COVID in children, recently compounds containing multiple micronutrients and lactoferrin have been proposed as a possible treatment strategy, due to the long-standing experience gained from other gastrointestinal conditions. In particular, lactoferrin is a pleiotropic glycoprotein with antioxidant, anti-inflammatory, antithrombotic, and immunomodulatory activities. Moreover, it seems to have several physiological functions to protect the gastrointestinal tract.
In this regard, we described the resolution of symptoms after the start of therapy with high doses of oral lactoferrin in two patients referred to our post-COVID pediatric unit due to chronic gastrointestinal symptoms after SARS-CoV-2 infection.
Source: Morello R, De Rose C, Cardinali S, Valentini P, Buonsenso D. Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review. Children. 2022; 9(10):1446. https://doi.org/10.3390/children9101446 (Full text)

Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: A prospective observational cohort study

Abstract:

Background: Long COVID in children and adolescents remains poorly understood due to a lack of well-controlled studies with long-term follow-up. In particular, the impact of the family context on persistent symptoms following SARS-CoV-2 infection remains unknown. We examined long COVID symptoms in a cohort of infected children, adolescents, and adults and their exposed but non-infected household members approximately 1 year after infection and investigated clustering of persistent symptoms within households.

Methods: 1267 members of 341 households (404 children aged <14 years, 140 adolescents aged 14-18 years and 723 adults) were categorized as having had either a SARS-CoV-2 infection or household exposure to SARS-CoV-2 without infection, based on three serological assays and history of laboratory-confirmed infection. Participants completed questionnaires assessing the presence of long COVID symptoms 11-12 months after infection in the household using online questionnaires.

Findings: The prevalence of moderate or severe persistent symptoms was statistically significantly higher in infected than in exposed women (36.4% [95% CI: 30.7-42.4%] vs 14.2% [95% CI: 8.7-21.5%]), infected men (22.9% [95% CI: 17.9-28.5%] vs 10.3% [95% CI: 5.8-16.9%]) and infected adolescent girls (32.1% 95% CI: 17.2-50.5%] vs 8.9% [95%CI: 3.1-19.8%]). However, moderate or severe persistent symptoms were not statistically more common in infected adolescent boys aged 14-18 (9.7% [95% CI: 2.8-23.6%] or in infected children <14 years (girls: 4.3% [95% CI: 1.2-11.0%]; boys: 3.7% [95% CI: 1.1-9.6%]) than in their exposed counterparts (adolescent boys: 0.0% [95% CI: 0.0-6.7%]; girls < 14 years: 2.3% [95% CI: 0·7-6·1%]; boys < 14 years: 0.0% [95% CI: 0.0-2.0%]). The number of persistent symptoms reported by individuals was associated with the number of persistent symptoms reported by their household members (IRR=1·11, p=·005, 95% CI [1.03-1.20]).

Interpretation: In this controlled, multi-centre study, infected men, women and adolescent girls were at increased risk of negative outcomes 11-12 months after SARS-CoV-2 infection. Amongst non-infected adults, prevalence of negative outcomes was also high. Prolonged symptoms tended to cluster within families, suggesting family-level interventions for long COVID could prove useful.

Funding: Ministry of Science, Research and the Arts, Baden-Württemberg, Germany.

Source: Haddad A, Janda A, Renk H, Stich M, Frieh P, Kaier K, Lohrmann F, Nieters A, Willems A, Huzly D, Dulovic A, Schneiderhan-Marra N, Jacobsen EM, Fabricius D, Zernickel M, Stamminger T, Bode SFN, Himpel T, Remppis J, Engel C, Peter A, Ganzenmueller T, Hoffmann GF, Haase B, Kräusslich HG, Müller B, Franz AR, Debatin KM, Tönshoff B, Henneke P, Elling R. Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: A prospective observational cohort study. EBioMedicine. 2022 Sep 22;84:104245. doi: 10.1016/j.ebiom.2022.104245. Epub ahead of print. PMID: 36155957; PMCID: PMC9495281. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495281/ (Full text)