Tag: pediatric long covid

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)

Prevalence and clinical presentation of long COVID in children: a systematic review

Abstract:

A systematic literature review was conducted up to 15th February 2022 to summarize long COVID evidence and to assess prevalence and clinical presentation in children and adolescents. Articles reporting long COVID prevalence and symptoms based on original data in the paediatric population were included. Case series quality was assessed through the JBI Critical Appraisal Checklist. For observational studies, adherence to STROBE checklist was evaluated. Twenty-two articles were included: 19 observational studies (12 cohort/7 cross-sectional) and 3 case series. Nine studies provided a control group. We found a high variability in terms of prevalence (1.6-70%). The most frequently reported symptoms were fatigue (2-87%), headache (3.5-80%), arthro-myalgias (5.4-66%), chest tightness or pain (1.4-51%), and dyspnoea (2-57.1%). Five studies reported limitations in daily function due to long COVID. Alterations at brain imaging were described in one study, transient electrocardiographic abnormalities were described in a minority of children, while most authors did not evidence long-term pulmonary sequelae. Older age, female sex, and previous long-term pathological conditions were more frequently associated with persistent symptoms.

Conclusion: Long COVID evidence in children is limited, heterogeneous, and based on low-quality studies. The lockdown consequences are difficult to distinguish from long COVID symptoms. High-quality studies are required: WHO definition of long COVID should be used, controlled clinical studies should be encouraged, and the impact of new variants on long COVID prevalence should be investigated to ensure an objective analysis of long COVID characteristics in children and a proper allocation of healthcare system resources.

What is known: • Children rarely develop a severe respiratory disease in the acute phase of COVID-19. • A limited number of patients develop a multisystem inflammatory condition that can lead to multiorgan failure and shock.

What is new: • Persistent symptoms after SARS-CoV-2 infection are reported in children and limitations in daily function due to long COVID symptoms affect school attendance. • Functional complaints of post-acute COVID are difficult to be distinguished from those due to social restrictions.

Source: Pellegrino R, Chiappini E, Licari A, Galli L, Marseglia GL. Prevalence and clinical presentation of long COVID in children: a systematic review. Eur J Pediatr. 2022 Sep 15:1–15. doi: 10.1007/s00431-022-04600-x. Epub ahead of print. PMID: 36107254; PMCID: PMC9476461.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476461/ (Full text)

Pulmonary Dysfunction after Pediatric COVID-19

Abstract:

Background: Long COVID occurs in lower frequency in children and adolescents than in adults. Morphologic and free-breathing phase-resolved functional low-field MRI may identify persistent pulmonary manifestations after SARS-CoV-2 infection.

Purpose: To characterize both morphologic and functional changes of lung parenchyma on low-field MRI in children and adolescents with post COVID-19 compared with healthy controls.

Materials and Methods: Between August and December 2021, a cross-sectional, prospective clinical trial using low-field MRI was performed in children and adolescents from a single academic medical center. The primary outcome was the frequency of morphologic changes on MRI. Secondary outcomes included MRI-derived functional proton ventilation and perfusion parameters. Clinical symptoms, the duration from positive RT-PCR test and serological parameters were compared with imaging results. Nonparametric tests for pairwise and corrected tests for groupwise comparisons were applied to assess differences in healthy controls, recovered participants and with long COVID.

Results: A total of 54 participants post COVID-19 infection (mean age, 11 years ±3 [SD], 56 males) and 9 healthy controls (mean age, 10 years ±3 [SD], 70 males) were included: 29 (54%) in the COVID-19 group had recovered from infection and 25 (46%) were classified as having long COVID on the day of enrollment. Morphologic abnormality was identified in one recovered participant. Both ventilated and perfused lung parenchyma (V/Q match) was reduced from 81±6.1% in healthy controls to 62±19% (P =.006) in the recovered group and 60±20% (P=.003) in the long COVID group. V/Q match was lower in post COVID patients with infection less than 180 days (63±20%, P=.03), 180 to 360 days (63±18%, P=0.03) and 360 days ago (41±12%, P<.001) as compared with the never-infected healthy controls (81±6.1%).

Conclusion: Low-field MRI showed persistent pulmonary dysfunction in both children and adolescents recovered from COVID-19 and with long COVID.

ClinicalTrials.gov: NCT04990531

Source: Heiss R, Tan L, Schmidt S, Regensburger AP, Ewert F, Mammadova D, Buehler A, Vogel-Claussen J, Voskrebenzev A, Rauh M, Rompel O, Nagel AM, Lévy S, Bickelhaupt S, May MS, Uder M, Metzler M, Trollmann R, Woelfle J, Wagner AL, Knieling F. Pulmonary Dysfunction after Pediatric COVID-19. Radiology. 2022 Sep 20:221250. doi: 10.1148/radiol.221250. Epub ahead of print. PMID: 36125379.

Long COVID in children and adolescents

Abstract:

Purpose of review: Although acute COVID-19 has been milder in children and young people compared with adults, there is a concern that they may suffer persistent symptoms. There is a need to define the clinical phenotype, determine those most at risk, the natural course of the condition and evaluate preventive and therapeutic strategies for both mental health and physical symptoms.

Recent findings: More recent studies with control groups reported a lower prevalence of persistent symptoms in children and young people exposed to SARS-CoV-2. A systematic review and meta-analysis found that the frequency of the majority of reported persistent symptoms is similar in SARS-CoV-2 positive cases and controls. Children and young people infected with SARS-COV-2 had small but significant increases in persisting cognitive difficulties, headache and loss of smell. Factors associated with persisting, impairing symptoms include increased number of symptoms at the time of testing, female sex, older age, worse self-rated physical and mental health, and feelings of loneliness preinfection.

Summary: This review highlights the importance of a control group in studies following SARS-CoV-2 infection, the need for case definitions and research to understand the outcomes of long COVID in children and young people.

Source: Stephenson T, Shafran R, Ladhani SN. Long COVID in children and adolescents. Curr Opin Infect Dis. 2022 Sep 12. doi: 10.1097/QCO.0000000000000854. Epub ahead of print. PMID: 36094094.  https://journals.lww.com/co-infectiousdiseases/Fulltext/2022/10000/Long_COVID_in_children_and_adolescents.14.aspx (Full text)

SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy

Abstract:

Background: In utero transmission of SARS coronavirus 2 (SARS-CoV-2) has not been fully investigated. We investigated whether newborns of mothers with COVID-19 during pregnancy might harbor SARS-CoV-2 in the gastrointestinal tract.

Methods: This cohort study investigated stool from 14 newborns born at 25-41 weeks admitted at delivery to our urban academic hospital whose mothers had COVID-19 during pregnancy. Eleven mothers had COVID-19 resolved more than 10 weeks before delivery. Newborn stool was evaluated for SARS-CoV-2 RNA, Spike protein, and induction of inflammatory cytokines interleukin-6 (IL-6) and interferon-γ (IFN-γ) in macrophages.

Results: Despite negative SARS CoV-2 nasal PCRs from all newborns, viral RNAs and Spike protein were detected in the stool of 11 out of 14 newborns as early as the first day of life and increased over time in 6. Stool homogenates from all 14 newborns elicited elevated inflammatory IL-6 and IFN-γ from macrophages. Most newborns were clinically well except for one death from gestational autoimmune liver disease and another who developed necrotizing enterocolitis.

Conclusions: These findings suggest in utero transmission of SARS-CoV-2 and possible persistent intestinal viral reservoirs in the newborns. Further investigation is required to understand the mechanisms and their clinical implications.

Impact: SARS-CoV-2 RNAs or Spike protein was detected in the stool of 11 out of 14 preterm newborns born to mothers with resolved COVID-19 weeks prior to delivery despite negative newborn nasal PCR swabs. These novel findings suggest risk of in utero SARS-CoV-2 transmission to the fetal intestine during gestation. The presence of SARS-CoV-2 RNAs and Spike protein in the intestines of newborns may potentially impact the development of the gut microbiome and the immune system; the long-term health impact on the preterm infants should be further investigated.

Source: Jin JC, Ananthanarayanan A, Brown JA, Rager SL, Bram Y, Sanidad KZ, Amir M, Baergen RN, Stuhlmann H, Schwartz RE, Perlman JM, Zeng MY. SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy. Pediatr Res. 2022 Aug 19. doi: 10.1038/s41390-022-02266-7. Epub ahead of print. PMID: 35986143. https://www.nature.com/articles/s41390-022-02266-7 (Full text)

Long-COVID in immunocompromised children

Abstract:

Coronavirus disease 2019 (COVID-19) can lead to an illness characterized by persistent symptoms which affect various organs and systems, known as long-COVID. This study aimed to assess the prevalence and clinical characteristics of long-COVID in children with immunodeficiency, in comparison to those without. A self-constructed questionnaire was created, which included questions regarding the child’s general health, the course of their COVID-19, their symptoms of long-COVID and its impact on their daily functioning, the diagnosis of multisystem inflammatory syndrome (MIS-C), and vaccination status. The questionnaire was completed by parents of 147 children – 70 children with a diagnosis of immunodeficiency (47.6%) and 77 who were immunocompetent (52.4%).

Immunocompetent children were more significantly affected by long-COVID than those immunocompromised. Its prevalence in the first 12-week post-infection was 60.0% and 35.7% in these groups, respectively. Beyond this period, these percentages had dropped to 34.6% and 11.43%, respectively. Children who were immunocompetent reported more often symptoms of fatigue, reduced exercise tolerance, and difficulty concentrating. Meanwhile, there was a slight increase in complaints of gastrointestinal symptoms in immunocompromised patients. The risk of developing long-COVID increased with age and COVID-19 severity in both groups. Furthermore, the daily activities of immunocompetent children were limited more frequently (41.8%) than for those who were immunocompromised (25%).

Conclusions: Although immunocompromised children experienced long-COVID, its prevalence and impact on daily functioning were significantly lower than among immunocompetent children. However, as the pathomechanisms of long-COVID are not yet fully understood, it is not currently possible to fully explain these findings.

What is known: • Long COVID is characterized by persistent symptoms following COVID-19, which can affect various tissues and organs, as well as mental health. • Due to the similar course of COVID-19 – mainly mild or asymptomatic – among children with and without immunodeficiency, the question arises, over whether the prevalence and severity of long-COVID is also similar in both groups.

What is new: • Immunocompromised children also suffer from long-COVID, but the prevalence is significantly lower than in the immunocompetent group of children. • The potential causes of less frequent and milder long-COVID in this group may be the milder course of COVID-19 and the state of reduced immunity protecting against neuroinflammation.

Source: Kuczborska K, Buda P, Książyk J. Long-COVID in immunocompromised children. Eur J Pediatr. 2022 Jul 14:1–9. doi: 10.1007/s00431-022-04561-1. Epub ahead of print. PMID: 35834042; PMCID: PMC9281224.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281224/ (Full text)