|Year : 2021 | Volume
| Issue : 1 | Page : 6-10
Complications of COVID-19 in children and the approach to the affected children in pediatric primary care
Paediatric Pulmonology, Paediatric Department, 2nd Faculty of Medicine, Charles University Prague, University Hospital Motol, Prague, Czech Republic
|Date of Submission||15-Jul-2021|
|Date of Acceptance||18-Jul-2021|
|Date of Web Publication||13-Jan-2022|
Paediatric Pulmonology, Paediatric Department, 2nd Faculty of Medicine, Charles University Prague, University Hospital Motol, Prague.
Source of Support: None, Conflict of Interest: None
Pandemics of the coronavirus SARS-Cov-2 has been circulating the world since the beginning of 2020 in several waves leaving behind many millions of affected individuals and very many fatalities. In children, the course of the disease has generally been milder that in adults; however, there was a wide range of possible serious complications observed including the pediatric fatalities. In this article, we review possible complications of COVID-19 in children and also focus on the role of pediatric primary care practitioners in the diagnosis and management of this serious disease.
Keywords: Children, complications, COVID-19, epidemiology, MIS-C, novel coronavirus, PIMS-TS, primary care, SARS-CoV-2
|How to cite this article:|
Pohunek P. Complications of COVID-19 in children and the approach to the affected children in pediatric primary care. Pediatr Respirol Crit Care Med 2021;5:6-10
|How to cite this URL:|
Pohunek P. Complications of COVID-19 in children and the approach to the affected children in pediatric primary care. Pediatr Respirol Crit Care Med [serial online] 2021 [cited 2022 May 25];5:6-10. Available from: https://www.prccm.org/text.asp?2021/5/1/6/335730
| Introduction|| |
Since the first reports of novel coronavirus virus infection (SARS-CoV-2) causing pneumonia in adults came from China in the end of 2019, very soon also the pediatricians became highly alerted. Along with the reports of growing number of cases of the new COVID-19 disease in adults, first reports also came about children affected by the same disease. The first papers about the symptoms and severity suggested that children did suffer from similar symptoms as adults; however, from the very beginning, the reported experience was that the course of the disease in children was milder than that in adults and also the ICU admissions and fatalities were much less frequent than in the adults. Nevertheless, first Chinese epidemiological analyses suggested that individuals of all ages were susceptible to COVID-19 with no significant sex difference. Especially young children, particularly infants, were vulnerable to this infection. Most infections in children came from the family clustering, and children were specific victims of the human-to-human transmission with the close family contacts representing the highest risk. The first reported hospitalized infants from China due to the COVID-19 infection had at least one family member infected, with the infant’s infection occurring only after the family members’ infection. Fortunately, none of these children required intensive care or had any severe complications.
With the ongoing pandemics and growing numbers of cases worldwide, the experience and knowledge about the disease have substantially expanded.
As of April 5, 2021 there have been 131,020,967 confirmed cases of COVID-19 globally, including 2,850,521 deaths, reported to WHO. This makes the current overall mortality rate 2.18%. Interestingly, in some initial reports, the overall published mortality was higher. By April 16, 2020, 1,991,562 confirmed cases were reported with 130,885 deaths and thus the mortality rate was 6.57%. This change apparently reflects changing of the approach to the disease and the increased testing of asymptomatic individuals, mainly because of increased detection of contacts and higher rate of regional testing in some areas of the world. Also, there has been a substantial progress in the treatment as several treatment modalities have been introduced during the last year that may have improved prognosis in severe cases. However, the reporting of severity of the COVID-19 may still be biased by many factors and may be largely dependent on the local systems of detections and organization of epidemiological surveillance and health care. Initially, the reported overall mortality rate in the highly affected areas was rather variable but currently has stabilized around 2% of all cases (1.8% in the USA, 2.5% in Brazil, 1.3% in India, 2.2% in Russia, 3% in Italy, and 2.9% in the UK).
The epidemiological data in children may be even less reliable than in adults as many cases may escape detection. In the initial reports, children represented about 2% of all reported cases in China and approximately 1.5% in Europe and in the USA. Children are certainly much less tested, and many of those tested come from testing of the family contacts. This may increase the probability of positive result even in an asymptomatic child. There were no systematic studies testing large population-based cohorts of children that could provide more accurate data about the true incidence of SARS-CoV-2 positivity of children in various age groups and in different regions of the world. Logically, the initial reports about the symptoms, severity, and course of the disease in children came from the most affected areas of the world such as China and Italy. Some studies indicated that symptomatic children often presented with mild symptoms, mostly presenting as mild febrile upper respiratory tract disease. However, even these data were somewhat inconsistent as the frequency of such symptoms was reported in a rather wide range, between 10% and 60% of all diagnosed children. This again may be related to imprecise denominators as the studied populations were definitely somewhat preselected, based on the presentation and reason for testing. The course of the disease in diagnosed children tended to be shorter than that in adults. Besides mild respiratory symptoms, also gastrointestinal symptoms were reported, such as abdominal pain, nausea, vomiting, and diarrhea. Nevertheless, children with severe disease were also reported from the very beginning of the data gathering. Again, the initial data came from the first areas of the disease outbreak. Chinese studies of various powers and various numbers of evaluated subjects indicated that between 2.5% and 5% of all pediatric cases had some form of severe disease., One systematic review from China reported moderate course of the disease, mostly clinically presenting as mild pneumonia, in 39–82% of the patients. However, in a German study among children admitted to the hospital, up to 8% of the children presented with severe or very severe disease, including deaths.
Interestingly, while in adults the most vulnerable age group includes seniors, in children the age comes apparently as an inversely related risk factor for a severe course of the disease. The early CDC reports from the United States found rather a wide range of hospitalized children (5.7–20%), most of these being infants. Similarly, reports from Italy mapping the situation in 11 pediatric hospitals and 51 pediatric units found that admissions were more needed in the younger age groups. Fortunately, compared with adults and seniors, the overall mortality in children remains very low. The current US CDC analysis (as of April 5, 2021) shows the children in the age from 0 to 17 years to comprise 11.8% of all US COVID-19 cases with the mortality ≤ 0.1%.
| Complications of COVID-19|| |
Although most symptomatic patients with COVID-19 manifest with fever and respiratory symptoms of various severity, SARS-CoV-2 infection may also affect other organs and present with more or less expressed extra-respiratory symptoms. Loss of smell and diminished taste have been described as rather typical early symptoms in about 10% of adults with possible persistence for some time after resolution of the respiratory manifestation. These symptoms were, however, much less prevalent in younger children. In a growing number, some adult case reports and small series reported extra-pulmonary manifestations, including gastrointestinal, cardiac, hepatic, renal, neurological, ocular, or hematological symptoms. Occasionally, these extra-respiratory symptoms were the initial manifestation of SARS-CoV-2 infection, prior to development of fever or respiratory manifestations. Initially, complications were mainly reported from seniors and patients with pre-existing chronic conditions such as obesity, cardiac disease, hypertension, or diabetes. It has not yet been fully elucidated to what extent complications are caused by the deterioration of a pre-existing condition in a general cytokine-driven inflammation during the infection and how much these complications may be caused by a direct effect of the virus attacking the target tissue. More and more reports pointed to the vascular involvement, including endothelial injury, microangiopathy, and thromboembolic complications. Comparison of the autopsy findings in the lungs of patients who died from COVID-19 and those who died from influenza-related ARDS showed a marked difference in the vascular involvement, with severe endothelial injury associated with the intracellular detection of the virus, thrombosis with microangiopathy, and marked angiogenesis characteristic for the COVID-19-related deaths. A vascular damage has also been documented in skin as vasculitic rash or chilblains; a concurrent occurrence of chilblains and retinal vasculitis has also been described.,
Fortunately, such thrombotic episodes were much less reported in children than in adults. Generally, it seems that the vessels of children do not respond to the virus-induced cytokine-driven endothelial injury as much as in adults.
Nevertheless, the most severe complications in children have been reported from various SARS-CoV-2-affected areas as series of Kawasaki-like disease. While the presentation and clinical course shared most features with the classical Kawasaki disease, reported cases were not limited to the young children but also occurred in older children and adolescents. In a French report of 21 cases [median age 7.9 (range 3.7–16.6) years] with Kawasaki-like multisystem inflammatory syndrome, 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. Most patients (17–81%) required intensive care support. All of these 21 patients had marked gastrointestinal symptoms and high inflammatory activity. All patients received intravenous immunoglobulin (IVIG) and 48% also received corticosteroids. The outcome was good in all patients with moderate coronary artery dilations found only in 24%.
In another report, a 30 times increased incidence of Kawasaki-like disease after the outbreak of COVID-19 has been reported from the highly affected Bergamo area in Italy. Affected children presented with intense inflammatory response resembling macrophage activation syndrome and with frequent cardiac disease. In a series of 35 children admitted in 14 centers in France and Switzerland over a 2-month period with cardiac injury and cardiogenic shock associated with SARS-CoV-2 infection, 28% required ECMO support. They responded favorably to IVIGs with one-third requiring additional systemic corticosteroids (CS).
This clinical presentation has been later defined as a separate disease labeled as PIMS-TS (pediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV-2) or MIS-C (multisystem inflammatory syndrome in children). In a recently published meta-analysis analyzing 953 reported patients from 68 carefully selected studies, the median age of affected children was 8.4 years which was significantly different from the non-COVID children with Kawasaki disease (median age 2.0–2.7 years). Fever was a leading symptom in almost all patients (99.4%), in 27% lasting more than 5 days. Gastrointestinal symptoms, such as abdominal pain, diarrhea, and vomiting, were present in 85.6% of cases. Cardiovascular manifestations were frequent (79.3%): mainly tachycardia, hypotension or cardiogenic shock, myocarditis, and decreased left ventricular ejection fraction. Coronary dilatation or development of aneurysms of coronary arteries was found only in 11.6% and 10.3%, respectively. About half of the patients had respiratory symptoms, mainly multiple pulmonary infiltrates, dyspnea, or upper airway symptoms. Polymorphous exanthema (54.9%) and non-purulent conjunctivitis (49.8%) were frequent. Among biological markers, C-reactive protein, ferritin, and interleukin-6 were typically markedly elevated. Interestingly, the inflammatory activity was substantially higher when compared with historical Kawasaki disease cohorts. Treatment of this condition has been originally derived from the recommendations in the Kawasaki disease, mainly using IVIG and CS. Gradually, with growing experience, some management recommendations and guidelines were published that address the complexity of treatment. Besides the well-established IVIG and CS, great attention is given to management of the coagulation system using the anti-coagulation and anti-aggregation treatments., From the available data, it can be concluded that if this condition is recognized early and treatment started immediately, the prognosis is very good and long-term sequelae are rare.
Neurological complications have also been described mainly in adults but some reports about pediatric cases also appeared. These may be part of the multiorgan systemic inflammatory syndrome or as an isolated complication. Isolated cases of COVID-19 disease-associated Guillain–Barré syndrome have been described.
Attention has been paid also to the children who may be at risk of severe course of the disease because of pre-existing conditions and comorbidities. Interestingly, preliminary data about children on immunosuppressive treatment because of underlying autoimmune diseases did not reveal higher susceptibility to the SARS-CoV-2 infection or more severe course of the disease. Patients with a congenital heart disease are also considered at potential high risk of complications. Interestingly, in an Italian study in 4 children and 72 adults with congenital heart disease, no severe symptoms or complications were registered. Still, as there is a well-documented risk of myocardial affection by the virus, these patients should be closely followed. Traditionally, patients with chronic respiratory diseases are mentioned as carrying higher risk of infection and possibly also a more severe course of the disease. However, it seems from the available evidence that patients with cystic fibrosis are not affected with any marked difference to the general population. This may, of course, be result of generally much higher compliance of these patients and their families with all the suggested protective measures. There are no consistent data on pediatric patients with other chronic respiratory conditions, such as primary ciliary dyskinesia or bronchiolitis obliterans. Patients with asthma have also been traditionally considered at higher risk; however, there is no real evidence that children with well-controlled asthma do carry any higher risk of infection or severe disease. Patients with asthma should mainly properly follow their treatment plans and use their prescribed preventative medication with the exception of nebulizers because of the possibility of aerosolizing the infection in their environment. More studies are definitely needed, and long-term follow-up of children and adults with asthma may show long-term prognosis of SARS-CoV-2-infected patients in the future.
| Approach to the Children with COVID-19 in the Pediatric Primary Care|| |
The COVID-19 pandemic represents a new challenge to the pediatric primary care. So far, there has been no similar situation with a wide-spread highly transmissible infection and so many asymptomatic potentially infective carriers. Asymptomatic children may act as a reservoir of the infection and may disseminate the infection, especially if in close contact with their peers in schools. Symptomatic children mostly do present with mild respiratory complaints that are hardly distinguishable from any other viral infections. This will be even more difficult during the autumn and winter with emergence of other usual viruses and especially during the usual influenza outbreaks. Pediatric primary care physicians need therefore to modify their practice, introducing more preventative measures and precautions into their routines. They should be aware of the epidemiological situation in their areas and follow closely the development of COVID-19 incidence. Children with respiratory symptoms (cough, sore throat, and fever) should generally be considered positive and isolated primarily within the family. Children with positive family contacts should be tested depending on the availability or at least followed up as there is a high risk of asymptomatic or oligosymptomatic infection. The arrangement of primary care practice should be re-arranged to reduce any contacts between patients. For children with mild symptoms, the visits should be reduced and distant follow-up arranged (phone consultations or video conferencing if possible). Parents should be properly instructed about the symptoms and made aware of signs of respiratory compromise (more frequent dry coughing, tachypnea, retractions, dyspnea). In case of any signs of more severe course, the patient should be seen with all the precaution measures and oxygen saturation checked. Patients with any hypoxemia need to be referred to the hospital for oxygen supplementation and further care. Always, the cardiac status should be properly checked. Inappropriate tachycardia, arrhythmia, chest pain, and fatigue may signal the development of myocarditis that also needs referral to the hospital for further diagnosis and treatment. This may go isolated or appear as part of the PIMS-TS. All patients should be always thoroughly evaluated for other possible complications such as gastrointestinal disease, neurological complications, etc. In young patients with more pronounced gastrointestinal symptoms, proper hydration should be maintained. The younger the child, the lower the threshold for referring for admission and inpatient treatment.
Of course, any patients with some underlying condition that might increase the risk of severe course of the disease should be referred rather early. These are mainly patients with severe immunocompromised conditions (current or recent chemotherapy, any post-transplant patients, primary immunodeficiency, HIV infection, severe heart disease, severe persistent asthma or other chronic lung diseases, chronic lung disease of immaturity, neuromuscular disease, severe poorly controlled diabetes, chronic kidney failure). In children with prolonged fever, the PIMS-TS should be considered irrespective of the history regarding possible COVID-19. As PIMS-TS can develop even in children with very mild disease or even asymptomatic SARS-CoV-2 positivity, the symptoms and signs of this condition should be searched for actively.
Primary care physician is also responsible for evaluation of any possible collateral social issues. There have been reports of increased occurrence of home violence on children during the coronavirus lockdown, including sexual abuse. Other mental issues that must be detected early and referred timely to the psychologist or psychiatrist may be related to the isolation and lack of contact with other children or an overload with tasks during the remote education.,
| Conclusion|| |
The new global pandemic of SARS-CoV-2 comes as a new experience and brings new challenges to the healthcare professionals on all levels of care. So far, in pediatric patients, the disease presents as milder than in adults but the risk of severe course or severe complications is not negligible. Primary care physicians must be aware of the epidemiology of the disease, modify their practice, and increase their alertness. Any possible complications, especially signs of respiratory failure, should be detected early, and the patient must be referred for specialized inpatient care. The threshold for referral must be rather low in patients with any significant underlying condition that might be associated with increased risk of severe disease or impaired prognosis.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al
; China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020;382:727-33.
Mao LJ, Xu J, Xu ZH, Xia XP, Li B, He JG, et al
. A child with household transmitted COVID-19. BMC Infect Dis 2020;20:329.
Ludvigsson JF Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr2020;109:1088-95.
Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al
. Epidemiology of COVID-19 among children in China. Pediatrics2020;145:e20200702.
Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang ZJ Novel coronavirus infection in hospitalized infants under 1 year of age in China. JAMA 2020;323:1313-4.
WHO Coronavirus Disease (COVID-19) Dashboard | WHO Coronavirus Disease (COVID-19) Dashboard. Available from: https://covid19.who.int/ (accessed: April 6, 2021).
Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). 28 February 2020. Available from: https://www.who.int/publications/i/item/report-of-the-who-china-joint-mission-on-coronavirus-disease-2019-(covid-19) (accessed: June 7, 2021).
Streng A, Hartmann K, Armann J, Berner R, Liese JG [COVID-19 in hospitalized children and adolescents]. Monatsschr. Kinderheilkd 2020. doi:10.1007/s00112-020-00919-7
CDC COVID-19 Response Team. Coronavirus Disease 2019 in Children - United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep 2020;69:422-6.
Garazzino S, Montagnani C, Donà D, Meini A, Felici E, Vergine G; Italian SITIP-SIP Pediatric Infection Study Group; Italian SITIP-SIP SARS-CoV-2 paediatric infection study group*. Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020. Euro Surveill 2020;25:2000600.
CDC. Demographic trends of COVID-19 cases and deaths in the US reported to CDC. 2021. Available from: https://covid.cdc.gov/covid-data-tracker/?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fcases-updates%2Fcases-in-us.html#demographics (accessed: April 6, 2021).
Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S, et al
. Coronavirus Disease 2019 Case Surveillance—United States, January 22–May 30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:759-65.
Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al
. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med2020;383:120-8.
Colmenero I, Santonja C, Alonso-Riaño M, Noguera-Morel L, Hernández-Martín A, Andina D, et al
. SARS‐CoV‐2 endothelial infection causes COVID‐19 chilblains: Histopathological, immunohistochemical and ultrastructural study of seven paediatric cases. Br J Dermatol 2020;183:729-37.
Quintana-Castanedo L, Feito-Rodríguez M, Fernández-Alcalde C, Granados-Fernández M, Montero-Vega D, Mayor-Ibarguren A, et al
. Concurrent chilblains and retinal vasculitis in a child with COVID‐19. J Eur Acad Dermatol Venereol2020;34:e764-6.
Cyranoski D Why children avoid the worst coronavirus complications might lie in their arteries. Nature 2020;582:324-5.
Toubiana J, Poirault C, Corsia A, Bajolle F, Fourgeaud J, Angoulvant F, et al
. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: Prospective observational study. BMJ 2020;369:m2094.
Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, et al
. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: An observational cohort study. Lancet 2020;395:1771-8.
Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, et al
. Acute heart failure in multisystem inflammatory syndrome in children in the context of global SARS-CoV-2 pandemic. Circulation 2020;142:429-36.
Zhao Y, Yin L, Jenil P, Tang L, Huang Y The inflammatory markers of multisystem inflammatory syndrome in children (MIS‐C) and adolescents associated with COVID‐19: A meta‐analysis. J Med Virol2021;93:4358-69.
Harwood R, Allin B, Jones CE, Whittaker E, Ramnarayan P, Ramanan AV; PIMS-TS National Consensus Management Study Group. A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): Results of a national Delphi process. Lancet Child Adolesc Health 2021;5:133-41.
Jonat B, Gorelik M, Boneparth A, Geneslaw AS, Zachariah P, Shah A, et al
. Multisystem inflammatory syndrome in children associated with coronavirus disease 2019 in a Children’s Hospital in New York city: Patient characteristics and an institutional protocol for evaluation, management, and follow-up. Pediatr Crit Care Med 2021;22:e178-91.
Schupper AJ, Yaeger KA, Morgenstern PF Neurological manifestations of pediatric multi-system inflammatory syndrome potentially associated with COVID-19. Childs Nerv Syst 2020;36:1579-80.
Khalifa M, Zakaria F, Ragab Y, Saad A, Bamaga A, Emad Y, et al
Guillain-Barré syndrome associated with severe acute respiratory syndrome coronavirus 2 detection and coronavirus disease 2019 in a child. J Pediatric Infect Dis Soc 2020;9:510-3.
Marlais M, Wlodkowski T, Vivarelli M, Pape L, Tönshoff B, Schaefer F, et al
. The severity of COVID-19 in children on immunosuppressive medication. Lancet Child Adolesc Health 2020;4:e17-8.
Sabatino J, Ferrero P, Chessa M, Bianco F, Ciliberti P, Secinaro A, et al
. COVID-19 and congenital heart disease: Results from a nationwide survey. J Clin Med 2020;9:1774.
Colombo C, Burgel PR, Gartner S, van Koningsbruggen-Rietschel S, Naehrlich L, Sermet-Gaudelus I, et al
. Impact of COVID-19 on people with cystic fibrosis. Lancet Respir Med 2020;8:e35-6.
Pennington E Asthma increases risk of severity of COVID-19. Cleve Clin J Med2020. doi:10.3949/ccjm.87a.ccc002
Castro-Rodriguez JA, Forno E Asthma and COVID-19 in children: A systematic review and call for data. Pediatr Pulmonol 2020;55:2412-8.
Fegert JM, Vitiello B, Plener PL, Clemens V Challenges and burden of the coronavirus 2019 (COVID-19) pandemic for child and adolescent mental health: A narrative review to highlight clinical and research needs in the acute phase and the long return to normality. Child Adolesc Psychiatry Ment Health 2020;14:20.
Boserup B, McKenney M, Elkbuli A Alarming trends in US domestic violence during the COVID-19 pandemic. Am J Emerg Med 2020;91:3-5.