Post-COVID-19 Conditions in Children and Adolescents

Over 14.2 million children have tested positive for SARS-CoV-2 in the United States. This is likely a large underestimate, given that many tests have been performed at home. Although some children and adolescents may have less severe acute illness than adult populations, COVID-19 can lead to many secondary conditions, which can range from mild to severe, with some becoming chronic. Long-term effects from SARS-CoV-2 infection may be significant, regardless of the initial disease severity.

Pediatricians play an important role in caring for children and adolescents during and following a SARS-CoV-2 infection. Pediatric visits are critical to monitor complete resolution of COVID-19 signs and symptoms, administer COVID-19 and other routine vaccines, screen for and address mental health concerns, document physical and psychosocial development, coordinate care with specialists as appropriate, and emphasize anticipatory guidance for optimal health. Telehealth is playing an increasingly important role in follow-up for these patients with potentially long-term signs and symptoms that require ongoing monitoring. Guidance on routine care during the COVID-19 pandemic can be found here.

This interim guidance provides pediatricians with direction to navigate the follow-up care of infants, children, and adolescents following a SARS-CoV-2 infection.

Do all children who have experienced a SARS-CoV-2 infection, whether symptomatic or not, require a follow-up visit?

All patients who test positive for a SARS-CoV-2 infection should have at least one follow-up conversation or visit with their primary care medical home. We recommend that this encounter occur prior to resuming sports or physical activity or within 2 to 4 weeks of a positive SARS-CoV-2 test, whichever is sooner. The medical home is a trusted source of information for patients and families, including information about asymptomatic infection or symptomatic COVID-19 and its sequelae. Because of the wide range of post-COVID-19 manifestations, a coordinated conversation is necessary to monitor residual symptoms, explore the development of any new signs or symptoms, and help guide return to activities of daily living (eg, sports, school, camp, employment, volunteer activities).

Acute COVID-19 severity does not necessarily predict subsequent or ongoing signs or symptoms. For asymptomatic infection or mild disease severity (<4 days of fever >100.4°F; <1 week of myalgia, chills, and lethargy), a follow-up video visit, phone call, or other electronic communication (eg. portal message) is recommended. Guidance should be provided to the family to contact their pediatrician and/or schedule an in-person visit if the patient experiences new or ongoing symptoms. A pediatric patient with moderate disease (>4 days of fever >100.4°F; >1 week of myalgia, chills, or lethargy; non-ICU hospital stay) or severe disease (ICU stay and/or intubation) may be at greater risk for subsequent cardiovascular disease; therefore, an in-person visit is recommended. For patients with moderate disease, follow-up visits should take place after the recommended isolation period and prior to return to physical activity. Telehealth has become invaluable in providing health care to individuals during the COVID-19 pandemic and can also be a useful tool in providing care to individuals with post-COVID-19 conditions. See the AAP telehealth policy statement. Patients with continued symptoms should receive coordinated follow-up depending on the specific signs or symptoms (see below) and their duration.

What should the pediatrician discuss in the evaluation of a child or adolescent after a SARS-CoV-2 infection, regardless of residual symptoms?

COVID-19 Vaccination
COVID-19 vaccination is recommended for all children who do not have contraindications, including those who have a history of previous SARS-CoV-2 infection. Vaccination can occur immediately following the recommended isolation period unless the patient has a history of multisystem inflammatory syndrome in children (MIS-C), in which case delaying vaccination until after they have recovered from illness (including return to normal cardiac function) and for at least 90 days following their diagnosis of MIS-C should be considered (see AAP interim guidance on MIS-C and the Centers for Disease Control and Prevention [CDC] Interim Clinical Consideration for Use of COVID-19 Vaccines Currently Authorized in the US). Further AAP guidance can be found here.

Return to Daily Living
Children and adolescents need to reestablish connections with their friends, peers, and nonparental adults in an environment that supports their development and overall well-being. Pediatricians should identify all necessary supports to facilitate return to activities of daily living (including return to learning, play, and employment). Patients with ongoing symptoms may require additional support in their efforts on return to learning. This might include gradual return to school and cognitive activities based on tolerance; addition of cognitive “rest periods” throughout the school day; interval academic accommodations such as a 504 plan; close monitoring and communication by the family, school, and pediatrician to assess progress; and other academic adjustments or accommodations as needed. It is essential that children and adolescents are supported in catching up on work accrued during the acute illness and that schools avoid penalizing students for ongoing or residual symptoms that affect learning and completion of assignments.

Return to Sports or Physical Activity
All children and adolescents should connect with their pediatrician prior to returning to physical activity, as outlined in the AAP Return to Sports and Physical Activity interim guidance. Children and adolescents who had moderate or severe symptoms within 6 months require a preparticipation examination, including an American Heart Association (AHA) screening and electrocardiogram or cardiology evaluation to guide return to sports. Guidance on coding for this visit is provided in the AAP Coding During the COVID-19 Public Health Emergency Fact Sheet (see Providing Preventive Medicine Services During the PHE).

Return to Camp
Decisions on camp attendance and participation should consider the facility, the expectations of participation, any residual symptoms, and the camp’s ability to identify and support the camper’s/camp counselor’s needs (see American Camp Association COVID-19 Resource Center for Camps and the CDC general COVID-19 guidance).

Return to Child Care, School (K-12), and Higher Education
Return to school and child care is a critical factor for education and social well-being in children. This guidance from the AAP, along with local health department information, can help to guide parents and children as they return to normal daily living. Further information from the CDC can be found here. Return to higher education may require additional thought for students and families. Further information can be found here.

Multisystem Inflammatory Syndrome in Children (MIS-C)
MIS-C is a rare complication that typically occurs 2 to 4 weeks following SARS-CoV-2 infection. A persistent fever without a clear clinical source that is accompanied by new signs or symptoms or coincident with recent exposure to a person with COVID-19 should raise suspicion of possible MIS-C. Some signs and symptoms of acute illness progress rapidly, and children and adolescents may develop hemodynamic compromise. These patients should be followed and cared for in a hospital with tertiary pediatric/cardiac intensive care units whenever possible, as outlined in the AAP MIS-C interim guidance.

Patients and families should be instructed about signs and symptoms that require further evaluation even if new concerns are likely unrelated to a recent COVID-19 illness. Additional information on MIS-C can be found at https://www.cdc.gov/mis/hcp/index.html.

Do children or adolescents who previously were SARS-CoV-2 positive need testing if they have a known exposure or develop new COVID-19 symptoms?

Although testing was generally not recommended for asymptomatic patients who had tested positive within the past 3 months, with new variants circulating, breakthrough infections being reported, and data continuing to accumulate regarding longevity of immunity from natural infection or vaccination, it may be reasonable to re-test within the 3 month window in patients with a known exposure and compatible symptoms. The AAP has developed interim guidance on testing, which provides additional information.

Is there a role for serum antibody testing in children or adolescents after a documented SARS-CoV-2 infection?

Although qualitative and quantitative antibody testing are available, they are not recommended by the AAP or CDC for routine use. Further guidance on COVID-19 testing is available here.

Do children and adolescents experience post-COVID-19 conditions?

“Post-COVID-19 condition” is an umbrella term that encompasses physical and mental health consequences experienced by some patients that are present 4 or more weeks following a SARS-CoV-2 infection (See CDC Interim Guidance on Post-COVID Conditions). Some of these symptoms are minor, do not interfere with activities of daily life, and will self-resolve; however, some are more persistent and disruptive, which fall under the syndrome of post-acute sequelae of COVID (PASC)/long COVID. The World Health Organization (WHO) recently developed a consensus definition of pediatric PASC, which is defined as the presence of one or more new, persistent physical symptoms, which may fluctuate and relapse, that lasts at least 12 weeks after confirmed initial SARS-CoV-2 infection and impairs daily function.¹

The reported prevalence of pediatric post-COVID-19 conditions has varied widely in the medical literature, with estimates that anywhere between 2% to 66% of SARS-CoV-2-infected children and adolescents experience new persistent or prolonged symptoms after recovery of their acute illness. A recent meta-analysis, which evaluated 21 studies and over 80,000 children, determined that 25% of SARS-CoV-2-positive children had persistent symptoms at 4 weeks after acute COVID-19.² Additional recent studies have compared the prevalence of persistent post-COVID-19 symptoms in children with documented COVID-19 compared with those without a history of SARS-CoV-2 infection (controls) and found the prevalence of pediatric PASC at 90 days postinfection to be 2% to 5%. ^3,4 The prevalence of WHO-defined pediatric PASC in children with a history of COVID-19 is most likely between 2% and 10%, which still represents up to 1.4 million children in the United States.

Pediatric PASC is a heterogenous condition that can present with up to 60 signs or symptoms in various combinations. However, patterns and trends in these symptoms have begun to emerge as more data are collected on this population. A recent report published by the CDC demonstrated that children younger than 18 years with previous SARS-CoV-2 infection were at greater risk for certain post-COVID-19 symptoms and conditions, including fatigue, dyspnea, anosmia/parosmia, and circulatory signs and conditions (including pulmonary embolism, venous thromboembolism, and thromboembolic events) compared with those who did not have a previous SARS-CoV-2 infection. ^5,6 Across the pediatric PASC literature, the most commonly reported symptoms include fatigue, headache, stomach/abdominal pain, muscle aches, postexertional malaise, and rash. ^7,8,9,10,11

As of August 17, 2022, there is no single, validated laboratory test in the clinical setting that can definitively distinguish pediatric PASC from conditions of other etiologies. Several potential biomarkers have been proposed following the results of research studies, which include low cortisol and adrenocorticotropic hormone (ACTH), markers of endovascular dysfunction and impaired fibrinolysis (such as abnormal platelet thromboelastography) ^12,13 and even persistently positive SARS-CoV-2 RNA in blood and bodily fluids, but these require validation in larger populations and guidance for operationalization in a clinic setting. Current recommendations for evaluation and management of pediatric PASC include a stepwise approach, with initial conservative evaluation to be performed in a primary care based setting in the period of 4 to 12 weeks following infection. During this initial period of evaluation, pediatricians should focus on determining level of symptom interference with daily functioning, enforcing and aiding a return to healthy lifestyle habits (sleep, diet, light activity as tolerated without symptom exacerbation) and ruling out other causes of ongoing symptoms. Initial tests to be considered during this period include complete blood count (CBC) with differential, comprehensive metabolic panel (CMP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, thyroid-stimulating hormone (TSH) with or without free thyroxine (T4), vitamin D level, and EBV antibody panel.¹⁴ If symptoms persist beyond 12 weeks (3 months) and/or are impacting the patient’s ability to perform normal activities, then additional diagnostic testing, and ideally, referral to or consultation with a multidisciplinary pediatric post-COVID-19 clinic should be considered. If a multidisciplinary pediatric post-COVID-19 clinic is not readily available, consider referral to a pediatric medical subspecialist on the basis of the most problematic signs and symptoms.

What are some of the ongoing or residual symptoms known to occur after a SARS-CoV-2 infection in children or adolescents as a part of PASC/long COVID and how might they be evaluated and managed?

Respiratory. Because the lungs are the most commonly affected organ for patients with SARS-CoV-2 infection, persistent respiratory signs and symptoms following acute COVID-19 are not uncommon, although are notably less common in pediatric patients compared with adults. The symptoms include chest pain, cough, and dyspnea. The time to improvement depends on the premorbid condition and the severity of the illness. Some of these symptoms can last for 3 months or longer. Follow-up chest imaging is needed for persistent respiratory symptoms or patients who had pulmonary abnormality identified during the acute infection. Children 6 years or older who have persistent symptoms should receive pulmonary function testing. For any patient with persistent exercise-induced dyspnea after initial cardiopulmonary evaluation, including evaluation for thromboembolic disease and heart disease, cardiopulmonary exercise testing can be performed to assess for deconditioning or pulmonary/cardiac limitation under stress.

Cardiac. One of the most concerning aspects of SARS-CoV-2 infection is the potential risk for cardiac involvement, which can be part of the initial disease presentation (including MIS-C), observed as a sequela of the disease or, much less commonly, as a potential risk following the mRNA COVID-19 vaccines.

Myocarditis can develop after COVID-19 infection with presenting signs or symptoms that include chest pain, shortness of breath, arrhythmias, and fatigue. In more severe cases, myocarditis can lead to heart failure, myocardial infarction, stroke, or sudden cardiac arrest. Although the etiology of myocardial involvement is unclear, it appears to be related to either the virus itself or potentially the host immune response to the virus. Typically, myocarditis occurs in the acute or subacute period after initial SARS-CoV-2 infection. Myocarditis is much more common, and the risks to the heart are potentially much more severe, with SARS-CoV-2 infection than with COVID-19 vaccination.

Anosmia and/or Ageusia. COVID-19 can result in changes to smell and taste, particularly in adolescents. As many as 1 out of 4 individuals 10 to 19 years of age develop anosmia. Beyond the ability to detect dangerous odors, reduction or loss of the sense of smell (anosmia) or taste (ageusia) or abnormal sense of smell/taste (parosmia) can affect the nutritional status, mood, and quality of life in children and adolescents. Symptom report can be challenging in very young children, but reduced oral intake, changes in feeding behaviors, or gagging with/avoidance of previously well-tolerated food could indicate changes in smell or taste resulting from COVID-19. Persistent anosmia may warrant further evaluation, nutrition optimization, and olfactory testing, and olfactory training should be considered, the supplies for which can be obtained over the counter by families.

Neurodevelopmental. An age-specific history and evaluation for neurodevelopmental impairment is recommended to assess any changes or delays in cognitive, language, academic, motor, or mood/behavioral domains.¹⁵ Acute COVID-19 can result in neuroinflammatory disorders (eg, stroke, encephalitis). Significant injury will result in readily apparent motor, cognitive, and/or language deficits (eg, right hemiplegia and aphasia following left middle carotid artery infarct). However, more subtle neurodevelopmental sequelae that still impact optimal daily function are also possible. Persistent signs or symptoms require referral to either a neurodevelopmental neurologist, developmental and behavioral pediatrician, neuropsychologist, speech language pathologist, psychologist, and/or physical or occupational therapists.

Cognitive Fogginess or Fatigue. “Brain fog” (a generic term that refers to unclear or “fuzzy” thinking, inattention, difficulty with concentration or memory) is a frequent neurologic complaint in adults following SARS-CoV-2 infection. School aged-children and adolescents may also complain about neurocognitive changes following SARS-CoV-2 infection as compared with baseline function. These changes can manifest as inattentiveness, seeming to be more forgetful to a parent, slower in reading or processing, requiring more repetition in learning, and less endurance and/or requiring more breaks when reading or performing other cognitive tasks. It is critical to treat any behaviors that may potentially impact cognitive functioning, including but not limited to getting adequate nighttime sleep, maintaining a consistent sleep/wake schedule with daily activities, avoiding alcohol and drugs, or addressing stressors. For cognitive complaints that persist and result in functional impairment, a targeted neuropsychological evaluation can identify the basis for these signs or symptoms and guide the development of an appropriate, often multidisciplinary, treatment plan. School accommodations, such as a 504 plan, should also be discussed.

Physical Fatigue/Poor Endurance. Following SARS-CoV-2 infection, children and adolescents may complain of easy fatigability, decreased endurance and postexertional malaise or worsening of symptoms. Cardiac evaluation should be performed for patients with significant fatigue who also demonstrate any “red flag” cardiac symptoms, such as syncope, radiating chest pain, or chest pain with exertion, prior to return to any exercise. Encouraging a consistent daily schedule is helpful. An individualized, goal-driven, gradual increase in physical activity, as tolerated, may be beneficial; however, a subset of patients with post-COVID-19 experience significant postexertional exacerbation of their fatigue and other symptoms after a day of activity while they are “feeling good,” resulting in a “push and crash” cycle, which can slow down their overall trajectory of improvement. Traditional reconditioning protocols can be detrimental and mentally and emotionally aggravating for this population.¹⁶ For these patients, a return to physical activity should be closely monitored by a pediatrician or physical therapist with specialized training or knowledge of postexertional malaise, which differs from a traditional physical therapy reconditioning approach.¹⁷ Existing protocols for this type of recovery (such as the Levine protocol) exist for patients with dysautonomia (and postural orthostatic tachycardia syndrome [POTS]) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and are available on the internet.

Headache. Headache is a common symptom during and following SARS-CoV-2 infection. The history, evaluation, and management are the same as any child presenting with headache—evaluating for “red flag” characteristics (eg. focal or side-locked headache, vomiting that is persistent or worsening, focal neurologic symptoms, etc), associated neurologic findings, and other possible causes of headache. In addition to the potential underlying pathophysiologic mechanisms behind long COVID that remain under investigation, post-COVID-19 headache may be related to situational factors such as change in routine, medication overuse, changes in sleep hygiene, poor hydration and/or nutrition, lack of aerobic exercise, and other stressors. Management of headaches during recovery from infection is similar to other postviral syndromes or postconcussive headaches. Lifestyle factors are typically addressed first; however, if headache symptoms are severe enough to impede recovery, preventive medication may need to be initiated.

Mental Health/Behavioral Health Sequelae. Pediatricians should be aware of the impact of stress and adjustment disorders when diagnosing and managing new symptoms in children who have experienced SARS-CoV-2 infection and/or COVID-19 disease. Following SARS-CoV-2 infection, mental health sequelae are very common and likely multifactorial. The AAP has published interim guidance on integrating and supporting the emotional and behavioral health needs of families affected during the COVID-19 pandemic.

How should the pediatrician approach children and adolescents with previously identified underlying mental or behavioral conditions who have experienced COVID-19?

For individuals with existing mental/behavioral illness, events surrounding COVID-19 (hospitalization, isolation, absence from school activities) may exacerbate symptoms. A team-based approach is recommended for those with significant physical impairments or with multiple comorbidities. This team-based approach should be coordinated by the primary care pediatrician, incorporating medical, surgical, occupational, and behavioral specialists as needed. Guidance on managing children with special health care needs during the COVID-19 pandemic can be found here.