Does Long COVID Exist in the Pediatric Age Group?

Patient Presentation
A 16-year-old male came to clinic for his sports physical examination. He had no overall concerns but it was noted that he had lost about 4 kilograms of weight. He complained that, “After I had COVID last fall, my sense of smell has never come back and everything just tastes like cardboard. I eat but I’m not really hungry or interested in food.” He noted that there were some foods with strong flavors that tasted somewhat different but not really any better. He was eating a balanced diet because “if I’m going to play well then I have to eat well.” The past medical history showed that he had a mild case of COVID 7 months previously.

The pertinent physical exam revealed normal vital signs and growth pattern except for the weight loss. His physical examination was normal.

The diagnosis of a healthy male was made with long standing anosmia and dysguesia. The pediatrician asked him to continue to monitor his weight and check back in 3 months to make sure he wasn’t losing an excessive amount of weight. She also mentally added him to her list of other patients with longer term symptoms of COVID including a younger girl with paresthesias and one of her partner’s patients with dysguesia of certain foods.

Discussion
With COVID-19, the scientific research process is playing out daily in the press where the general public can see for themselves and share in the new knowledge and frustrating events that occur usually behind the curtain of science. People try to understand the little snippets of new knowledge that come forth and how they fit into the COVID problem, and most importantly how it may affect themselves, the people they care about and their community. Patients and families daily ask questions of their health care providers who themselves have the same questions, and answer something like “We’re learning something new every day.”

Scientists grapple with a variety of the fundamental scientific questions for COVID or any other scientific research question including:

  • What is the disease and its variations? What are the agreed-upon definitions?
  • What is the incidence and prevalence and other epidemiological data of the disease?
  • What populations are affected or at higher or lower risk? Why does this appear to be the case? What population is even being studied in the research? Are the findings consistent across populations and locations?
  • What appears to mitigate or promulgate the disease process?
  • What alternative diagnoses need to be considered?
  • Are rare findings associated with the disease disease? Are they a cause of it? Are they just a random occurence?
  • What is the natural history of the disease? What are the long-term problems in 1, 5, 10 years or potentially over a lifetime?
  • What are the pros/cons of the medical decisions made today and what about the future?

It can be frustrating for both patients, families, health care providers and the scientific community to need to make important health care decisions based upon incomplete data, but COVID is not unique. Consider cancer treatment where despite having a great deal of research, often scientific data is not available which specifically matches the patient’s characteristics and medical situation. Therefore, the best-fit for the general characteristics and medical situation must be used for treatment decisions. Scientific research provides new treatments, but they are often used for small numbers of patients meeting specific criteria and therefore it is not known how the new treatment may affect a different or wider population, or what the long-term side effects are 1, 5, or 10 years later.

Learning Point
In the first few weeks to months after its description, it was noticed that some patients continued to have more than 1 symptom for weeks to months after the acute disease. This has been termed post-acute sequelae of SARS-CoV-2 (PASC) Long-haul COVID, or Long COVID among others. Initially it was first described in adult patients but then noticed in some pediatric patients as well. Different studies use different definitions but in general, the term Long COVID describes patients experiencing symptoms for more than 30 days (at least) or more after laboratory confirmatory testing of acute COVID. Patients do not have to be symptomatic.

In a population-based cohort of non-hospitalized patients, aged 12-82 years, researchers found that the prevalence of Long COVID was 68.7% at 30 days post-infection (N=303) and was 77.1% for those followed longer than 60 days (N=157). “The most common symptoms were fatigue (37.5%), shortness-of-breath (37.5%), brain fog (30.8%), and stress/anxiety (30.8%). Median number of symptoms was 3 (range 1-20).”

In one of the first studies of children performed in Italy (N=129, mean age 11 +/- 4.4 years) including 25.6% who were asymptomatic) who were assessed by telephone call 49-275 days after diagnosis (mean 162 days), it was found that 41.8% had recovered, but 35.7% had 1-2 symptoms and 22.5% had 3 or more. The most common symptoms were insomnia (18.5%), respiratory symptoms (14.7%), nasal congestion (12.4%), fatigue (10.8%), muscle problems (10.1%), concentration problems (10.1%) and joint pain (6.9%). The authors note that “An important and unexpected finding is that also children with asymptomatic or paucisymptomatic COVD-19 developed chronic, persisting symptoms, although followed-up for a relatively short time after diagnosis.” Given that COVID has only been identified for a relatively short time itself, these are important findings to be aware of for medical decision making.

In a prospective cohort in the United Kingdom (N=1734, ages 5-17 years using a mobile application device to assess symptoms, researchers found 4.4% had illness symptoms > 28 days and they usually had 2 symptoms. After 56 days, only 1.8% had symptoms and all had resolution by 8 weeks. Symptoms included headache, fatigue and loss of smell.

In a prospective study of children (N=90, ages 12 +/- 5 years) who presented to a designated Long COVID clinic at a tertiary pediatric care center, who were assessed 33-410 days after infection (mean 112 days), the median number of symptoms was 4 (range=1-14) with fatigue (71.1%), dyspnea (50%) and myalgia (45.6%) being the most common.

These studies show a small range of different types of studies, performed in different populations, with different definitions and assessments which then provide different answers. With more time, many of the fundamental scientific questions above should be further elucidated to better understand Long COVID in children.

Questions for Further Discussion
1. What is MIS-C? A review can be found here
2. Name some other recent emergent diseases?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: COVID-19.
To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Buonsenso D, Munblit D, De Rose C, et al. Preliminary evidence on long COVID in children. Acta Paediatr. 2021;110(7):2208-2211. doi:10.1111/apa.15870

Bell ML, Catalfamo CJ, Farland LV, et al. Post-acute sequelae of COVID-19 in a non-hospitalized cohort: Results from the Arizona CoVHORT. PLoS One. 2021;16(8):e0254347. doi:10.1371/journal.pone.0254347

Lewis D. Long COVID and kids: scientists race to find answers. Nature. 2021;595(7868):482-483. doi:10.1038/d41586-021-01935-7

Ashkenazi-Hoffnung L, Shmueli E, Ehrlich S, et al. Long COVID in Children: Observations From A Designated Pediatric Clinic. Pediatr Infect Dis J. Published online August 5, 2021. doi:10.1097/INF.0000000000003285

Children rarely get ‘long COVID.’ J Paediatr Child Health. Published online August 19, 2021:10.1111/jpc.15708. doi:10.1111/jpc.15708

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What are the Main Differences Between MIS-C and Kawasaki Disease?

Patient Presentation
The residents were talking before their continuity clinic and noted that 2 young teen patients had been recently admitted to the pediatric intensive care unit with multisystem inflammatory syndrome in children (MIS-C). “We had to put one of them on ECMO yesterday and today she is much more stable, but she still looks pretty bad,”” one resident remarked. “I was cross-covering a few days ago and saw the other patient. He looks worse than the Kawasaki Disease patient who wasn’t responding to IVIG I saw the week before,” she said. The attending knew that these diseases probably had similar underlying origins but wasn’t sure of the main differences between the two, so he reviewed the Centers for Disease Control current information about MIS-C.

Discussion
SARS-CoV-2 or COVID-19 was first observed in Wuhan China in late 2019. By March 2020 it had spread to become a world-wide pandemic and continues today despite vaccination and other public health measures. Early on people were worried that children would be the major age group affected, but the major groups were older individuals and those with underlying health problems. That is not to say that children are not affected as they were and could have severe disease. However as an overall group, they tend to get the virus and have less severe symptoms than adults. Severe disease is about 1% of pediatric cases compared to 10-20% for adults, and pediatric mortality is estimated at < 0.1% compared to 5-15% for adults.

Common presentations of COVID-19 in children include:

  • *Fever/chills
  • *Cough
  • *Diarrhea
  • Fatigue
  • Headache
  • Myalgia
  • Nausea/emesis
  • *Pharyngitis
  • Rhinorrhea
  • Anosmia/aguesia

* = very common symptoms especially for mild disease.

In April 2020 there were warnings “…about cases of older school-aged children and adolescents presenting with fever, hypotension, severe abdominal pain and cardiac dysfunction….”These children had laboratory findings of cytokine storm….Almost all of these children no longer required intensive care after only a few days and completely recovered, although rare deaths [occurred]….” These children and adolescents had a new condition called multisystem inflammatory syndrome in children or MIS-C. MIS-C has clinical similarities to Kawasaki Disease (KD) which is a medium-vessel vasculitis presenting predominantly with fever, lymphadenopathy, rash and mucositis. It’s etiology is undetermined but likely is viral. A brief review can be found here. There are different case definitions of MIS-C (see To Learn More below for references) with overlap with other problems such as KD, juvenile idiopathic arthritis (systemic onset), toxic shock syndrome other viral infections and inflammatory conditions of children.

Learning Point
Key differences between MIS-C and Kawasaki Disease include:

MIS-C Kawasaki Disease
Age Older children and adolescents, 8-10 years is common Generally < 5 years, peak ~10 months
Gender Male > Female Male > Female
Race/Ethnicity African/Hispanic/Latino > White East Asian
Labs High inflammatory markers and cytokine storm including leukopenia, high ventricular natriuretic peptide Not found, has neutrophilic leukocytosis usually
Fever Present Present
Respiratory symptoms Little Not present
Lymphadenopathy Not common More common
Skin Rash similar to KD but only seen < 50% of time Typical rash seen in most patients
Usual presentations Multiorgan system failure, Gastrointestinal problems incl. abdominal pain and diarrhea Does not have multiorgan system failure, GI symptoms usually not present
Cardiovascular problems Cardiac dysfunction seen when presenting especially with hemodynamic compromise, myocarditis and pericarditis, coronary artery aneurysms can be seen but small size or dilatation only Myocarditis is not common, usually not hemodynamically unstable at presentation, coronary artery aneurysms and dilatation are seen
Response to IVIG Often does not respond Usually responds

Questions for Further Discussion
1. What resources do you use to keep current with COVID-19 information and other emerging/emerged medical problems?
2. What are current treatments for MIS-C?
3. How does MIS-C differ from toxic shock syndrome?
4. What is the long term outcome of children with MIS-C?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: COVID-19.
To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nat Rev Immunol. Published online June 16, 2020:1-2. doi:10.1038/s41577-020-0367-5

Kabeerdoss J, Pilania RK, Karkhele R, Kumar TS, Danda D, Singh S. Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management. Rheumatol Int. Published online November 21, 2020:1-14. doi:10.1007/s00296-020-04749-4

Henderson LA, Canna SW, Friedman KG, et al. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 2. Arthritis Rheumatol. 2021;73(4):e13-e29. doi:10.1002/art.41616

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What Are Some Indications for a Vesicostomy?

Patient Presentation
A 15-month-old male came to clinic for his health maintenance visit. He had a past medical history of posterior urethral valves that were treated by ablation after a vesicostomy. The vesicostomy was still in place and his renal function were at the upper end of normal but stable. He had few problems with the vesicostomy including skin breakdown and some bleeding. Otherwise his parents had no concerns.

The pertinent physical exam showed a curious toddler exploring the examination room. His vital signs were normal including his blood pressure and his height and weight were at the 25% with mid-parental height at the 25-50%. His head circumference was 50%. His physical examination was normal except for the vesicostomy opening mid-way between the umbilicus and pubis. There was some mild irritation that was treated with a barrier emollient.

The diagnosis of a happy toddler with a vesicostomy was made. “At this point we’re happy with how things are going and there’s no problem with daycare. They just change his diaper like the rest of the kids but are really good about watching his skin. We’ll have to see how his kidneys do with more time and mad\ke some decisions about the vesicostomy. We’re not in a hurry to get rid of it as he’s doing so well with it and diapers are just normal at his age,” the parents remarked.

Discussion
A cutaneous vesicostomy is an incontinent diversion of the bladder to the external abdominal wall usually below the umbilicus that maintains a low-pressure urinary system. The urine drains into a collecting bag or hygiene product such as a diaper. It is usually used as a temporary diversion until bladder function resolves or another treatment can be carried out. However, it can also be used as a permanent diversion in some cases. A vesico-cutaneous fistula is similar but performed slightly differently. It is often intended to be a longer-term diversion procedure and is a continent diversion of the bladder.

Some of the conditions treated with a vesicostomy include:

  • Neuropathic bladder due to a brain, spinal cord or muscle problem such as spina bifida
  • Lower urinary tract obstruction e.g. posterior urethral valves
  • Dysfunctional voiding
  • Vesicoureteral reflux
  • Hydronephrosis
  • Congenital megaureter

Learning Point
Before a vesicostomy is performed other treatments are usually tried such as clean intermittent catheterization (CIC), anticholinergic medications and botulinum toxin injection. If these do not achieve satisfactory results then vesicostomy is considered. CIC is widely used with a low complication rate but it can have bleeding, stricture formation and creation of a false tract. Cholinergic medications may have unwanted side effects (e.g. blurred vision, abdominal pain, constipation, diarrhea, etc.) that cause discontinuation. Botulinum toxin is temporary, usually for a few months, and may only work 50% of the time.

The hoped for outcomes of a vesicostomy are protection of the upper urinary tract, decreased rates of febrile urinary tract infection, delaying the need for other procedures such as bladder augmentation and importantly to preserve renal function. Therefore the indications for a vesicostomy include:

  • Treatment failure
  • Treatment refusal, e.g. refusing CIC due to age, anatomy, sensation issues
  • Upper urinary tract deterioration
    • Recurrent febrile urinary tract infection
    • High pressure bladder
    • Worsening renal failure
  • Temporary diversion until other treatment can be instituted

Vesicostomy is a good procedure for many patients but complications occur in about 30-40% of patients including dermatitis, febrile UTI, mucosal prolapse or stenosis of the stoma.
Incontinence is not a complication as it is expected post-procedure but this may not be acceptable to patients long term.

Questions for Further Discussion
1. What can be the roles of a primary care physician on a multi-specialty team providing specialty care?
2. What are causes of antenatal hydronephrosis? A review can be found here
3. How is bladder dysfunction categorized? A review can be found here

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Ostomy, Urinary Incontinence, and Urine and Urination.

To view current news articles on this topic check Google News.

Yang. W, Chang P.-Y, Lai J.-Y, Change C.-H, Tseng M.-H. Vesico-cutaneous fistula: A simple method for continent urinary diversion J Pediatr Urol. 2014;10:1227-1231.

Donmez MI, Carrasco A, Saltzman AF, Vemulakonda V, Wilcox DT. Long-term outcomes of cutaneous vesicostomy in patients with neuropathic bladder caused by spina bifida. J Pediatr Urol. 2017;13(6):622.e1-622.e4. doi:10.1016/j.jpurol.2017.05.015

Sharifiaghdas F, Mirzaei M, Nikravesh N. Can transient resting of the bladder with vesicostomy reduce the need for a major surgery in some patients? J Pediatr Urol. 2019;15(4):379.e1-379.e8. doi:10.1016/j.jpurol.2019.03.026

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Is It or Isn’t It Abnormal in This Classification System?

Patient Presentation
A 6-year-old male came to clinic for a second opinion regarding the results of a head computed tomography study. Two weeks previously, the patient had fallen off from a slide onto hard ground. He had loss of consciousness for at least 1 minute and had been awake but very groggy in the emergency room. He had emesis three times so head imaging was done. It was negative for any acute bleeding or obvious injury, but it was noted that his cerebellar tonsils were 4 mm below the foramen magnum and there was concern for a Chiari I malformation. The patient had recovered without incident but his local nurse practitioner was unsure what to do about these incidental findings so she referred him for the second opinion. The past medical history was non-contributory. The family history was positive for migraine in the maternal family and a paternal second cousin with a neurological genetic disease of unknown type. The review of systems was normal and he had no headaches, balance or muscle problems.

The pertinent physical exam showed a smiling boy with growth parameters in the 50-75% and normal vital signs. HEENT was normal including pupils. His skin examination showed a few freckles on arms and face. Neurological examination was normal including gait and fine motor activities. His spine had no identifiable defects and he appeared to have full range of motion in his joints including his neck.

The diagnosis of of a healthy boy who had recovered from his head trauma was made. The pediatrician was able to determine that the cerebellar tonsils should be 3 mm or less to be considered normal and 5 mm or more to be considered abnormal for a Chiari I malformation. The pediatrician noted that the child had been perfectly well before this and probably would continue to be. However, it was possible that this should be followed at intervals and neurosurgery usually followed or treated these patients. The parents expressed that they also were very anxious about this and wanted to talk more with a specialist. Therefore the patient was referred and the neurosurgeon felt that this was a normal variant which did not need specific followup. He did caution that if the patient did develop any more consistent or increasing neurological problems that consultation should be sought just like any patient without this finding.

Discussion
Chiari I malformations have caudal displacement of cerebellar tonsils with elongation of the 4th ventricle. It is associated with syringomyelia in up to 80% of patients. Syringomyelia is a cyst-like formation within the spinal cord that contains altered glial elements. This may be asymptomatic or have symptoms occurring from infancy to adulthood. Most patients present in the 3rd decade. Hydrocephalus may be present. A review can be found here.

Classifying information and diseases is important in clinical care as it can help determine treatment and prognosis, and improves communication among clinicians and facilitates research.

There are 5 ways to organize and classify information, sometimes referred to as LATCH. These types are often used together sequentially. For example, restaurants in particular city (location), then by cuisine type (category) and then name (alphabetical).

  • Location – this commonly uses a visual representation of a physical space such as a map. In medicine, anatomic location is very important especially in the surgical, radiology, and oncology specialties.
  • Alphabetical – this is helpful when the terms and definitions are already known by people. It can be less helpful if people are not aware. It is very good for lists or as a secondary method of information organization.
  • Time – chronological organization is used for events. In medicine this a major organizer of the medical chart. Age of the patient is also important for developing a differential diagnosis especially in pediatrics. It is also helpful for understanding processes such as quality improvement.
  • Category – this is probably the broadest way to organize information. Medical specialties and patient problems lists are organized this way.
  • Hierarchy – this method shows how information is related to each other and potentially may indicate importance or rank. For example, pediatrics – pediatric neurology – muscle diseases – spinal muscle atrophy.

Learning Point
Disease classification systems help to define the problem. They allow everyone to understand and use the definitions more consistently. If people all agree on the terminology, it makes mis-understandings less likely. This is important in clinical care but is also especially important in quality improvement and research where treatments and outcomes must be clearly understood based on a very specific type of problem.

Take, for example, growth plate fractures. The Salter-Harris classification system uses an anatomical approach to define 5 different growth plate fractures. Using this location categorization, the radiologist and orthopaedic surgeon can quickly have a shared understanding of the fracture type, and treatment decisions and natural history will be made and based on the classification, as type 1 fractures are treated conservatively and have generally good outcomes, and types 4 and 5 are treated surgically and have poorer expected outcomes.

Some classification schemes are objective in that they discriminate between each class, but are qualitative as it is up to the clinician to determine the classification. This can be more difficult when a clinician is trying to assign a discrete classification to something that is a continuous process such as Tanner staging for pubertal development. With Tanner staging there are 5 distinct stages, however as puberty is a continuum, patients still must cross the line between the stages and therefore clinicians will often record Tanner II-III or IV-V in their chart. Another example is the Bristol Stool Scale for fecal stool classification. This is a visual tool of 7 different stool types and patients often indicate several of the classifications to describe even their “normal” stool pattern. Another example is the Mallampati airway visualization score which can be impeded by patient cooperation with the examination and therefore the classification may not be as accurate as one tries to make it. These types of classification schemes are very important to help guide evaluation, management and treatment but many times in clinical care are used less rigidly, i.e. it is more important to know the patient generally has harder or softer stools than the exact 1-7 category.

Classification schemes using measurements can potentially be more reproducible, precise and accurate. Examples would be measurements of a skin macule, radiographic measurements (i.e. organ or mass size), and surgical specimens. These are continuous variables where often someone is looking to determine a specific size or “cut-off” where it is more likely to indicate a more serious problem. For example, the thickness of the pylorus in a newborn is considered normal up to 3.5 mm. If it larger then pyloric stenosis is more likely in the setting of a frequently vomiting neonate. Cancer classification schemes use size as an important characteristic and look for changes in size to help determine response to treatment as well. There often is a grey zone too between what may be clearly normal and what is diseased and patients will fall into these areas too.

There are other classification schema which are more difficult to apply even when they are well-established and understood. A common pediatric example is otitis media. Clinicians know that otitis media with suppurative effusion should be distinguished from otitis media with serous effusion as it is one of the key characteristics that helps determine if antibiotics are indicated. However patient cooperation, crying, temperature, and especially cerumen make it very difficult to examine the middle ear and determine if an effusion is present and what type of effusion it is.

Sometimes there are more than one classification system for different medical problems, which can be caused by different or disputed terminology, and evolving scientific understanding of disease processes. Classification of cancers is a classic example. Therefore it can be very important to understand which classification system is being used.

Questions for Further Discussion
1. List some other common classification systems that you use frequently?
2. What are indications for head imaging after head injury?
3. What are indications for a neurosurgery consultaton?
4. What are some ways that “cut-off” values are determined?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Chiari Malformation

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Chatrath A, Marino A, Taylor D, Elsarrag M, Soldozy S, Jane JA Jr. Chiari I malformation in children-the natural history. Childs Nerv Syst. 2019 Oct;35(10):1793-1799. doi: 10.1007/s00381-019-04310-0.

Talamonti G, Marcati E, Gribaudi G, Picano M, D’Aliberti G. Acute presentation of Chiari 1 malformation in children. Childs Nerv Syst. 2020 May;36(5):899-909. doi: 10.1007/s00381-020-04540-7.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa