Croup Is A Common Manifestation In Children Infected With The Omicron Variants


A new study conducted by researchers from the Division of Emergency Medicine, Children’s Healthcare of Atlanta at Scottish Rite, Atlanta-USA has found that most pediatric patients develop croup upon being infected with the SARS-CoV-2 Omicron variants.

The study findings were published in the peer reviewed Journal of Pediatric Infectious Diseases Society.

During a 3-week period from December 13, 2021 through January 2, 2022, we found a substantial increase in croup presentations during a decline in the prevalence of all other respiratory viral pathogens known to cause croup.

These patients presented during a surge of the SARS-CoV-2 Omicron variant, which was first identified in South Africa in November 2021 and became the dominant circulating strain in metropolitan Atlanta by mid-December 2021 [9].

While our case series of 24 patients with croup associated with SARS-CoV-2 showed frequent hospitalization (45.8%) and ICU admission (18.2%), interpretation of clinical severity is limited by the fact that RVP testing was done in only a fraction of those with croup and was more likely to have been done in more ill-appearing patients needing hospital admission.

The Omicron variant has been associated with increased transmissibility and attenuated lower respiratory tract disease in comparison to SARS-CoV-2 Delta variant [10–12]. Although previous reports indicate that croup associated with SARS-CoV-2 presentation likely existed prior to emergence of the Omicron variant [4–8], the frequency increased substantially during the Omicron outbreak.

Additionally, the proportion of 0- to 4-year-old children diagnosed with COVID-19 nearly doubled during Omicron, in comparison to the Delta-dominant period. These data underscore the ongoing need for vaccination efforts in this susceptible population.

As with any observational data, bias could have played a role in the identification of croup and COVID-19 during the Omicron study period. However, the magnitude of change we detail between the 2 study periods makes this less likely.

Altogether, our observational clinical findings support recent animal and ex vivo models suggesting that in comparison to Delta, the Omicron variant displays upper respiratory tissue tropism, a process by which a pathogen adapts to new tissue as an infectious target, as a means of improving fitness for survival and transmissibility.

As a subset of upper respiratory tract infection, croup in children has an “adult” equivalent: laryngitis. Interestingly, a recent study in Sweden described a series of young adult patients presenting with odynophagia and laryngitis in the setting of Omicron infection, adding further support for evolving tissue tropism [13].

Fever and cough remain the most common clinical presentations, although atypical presentations such as “COVID toes,” anosmia, and croup may be present. Children are at risk for post-infectious complications such as MIS-C and long COVID. Nucleic acid amplification tests through respiratory PCR remain the mainstay of diagnosis. The mainstay of management remains supportive care and prevention through vaccination is highly recommended.

In patients at increased risk of progression, interventions such as monoclonal antibody therapy, PO Paxlovid, or IV remdesivir × 3 days should be considered. In patients with severe disease, the use of remdesivir, dexamethasone, and immunomodulatory agents (tocilizumab, baricitinib) is recommended. Children can be at risk for thrombosis from COVID-19 and anticoagulation is recommended in children with markedly elevated D-dimer levels or superimposed clinical risk factors for hospital associated venous thromboembolism.

Clinical Manifestations
Pediatric cases of COVID-19 have traditionally presented with milder symptoms and lower risks of hospitalization and death when compared to adults [5]. Additionally, a large percentage of pediatric COVID-19 infections are asymptomatic. The reported total percentage of asymptomatic pediatric COVID-19 cases range from a rate of 15% [5] to 65% [10].

The clinical presentation of COVID-19 in children varies by age group. Children ≤ 9 years of age the most commonly presents with fever (46%), cough (37%), headache (15%), diarrhea (14%), and sore throat (13%). While older children 10–19 years of age are more likely to have symptoms similar to COVID-19 in adults with headache (42%), cough (41%), fever (35%), myalgia (30%), sore throat (29%), and shortness of breath (16%) [5]. Of note, the incidence of rhinorrhea is typically low in children with COVID-19 (ranging from 10 to 22%) [11]. Anosmia is a rare finding in children [12, 13], but has been reported as the strongest predictor of a positive test for COVID-19 [14]. Additionally, the Omicron variant may be significantly more associated with the development of croup in pediatric patients than prior variants of SARS-CoV-2. A recent review showed that patients who presented with croup in the Omicron surge were more likely to test positive for COVID-19 than during the Delta surge (48.2% vs 2.8%) [15].

Cutaneous findings can be associated with COVID-19. Unlike adult patients, pediatric COVID-19 patients are often asymptomatic except for these cutaneous manifestations [16•]. Indeed, > 90% of patients may be asymptomatic or have mild/moderate disease in which the diagnosis of COVID-19 was overlooked [17•]. Cutaneous findings can range from rash (maculopapular, urticarial, vesicular) to painful lesions on the finger and feet that resemble chilblains (“COVID toes”). These cutaneous lesions typically present on the feet (74–100%) but have been reported on the hands as well.

The lesions usually present as multiple, round erythematous, violaceous, or purpuric patches and swellings which can evolve to become vesiculobullous or present with dark-purple or black crusts. The most commonly affected regions are the plantar region and lateral aspect of the feet and heels. Additional cutaneous manifestations include erythema multiforme, urticaria, and vesicular exanthema [18•].

Severe disease manifestation of COVID-19 in pediatrics presents in a similar clinical spectrum as in adults. Children may present with respiratory failure, myocarditis, shock, acute renal failure, coagulopathy, neurological involvement (encephalopathy, stroke, cerebral edema, Guillain-Barré syndrome), and multi-system organ failure [19, 20]. Hospitalization rate of children with COVID-19 has ranged from 0.7% (2/22) to 3.8% (5/20) in the USA from May 2020 to February 2022. Approximately 0.01% of all pediatric COVID-19 cases resulted in death [2].

Of hospitalized children, approximately 30% had severe COVID-19 and 0.5% died during hospitalization in a review of 3106 hospitalized children by Woodruff et al. Risk factors for severe disease were stratified by age group. For children < 2 years of age, risk factors were chronic lung disease (aRR 2.2), neurologic disorders (aRR 2.0), cardiovascular disease (aRR 1.7), prematurity (aRR 1.6), and airway abnormality (aRR 1.6).

Among children 2–17 years, risk factors included feeding tube dependence (aRR 2.0), diabetes mellitus (aRR 1.9), and obesity (aRR 1.2). Additionally, infants < 1 year of age had the highest rates of hospitalization and severe COVID-19 compared to other age groups. Hispanic and non-Hispanic black children had higher rates of hospitalization than non-Hispanic white children. However, once hospitalized, these children were not at increased risk of severe disease when compared to white children once controlled for the presence of underlying medical conditions [21••].

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