Do the symptom profiles among children with SARS-CoV-2 infection differ by variant type?

In a recent study published in the JAMA Network Open, researchers performed a comparative analysis of symptoms related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in children.

Background

The emergence of SARS-CoV-2 variants of concern (VoC) with diverse transmissibility patterns has affected the progression of the coronavirus disease 2019 (COVID-19) pandemic. As the virus evolved, so did disease symptoms and severity.

The Omicron variant can infect the upper airways and replicate more rapidly in the bronchus than in the lung parenchyma as compared to other variants. Omicron infection symptoms differ from those related to the Delta VOC in adults, and the mortality rate is lower. While Omicron infection among children has been linked to croup as well as upper airway disease, none of the studies have compared the prevalence of symptoms between the SARS-CoV-2 original strain and the most recent VoC, and disease severity is little understood.

About the study

In the present study, researchers assessed COVID-19 symptoms, emergency department (ED) chest radiographs, treatments, as well as outcomes associated with SARS-CoV-2 variants in children.

This observational cohort study enrolled children and adolescents tested for acute COVID-19 and visited one of 14 Canadian urban pediatric EDs between 4 August 2020 and 22 February 2022. The team reported data according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

Participants were aged less than 18 years and tested SARS-CoV-2 positive via nucleic acid test performed on samples obtained from the nasopharynx, throat, or nares. The research assistants contacted all possibly eligible children via telephone, beginning with the first child evaluated daily.

The study's primary outcome involved the detection and number of manifested symptoms observed between illness onset and study enrolment. The team classified the symptoms into groups, including gastrointestinal, lower respiratory, hydration, neurological, musculoskeletal, oral or rash changes, upper respiratory, and systemic symptom groups. Additionally, ageusia or anosmia, cough, fever, and conjunctivitis were evaluated separately without grouping with other symptoms.

The secondary outcomes were as follows: (1) detection of core SARS-CoV-2 infection symptoms; (2) requirement of chest radiography performance and treatment; and (3) hospital admission, intensive care unit (ICU) admission, and return visits to any ED or any health care provider within 14 days since the index ED visit.

Results

Almost 1,440 of 7,272 eligible individuals tested positive for SARS-CoV-2 infection. The median age of the 1,440 study participants was two years, with 801 males and 639 females comprising the participant population. A total of 388 people were tested for VoC, resulting in the identification of 158 Alpha, 177 Delta, and 46 Omicron VOCs, along with one Beta and six Gamma VOCs. Concomitant respiratory viruses were detected most commonly in Delta-infected children. Among the 998 participants who were queried about their child's COVID-19 vaccination status, 80 were vaccinated with one dose, 816 were unvaccinated, and 102 were uncertain.

Individually, cough, fever, and rhinorrhea were the most prevalent symptoms. Individuals diagnosed with the original-type virus most often exhibited abdominal pain, anosmia, ageusia, and myalgias. Individuals infected with Alpha had the lowest incidence of drowsiness, conjunctivitis, oral alterations, sore throat, and rhinorrhea. Individuals infected with Delta typically experienced cough, conjunctivitis, and upper respiratory tract symptoms, whereas those infected with Omicron were typically sleepy, febrile, and breathless. Individuals with the Alpha variant reported the fewest symptoms overall. Only 85 out of 237 affected individuals reported at least seven symptoms.

Delta and Omicron infections were related to cough and fever as per the multivariable model. Omicron infection was related to lower respiratory tract symptoms as well as systemic symptoms, whereas Delta infection was related to upper respiratory tract symptoms. Additionally, musculoskeletal symptoms were more strongly related to the original-type virus than other VoC. Ageusia or anosmia, as well as rash or oral alterations, were associated with infection due to the Alpha and Omicron strains to a lesser extent than the original type.

The majority of study participants reported core COVID-19 symptoms. These symptoms were most prevalent among persons infected with Omicron and least prevalent among those infected with Alpha. Compared to patients infected with Alpha and Delta VOCs, Omicron patients were more likely to have chest radiography and receive intravenous fluids.

Omicron-infected children also were more likely to be prescribed corticosteroids than those with other variant infections. In addition, those with Omicron patients were more likely to visit EDs than those with Delta infection. In total, 164 children were hospitalized, and nine were admitted to the ICU, with no variation between the two groups.

Conclusion

The study findings showed that children infected with the SARS-CoV-2 Omicron VOC were likelier to exhibit fever, systemic signs, and lower respiratory tract symptoms than those with earlier variants.

These findings emphasized the significance of maintaining vigilance in changing clinical manifestations and evaluating patients when clinically required. Notably, although the characteristics of presenting COVID-19 symptoms have altered as SARS-CoV-2 has evolved, the proportion of pediatric COVID-19 patients who experience adverse outcomes has remained steady, in contrast to adults.

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.