Differences in SARS-CoV-2 Clinical Manifestations and Disease Severity in Children and Adolescents by Infecting Variant

Abstract

rapidly spread worldwide, causing a global pandemic with major social and economic disruption. Although the effects of COVID-19 have been greater in adults, children also are infected with SARS-CoV-2, and COVID-19 can lead to severe outcomes in pediatric patients (1-3). Nevertheless, the spectrum of clinical manifestations in children is broad and ranges from asymptomatic to mild upper respiratory infection to pneumonia or the more severe multisystem inflammatory syndrome in children (MIS-C), which typically occurs 2 to 6 weeks after acute SARS-CoV-2 infection (4-7).Since the COVID-19 pandemic began, different SARS-CoV-2 variants have circulated worldwide. In the United States, the first variant that replaced the original strain was the Alpha variant (B 1.1.7) that circulated during April-June 2021. The Delta variant (B1.617.2) followed soon after and became predominant during July-mid-December 2021. Since then, different sublineages of Omicron quickly replaced other variants as the predominant variant as of September 2022. These newer variants have demonstrated higher transmissibility and have disproportionally affected unvaccinated persons and other vulnerable populations including children; rates of hospitalization have increased 5-fold to 10-fold in children, depending on the variant and age group (8-13). Epidemiologic studies that rely on SARS-CoV-2 circulation patterns have provided robust information; however, the role of specific SARS-CoV-2 variants on clinical disease severity in children and adolescents with COVID-19 is not fully known.The objective of this study was to assess whether distinct SARS-CoV-2 variants were associated with differences in clinical and laboratory data and cycle threshold (Ct) values (as a surrogate of viral load) in children and adolescents with COVID-19. The Nationwide Children's Hospital (NCH; Columbus, OH, USA) Institutional Review Board approved the study (#STUDY00002002).

The diversity in the clinical features of children hospitalized with COVID‐19 during the nonvariant, Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529) variant periods of SARS CoV‐2: Caution for neurological symptoms in Omicron variant

“…Our findings support previous observations in other countries. 7,11,12 Contrary to our study, other retrospective studies have found that the Omicron period is less severe than different periods, including the Delta predominant period. This heterogeneity among research results may affect study design.…”

“…Also, it was observed that the age distribution of hospitalized patients changed in the Omicron period compared to other periods; the proportion of children <1‐year‐old increased, and the proportion of children aged ≥12 years decreased. Our results were in line with research from the United States, the United Kingdom, and Germany that found a higher percentage of newborns and young children hospitalized with COVID‐19 during the Omicron wave 7–10 . A similar observation was also emphasized in studies in different regions 11–14 .…”

“…As a result of our study, the clinical progression scale, need for oxygen support, and PICU admission were not different according to SARS‐CoV‐2 periods in children hospitalized with COVID‐19. Our findings support previous observations in other countries 7,11,12 . Contrary to our study, other retrospective studies have found that the Omicron period is less severe than different periods, including the Delta predominant period.…”

“…This result was consistent with studies indicating that Omicron caused more severe inflammation in the upper respiratory tract than in the lung 16,17 . In contrast, a US study in the first period of the Omicron wave reported increased respiratory symptoms in hospitalized patients in Omicron compared to nonvariant 7 . Unlike the nonvariant period, detecting RSV, hMPV, and influenza coinfections in children with Omicron infections may have contributed to their results.…”

“…16,17 In contrast, a US study in the first period of the Omicron wave reported increased respiratory symptoms in hospitalized patients in Omicron compared to nonvariant. 7 Unlike the nonvariant period, detecting RSV, hMPV, and influenza coinfections in children with Omicron infections may have contributed to their results. Recent studies have reported an increased rate of croup during the Omicron wave.…”