Comparison of the First and Second Waves of the Coronavirus Disease 2019 Pandemic in Children and Adolescents in a Middle-Income Country: Clinical Impact Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Gamma Lineage

Abstract

Objective To evaluate the severity and clinical outcomes of the SARS-CoV-2 gamma variant in children and adolescents hospitalized with COVID-19 in Brazil. Study design In this observational retrospective cohort study, we performed an analysis of all 21,591 hospitalized patients aged < 20 years with confirmed SARS-CoV-2 infection registered in a national database in Brazil. The cohort was divided into two groups according to the predominance of SARS-CoV-2 lineages (WAVE1, n = 11,574 and WAVE2, n = 10,017). The characteristics of interest were age, sex, geographic region, ethnicity, clinical presentation, and comorbidities. The primary outcome was time to death, which was evaluated by competing-risks analysis, using cumulative incidence function. A predictive Fine-Gray competitive risks model was developed based on WAVE1 cohort with temporal validation in WAVE2 cohort. Results Children and adolescents admitted during the second wave had significantly more hypoxemia (52.5% vs. 41.1%, P < 0.0001), admission to ICU (28.3% vs. 24.9%, P < 0.0001), and needed more non-invasive ventilatory support (37.3% vs. 31.6%, P < 0.0001). The in-hospital deaths and death rates in the first and second waves were respectively 896 (7.7%) and 765 (7.6%) (P=0.07). The prediction model of death included age, ethnicity, region, respiratory symptoms, and comorbidities. In the validation set (WAVE2), the C statistics was 0.750 (95%CI, 0.741 to 0.758, P < 0.0001). Conclusions This large national study found a more severe spectrum of risk for pediatric patients with COVID-19 caused by the Gamma variant. However, there was no difference regarding the probability of death between the waves.

Outcomes and risk factors for death among hospitalized children and adolescents with kidney diseases and COVID-19: an analysis of a nationwide database

“…The rationale for separating the sample into two waves was due to the emergence of the Gamma variant identified in January 2021 in the city of Manaus, Brazil [ 15 ]. This strain became predominant in Brazil in mid-February 2021 and was characterized by greater transmissibility and a more severe spectrum of the disease in both adult and pediatric populations [ 14 , 16 ]. Detailed information about included and excluded cases are displayed in the flowchart (Fig.…”

“…We used various strategies to partially overcome this problem. We describe these strategies in detail elsewhere [ 14 ]. Briefly, patients with missing information about the primary outcome were removed from the survival analyses.…”

“…We recently analyzed data in children and adolescents hospitalized with COVID-19 from the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe) database, a Brazilian national registry [ 6 , 14 ]. We described clinical outcomes and risk factors for death related to the first and second waves of COVID-19 in the Brazilian pediatric population.…”

Risk factors for COVID ‐19‐related mortality in hospitalized children and adolescents with diabetes mellitus: An observational retrospective cohort study

“… 14 This lineage became predominant in Brazil around February 2021 and was characterized by an increased transmissibility and with more severe spectrum of the disease both in adults and children. 13 , 15 …”

“…We describe these strategies in detail elsewhere. 13 Briefly, in the first step, patients with missing information about the primary outcome were removed from the survival analyses. For those cases with missing data on a particular symptom or comorbidity, we assumed that the clinical condition was absent.…”