Introduction
At the end of 2019, a pneumonia outbreak with unknown etiology was reported in Wuhan, China.[1, 2] The World Health Organization (WHO) officially named this disease Coronavirus Disease-2019 (COVID-19), which was later identified to be caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[3] The worldwide pandemic has significantly impacted public health and the global economy.[4] Preventive measures were enforced to reduce social distancing, including limited gatherings, school closures, and restricted travel to reduce transmission.[3, 5]
The clinical spectrum of COVID-19 ranges from asymptomatic to fatal disease. Unfavorable outcomes were associated with the age and comorbidities of patients,[6, 7] particularly those older than 65 years and individuals with diabetes mellitus or renal disease.[8-10] Children infected with SARS-CoV-2 generally have mild symptoms and a low mortality rate,[11-13] with a lower likelihood of severe symptoms in children than in adults.[14-16] The SARS-CoV-2 viral-host response plays an important role in the pathogenesis of the disease, including changes in the biological responses of peripheral immune cells and the levels of proinflammatory cytokines. Lymphopenia is a common clinical characteristic symptom observed in COVID-19 patients, especially in critical cases,[2, 15-20] with up to 83.2% of patients showing lymphopenia during admission.[21] Moreover, symptomatic children with COVID-19 were found to have higher viral load, lower total lymphocyte count, lower lymphocyte subsets, and elevated interleukin 6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) levels compared with asymptomatic patients.[22, 23] The data collectively suggest that altered immune cell subsets could be a prognostic factor for COVID-19[24], especially in critical cases.[25] There are knowledge gaps in degree of host immune responses among patients in terms of age, which could help to identify beneficial factors associated with lower disease severity due to SARS-CoV-2 infections.
The long-term persistence of T cell memory is important in mediating both cellular and humoral immunity against SARS-CoV-2 reinfections.[26, 27] Patients infected with SARS-CoV-2 virus show T cell memory along with neutralizing antibodies and polyfunctional T cell responses.[26, 28] This T cell memory is capable of being reactivated in patients with mild symptoms up to 8 months after recovery.[29, 30] Epitope identification studies of SARS-CoV-2 T cells have demonstrated that both CD4+ and CD8+ T cells respond to a broad spectrum of structural and non-structural proteins (NSP) of the SARS-CoV-2 virus. T cells showed immunodominant responses to spike (S), membrane (M), and nuclear (N) structural proteins, whereas B cells showed sub-dominant responses to ORF-1 ab-encoded NSPs.[31, 32] However, current knowledge of SARS-CoV-2 immune responses specific to pediatric patients is still lacking, such as the immunodominance of SARS-CoV-2 epitopes and durability of antibodies after an infection.
Given the fundamental differences in the immunity of adults and children,[33] we assessed the adaptive SARS-CoV-2-specific immune responses in children and adolescents recovered from COVID-19.