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.