Virological and immunological features of SARS‐COV‐2 infected children with distinct symptomatology

Abstract

Background Although SARS‐CoV‐2 immunizations have started in most countries, children are not currently included in the vaccination programs; thus, it remains crucial to define their anti‐SARS‐CoV‐2 immune response in order to minimize the risk for other epidemic waves. This study sought to provide a description of the virology ad anti‐SARS‐CoV‐2 immunity in children with distinct symptomatology. Methods Between March and July 2020, we recruited 15 SARS‐CoV‐2 asymptomatic (AS) and 51 symptomatic (SY) children, stratified according to WHO clinical classification. We measured SARS‐CoV‐2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swab samples. To define anti‐SARS‐CoV‐2 antibodies, we measured neutralization activity and total IgG load (DiaSorin). We also evaluated antigen‐specific B and CD8+T cells, using a labeled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. Results Virological profiling showed that AS patients had lower viral load at diagnosis ( p = .004) and faster virus clearance ( p = .0002) compared with SY patients. Anti‐SARS‐CoV‐2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY patients showed similar titers of SARS‐CoV‐2 IgG, levels of neutralizing activity, and frequency of Ag‐specific B and CD8+ T cells, whereas pro‐inflammatory plasma protein profile was found to be associated with symptomatology. Conclusion We demonstrated the development of anti‐SARS‐CoV‐2 humoral and cellular response with any regard to symptomatology, suggesting the ability of both SY and AS patients to contribute toward herd immunity. The virological profiling of AS patients suggested that they have lower virus load associated with faster virus clearance.

Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol

“…For example, age-related decline and dysregulation of immune function, such as immunosenescence and inflammaging, can explain a gradient of severity of PASC as age increase ( 27 ). Also, younger children have more frequently an asymptomatic disease which, in previous studies, have been associated with lower virus load and faster virus clearance ( 28 , 29 ). This can support the hypothesis that asymptomatic children have lower risks of developing PASC, although in our study only 20 children were asymptomatic limiting the possibility of a statistical analyses aimed at defining this.…”

Asymptomatic and Mild SARS-CoV-2 Infections Elicit Lower Immune Activation and Higher Specific Neutralizing Antibodies in Children Than in Adults

“…Higher levels of activated CD4 and CD8 T cells were described in COVID-19 pediatric patients with MIS-C (22)(23)(24). COVID-19 children without or with mild/moderate clinical manifestations showed similar frequencies of activated CD4 and CD8 cells compared to age-matched control (15,22,25). In agreement with these findings, the present study found no differences between COVID-19 and non-COVID-19 children, and for the first time, we demonstrated that COVID-19 adults, mostly asymptomatic/mildly symptomatic, have a higher expression of both activated T and B cells, not only compared to non-COVID-19 adults but also compared to COVID-19 children.…”

“…The data available in the pediatric population are controversial. Some studies found higher levels in symptomatic children compared to asymptomatic children (25,31), while other reports found no association of viral load and disease severity (5,32). A recent study, conducted in COVID-19 children within their first week from baseline (symptom onset and/or first positive virus detection) demonstrated an inverse relationship between viral load and nAbs, and the estimation of virus under curve from NPS, collected every 48 h up to undetectable viral load, confirmed the impact of nAbs on virus clearance (15).…”

COVID-19 in children: From afterthought to unknown

“…A number of recent studies have clarified that the COVID-19 clinical burden in children is mostly due to over-inflammation and immune cells dysregulation. 8 , 9 It must be noted that an apparently similar hyperinflammation status that characterizes severely ill COVID-19 adults could also be present in children. Critically ill children present with a pro-inflammatory syndrome characterized by a phenotypic picture resembling Kawasaki disease (KD) or toxic shock syndrome possibly related to COVID-19.…”