ABSTRACT
BACKGROUND: Despite 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 seeks 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 children (SY), stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swabs 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 labelled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS had lower viral load at diagnosis (p=0.004) and faster virus clearance (p=0.0002) compared to SY. Anti-SARS CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY 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 associated to symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regards to symptomatology, suggesting the ability of both SY and AS to contribute towards herd immunity. The virological profiling of AS suggested that they have lower virus load associated with faster virus clearance.
Subject(s)
Immunologic Deficiency Syndromes , Asymptomatic DiseasesABSTRACT
Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic aspects of SARS-CoV-2 infection in infants, children and adolescents, focusing on risk factors for complicated and critical disease.Methods: The present study is a multicenter Italian study promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled starting from March 2020. An adequate follow-up to outline outcome was required (at least 2 weeks).Findings: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4;12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19, with a median hospital stay of 6 days (IQR 4;10). Age was inversely related to hospital admission (p Mycoplasma pneumoniae co-infections, underlying clinical conditions, age between 5 and 9 years and lymphopenia were statistically related to ICU admission (p< 0.05). Multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) was diagnosed in 30 children (3.9%). All but three children recovered.Interpretation: Complications of COVID-19 in children are related to the presence of co-morbidities. The length of hospital stay and the risk of complications increase with age. Viral co-infections are additional risk factors for disease progression and high CRP levels and lymphopenia may be predictive markers of severe clinical pictures. MIS-C is a risk factor for ICU admission. Outside MIS-C, most children with COVID-19 require only supportive therapy.Funding Statement: None.Declaration of Interests: None.Ethics Approval Statement: The study received ethical approval on 24 March 2020 (protocol number 0031296) and data collection was allowed by written consent of at least one parent.
Subject(s)
COVID-19 , Communicable DiseasesABSTRACT
As the global COVID-19 pandemic progresses and with the school reopening, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children in order to define possible immunization strategies and reconsider pandemic control measures. We analyzed anti-SARS-CoV-2 antibodies (Ab) and their neutralizing activity (PRNT) in 42 COVID-19-infected children 7 days after symptoms onset. Individuals with specific humoral responses presented faster virus clearance, and lower viral load associated to a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2 specific CD4-CD40L+ T-cells and Spike specific B-cells were associated with the anti-SARS-CoV-2 Ab and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, with PRNT+ patients showing higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work shed lights on cellular and humoral anti-SARS-CoV-2 responses in children which may drive future vaccination trials endpoints and quarantine measures policies.Funding: This work was made possible by support from Bambino Gesù Children’s Hospital ricerca corrente 2020 to NC and ricerca corrente 2019 to PP, by PENTA and by Fondazione Cassa di Risparmio di Padova e Rovigo, Progetti di Ricerca Covid-19 (ADR participant).Conflict of Interest: The authors declare no competing interests.Ethical Approval: Local ethical committee approved the study and written informed consent was obtained from all participants or legal guardians.