Asymptomatic sars-cov-2 children have lower infectivity and intact memory responses

ABSTRACT

Background: SARS-CoV-2 (CoV-2) infected children often range from being paucysymptomatic to fully asymptomatic. The impact of this population on the epidemics due to their ability to transmit the virus and achieve protective immunity has been poorly defined. We explored CoV-2 infectivity potential and anti-CoV-2 cellular (CD8, NK and B) and humoral response in symptomatic (SY) and asymptomatic (AS) CoV-2 infected children, screened for a family member resulted infected. Methods: CoV-2 viral load was measured by RT-PCR and digital droplet PCR (ddPCR) on longitudinal samples of nasopharyngeal swabs in 9 AS and 33 SY (samples were paired according to symptoms'onset for SY and first family contact for AS). Virus infectivity was tested by Virus focus forming assay (FFA). CoV-2 antibodies were investigated by Diasorin (CoV-2 Ab) and Ab-mediated neutralization activity (PRNT) at diagnosis, (samples collected >5 days from symptoms onset in SY, or from first family contact in AS were excluded from this timepoint), and in the convalescent phase (CP) (10-14 days after infection). Cellular response was analyzed by flow cytometry 1) Ag-specific B cells, by a S1+S2 CoV2-R-PE probe;2) Ag-specific CD8+T cells by ICAM+;3) natural-killer (NK) phenotype. Mann-Whitney was used for comparison;linear regression was used to evaluate the associations between virus load and infectivity. Results: AS showed lower viral load (p=0.004) and faster virus clearance (p=0.0002) compared to SY. Virus infectivity was associated with ddPCR (rho=0.66;p=0.002). ASY and SY showed similar levels of CoV-2 Ab and PRNT, at both diagnosis and at follow up. During the CP, the proportion of CoV-2 Ab negative was 33,3% for both groups and PRNT was negative in 16,6% and 15,7% of AS and SY respectively. Anti-CoV-2 cellular immunity was comparable between ASY and SY. Indeed Ag-specific B cells and CD8 T cells were detectable despite symptomatology and no major differences were found between the groups. Total NK frequency was similar between the groups, while a regulatory NK subset (CD56bright NK cells) was higher in AS compared to SY (p=0.01). Conclusion: These data show that AS have a lower infectivity potential compared to SY suggesting that mitigated restrictive measures or alternative screening may be considered for this population. In addition, these patients showed an intact ability to produce humoral and cellular CoV-2 specific responses hence contributing to achieve herd immunity as much as SY.