Humoral and circulating follicular helper T cells responses in hospitalized infants with COVID-19

Abstract

Background: Marked progress is achieved in understanding the physiopathology of COVID-19 pandemic. However, CD4+ TFH cell subset, which is critical for eliciting neutralizing antibodies, is poorly understood during pediatric COVID-19.Aims: To characterize the circulating TFH (cTFH) cell subset and to determine SARS-CoV-2 IgM and IgG antibody response in children hospitalized with acute mild and severe (pediatric multisystem inflammatory syndrome, PIMS) COVID-19, compared to pre-pandemic controls.Methods:Sera (n=337) and PBMCs (n=41) from hospitalized COVID-19 children (age 1-14yr.) during different phases after disease onset and healthy donors (n=15, age 1-10 yr., HD) were collected to evaluate:1.Memory cTFH subset (CD3+CD4+CD45RA-CXCR5+) and cTFH profiles (cTFH1 ?non-efficient helper associated with a suboptimal antibody production-, cTFH2, and cTFH17, ?efficient helpers) by flow cytometry during 1st week of COVID-19 diagnosis.2.Anti-SARS-CoV-2 Spike RBD IgM and IgG serum levels during the 1st week and/or 21 days after symptoms onset by ELISA.Results: Mild COVID (n=30) showed a cTFH profile similar to HD (n=15). However, we detected a decrease of %cTFH1 (*) but an increase of %cTFH17 (**) in peripheral blood of PIMS infants (n=11) compared to both mild COVID-19 and HD. Indeed, the ratio (cTFH2 and cTFH17)/cTFH1 was increase in PIMS (**). Seropositivity rates were 28% for IgM (n=109) and 25% for IgG (n=337) among children during 1st week of diagnosis, and 63% for IgM (n=51) and 64% for IgG (n=55) after 21 days of symptoms onset. All children with PIMS reached the maximum detectable IgG OD. Interestingly, %cTFH17 positively correlated with αnti-SARS-CoV-2 IgG OD (*).Conclusion: Our results showed that COVID-19 infected children displayed multiple hallmarks of effective humoral response, although the neutralizing activity of antibodies remains to be elucidated. Moreover, the elevated levels of antibodies in PIMS infants point towards their role in severity of disease.