Objectives . To directly measure SARS-CoV-2 infection in diverse schools with either remote or onsite learning . Methods . 4 schools participated . Schools A and B served low-income Hispanic learners, school C special needs, and all three provided predominantly remote instruction . School D served middle and upper-middle income, White learners, with predominantly onsite instruction . 320 learners [10.5+/-2.1 (SD); 7-17 y.o .]; 86% had phlebotomy . Testing occurred early in the fall (2020), at lower levels of COVID-19, and 6-8 weeks later during the fall-winter surge (tenfold increase in COVID-19 cases).

Results: Nasal RT-qPCR for SARS-CoV-2 and 21 respiratory pathogens was performed . Phlebotomy was obtained for circulating immunity . Face covering and physical distancing fidelity was measured by direct observation . 17 learners were SARS-CoV-2 positive during the surge . School A (97% remote) had the highest infection rate (9/70 , 12.9%, p <0.01) and IgG positivity rate (13/70 , 18.6 %). School D had the lowest infection and IgG positive rate (1/86 , 1.2 %). Mitigation compliance [physical distancing (mean 87.4 %) and face covering (91.3 %) ] was high at all schools . Learners with documented SARS-CoV-2 infection had neutralizing antibodies (94.7 %), broad and robust interferon-gamma T cell responses, reduced frequencies of monocytes, and lower levels of circulating inflammatory mediators .

Conclusions: Infection in the schools reflected regional rates rather than remote or onsite learning modalities . Schools can implement successful mitigation strategies across a wide range of income, school-type, and student diversity . Reduced monocyte and immune mediator concentrations coupled with robust humoral and cellular immunity may explain the generally milder symptoms in school-aged children.