Low levels of protective humoral immunity following mild or asymptomatic infection with SARS-CoV-2 in a community-based serological study

McDade, T. W.; Sancilio, A.; D'Aquila, R. T.; Mustanski, B.; Vaught, L. A.; Reiser, N. L.; Velez, M. P.; Hsieh, R. R.; Ryan, D. T.; Saber, R.; McNally, E. M.; Demonbreun, A. R.

The degree of protective humoral immunity after mild or asymptomatic SARS-CoV-2 infection is not known. We measured antibody-mediated neutralization of spike protein-ACE2 receptor binding (a surrogate measure of protection against SARS-CoV-2 infection) in a large and diverse community-based seroprevalence study. Comparisons were made across three groups of seropositive participants that differed in the severity of infection and engagement with clinical care (N=790). The clinical group was seropositive for prior infection, symptomatic, and diagnosed with COVID-19 by a healthcare provider. The symptomatic group was seropositive and reported one or more symptoms of infection but received no clinical care. The asymptomatic group was seropositive but reported no symptoms. 86.2% of all infections were mild or asymptomatic; 13.8% received clinical care. Of the clinical cases, 96.3% were outpatient; only 3.7% required hospitalization. Moderate or high levels of neutralizing activity were detected following 27.5% of clinical infections, in comparison with 5.4% of symptomatic and 1.5% of asymptomatic infections. The majority of infections in the general population are mild or asymptomatic and likely result in low levels of antibody-mediated protective immunity.