Significance The COVID-19 pandemic continues to ravage our society, posing serious economic, social, health, and educational concerns in communities. Understanding the human humoral immune response to COVID-19 infection will greatly inform public health measures to help contain the spread of the disease in the foreseeable future. Here, we present an orthogonal approach to SARS-CoV-2 antibody testing using distinct viral antigens. Using this testing platform, we conducted a community-based analysis of patients with varying experiences with COVID-19. The data from our study show correlations between IgG titer and clinical features (i.e. length and severity of COVID-19 illness) and that IgG titers against SARS-CoV-2 may persist for more than 4 mo post onset of COVID-19 illness. Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the current pandemic remains a field of immense interest and active research worldwide. Although the severity of acute infection may depend on the intensity of innate and adaptive immunity, leading to higher morbidity and mortality, the longevity of IgG antibodies, including neutralizing activity to SARS-CoV-2, is viewed as a key correlate of immune protection. Amid reports and concern that there is a rapid decay of IgG antibody levels within 1 mo to 2 mo after acute infection, we set out to study the pattern and duration of IgG antibody response to various SARS-CoV-2 antigens in asymptomatic and symptomatic patients in a community setting. Herein, we show the correlation of IgG anti-spike protein S1 subunit, receptor binding domain, nucleocapsid, and virus neutralizing antibody titers with each other and with clinical features such as length and severity of COVID-19 illness. More importantly, using orthogonal measurements, we found the IgG titers to persist for more than 4 mo post symptom onset, implying that long-lasting immunity to COVID-19 from infection or vaccination might be observed, as seen with other coronaviruses such as SARS and Middle East respiratory syndrome.
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