Fever, Diarrhea, and Severe Disease Correlate with High Persistent Antibody Levels against SARS-CoV-2

Lasting immunity will be critical for overcoming COVID-19. However, the factors associated with the development of high titers of anti-SARS-CoV-2 antibodies and how long those antibodies persist remain incompletely defined. In particular, an understanding of the relationship between COVID-19 symptoms and anti-SARS-CoV-2 antibodies is limited. To address these unknowns, we quantified serum anti-SARS-CoV-2 antibodies in clinically diverse COVID-19 convalescent human subjects five weeks (n=113) and three months (n=79) after symptom resolution with three methods: a novel multiplex assay to quantify IgG against four SARS-CoV-2 antigens, a new SARS-CoV-2 receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralizing assay. We then identified clinical and demographic factors, including never before assessed COVID-19 symptoms, that consistently correlate with high anti-SARS-CoV-2 antibody levels. We detected anti-SARS-CoV-2 antibodies in 98% of COVID-19 convalescent subjects five weeks after symptom resolution and antibody levels did not decline at three months. Greater disease severity, older age, male sex, higher body mass index, and higher Charlson Comorbidity Index score correlated with increased anti-SARS-CoV-2 antibody levels. Moreover, we report for the first time that COVID-19 symptoms, most consistently fever, body aches, and low appetite, correlate with higher anti-SARS-CoV-2 antibody levels. Our results provide robust and new insights into the development and persistence of anti-SARS-CoV-2 antibodies.