Distinct early serological signatures track with SARS-CoV-2 survival

Atyeo, Caroline; Fischinger, Stephanie; Zohar, Tomer; Slein, Matthew D.; Burke, John; Loos, Carolin; McCulloch, Denise J.; Newman, Kira L.; Wolf, Caitlin; Yu, Jingyou; Shuey, Kiel; Feldman, Jared; Hauser, Blake Marie; Caradonna, Tim; Schmidt, Aaron; Suscovich, Todd J.; Linde, Caitlyn; Cai, Yongfei; Barouch, Dan; Ryan, Edward T.; Charles, Richelle C.; Lauffenburger, Douglas; Chu, Helen; Alter, Galit

Summary As SARS-CoV-2 infections and death counts continue to rise, it remains unclear why some individuals recover from infection whereas others rapidly progress and die. While the immunological mechanisms that underlie different clinical trajectories remain poorly defined, pathogen-specific antibodies often point to immunological mechanisms of protection. Here, we profiled SARS-CoV-2–specific humoral responses on a cohort of 22 hospitalized individuals. Despite inter-individual heterogeneity, distinct antibody signatures resolved individuals with different outcomes. While no differences in SARS-CoV-2-specific IgG levels were observed, spike–specific humoral responses were enriched among convalescent individuals, whereas functional antibody responses to the nucleocapsid were elevated in deceased individuals. Furthermore, this enriched immunodominant S-specific antibody profile in convalescents was confirmed in a larger validation cohort. These results demonstrate that early antigen-specific and qualitative features of SARS-CoV-2-specific antibodies, point to differences in disease trajectory, highlighting the potential importance of functional antigen-specific humoral immunity to guide patient care and vaccine development.