Observational Report on Functional SARS-CoV-2 Immune Responses in Immune Competent and Compromised Individuals

ObjectivesDurable immune responses against SARS-CoV-2 are generally observed in previously infected individuals. Immunocompromised individuals may show less durable responses. Investigation of immune responses is needed to inform individuals on whether measures such as boosters may be advisable. MethodsThree SARS-CoV-2 ELISA tests were utilized to monitor responses in 82 individuals in the United States [nucleocapsid protein (N)-specific antibody and spike RBD (receptor binding domain)-specific neutralizing antibody (nAb), and spike-specific interferon-{gamma} (IFN-{gamma}) release by T cells]. De-identified case reports highlight results for this cohort; 21 previously infected and vaccinated, 57 never infected and vaccinated, 2 breakthrough infections post-vaccination and 2 neither infected nor vaccinated. ResultsThe vaccines generated nAb responses in naive donors, and in previously infected individuals with waning responses, immunosuppression, or weak infection responses. The cutoff for the nAb potency was established at 41.1 IU/mL when calibrated to the WHO International Standard (IU) using the NCI SARS-CoV-2 Standard. This relationship has the critical potential to allow comparisons of nAb measures to be utilized in studies of correlates of protection. Further, previously infected donors demonstrated robust T cell activity, while vaccinated and infection-naive individuals had lower responses. ConclusionsCalibrated ELISA tests may aid broad vaccination strategies given their low cost and wide accessibility. Additional studies that relate measures of the adaptive responses to immunity from serious disease and infection are needed.