Abstract: The clinical impact of anti-spike monoclonal antibodies (mAb) in  Coronavirus Disease 2019 (COVID-19) breakthrough infections is unclear.  We present the results of an observational prospective cohort study  assessing and comparing COVID-19 progression in high-risk outpatients  receiving mAb according to primary or breakthrough infection. Clinical,  serological and virological predictors associated with 28-day  COVID-19-related hospitalization were identified using multivariate  logistic regression and summarized with odds ratio (aOR) and 95%  confidence interval (CI). A total of 847 COVID-19 outpatients were  included: 414 with primary and 433 with breakthrough infection.  Hospitalization was observed in 42/414 (10.1%) patients with primary and  8/433 (1.8%) patients with breakthrough infection (p < 0.001). aOR  for hospitalization was significantly lower for breakthrough infection  (aOR 0.12, 95%CI: 0.05-0.27, p < 0.001) and higher for  immunocompromised status (aOR:2.35, 95%CI:1.08-5.08, p = 0.003),  advanced age (aOR:1.06, 95%CI: 1.03-1.08, p < 0.001), and male gender  (aOR:1.97, 95%CI: 1.04-3.73, p = 0.037). Among the breakthrough  infection group, the median SARS-CoV-2 anti-spike IgGs was lower (p <  0.001) in immunocompromised and elderly patients >75 years compared  with that in the immunocompetent patients. Our findings suggest that,  among mAb patients, those with breakthrough infection have significantly  lower hospitalization risk compared with patients with primary  infection. Prognostic algorithms combining clinical and  immune-virological characteristics are needed to ensure appropriate and  up-to-date clinical protocols targeting high-risk categories.

Keywords: COVID-19 breakthrough infection; COVID-19 early treatment; anti-spike monoclonal antibodies.