Immunity response against mild-to-moderate breakthrough COVID-19

ABSTRACT BACKGROUND The Omicron variant prevails the Delta variant after December 2021 in Thailand. Both variants of concern embody diverse epidemiological trends and immunogenicity, raising enormous public health concerns. We determined whether biological and clinical characteristics and immunogenicity of patients differ between Delta and Omicron during post-coronavirus disease 2019 (COVID-19) stage. METHODS A retrospective cohort study involved patients with mild-to-moderate COVID-19 who were under a home isolation (HI) strategy. Clinical outcomes and laboratory data of 2704 and 2477 patients during the Delta and Omicron pandemics were analyzed, respectively. We evaluated anti-receptor binding domain immunoglobulin G (anti-RBD IgG) and surrogate viral neutralizing (sVNT) activity in a subset of 495 individuals post-COVID-19 infection during the Delta pandemic. RESULTS Eighty-four percent of all patients received antiviral treatment. The peak cycle threshold (Ct) values, which inversely related to viral load, were lower in the Omicron (19 [IQR=17-22]) compared with the Delta (21 [IQR=18-26]; p<0.001), regardless of vaccination status. Upper respiratory tract symptoms were common signs during the Omicron compared with the Delta pandemic. At least two-dose vaccination reduced the chance of hospital readmissions by 10–30% and death by less than 1%. Furthermore, anti-RBD IgG and sVNT against the Delta variants tended to be higher among the older individuals after post-COVID 19 infections and expressed in the long interval after two-dose vaccination than in other groups. CONCLUSIONS Mild-to-moderate Delta and Omicron breakthrough infection with prior full vaccination is limitedly immunogenic; thereby exerting reduced protection against reinfection and infection from novel variants. However, this may be only sufficient to prevent hospitalization and death, particularly in countries where vaccines are limited. ( ClinicalTrials.gov number, NCT05328479 .)