Increased vaccine sensitivity of an emerging SARS-CoV-2 variant

Abstract

Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with enhancements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and ≥5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater point estimates of protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of ≥4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and ≥2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses.

Fig. 1. Trends in SARS-CoV-2 infection diagnoses within the KPSC population.

Panels illustrate A frequency of SARS-CoV-2 detections via ThermoFisher TaqPath COVID-19 combo kit assay (TF; blue) and other assays (pink), across all settings; B frequency of SARS-CoV-2 detections among hospitalized patients; C frequency of samples with S-gene detection (green) or S-gene target failure (SGTF; violet), among outpatient cases tested via the TF assay; D proportion of outpatient cases with S-gene detection, among all positive outpatient cases tested with the TF assay. For consistency with panel (C), the proportion of isolates with S-gene detection (XBB/XBB.1.5 lineages) is illustrated in green in panel (D). Data include 80,894 cases, among whom 31,739 were tested using the TF assay and are represented in panels (C) and (D).