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Anti-Spike IgG antibodies against SARS-CoV-2, which are elicited by vaccination and infection, are correlates of protection against infection with pre-Omicron variants. Whether this association can be generalized to infections with Omicron variants is unclear. We conducted a retrospective cohort study with 8457 blood donors in Tyrol, Austria, analyzing 15,340 anti-Spike IgG antibody measurements from March 2021 to December 2022 assessed by Abbott SARS-CoV-2 IgG II chemiluminescent microparticle immunoassay. Using a Bayesian joint model, we estimated antibody trajectories and adjusted hazard ratios for incident SARS-CoV-2 infection ascertained by self-report or seroconversion of anti-Nucleocapsid antibodies. At the time of their earliest available anti-Spike IgG antibody measurement (median November 23, 2021), participants had a median age of 46.0 years (IQR 32.8-55.2), with 45.3% being female, 41.3% having a prior SARS-CoV-2 infection, and 75.5% having received at least one dose of a COVID-19 vaccine. Among 6159 participants with endpoint data, 3700 incident SARS-CoV-2 infections with predominantly Omicron sublineages were recorded over a median of 8.8 months (IQR 5.7-12.4). The age- and sex-adjusted hazard ratio for SARS-CoV-2 associated with having twice the anti-Spike IgG antibody titer was 0.875 (95% credible interval 0.868-0.881) overall, 0.842 (0.827-0.856) during 2021, and 0.884 (0.877-0.891) during 2022 (all p < 0.001). The associations were similar in females and males (P interaction  = 0.673) and across age (P interaction  = 0.590). Higher anti-Spike IgG antibody titers were associated with reduced risk of incident SARS-CoV-2 infection across the entire observation period. While the magnitude of association was slightly weakened in the Omicron era, anti-Spike IgG antibody continues to be a suitable correlate of protection against newer SARS-CoV-2 variants., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Immunocompromised patients (ICPs) have an increased risk for a severe and prolonged COVID-19. SARS-CoV-2 monoclonal antibodies (mAbs) were extensively used in these patients, but data from randomized trials that focus on ICPs are lacking. We evaluated the clinical and virological outcome of COVID-19 in ICPs treated with mAbs across SARS-CoV-2 variants., Methods: In this multicenter prospective cohort study, we enrolled B-cell- and/or T-cell-deficient patients treated with casirivimab/imdevimab, sotrovimab, or tixagevimab/cilgavimab. SARS-CoV-2 RNA was quantified and sequenced weekly, and time to viral clearance, viral genome mutations, hospitalization, and death rates were registered., Results: Two hundred and forty five patients infected with the Delta (50%) or Omicron BA.1, 2, or 5 (50%) variant were enrolled. Sixty-seven percent were vaccinated; 78 treated as outpatients, of whom 2 required hospital admission, but both survived. Of the 159 patients hospitalized at time of treatment, 43 (27%) required mechanical ventilation or died. The median time to viral clearance was 14 days (interquartile range, 7-22); however, it took >30 days in 15%. Resistance-associated spike mutations emerged in 9 patients in whom the median time to viral clearance was 63 days (95% confidence interval, 57-69; P < .001). Spike mutations were observed in 1 of 42 (2.4%) patients after treatment with 2 active mAbs, in 5 of 34 (14.7%) treated with actual monotherapy (sotrovimab), and 3 of 20 (12%) treated with functional monotherapy (ie, tixagevimab/cilgavimab against tixagevimab-resistant variant)., Conclusions: Despite treatment with mAbs, morbidity and mortality of COVID-19 in ICPs remained substantial. Combination antiviral therapy should be further explored and may be preferred in severely ICPs., Competing Interests: Potential conflicts of interest. B. R. reports membership on advisory boards for AstraZeneca, Roche, and Pfizer; and receipt of consulting fees from Roche, AstraZeneca and Pfizer. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)