Hospitalised patients with breakthrough COVID-19 following vaccination during two distinct waves in Israel, January to August 2021: a multicentre comparative cohort study

Background Changing patterns of vaccine breakthrough can clarify vaccine effectiveness. Aim To compare breakthrough infections during a SARS-CoV-2 Delta wave vs unvaccinated inpatients, and an earlier Alpha wave. Methods In an observational multicentre cohort study in Israel, hospitalised COVID-19 patients were divided into three cohorts: breakthrough infections in Comirnaty-vaccinated patients (VD; Jun–Aug 2021) and unvaccinated cases during the Delta wave (ND) and breakthrough infections during an earlier Alpha wave (VA; Jan–Apr 2021). Primary outcome was death or ventilation. Results We included 343 VD, 162 ND and 172 VA patients. VD were more likely older (OR: 1.06; 95% CI: 1.05–1.08), men (OR: 1.6; 95% CI: 1.0–2.5) and immunosuppressed (OR: 2.5; 95% CI: 1.1–5.5) vs ND. Median time between second vaccine dose and admission was 179 days (IQR: 166–187) in VD vs 41 days (IQR: 28–57.5) in VA. VD patients were less likely to be men (OR: 0.6; 95% CI: 0.4–0.9), immunosuppressed (OR: 0.3; 95% CI: 0.2–0.5) or have congestive heart failure (OR: 0.6; 95% CI: 0.3–0.9) vs VA. The outcome was similar between all cohorts and affected by age and immunosuppression and not by vaccination, variant or time from vaccination. Conclusions Vaccination was protective during the Delta variant wave, as suggested by older age and greater immunosuppression in vaccinated breakthrough vs unvaccinated inpatients. Nevertheless, compared with an earlier post-vaccination period, breakthrough infections 6 months post-vaccination occurred in healthier patients. Thus, waning immunity increased vulnerability during the Delta wave, which suggests boosters as a countermeasure.


Supplementary material:
Hospitalized patients with breakthrough COVID-19 six month following Comirnaty vaccination compared to unvaccinated inpatients and to inpatients with breakthrough infection six weeks following vaccination -a multicenter comparative cohort study Contents: Page S1: Specifications of laboratory methods used in study hospitals (PCR, serology) 2  Figure S4: Forest plot displaying a regression analysis comparing breakthrough infections during a delta-predominant late wave (VD cohort) to non-vaccinated patients in the same wave (ND cohort). 5 Figure S5: Forest plot displaying a regression analysis comparing breakthrough infections during a delta-predominant late wave (VD cohort) to an alphapredominant earlier wave (VA cohort).
This supplementary material is hosted by Eurosurveillance as supporting information alongside the article, on behalf of the authors, who remain responsible for the accuracy and appropriateness of the content. The same standards for ethics, copyright, attributions and permissions as for the article apply. Supplements are not edited by Eurosurveillance and the journal is not responsible for the maintenance of any links or email addresses provided therein.

S1: Specifications of laboratory methods used in study hospitals
PCR tests for SARS-CoV-2 RNA, that were used in various participating hospitals: This supplementary material is hosted by Eurosurveillance as supporting information alongside the article, on behalf of the authors, who remain responsible for the accuracy and appropriateness of the content. The same standards for ethics, copyright, attributions and permissions as for the article apply. Supplements are not edited by Eurosurveillance and the journal is not responsible for the maintenance of any links or email addresses provided therein. This supplementary material is hosted by Eurosurveillance as supporting information alongside the article, on behalf of the authors, who remain responsible for the accuracy and appropriateness of the content. The same standards for ethics, copyright, attributions and permissions as for the article apply. Supplements are not edited by Eurosurveillance and the journal is not responsible for the maintenance of any links or email addresses provided therein.

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This supplementary material is hosted by Eurosurveillance as supporting information alongside the article, on behalf of the authors, who remain responsible for the accuracy and appropriateness of the content. The same standards for ethics, copyright, attributions and permissions as for the article apply. Supplements are not edited by Eurosurveillance and the journal is not responsible for the maintenance of any links or email addresses provided therein. Figure S4: Forest plot displaying a regression analysis comparing breakthrough infections during a deltapredominant late wave (VD cohort) to non-vaccinated patients in the same wave (ND cohort). Vertical bars and whiskers signify odds ratio (VD vs. ND cohort) and 95% confidence intervals (CI). Statistically significant variables are emphasized by a thicker line.

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This supplementary material is hosted by Eurosurveillance as supporting information alongside the article, on behalf of the authors, who remain responsible for the accuracy and appropriateness of the content. The same standards for ethics, copyright, attributions and permissions as for the article apply. Supplements are not edited by Eurosurveillance and the journal is not responsible for the maintenance of any links or email addresses provided therein. Figure S5: Forest plot displaying a regression analysis comparing breakthrough infections during a deltapredominant late wave (VD cohort) to an alpha-predominant earlier wave (VA cohort). Vertical bars and whiskers signify odds ratio (VD vs. VA cohort) and 95% confidence intervals (CI). Statistically significant variables are emphasized by a thicker line.