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Background <p>Healthcare workers (HCWs) face high occupational exposure to SARS-CoV-2 and are a priority group for vaccination. Both natural infection and vaccination—individually or combined as hybrid immunity—confer protection against SARS-CoV-2 infection. This study aimed to evaluate the protection conferred by hybrid, infection-induced, and booster vaccine-induced immunity against laboratory-confirmed SARS-CoV-2 infections in HCWs during the circulation of three pandemic and one post-pandemic Omicron sublineages.</p> Methods <p>We conducted a prospective cohort study of HCWs from 18 hospitals across nine European countries. Participants underwent RT-PCR testing at enrolment and during weekly or fortnightly follow-ups. The study period was divided based on dominant Omicron sublineage circulation: BA.1/2 (Dec 16, 2021–Jun 1, 2022), BA.4/5/BQ.1 (Jun 2–Dec 31, 2022), BA.2/XBB (Jan 1–May 2, 2023), and post-pandemic XBB.1.5/BA.2.86 (Sep 1, 2023–May 21, 2024). Participants were classified into four groups: hybrid (prior infection and recent booster vaccination 7–179&#xa0;days), infection-induced (prior infection, no recent vaccination), vaccine-induced immunity (recent booster vaccination, no prior infection), and a reference group (no prior infection, no recent booster vaccination). Adjusted hazard ratios (aHRs) for infection were estimated using Cox regression, adjusting for hospital, age, sex, chronic condition, and patient-facing role.</p> Results <p>A total of 3 133 HCWs were included: 2572 (82%) female, 1734 (55%) aged 40–59, and 563 (29%) with ≥ 1 chronic condition. Hybrid immunity showed significant protection during BA.1/2 (aHR = 0.37, 95%CI 0.21–0.63), BA.4/5/BQ.1 (aHR = 0.36, 95%CI 0.22–0.58), and XBB.1.5/BA.2.86 (aHR = 0.53, 95%CI 0.37–0.74) periods. Infection-induced immunity was protective across all periods, most during BA.1/2 (aHR = 0.26, 95%CI 0.12–0.53), and least during BA.2/XBB (aHR = 0.66, 95%CI 0.36–1.22). Vaccine-induced immunity alone offered limited protection during BA.1/2 (aHR = 0.72, 95%CI 0.49–1.06) and BA.4/5/BQ.1 (aHR = 0.77, 95%CI 0.50–1.19), with wide confidence intervals suggesting low statistical significance.</p> Conclusions <p>Hybrid and infection-induced immunity groups were more protected against infection caused by earlier Omicron sub-lineages and more protected than vaccination alone, which had no significant protective effect. These findings highlight the need for adaptive public health strategies, including timely vaccine updates and understanding of prior SARS-CoV-2 infection to inform COVID-19 vaccination policies for HCWs in the post-pandemic era.</p>

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Hybrid, infection- and vaccination-induced protection against laboratory- confirmed SARS-CoV-2 infection in a European multi-centre prospective cohort of healthcare workers, 2021–2024

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  • 发表日期：

    2025年12月29日

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  • Madelyn Rojas-Castro,
  • Ranya Mulchandani,
  • Kim Brolin,
  • Zvjezdana Lovrić Makarić,
  • Anneli Uusküla,
  • Colm Bergin,
  • Catherine Fleming,
  • Paolo Bonfanti,
  • Rita Murri,
  • Viesturs Zvirbulis,
  • Dace Zavadska,
  • Konstanty Szuldrzynski,
  • Vânia Gaio,
  • Corneliu Petru Popescu,
  • Mihai Craiu,
  • Raluca-Maria Hrișcă,
  • Maria Cisneros,
  • Miriam Latorre-Millán,
  • Goranka Petrović,
  • Liss Lohur,
  • Jonathan McGrath,
  • Lauren Ferguson,
  • Anna Spolti,
  • Katleen De Gaetano Donati,
  • Ilze Abolina,
  • Dagne Gravele,
  • Ausenda Machado,
  • Simin Aysel Florescu,
  • Mihaela Lazar,
  • Pilar Subirats,
  • Laura Clusa,
  • Gordan Sarajlić,
  • Jacklyn Sui,
  • Claire Kenny,
  • Rosaria Santangelo,
  • Dainis Krievins,
  • Elza Anna Barzdina,
  • Camila Valadas Henriques,
  • Alma Gabriela Kosa,
  • Săftica-Mariana Pohrib,
  • Victor Daniel Miron,
  • Carmen Muñoz-Almagro,
  • Ana Maria Milagro,
  • Sabrina Bacci,
  • Camelia Savulescu,
  • Hanna Sepp,
  • Lisa Domegan,
  • Joan O’Donell,
  • Maeve Kernan,
  • Anne Moriarty,
  • Conor Moran,
  • Giulia De Angelis,
  • Giulia Menchinelli,
  • Cinzia Recine,
  • Silvia Zelli,
  • Benedetta Falasca,
  • Silvia Lamonica,
  • Zrinka Bošnjak,
  • Ana Budimir,
  • Tvrtko Žarko,
  • Božena Rašić,
  • Marko Ćurković,
  • Porin Makarić,
  • Senka Repovečki,
  • Kornelija Petir,
  • Irena Tabain,
  • Tatjana Vilibić Čavlek,
  • Janis Meisters,
  • Laura Zemite,
  • Hilda Darta Snipe,
  • Estere Ergle,
  • Ana Palmira Amaral,
  • João Almeida Santos,
  • Daniela Dias,
  • Licínia Gomes,
  • Miguel Lança,
  • Henrique Carvalho,
  • Jose Alves,
  • Daniel R. Codreanu,
  • Alexandru Marin,
  • Amaresh Pérez-Arguello,
  • Iolanda Jordan,
  • Juan Jose Garcia-Garcia,
  • Antonio Rezusta López,
  • Alexander Isaias Tristancho Baró,
  • Ignacio Ezpeleta Ascaso,
  • Sandra Dueñas Jollard,
  • Noelia Terren Marco,
  • Tamara Valero Vicente,
  • Nieves Felisa Martínez Cameo,
  • Yolanda Gracia Grataloup,
  • David Martínez Mateos,
  • Beatriz Gilaberte Angós,
  • Diego Ortega Larrea,
  • María Pilar Abad Alejaldre,
  • Cristina Carrasco Carbó,
  • Carmen Martínez Giménez,
  • Maria Gemma Martínez Andrés,
  • Bruno del Moral Redolat,
  • Ana Maria Sabio Blasco,
  • Raquel Guiomar,
  • Aryse Melo,
  • Francisco Pozo,
  • Iris Ganser,
  • Cristina López,
  • Albert Prats,
  • Antony Nardone

摘要

Background

Healthcare workers (HCWs) face high occupational exposure to SARS-CoV-2 and are a priority group for vaccination. Both natural infection and vaccination—individually or combined as hybrid immunity—confer protection against SARS-CoV-2 infection. This study aimed to evaluate the protection conferred by hybrid, infection-induced, and booster vaccine-induced immunity against laboratory-confirmed SARS-CoV-2 infections in HCWs during the circulation of three pandemic and one post-pandemic Omicron sublineages.

Methods

We conducted a prospective cohort study of HCWs from 18 hospitals across nine European countries. Participants underwent RT-PCR testing at enrolment and during weekly or fortnightly follow-ups. The study period was divided based on dominant Omicron sublineage circulation: BA.1/2 (Dec 16, 2021–Jun 1, 2022), BA.4/5/BQ.1 (Jun 2–Dec 31, 2022), BA.2/XBB (Jan 1–May 2, 2023), and post-pandemic XBB.1.5/BA.2.86 (Sep 1, 2023–May 21, 2024). Participants were classified into four groups: hybrid (prior infection and recent booster vaccination 7–179 days), infection-induced (prior infection, no recent vaccination), vaccine-induced immunity (recent booster vaccination, no prior infection), and a reference group (no prior infection, no recent booster vaccination). Adjusted hazard ratios (aHRs) for infection were estimated using Cox regression, adjusting for hospital, age, sex, chronic condition, and patient-facing role.

Results

A total of 3 133 HCWs were included: 2572 (82%) female, 1734 (55%) aged 40–59, and 563 (29%) with ≥ 1 chronic condition. Hybrid immunity showed significant protection during BA.1/2 (aHR = 0.37, 95%CI 0.21–0.63), BA.4/5/BQ.1 (aHR = 0.36, 95%CI 0.22–0.58), and XBB.1.5/BA.2.86 (aHR = 0.53, 95%CI 0.37–0.74) periods. Infection-induced immunity was protective across all periods, most during BA.1/2 (aHR = 0.26, 95%CI 0.12–0.53), and least during BA.2/XBB (aHR = 0.66, 95%CI 0.36–1.22). Vaccine-induced immunity alone offered limited protection during BA.1/2 (aHR = 0.72, 95%CI 0.49–1.06) and BA.4/5/BQ.1 (aHR = 0.77, 95%CI 0.50–1.19), with wide confidence intervals suggesting low statistical significance.

Conclusions

Hybrid and infection-induced immunity groups were more protected against infection caused by earlier Omicron sub-lineages and more protected than vaccination alone, which had no significant protective effect. These findings highlight the need for adaptive public health strategies, including timely vaccine updates and understanding of prior SARS-CoV-2 infection to inform COVID-19 vaccination policies for HCWs in the post-pandemic era.