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. 2023 Nov 2;11(11):1684.
doi: 10.3390/vaccines11111684.

Older Age, a High Titre of Neutralising Antibodies and Therapy with Conventional DMARDs Are Associated with Protection from Breakthrough Infection in Rheumatoid Arthritis Patients after the Booster Dose of Anti-SARS-CoV-2 Vaccine

Andrea Picchianti-Diamanti  1 , Assunta Navarra  2 , Alessandra Aiello  3 , Bruno Laganà  1 , Gilda Cuzzi  3 , Andrea Salmi  3 , Valentina Vanini  3   4 , Fabrizio Maggi  5 , Silvia Meschi  5 , Giulia Matusali  5 , Stefania Notari  6 , Chiara Agrati  6   7 , Simonetta Salemi  1 , Roberta Di Rosa  1 , Damiano Passarini  1 , Valeria Di Gioia  1 , Giorgio Sesti  1 , Fabrizio Conti  8 , Francesca Romana Spinelli  8 , Angela Corpolongo  9 , Maria Sole Chimenti  10 , Mario Ferraioli  11 , Gian Domenico Sebastiani  11 , Maurizio Benucci  12 , Francesca Li Gobbi  12 , Anna Paola Santoro  13   14 , Andrea Capri  13 , Vincenzo Puro  13 , Emanuele Nicastri  9 , Delia Goletti  3
Affiliations

Older Age, a High Titre of Neutralising Antibodies and Therapy with Conventional DMARDs Are Associated with Protection from Breakthrough Infection in Rheumatoid Arthritis Patients after the Booster Dose of Anti-SARS-CoV-2 Vaccine

Andrea Picchianti-Diamanti et al. Vaccines (Basel). .

Abstract

Objectives: We aimed to analyse the incidence and severity of breakthrough infections (BIs) in rheumatoid arthritis (RA) patients after a COronaVIrus Disease 2019 (COVID-19) vaccination booster dose. Methods: We enrolled 194 RA patients and 1002 healthcare workers (HCWs) as controls. Clinical, lifestyle and demographic factors were collected at the time of the third dose, and immunogenicity analyses were carried out in a subgroup of patients at 4-6 weeks after the third dose. Results: BIs were experienced by 42% patients (82/194) with a median time since the last vaccination of 176 days. Older age (>50 years; aHR 0.38, 95% CI: 0.20-0.74), receiving conventional synthetic disease modifying antirheumatic drugs (csDMARDs) (aHR 0.52, 95%CI: 0.30-0.90) and having a titre of neutralising antibodies >20 (aHR 0.36, 95% CI: 0.12-1.07) were identified as protective factors. Conversely, anti-IL6R treatment and anti-CD20 therapy increased BI probability. BIs were mostly pauci-symptomatic, but the hospitalisation incidence was significantly higher than in HCWs (8.5% vs. 0.19%); the main risk factor was anti-CD20 therapy. Conclusions: Being older than 50 years and receiving csDMARDs were shown to be protective factors for BI, whereas anti-IL6R or anti-CD20 therapy increased the risk. Higher neutralising antibody titres were associated with a lower probability of BI. If confirmed in a larger population, the identification of a protective cut-off would allow a personalised risk-benefit therapeutic management of RA patients.

Keywords: SARS-CoV-2; booster; immunogenicity; immunosuppressive therapy; neutralising antibodies; protective immunity; rheumatoid arthritis; vaccine.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Unadjusted Kaplan-Meier curves estimating the cumulative probability of SARS-CoV-2 infection after third-dose vaccination among 194 RA patients according to the age group (A), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (B) and anti-IL6R treatment (C).
Figure 2
Figure 2
Unadjusted Kaplan-Meier curves estimating the probability of SARS-CoV-2 infection in RA patients according to anti-S/RBD-IgG in binding antibody units (BAU) (A), neutralising antibodies (nAbs) (B) and T cell-specific response evaluated with IFN-γ detection in picograms (C). Abbreviations: anti-S/RBD: anti-spike receptor binding domain; BAU: binding antibody units; nAbs: neutralising antibodies; IFN: interferon; pg: picograms.
See this image and copyright information in PMC

References

    1. World Health Organization (WHO) Statement on the Fifteenth Meeting of the IHR (2005) Emergency Committee on the COVID-19 Pandemic. [(accessed on 5 September 2023)]. Available online: https://www.who.int/news/item/05-05-2023-statement-on-the-fifteenth-meet....
    1. Tarke A., Coelho C.H., Zhang Z., Dan J.M., Yu E.D., Methot N., Bloom N.I., Goodwin B., Phillips E., Mallal S., et al. SARS-CoV-2 Vaccination Induces Immunological T Cell Memory Able to Cross-Recognize Variants from Alpha to Omicron. Cell. 2022;185:847–859.e11. doi: 10.1016/j.cell.2022.01.015. - DOI - PMC - PubMed
    1. Araf Y., Akter F., Tang Y.-D., Fatemi R., Parvez M.S.A., Zheng C., Hossain M.G. Omicron Variant of SARS-CoV-2: Genomics, Transmissibility, and Responses to Current COVID-19 Vaccines. J. Med. Virol. 2022;94:1825–1832. doi: 10.1002/jmv.27588. - DOI - PMC - PubMed
    1. Stefanelli P., Trentini F., Petrone D., Mammone A., Ambrosio L., Manica M., Guzzetta G., d’Andrea V., Marziano V., Zardini A., et al. Tracking the Progressive Spread of the SARS-CoV-2 Omicron Variant in Italy, December 2021 to January 2022. Eurosurveillance. 2022;27:2200125. doi: 10.2807/1560-7917.ES.2022.27.45.2200125. - DOI - PMC - PubMed
    1. Levin E.G., Lustig Y., Cohen C., Fluss R., Indenbaum V., Amit S., Doolman R., Asraf K., Mendelson E., Ziv A., et al. Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months. N. Engl. J. Med. 2021;385:e84. doi: 10.1056/NEJMoa2114583. - DOI - PMC - PubMed