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Impact of influenza immunity on the mortality among older adults hospitalized with COVID-19: a retrospective cohort study

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Abstract

It has been suggested that the outcomes of coronavirus disease 2019 (COVID-19) are better in individuals having recently received an influenza vaccine than in non-vaccinated individuals. We hypothesized that this association depends on the humoral responses against influenza viruses. We aim to assess the relationship between the humoral immunity against influenza and the 3-month all-cause mortality among hospitalized older patients with COVID-19. We performed an exploratory retrospective study of older patients (aged 65 and over) hospitalized for confirmed COVID-19 between November 2020 and June 2021. Previous humoral responses to influenza viruses were assessed using a hemagglutination inhibition assay on routinely collected blood samples. The study’s primary outcome was the 3-month all-cause mortality, and the secondary outcomes were severe COVID-19 (oxygen requirement ≥ 6 L/min or ventilatory support) and complications (kidney or heart failure, thrombosis and bacterial infection). In the cohort of 95 patients with COVID-19, immunity against influenza vaccine subtypes/lineages was not significantly associated with 3-month all-cause mortality, with an OR [95%CI] of 0.22 [0.02–1.95] (p = 0.174) for the H1N1pdm09 subtype, 0.21 [0.03–1.24] (p = 0.081) for A/Hong Kong/2671/2019 H3N2 subtype, 1.98 [0.51–8.24] (p = 0.329) for the B/Victoria lineage, and 1.82 [0.40–8.45] (p = 0.437) for the B/Yamagata lineage. Immunity against influenza vaccine subtypes/lineages was also not significantly associated with severity and complication. Immunity against influenza subtypes/lineages included in the 2020–2021 vaccine was not associated with a lower 3-month all-cause mortality among COVID-19 hospitalized patients.

Trial registration: The study was approved by a hospital committee with competency for research not requiring approval by an institutional review board (Tours University Medical Center, Tours, France: reference: 2021_015). All patients give the informed consent.

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ADL:

Activities of daily living

CI:

Confidence interval

COVID-19:

Coronavirus disease 2019

HIA:

Hemagglutination inhibition assay

IFN:

Interferon

IIV:

Inactivated influenza vaccine

IQR:

Interquartile range

OR:

Odds ratio

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus 2

SD:

Standard deviation

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Acknowledgements

We especially thank Professor P-F. Dequin (Department of Intensive Care Medicine, Tours University Medical Center, Tours, France), Professor G. Desoubeaux (Laboratory of Parasitology—Mycology—Tropical Medicine, Tours University Medical Center), Dr. M. Gabteni (Emergency Department, Tours University Medical Center), Professor F. Maillot (Department of Internal Medicine and Clinical Immunology, Tours University Medical Center), and Professor S. Marchand Adam (Pulmonology Department, Tours University Medical Center) for providing patient care in the present study as part of their clinical activity. We thank the GINGER group for its support. We also thank all the practitioners who cared for patients in the ED or in other departments and/or who helped to design the study. Lastly, we thank David Fraser PhD (Biotech Communication SARL, Ploudalmézeau, France) for copy-editing assistance.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Division of Geriatric Medicine, Tours University Medical Center, 37044, Tours, France

    Matthieu Coulongeat, Amal Aidoud, Camille Debacq, Victoire Leroy & Bertrand Fougère

  2. Division of Geriatric Medicine, University Hospital Center of ORLEANS, 45100, Orléans, France

    Matthieu Coulongeat

  3. Service de Bactériologie-Virologie-Hygiène, CHRU de Tours, Tours, France

    Julien Marlet

  4. INSERM U1259, Université de Tours, 37044, Tours, France

    Julien Marlet

  5. Tours University, EA4245 Transplantation, Immunologie, Inflammation, Tours, France

    Amal Aidoud

  6. Institut Pasteur, Université Paris Cité, CNRS UMR3569, Unité de Génétique Moléculaire Des Virus À ARN, 75015, Paris, France

    Flora Donati, Sylvie Van Der Werf & Sandie Munier

  7. Institut Pasteur, CNR Virus Des Infections Respiratoires, 75015, Paris, France

    Flora Donati, Sylvie Van Der Werf & Sandie Munier

  8. Service de Maladies Infectieuses Et Tropicales (SMIT), Centre Hospitalier Universitaire de Tours, 37044, Tours, France

    Simon Jamard & Adrien Lemaignen

  9. Centre Mémoire Ressources Et Recherche (CMRR), Centre Hospitalier Universitaire de Tours, 37044, Tours, France

    Victoire Leroy

  10. Education, Ethics, Health (EA 7505), Tours University, 37044, Tours, France

    Victoire Leroy & Bertrand Fougère

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  1. Matthieu Coulongeat
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  2. Julien Marlet
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  3. Amal Aidoud
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  4. Flora Donati
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Coulongeat, Marlet, Donati and Munier. Jamard performed the statistical analysis. The first draft of the manuscript was written by Coulongeat, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Matthieu Coulongeat.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Tours University Medical Center in 2021 (reference: 2021 015). In line with the French legislation on noninterventional studies of anonymized clinical data, the study database was registered at Tours University Medical Center (Tours, France; reference: 2021_034).

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Informed consent was obtained from all individual participants included in the study.

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Coulongeat, M., Marlet, J., Aidoud, A. et al. Impact of influenza immunity on the mortality among older adults hospitalized with COVID-19: a retrospective cohort study. Clin Exp Med 23, 4955–4965 (2023). https://doi.org/10.1007/s10238-023-01203-0

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