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Heat shock protein 27 in the pathogenesis of COVID-19 and non-COVID acute respiratory distress syndrome

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Cell Stress and Chaperones Aims and scope

Abstract

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure in intensive care units that has increased dramatically as a result of the COVID-19 pandemic. In both COVID-19 and non-COVID ARDS, the pathogenesis of lung injury involves local (pulmonary) and systemic inflammation, leading to impaired gas exchange, requirement for mechanical ventilation, and a high risk of mortality. Heat shock protein 27 (HSP27) is a chaperone protein expressed in times of cell stress with roles in modulation of systemic inflammation via the NF-κB pathway. Given its important role as a modulator of inflammation, we sought to investigate the role of HSP27 and its associated auto-antibodies in ARDS caused by both SARS-CoV-2 and non-COVID etiologies. A total of 68 patients admitted to the intensive care unit with ARDS requiring mechanical ventilation were enrolled in a prospective, observational study that included 22 non-COVID-19 and 46 COVID-19 patients. Blood plasma levels of HSP27, anti-HSP27 auto-antibody (AAB), and cytokine profiles were measured on days 1 and 3 of ICU admission along with clinical outcome measures. Patients with COVID-19 ARDS displayed significantly higher levels of HSP27 in plasma, and a higher ratio of HSP27:AAB on both day 1 and day 3 of ICU admission. In patients with COVID-19, higher levels of circulating HSP27 and HSP27:AAB ratio were associated with a more severe systemic inflammatory response and adverse clinical outcomes including more severe hypoxemic respiratory failure. These findings implicate HSP27 as a marker of advanced pathogenesis of disease contributing to the dysregulated systemic inflammation and worse clinical outcomes in COVID-19 ARDS, and therefore may represent a potential therapeutic target.

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Data Availability

All data required to interpret the results of this study are included in the manuscript. Datasets are available upon request.

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Acknowledgements

The authors would like to acknowledge Zdenka Slavikova who assisted with recruitment of patients and sample collection, as well as the patients, families, and ICU staff who contributed to this research.

Funding

Funding for this work was provided by the Canadian Institutes for Health Research and Alberta Health Services operating grants (to BM).

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Authors and Affiliations

  1. Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, University of Calgary, Calgary, Canada

    Michael H. Chiu, Edward R. O’Brien & Jingti Deng

  2. Department of Critical Care Medicine, University of Calgary, Calgary, Canada

    Michael H. Chiu, Benjamin Gershkovich, Ian-Ling Yu & Braedon McDonald

  3. Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Michael H. Chiu, Ian-Ling Yu & Braedon McDonald

  4. Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada

    Ian-Ling Yu & Braedon McDonald

Authors
  1. Michael H. Chiu
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  2. Benjamin Gershkovich
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  3. Ian-Ling Yu
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  4. Edward R. O’Brien
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  5. Jingti Deng
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  6. Braedon McDonald
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Correspondence to Michael H. Chiu.

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Chiu, M.H., Gershkovich, B., Yu, IL. et al. Heat shock protein 27 in the pathogenesis of COVID-19 and non-COVID acute respiratory distress syndrome. Cell Stress and Chaperones 28, 877–887 (2023). https://doi.org/10.1007/s12192-023-01381-6

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  • DOI: https://doi.org/10.1007/s12192-023-01381-6

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