Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Clinical Relevance of Elevated Soluble ST2, HSP27 and 20S Proteasome in Patients with COVID-19

Version 1 : Received: 17 August 2021 / Approved: 23 August 2021 / Online: 23 August 2021 (13:23:05 CEST)

How to cite: Wendt, R.; Lingitz, M.; Laggner, M.; Mildner, M.; Traxler, D.; Graf, A.; Krotka, P.; Moser, B.; Hoetzenecker, K.; Kalbitz, S.; Luebbert, C.; Beige, J.; Ankersmit, H.J. Clinical Relevance of Elevated Soluble ST2, HSP27 and 20S Proteasome in Patients with COVID-19. Preprints 2021, 2021080440 (doi: 10.20944/preprints202108.0440.v1). Wendt, R.; Lingitz, M.; Laggner, M.; Mildner, M.; Traxler, D.; Graf, A.; Krotka, P.; Moser, B.; Hoetzenecker, K.; Kalbitz, S.; Luebbert, C.; Beige, J.; Ankersmit, H.J. Clinical Relevance of Elevated Soluble ST2, HSP27 and 20S Proteasome in Patients with COVID-19. Preprints 2021, 2021080440 (doi: 10.20944/preprints202108.0440.v1).

Abstract

Although, severe acute respiratory syndrome coronavirus – 2 (SARS-CoV 2) represents one of the biggest challenges in the world today, the exact immunopathogenic mechanism that leads to severe or critical Coronavirus Disease 2019 (COVID-19) has remained incompletely understood. Several studies have indicated that high systemic plasma levels of inflammatory cytokines result in the so-called “cytokine storm”, with subsequent development of microthrombosis, disseminated intravascular coagulation, and multiorgan-failure. Therefore, we reasoned that elevated inflammatory cytokine might act as prognostic factors. Here, we analyzed 245 serum samples of patients with COVID-19, collected at hospital admission. We assessed the levels of heat shock protein 27 (HSP27), soluble suppressor of tumorigenicity- 2 (sST2), caspase cleaved cytokeratin 18 (cCK18), 20S proteasome, and tumor necrosis factor receptor 1 (TNFR-1) and explored their associations with overall-, 30-, 60-, 90-day- and in-hospital mortality. Moreover, we investigated their association with the risk of ventilation. We demonstrated that increased serum sST2 was uni- and multivariably associated with all endpoints. However, we also identified 20S proteasome as independent prognostic factor for in-hospital mortality. Furthermore, elevated HSP27, sST2, and 20S proteasome levels at hospital admission were univariably associated with higher risk of invasive ventilation. These findings could help to identify high-risk patients early in the course of COVID-19.

Keywords

COVID-19; HSP27; sST2; ARDS; biomarker

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