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

SIMPLE SUMMARY: Since the outbreak of the Coronavirus Disease (COVID-19) disease in 2019 immunological research is continuing to debunk contingent pathomechanistic interpretations. Currently the COVID-2019 infection is described in humans as a state of hyperinflammation. As the COVID-2019 pandemic continued we collected serum (first blood draw) from patients that were admitted to the hospital (2020/21). Here we show that proteins that indicate “immune decay” (heat shock protein 27 and 20S proteasome) and immune suppressive soluble suppression of tumorigenicity 2 (sST2) were massively increased in those COVID-19 patients. In addition, we demonstrated that those proteins were associated with mortality, invasive ventilation, and oxygen support. Facit: Our results indicate that COVID-19 disease can also be construed as disease that causes an immunological disintegration. Historically it is notable to report that sepsis pathophysiology underwent a similar metamorphosis. Until 2003 the clinical picture of sepsis was seen as a consequence of a hyperactive immune system. This scientific interpretation tottered, and clinical research has evidenced that septic patients are in a state of immunologic default. Based on our serological data we believe that the concept of “COVID-19 induced hyperinflammation” is ready to undergo a critical appraisal and calls for cytoprotective therapeutic interventions. 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 those elevated inflammatory molecules 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) and 20S proteasome at hospital admission 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. Furthermore, we also identified 20S proteasome as independent prognostic factor for in-hospital mortality (sST2, AUC = 0.73; HSP27, AUC = 0.59; 20S proteasome = 0.67). Elevated sST2, HSP27, and 20S proteasome levels at hospital admission were univariably associated with higher risk of invasive ventilation (OR = 1.8; p < 0.001; OR = 1.1; p = 0.04; OR = 1.03, p = 0.03, respectively). These findings could help to identify high-risk patients early in the course of COVID-19.