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Soluble CD137 as a potential biomarker for severe COVID-19
Mariana de Oliveira Marques1, André Abdo2, Priscilla Brito Silva3
1Hospital Alemão Oswaldo Cruz, João Julião 331, São Paulo, Brasil; Clinical and Experimental Oncology Department. Universidade Federal de São Paulo. Diogo de Faria 824, São Paulo, Brasil.
Insights
Researchers identified soluble CD137 (sCD137) as a potential biomarker for severe COVID-19. Increased sCD137 levels in critically ill patients correlated with a higher risk of mechanical ventilation and worse disease severity.
Area of Science:
- Immunology
- Virology
- Critical Care Medicine
Background:
- Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, led to a global pandemic with a high burden on healthcare systems.
- Identifying biomarkers for COVID-19 severity is crucial for managing critically ill patients and preventing healthcare system collapse.
Purpose of the Study:
- To evaluate the profile of cytokines, cytokine receptors, and growth factors in severe COVID-19 patients.
- To identify potential biomarkers and therapeutic targets for severe COVID-19.
Main Methods:
- Prospective study of 62 adult severe COVID-19 patients admitted to the ICU in São Paulo, Brazil.
- Whole blood analysis of 17 cytokines, cytokine receptors, and growth factors.
- Mechanical ventilation need used as the primary endpoint due to low mortality.
Main Results:
- A distinct pattern of soluble CD137 (sCD137) was observed in critically ill COVID-19 patients.
- Increased sCD137 levels directly correlated with a worse clinical outcome.
- Higher sCD137 levels were associated with an increased risk of mechanical ventilation and higher WHO clinical scores.
Conclusions:
- Soluble CD137 (sCD137) shows potential as a reliable biomarker for COVID-19 severity.
- The study suggests sCD137 as a potential therapeutic target for severe SARS-CoV-2 infection.
Abstract:
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly pathogenic infection responsible for the world pandemic in 2020. COVID-19 is characterized by an increased number of critically ill patients with a high risk of health care system collapse. Therefore, the search for severity biomarkers and potential therapies is crucial. In this study, we evaluated SARS-CoV-2 -induced cytokines, cytokines receptors and growth factors profile, in critical COVID-19 patients admitted in intensive care unit (ICU) aiming to identify potential biomarkers and therapeutic targets. We designed a prospective study enrolling 62 adults with severe COVID-19 during the first two Brazilian COVID-19 waves (from May to July 2020 and December 2020 to May 2021), convenience samples recruitment in first 24 hours and then, every 4 days until day 20 of ICU admission from a tertiary hospital in São Paulo, Brazil. Controls were healthy blood donors. Whole blood was used to evaluate 17 cytokines, cytokines receptors and growth factors. Due to low mortality rate, we used the need of mechanical ventilation as primary endpoint. In our analysis, we found a different pattern in soluble CD137 (sCD137) in critically ill patients with COVID-19, with a direct relationship between increased levels and worse clinical outcome. sCD137 was related with increased risk of mechanical ventilation and World Health Organization (WHO) clinical score for disease severity. CD137 is a tumor necrosis factor receptor (TNF) family member, mainly responsible for T-cell activation. Soluble isoforms of immune checkpoints competitively regulate function of their membrane-bound counterparts. Our study demonstrated the onward increase in sCD137 levels during severe SARS-CoV-2 infection and its correlation with worse outcomes, suggesting sCD137 as a potential reliable severity biomarker.
