Soluble CD137 as a potential biomarker for severe COVID-19

Mariana de Oliveira Marques; André Abdo; Priscilla Brito Silva; Amilton Silva Junior; Lucas Bassolli de Oliveira Alves; José Victor Gomes Costa; Josiane Martin; Philip Bachour; Otavio C G Baiocchi

doi:10.1016/j.imlet.2022.07.003

Soluble CD137 as a potential biomarker for severe COVID-19

Immunol Lett. 2022 Jul 8:248:119-122. doi: 10.1016/j.imlet.2022.07.003. Online ahead of print.

Authors

Mariana de Oliveira Marques¹, André Abdo², Priscilla Brito Silva³, Amilton Silva Junior², Lucas Bassolli de Oliveira Alves², José Victor Gomes Costa², Josiane Martin², Philip Bachour², Otavio C G Baiocchi⁴

Affiliations

¹ Hospital 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.
² Hospital Alemão Oswaldo Cruz, João Julião 331, São Paulo, Brasil.
³ Clinical and Experimental Oncology Department. Universidade Federal de São Paulo. Diogo de Faria 824, São Paulo, Brasil.
⁴ Hospital 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. Electronic address: baiocchi@unifesp.br.

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.

Keywords: COVID-19; Cytokines; Soluble CD137; Soluble immune checkpoints.