TY - JOUR
T1 - Strem-1 predicts disease severity and mortality in covid-19 patients
T2 - Involvement of peripheral blood leukocytes and mmp-8 activity
AU - da Silva-Neto, Pedro V.
AU - de Carvalho, Jonatan C.S.
AU - Pimentel, Vinícius E.
AU - Pérez, Malena M.
AU - Toro, Diana M.
AU - Fraga-Silva, Thais F.C.
AU - Fuzo, Carlos A.
AU - Oliveira, Camilla N.S.
AU - Rodrigues, Lilian C.
AU - Argolo, Jamille G.M.
AU - Carmona-Garcia, Ingryd
AU - Neto, Nicola T.
AU - Souza, Camila O.S.
AU - Fernandes, Talita M.
AU - Bastos, Victor A.F.
AU - Degiovani, Augusto M.
AU - Constant, Leticia F.
AU - Ostini, Fátima M.
AU - Feitosa, Marley R.
AU - Parra, Rogerio S.
AU - Vilar, Fernando C.
AU - Gaspar, Gilberto G.
AU - da Rocha, José J.R.
AU - Feres, Omar
AU - Frantz, Fabiani G.
AU - Gerlach, Raquel F.
AU - Maruyama, Sandra R.
AU - Russo, Elisa M.S.
AU - Viana, Angelina L.
AU - Fernandes, Ana P.M.
AU - Santos, Isabel K.F.M.
AU - Bonato, Vânia L.D.
AU - Boechat, Antonio L.
AU - Malheiro, Adriana
AU - Sadikot, Ruxana T.
AU - Dias-Baruffi, Marcelo
AU - Cardoso, Cristina R.B.
AU - Faccioli, Lúcia H.
AU - Sorgi, Carlos A.
N1 - Funding Information:
Acknowledgments: The authors acknowledge the support of the ICU team of doctors, nurses, physiotherapists, and the collaboration of Hospital Santa Casa de Misericórdia of Ribeirão Preto and Hospital São Paulo of Ribeirão Preto; the laboratory support from Supera Parque-Innovation and Technology Park-Ribeirão Preto/SP for testing infection by SARS-CoV-2 in healthy volunteers; and the valuable contribution by Municipal Health Department of Ribeirão Preto city and Analysis Service Clinics (SAC) from Faculdade de Ciências Farmacêuticas de Ribeirão Preto–USP. We are grateful to Fabiana R. de Moraes for helping with flow cytometer analysis; and Professors Victor Hugo Aquino Quintana, Márcia Regina von Zeska Kress, and Marcia Eliana da Silva Ferreira for sharing the viral BS-2 lab.
Funding Information:
This work was supported by Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo? FAPESP (grants #2020/05207-6, #2014/07125-6, and #2015/00658-1 for L.H.F., #2020/08534-8 for M.M.P.; grant #2020/05270-0 for V.L.D.B and grant #2021/04590-3 for C.A.S.). Additional support was provided by the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Educational Personnel (CAPES-Finance Code 001)), Funda??o de apoio ? Universidade de S?o Paulo?FUSP by USP VIDA program, Funda??o de Amparo ? Pesquisa do Estado do Amazonas-FAPEAM for A.M, A.L.B, D.M.T and C.A.S, and from Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico CNPq grant numbers: (CNPq grants 312606/2019-2 for M.D.B, 303259/2020-5 for L.H.F., and #309583/2019-5 for C.R.B.C.). R.T.S is funded by NIH (R01 HL144478) and the Department of Veterans Affairs (101 BX001786) and Funda??o de Amparo ? Pesquisa do Estado do Amazonas (FAPEAM) POSGRAD (Resolution 006/2020).
Funding Information:
Funding: This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo– FAPESP (grants #2020/05207-6, #2014/07125-6, and #2015/00658-1 for L.H.F., #2020/08534-8 for M.M.P.; grant #2020/05270-0 for V.L.D.B and grant #2021/04590-3 for C.A.S.). Additional support was provided by the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Educational Personnel (CAPES-Finance Code 001)), Fundação de apoio à Universidade de São Paulo–FUSP by USP VIDA program, Fundação de Amparo à Pesquisa do Estado do Amazonas-FAPEAM for A.M, A.L.B, D.M.T and C.A.S, and from Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq grant numbers: (CNPq grants 312606/2019-2 for M.D.B, 303259/2020-5 for L.H.F., and #309583/2019-5 for C.R.B.C.). R.T.S is funded by NIH (R01 HL144478) and the Department of Veterans Affairs (101 BX001786) and Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM) POSGRAD (Resolution 006/2020).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12
Y1 - 2021/12
N2 - Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.
AB - Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.
KW - Biomarker
KW - COVID-19
KW - Inflammation
KW - MMP-8
KW - STREM-1
UR - http://www.scopus.com/inward/record.url?scp=85121435253&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121435253&partnerID=8YFLogxK
U2 - 10.3390/v13122521
DO - 10.3390/v13122521
M3 - Article
C2 - 34960790
AN - SCOPUS:85121435253
SN - 1999-4915
VL - 13
JO - Viruses
JF - Viruses
IS - 12
M1 - 2521
ER -