Identification of immune markers response to SARS-CoV2 and its secondary bacterial infection
Abstract
To date, coronavirus disease 2019 (COVID-19) continues to cause havoc around the world. The serve/critically ill and secondary bacterial infections are important causes of morbidity and mortality. Although several studies highlighted the changes in the immune system of COVID-19 patients, the detailed information on the immune response in infections of different severity and secondary bacterial infections is still not well understood. In this study, 300 patients infected with a single-derived SARS-CoV-2 were recruited, and their clinical and laboratory information associated with the different severity were analyzed. Furthermore, the plasma cytokines/chemokines/growth factors associated with the different severity and secondary bacterial infections were compared to identify the response of immune markers to SARS-CoV2 and its secondary bacterial infection. The results revealed that the patients’ age, body mass index, white blood cell, lymphocyte, alanine transaminase, aspartate transaminase, and total bilirubin were associated with the severity of the disease. In addition, the high level of plasma vascular endothelial growth factor A (VEGF-A) and regulated upon activation, normal T-cell expressed and secreted (RANTES) could be used as an indicator of the disease severity for COVID-19 patients. Furthermore, we screened the low level of IP-10 associated with secondary bacterial infections. Finally, we identified the presepsin as a novel biomarker for the auxiliary diagnosis of secondary bacterial infection in the COVID-19 patients. Our findings provide important support for the classification of COVID-19 patients and a possible diagnostic path for those with a secondary bacterial infection.
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References
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17 Liu M, Guo S, Hibbert JM, et al. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine Growth Factor Rev. 2011;22(3):121-130. https://doi.org/10.1016/j.cytogfr.2011.06.001
18 Chen Y, Wang J, Liu C, et al. IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19. Mol Med. 2020;26(1):97. https://doi.org/10.1186/s10020-020-00230-x
19 Suffee N, Richard B, Hlawaty H, Oudar O, Charnaux N, Sutton A. Angiogenic properties of the chemokine RANTES/CCL5. Biochem Soc Trans. 2011;39(6):1649-1653. https://doi.org/10.1042/BST20110651
20 Wuest T, Zheng M, Efstathiou S, Halford WP, Carr DJ. The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization. PLoS Pathog. 2011;7(10):e1002278. https://doi.org/10.1371/journal.ppat.1002278
21 Singh A, Bisht P, Bhattacharya S, Guchhait P. Role of Platelet Cytokines in Dengue Virus Infection. Front Cell Infect Microbiol. 2020;10:561366. https://doi.org/10.3389/fcimb.2020.561366
22 Principi N, Esposito S. Biomarkers in Pediatric Community-Acquired Pneumonia. Int J Mol Sci. 2017;18(2):447. https://doi.org/10.3390/ijms18020447
23 Charalampous T, Kay GL, Richardson H, et al. Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection. Nat Biotechnol. 2019;37(7):783-792. https://doi.org/10.1038/s41587-019-0156-5
24 Garcin F, Leone M, Antonini F, Charvet A, Albanèse J, Martin C. Non-adherence to guidelines: an avoidable cause of failure of empirical antimicrobial therapy in the presence of difficult-to-treat bacteria. Intensive Care Med. 2010;36(1):75-82. https://doi.org/10.1007/s00134-009-1660-8
25 Stubljar D, Kopitar AN, Groselj-Grenc M, Suhadolc K, Fabjan T, Skvarc M. Diagnostic accuracy of presepsin (sCD14-ST) for prediction of bacterial infection in cerebrospinal fluid samples from children with suspected bacterial meningitis or ventriculitis. J Clin Microbiol. 2015;53(4):1239-1244. https://doi.org/10.1128/JCM.03052-14
26 Zhang X, Liu D, Liu YN, Wang R, Xie LX. The accuracy of presepsin (sCD14-ST) for the diagnosis of sepsis in adults: a meta-analysis. Crit Care. 2015;19(1):323. https://doi.org/10.1186/s13054-015-1032-4
27 Shozushima T, Takahashi G, Matsumoto N, Kojika M, Okamura Y, Endo S. Usefulness of presepsin (sCD14-ST) measurements as a marker for the diagnosis and severity of sepsis that satisfied diagnostic criteria of systemic inflammatory response syndrome. J Infect Chemother. 2011;17(6):764-769. https://doi.org/10.1007/s10156-011-0254-x
28 Gómez-Rial J, Currás-Tuala MJ, Rivero-Calle I, et al. Increased Serum Levels of sCD14 and sCD163 Indicate a Preponderant Role for Monocytes in COVID-19 Immunopathology. Front Immunol. 2020;11:560381. https://doi.org/10.3389/fimmu.2020.560381
29 L. Mabrey, E. D. Morrell et al. Plasma sCD14-ST, but Not sCD14, Is Inversely Associated with Risk for SARS-CoV2 Positivity and Positively Associated with COVID-19-Related Respiratory Failure in Critically Ill Patients Admitted Under Suspicion for COVID-19 Am J Respir Crit Care Med 2021;203:A2528. https://doi.org/10.1164/ajrccm-conference.2021.203.1_MeetingAbstracts.A2528
2 Martin-Loeches I, Guia MC, Vallecoccia MS, et al. Risk factors for mortality in elderly and very elderly critically ill patients with sepsis: a prospective, observational, multicenter cohort study Ann Intensive Care. 2019;9(1):26. https://doi.org/10.1186/s13613-019-0495-x
3 Perico L, Benigni A, Casiraghi F, Ng LFP, Renia L, Remuzzi G. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nat Rev Nephrol. 2021;17(1):46-64. https://doi.org/10.1038/s41581-020-00357-4
4 de Bruin S, Bos LD, van Roon MA, et al. Clinical features and prognostic factors in Covid-19:A prospective cohort study. EBioMedicine. 2021;67:103378. https://doi.org/10.1016/j.ebiom.2021.103378
5 Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol. 2020;11:1446. https://doi.org/10.3389/fimmu.2020.01446
6 Sinha P, Matthay MA, Calfee CS. Is a "Cytokine Storm" Relevant to COVID-19?. JAMA Intern Med. 2020;180(9):1152-1154. https://doi.org/10.1001/jamainternmed.2020.3313
7 Kitchens RL, Thompson PA. Modulatory effects of sCD14 and LBP on LPS-host cell interactions. J Endotoxin Res. 2005;11(4):225-229. https://doi.org/10.1179/096805105X46565
8 Del Valle DM, Kim-Schulze S, Huang HH, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-1643. https://doi.org/10.1038/s41591-020-1051-9
9 Rawson TM, Moore LSP, Zhu N, et al. Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing. Clin Infect Dis. 2020;71(9):2459-2468. https://doi.org/10.1093/cid/ciaa530
10 Tan W, Niu P, Zhao X, et al. Reemergent Cases of COVID-19 - Xinfadi Wholesales Market, Beijing Municipality, China, June 11, 2020. China CDC Wkly. 2020;2(27):502-504. https://doi.org/10.46234/ccdcw2020.132
11 Wang Q, Zhao X, Yue Z, et al. Increasing SARS-CoV-2 nucleic acid testing capacity during the COVID-19 epidemic in Beijing: experience from a general hospital. Emerg Microbes Infect. 2020;9(1):2358-2360. https://doi.org/10.1080/22221751.2020.1837016
12 Zhang Y, Pan Y, Zhao X, et al. Genomic characterization of SARS-CoV-2 identified in a reemerging COVID-19 outbreak in Beijing's Xinfadi market in 2020. Biosaf Health. 2020;2(4):202-205. https://doi.org/10.1016/j.bsheal.2020.08.006
13 Cai Q, Huang D, Yu H, et al. COVID-19: Abnormal liver function tests. J Hepatol. 2020;73(3):566-574. https://doi.org/10.1016/j.jhep.2020.04.006
14 Bertolini A, van de Peppel IP, Bodewes FAJA, et al. Abnormal Liver Function Tests in Patients With COVID-19: Relevance and Potential Pathogenesis. Hepatology. 2020;72(5):1864-1872. https://doi.org/10.1002/hep.31480
15 Kong Y, Han J, Wu X, Zeng H, Liu J, Zhang H. VEGF-D: a novel biomarker for detection of COVID-19 progression. Crit Care. 2020;24(1):373. https://doi.org/10.1186/s13054-020-03079-y
16 Woods SP, Babicz M, Shahani L, Colpo GD, Morgan EE, Teixeira AL. Brain-derived neurotrophic factor (BDNF) is associated with depressive symptoms in older adults with HIV disease. J Neurovirol. 2021;27(1):70-79. https://doi.org/10.1007/s13365-020-00916-2
17 Liu M, Guo S, Hibbert JM, et al. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine Growth Factor Rev. 2011;22(3):121-130. https://doi.org/10.1016/j.cytogfr.2011.06.001
18 Chen Y, Wang J, Liu C, et al. IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19. Mol Med. 2020;26(1):97. https://doi.org/10.1186/s10020-020-00230-x
19 Suffee N, Richard B, Hlawaty H, Oudar O, Charnaux N, Sutton A. Angiogenic properties of the chemokine RANTES/CCL5. Biochem Soc Trans. 2011;39(6):1649-1653. https://doi.org/10.1042/BST20110651
20 Wuest T, Zheng M, Efstathiou S, Halford WP, Carr DJ. The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization. PLoS Pathog. 2011;7(10):e1002278. https://doi.org/10.1371/journal.ppat.1002278
21 Singh A, Bisht P, Bhattacharya S, Guchhait P. Role of Platelet Cytokines in Dengue Virus Infection. Front Cell Infect Microbiol. 2020;10:561366. https://doi.org/10.3389/fcimb.2020.561366
22 Principi N, Esposito S. Biomarkers in Pediatric Community-Acquired Pneumonia. Int J Mol Sci. 2017;18(2):447. https://doi.org/10.3390/ijms18020447
23 Charalampous T, Kay GL, Richardson H, et al. Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection. Nat Biotechnol. 2019;37(7):783-792. https://doi.org/10.1038/s41587-019-0156-5
24 Garcin F, Leone M, Antonini F, Charvet A, Albanèse J, Martin C. Non-adherence to guidelines: an avoidable cause of failure of empirical antimicrobial therapy in the presence of difficult-to-treat bacteria. Intensive Care Med. 2010;36(1):75-82. https://doi.org/10.1007/s00134-009-1660-8
25 Stubljar D, Kopitar AN, Groselj-Grenc M, Suhadolc K, Fabjan T, Skvarc M. Diagnostic accuracy of presepsin (sCD14-ST) for prediction of bacterial infection in cerebrospinal fluid samples from children with suspected bacterial meningitis or ventriculitis. J Clin Microbiol. 2015;53(4):1239-1244. https://doi.org/10.1128/JCM.03052-14
26 Zhang X, Liu D, Liu YN, Wang R, Xie LX. The accuracy of presepsin (sCD14-ST) for the diagnosis of sepsis in adults: a meta-analysis. Crit Care. 2015;19(1):323. https://doi.org/10.1186/s13054-015-1032-4
27 Shozushima T, Takahashi G, Matsumoto N, Kojika M, Okamura Y, Endo S. Usefulness of presepsin (sCD14-ST) measurements as a marker for the diagnosis and severity of sepsis that satisfied diagnostic criteria of systemic inflammatory response syndrome. J Infect Chemother. 2011;17(6):764-769. https://doi.org/10.1007/s10156-011-0254-x
28 Gómez-Rial J, Currás-Tuala MJ, Rivero-Calle I, et al. Increased Serum Levels of sCD14 and sCD163 Indicate a Preponderant Role for Monocytes in COVID-19 Immunopathology. Front Immunol. 2020;11:560381. https://doi.org/10.3389/fimmu.2020.560381
29 L. Mabrey, E. D. Morrell et al. Plasma sCD14-ST, but Not sCD14, Is Inversely Associated with Risk for SARS-CoV2 Positivity and Positively Associated with COVID-19-Related Respiratory Failure in Critically Ill Patients Admitted Under Suspicion for COVID-19 Am J Respir Crit Care Med 2021;203:A2528. https://doi.org/10.1164/ajrccm-conference.2021.203.1_MeetingAbstracts.A2528
Authors
Li, A. (2022). Identification of immune markers response to SARS-CoV2 and its secondary bacterial infection. Journal of Current Medical Research and Opinion, 5(03). Retrieved from https://cmro.in/index.php/jcmro/article/view/501
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