Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia

Respiratory Research

Research

Anna Norrby-Teglund¹  Mattias Svensson¹  Martin Cornillet¹  Jakob Michaëlsson¹  Kirsten Moll¹  Majda Dzidic¹  Laura M. Palma Medina¹  Marina Garcia¹  Puran Chen¹  Johanna Emgård¹  Hans-Gustaf Ljunggren¹  Malin Flodström-Tullberg¹  Jonas Klingström¹  Susanna Brighenti¹  Jenny Mjösberg¹  Kimia T. Maleki¹  Benedict J. Chambers¹  Jagadeeswara Rao Muvva¹  Marcus Buggert¹  Karl-Johan Malmberg¹  Johan K. Sandberg¹  Niklas K. Björkström¹  Magda Lourda²  Egle Kvedaraite³  Sara Gredmark-Russ⁴  Åsa Parke⁵  Soo Aleman⁵  Kristoffer Strålin⁵  Christian Unge⁶  Lars I. Eriksson⁷  Olav Rooyackers⁸  Haris Babačić⁹  Maria Pernemalm⁹ 

[1] Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Alfred Nobels Allé 8, 141 52, Stockholm, Sweden;Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Alfred Nobels Allé 8, 141 52, Stockholm, Sweden;Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden;Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Alfred Nobels Allé 8, 141 52, Stockholm, Sweden;Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden;Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Alfred Nobels Allé 8, 141 52, Stockholm, Sweden;Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden;The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå, Sweden;Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden;Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden;Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden;Functional Area of Emergency Medicine, Karolinska University Hospital, Stockholm, Sweden;Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden;Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden;Division for Anesthesiology and Intensive Care, Department of Clinical Interventions and Technology CLINTEC, Karolinska Institutet, Stockholm, Sweden;Science for Life Laboratory, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden;

关键词: COVID-19;    Community acquired pneumonia;    Sepsis;    Septic shock;    Olink proximity extension assays;   

DOI  :  10.1186/s12931-023-02364-y

 received in 2022-10-28, accepted in 2023-02-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCOVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features.MethodsWe measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients.ResultsWe identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers.ConclusionsThis study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.

【 授权许可】

CC BY   
© The Author(s) 2023

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