Respiratory Research (Feb 2023)
Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia
- Laura M. Palma Medina,
- Haris Babačić,
- Majda Dzidic,
- Åsa Parke,
- Marina Garcia,
- Kimia T. Maleki,
- Christian Unge,
- Magda Lourda,
- Egle Kvedaraite,
- Puran Chen,
- Jagadeeswara Rao Muvva,
- Martin Cornillet,
- Johanna Emgård,
- Kirsten Moll,
- Karolinska K. I./K. COVID-19 Study Group,
- Jakob Michaëlsson,
- Malin Flodström-Tullberg,
- Susanna Brighenti,
- Marcus Buggert,
- Jenny Mjösberg,
- Karl-Johan Malmberg,
- Johan K. Sandberg,
- Sara Gredmark-Russ,
- Olav Rooyackers,
- Mattias Svensson,
- Benedict J. Chambers,
- Lars I. Eriksson,
- Maria Pernemalm,
- Niklas K. Björkström,
- Soo Aleman,
- Hans-Gustaf Ljunggren,
- Jonas Klingström,
- Kristoffer Strålin,
- Anna Norrby-Teglund
Affiliations
- Laura M. Palma Medina
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Haris Babačić
- Science for Life Laboratory, Department of Oncology and Pathology, Karolinska Institute
- Majda Dzidic
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Åsa Parke
- Department of Medicine Huddinge, Karolinska Institute
- Marina Garcia
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Kimia T. Maleki
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Christian Unge
- Department of Medicine Huddinge, Karolinska Institute
- Magda Lourda
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Egle Kvedaraite
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Puran Chen
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Jagadeeswara Rao Muvva
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Martin Cornillet
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Johanna Emgård
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Kirsten Moll
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Karolinska K. I./K. COVID-19 Study Group
- Jakob Michaëlsson
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Malin Flodström-Tullberg
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Susanna Brighenti
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Marcus Buggert
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Jenny Mjösberg
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Karl-Johan Malmberg
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Johan K. Sandberg
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Sara Gredmark-Russ
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Olav Rooyackers
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital
- Mattias Svensson
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Benedict J. Chambers
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Lars I. Eriksson
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital
- Maria Pernemalm
- Science for Life Laboratory, Department of Oncology and Pathology, Karolinska Institute
- Niklas K. Björkström
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Soo Aleman
- Department of Medicine Huddinge, Karolinska Institute
- Hans-Gustaf Ljunggren
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Jonas Klingström
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Kristoffer Strålin
- Department of Medicine Huddinge, Karolinska Institute
- Anna Norrby-Teglund
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- DOI
- https://doi.org/10.1186/s12931-023-02364-y
- Journal volume & issue
-
Vol. 24,
no. 1
pp. 1 – 19
Abstract
Abstract Background COVID-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. Methods We 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. Results We 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. Conclusions This 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.
Keywords