Platelet-derived mediators in hospitalized COVID-19 patients and associations to respiratory failure, ICU admittance and 60-day mortality

Kari Otterdal; Thor Ueland; Jan Cato Holter; Mari Kaarbø; Ylva Schanke; Beathe Kiland Granerud; Tuva B Dahl; Anders Tveita; Anders Benjamin Kildal; Lars Heggelund; Anne Hege Aamodt; Aleksander Rygh Holten; Kristian Tonby; Pål Aukrust; Anne Ma Dyrhol-Riise; Bente Halvorsen; Annika E Michelsen

doi:10.3389/fcvm.2026.1685861

Platelet-derived mediators in hospitalized COVID-19 patients and associations to respiratory failure, ICU admittance and 60-day mortality

Front Cardiovasc Med. 2026 Feb 25:13:1685861. doi: 10.3389/fcvm.2026.1685861. eCollection 2026.

Authors

Kari Otterdal¹, Thor Ueland^{1

2

3}, Jan Cato Holter^{2

4}, Mari Kaarbø⁴, Ylva Schanke¹, Beathe Kiland Granerud^{2

4}, Tuva B Dahl¹, Anders Tveita^{5

6}, Anders Benjamin Kildal^{7

8}, Lars Heggelund^{9

10}, Anne Hege Aamodt^{11

12

13}, Aleksander Rygh Holten^{2

14}, Kristian Tonby^{2

15}, Pål Aukrust^{1

2}, Anne Ma Dyrhol-Riise^{2

15}, Bente Halvorsen^{1

2}, Annika E Michelsen^{1

2}

Affiliations

¹ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
² Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
⁴ Department of Microbiology, Oslo University Hospital, Oslo, Norway.
⁵ Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway.
⁶ Department of Internal Medicine, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway.
⁷ Department of Anesthesiology and Intensive Care, University Hospital of North Norway, Tromsø, Norway.
⁸ Department of Clinical Medicine, Faculty of Health Science, UIT-The Arctic University of Norway, Tromsø, Norway.
⁹ Department of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway.
¹⁰ Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.
¹¹ Department of Neurology, Oslo University Hospital, Oslo, Norway.
¹² Department of Neuromedicine and Movement Science, the Norwegian University of Science and Technology, Trondheim, Norway.
¹³ Institute of Population Health, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom.
¹⁴ Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.
¹⁵ Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.

Abstract

Background: Platelet activation is documented in COVID-19, but data on platelet-derived mediators are scarce.

Objective: To examine the levels of various platelet-derived mediators in relation to adverse outcomes defined as the need for treatment at intensive care unit (ICU) and/or respiratory failure (RF) and 60-day total mortality in hospitalized COVID-19 patients.

Methods: Plasma levels of RANTES/CCL5, PF4/CXCL4, ENA78/CXCL5, NAP-2/CXCL7, SDF-1/CXCL12, P-selectin, soluble CD40 ligand (sCD40L) and vascular endothelial cell growth factor A (VEGF-A) were measured in 245 hospitalized COVID-19 patients and in a subpopulation of the patients, also at three, six and 12 months after hospitalization.

Results: Our main findings were: (i) High levels of P-selectin was associated with ICU/RF, while low levels of PF4/CXCL4, ENA-78/CXCL5 and NAP-2/CXCL7 were associated with 60-days mortality. (ii) Most of the mediators were normalized after hospitalization, but plasma levels of sCD40L, ENA-78/CXCL7 and VEGF-A were markedly elevated compared to healthy controls for up to 12 months after hospitalization. (iii) In vitro, inactivated SARS-CoV-2 induced a dose-dependent release of NAP-2, P-selectin, RANTES, sCD40L and VEGF-A from isolated platelets.

Conclusion: Our findings underscore the role of platelet-derived inflammatory mediators in the pathogenesis of COVID-19, potentially involving direct effects of SARS-CoV-2. The study also points to a persistent platelet activation following hospitalization.

Keywords: COVID-19; SARS-CoV-2; inflammation; platelets; thrombosis.