Markers of cellular senescence is associated with persistent pulmonary pathology after COVID-19 infection
Tove Lekva, Thor Ueland, Bente Halvorsen, Sarah Louise Murphy, Anne Ma Dyrhol‐Riise, Anders Tveita, Ane‐Kristine Finbråten, Alexander Mathiessen, Karl Erik Müller, Trond Mogens Aaløkken, Ole Henning Skjønsberg, Tøri Vigeland Lerum, Pål Aukrust, Tuva B. Dahl
Abstract
BACKGROUND: The lungs are the organ most likely to sustain serious injury from coronavirus disease 2019 (COVID-19). However, the mechanisms for long-term complications are not clear. Patients with severe COVID-19 have shorter telomere lengths and higher levels of cellular senescence, and we hypothesized that circulating levels of the telomere-associated senescence markers chitotriosidase, β-galactosidase, cathelicidin antimicrobial peptide and stathmin 1 (STMN1) were elevated in hospitalized COVID-19 patients compared to controls and could be associated with pulmonary sequelae following hospitalization. METHODS: Ninety-seven hospitalized patients with COVID-19 who underwent assessment for pulmonary sequelae at three-month follow-up were included in the study. β-Galactosidase and chitotriosidase were analysed by fluorescence; stathmin 1 and cathelicidin antimicrobial peptide were analysed by enzyme immuno-assay in plasma samples from the acute phase and after three-months. In addition, the classical senescence markers cyclin-dependent kinase inhibitor 1A and 2A were analysed by enzyme immuno-assay in peripheral blood mononuclear cell lysate after three months. RESULTS: We found elevated plasma levels of the senescence markers chitotriosidase and stathmin 1 in patients three months after hospitalization with COVID-19, and these markers in addition to protein levels of cyclin-dependent kinase inhibitor 2A in cell lysate, were associated with pulmonary pathology. The elevated levels of these markers seem to reflect both age-dependent (chitotriosidase) and age-independent (stathmin 1, cyclin-dependent kinase inhibitor 2A) processes. CONCLUSIONS: We suggest that accelerated ageing or senescence could be important for long-term pulmonary complications of COVID-19, and our findings may be relevant for future research exploring the pathophysiology and management of these patients.