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Infect Dis (Lond) . Markers of cellular senescence is associated with persistent pulmonary pathology after COVID-19 infection

tetano

Editor, Senior Moderator
Infect Dis (Lond)


. 2022 Aug 19;1-6.
doi: 10.1080/23744235.2022.2113135. Online ahead of print.
Markers of cellular senescence is associated with persistent pulmonary pathology after COVID-19 infection


Tove Lekva[SUP] 1 [/SUP], Thor Ueland[SUP] 1 2 3 [/SUP], Bente Halvorsen[SUP] 1 2 [/SUP], Sarah Louise Murphy[SUP] 1 2 [/SUP], Anne Ma Dyrhol-Riise[SUP] 2 4 [/SUP], Anders Tveita[SUP] 2 5 [/SUP], Ane-Kristine Finbråten[SUP] 6 [/SUP], Alexander Mathiessen[SUP] 7 [/SUP], Karl Erik Müller[SUP] 8 [/SUP], Trond Mogens Aaløkken[SUP] 2 9 [/SUP], Ole Henning Skjønsberg[SUP] 2 10 [/SUP], Tøri Vigeland Lerum[SUP] 2 10 [/SUP], Pål Aukrust[SUP] 1 2 3 11 [/SUP], Tuva Børresdatter Dahl[SUP] 1 12 [/SUP]



Affiliations

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.

Keywords: CHIT1; COVID-19; STMN1; senescence.




Tove Lekva[SUP] 1 [/SUP], Thor Ueland[SUP] 1 2 3 [/SUP], Bente Halvorsen[SUP] 1 2 [/SUP], Sarah Louise Murphy[SUP] 1 2 [/SUP], Anne Ma Dyrhol-Riise[SUP] 2 4 [/SUP], Anders Tveita[SUP] 2 5 [/SUP], Ane-Kristine Finbråten[SUP] 6 [/SUP], Alexander Mathiessen[SUP] 7 [/SUP], Karl Erik Müller[SUP] 8 [/SUP], Trond Mogens Aaløkken[SUP] 2 9 [/SUP], Ole Henning Skjønsberg[SUP] 2 10 [/SUP], Tøri Vigeland Lerum[SUP] 2 10 [/SUP], Pål Aukrust[SUP] 1 2 3 11 [/SUP], Tuva Børresdatter Dahl[SUP] 1 12 [/SUP]



Affiliations

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.

Keywords: CHIT1; COVID-19; STMN1; senescence.
 
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