Longer ICU stay and invasive mechanical ventilation accelerate telomere shortening in COVID-19 patients 1 year after recovery

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed.

Keywords: ARDS; COVID-19; ICU; IMV; Relative telomere length; SARS-CoV2.

Fig. 1

A Evolution of relative telomere length (RTL) in COVID-19 patients, stratified by length of stay (LOS) in the intensive care unit (ICU), need for invasive mechanical ventilation (IMV), and need for prone position, from baseline to one-year visit (12 months since hospital discharged). B Differences in RTL, one-year visit, in COVID-19 patients who required IMV and had X-ray images, comparing patients without radiological alterations and with fibrosis. Statistics: Data represent the crude means and 95% confidence interval for each group of patients. P-values were calculated using the Mann–Whitney test for transversal analysis and the Wilcoxon test for longitudinal analysis between paired samples. R and p-value in the scatter plot were calculated by a Spearman’s correlation. Statistical significance was determined as p ≤ 0.05. Abbreviations: RTL, Relative telomere length; ICU, Intensive care unit; IMV, Invasive mechanical ventilation