Lung Fibrosis Four Months After COVID-19 Is Associated with Severity of Illness, Duration of Mechanical Ventilation and Blood Leukocyte Telomere Length

Rationale: Over 60 million people have had coronavirus disease 2019 (COVID-19), but consequences of severe infection are unknown. We sought to characterize interstitial lung abnormalities (ILA) after COVID-19, and to identify risk factors for the development of lung fibrosis.Methods: We performed a prospective single-center cohort study with 4-month follow-up after COVID-19 hospitalization. We sequentially enrolled 76 community-dwelling adults who were hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and required supplemental oxygen between March and May 2020. Participants had no prior history of interstitial lung disease and were discharged to acute rehabilitation or home, with sampling weighted to include half who were mechanically ventilated. We used a radiologic scoring system to quantify non-fibrotic ILA (ground glass opacities alone) and fibrotic ILA (defined as presence of reticulations, traction bronchiectasis, or honeycombing) on chest high-resolution computed tomography scans four months after hospital admission. We assessed measures of severity of illness during hospitalization, as well as pulmonary function and leukocyte telomere length at followup. Results: Participants had a mean age of 54 (SD14) years;most were male (61%) and Hispanic (57%). Thirty-two (43%) required mechanical ventilation. After a median (IQR) of 4.4 (4.0-4.8) months following hospital admission, the most common ILAs were ground glass opacities, reticulations, and traction bronchiectasis, which correlated with lower diffusion capacity (ρ -0.34, - 0.64, and -0.49, respectively, all p<0.01). A total of 31 participants (41%) had no ILA, 13 (17%) had only non-fibrotic ILA, and 32 (42%) had fibrotic ILA. Fibrotic ILA was more common in mechanically ventilated patients (72%) than non-mechanically ventilated patients (20%), (p=0.001). In adjusted analyses, each 1 point increase in admission SOFA score, additional day of ventilator support, and 10% decrease in blood leukocyte telomere length were associated with fibrotic ILA [OR 1.49 (95%CI 1.17 - 1.89), 1.07 (95%CI 1.03-1.12), and 1.35 (95%CI 1.06 - 1.72), respectively].Conclusions: Radiographic evidence of lung fibrosis four months after severe COVID-19 infection is associated with initial severity of illness, duration of mechanical ventilation, and telomere length.