Association Between COVID-19 Infection and Pulmonary Fibrosis: A Nested Case-Control Study

Abstract

Background: Pulmonary fibrosis is associated with significant morbidity. Data are scarce on the link between coronavirus disease (COVID-19) and pulmonary fibrosis. We aimed to assess the association between COVID-19 with pulmonary fibrosis. Methods: We conducted a nested case-control study in a cohort of 2,894,801 adults without a diagnosis of pulmonary fibrosis. The underlying cohort consisted of members of the largest healthcare provider in Israel aged 18 years or older as of May 1, 2020. Subjects were followed up from cohort entry until June 30, 2022, for the occurrence of pulmonary fibrosis. Ten randomly selected controls were matched to each case of pulmonary fibrosis on age, sex, and calendar time. To account for surveillance bias a lag time of 60 days was used for ascertainment of prior COVID-19 and COVID-19 severity. Results: During follow-up 1284 patients were newly diagnosed with pulmonary fibrosis and matched with 12,840 controls. Multivariable conditional logistic-regression models showed that the odds ratio for pulmonary fibrosis was 1.80 (95% confidence interval, 1.47-2.19) in patients with COVID-19 compared with no COVID-19. The multivariable odds ratio for pulmonary fibrosis was 1.33 (1.06-1.68), 2.98 (1.16-7.65), and 9.30 (5.77-14.98) for mild, moderate, and severe COVID-19, respectively, compared with no COVID-19. The magnitude of the association was attenuated but remained statistically significant for severe disease when the lag time was extended to 180 days (1.08 [0.78-1.49], 2.37 [0.75-7.46], and 5.34 [2.75-10.36] for mild, moderate, and severe COVID-19, respectively). Conclusions: COVID-19 appears to be associated with an increased risk of pulmonary fibrosis and the magnitude of the association increases with COVID-19 severity.