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 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-severity. RESULTS During follow-up 1,284 patients were newly diagnosed with pulmonary fibrosis and matched with 12,840 controls. Multivariable conditional logistic-regression models showed that the OR for pulmonary fibrosis was 1.80 (95% CI, 1.47-2.19) in patients with COVID-19 compared to no COVID-19. The multivariable OR 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 to 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.