Incidence of new-onset pulmonary fibrosis 4.5 years post SARS-CoV-2 infection in an academic urban medical center

Abstract

The long-term risk of clinical new-onset pulmonary fibrosis (PF) and its various downstream impacts following SARS-CoV-2 infection remain incompletely characterized in existing literature. A retrospective cohort was analyzed using Montefiore Health System electronic health record data over 4.5 years (March 2020—August 2024). Hospitalized and non-hospitalized COVID-19 patients without prior PF diagnosis were matched 1:2 to COVID-19 negative controls. New-onset PF and subsequent downstream impacts were identified by diagnostic ICD-10 codes. Covariate balance was assessed and Fine-Gray subdistribution hazard ratio (sHR) models were used to estimate PF risk and logistic and Poisson regression models were used to assess post-PF secondary outcomes. Sensitivity analyses included multivariable cause-specific Cox proportional-hazard models, inverse probability weighting and analyses using a pre-pandemic historical control. After propensity score matching, both hospitalized COVID-19 patients (sHR = 2.05; 95% CI [1.69–2.4]) and non-hospitalized COVID-19 patients (sHR = 2.33; 95% CI [1.88–2.88]) demonstrated significantly increased risk of PF when compared to COVID-19 negative controls over up to 4.5-year follow-up period. In patients with new-onset PF, prior hospitalization with COVID-19 has associated with higher odds of pneumonia (OR = 4.84 [3.50–6.67]), bronchiolitis (OR = 3.45 [1.12–8.81]), respiratory failure (OR = 3.76 [2.72–5.16]), asthma exacerbation (OR = 2.54 [1.36–4.46]) and COPD exacerbation (OR = 2.91 [1.80–4.58]), whereas non-hospitalized COVID-19 patients exhibited increased odds of pneumonia (OR = 1.98 [1.25–3.06]) and asthma exacerbation (OR = 2.06[1.00–3.86]). Similarly, hospitalized COVID-19 patients showed increased risk of PH (RR = 1.66[1.01–2.71]) and non-hospitalized patients showed an increased risk of PE (RR = 2.68[1.14–6.35]). In a diverse cohort with up to 4.5 years follow-up, we found both hospitalized and non-hospitalized COVID-19 patients have a higher long-term risk of new-onset PF and higher burden of subsequent downstream respiratory complications compared to matched non-COVID-19 controls. These findings demonstrate post-COVID-19 PF as a relevant and clinically significant outcome and suggest the need for long-term surveillance, risk stratification, and targeted intervention.