Risk of interstitial lung disease in COVID-19 patients with autoimmune diseases treated with antiviral agents: a retrospective cohort study

BackgroundThe safety of Paxlovid and Molnupiravir in COVID-19 patients with autoimmune diseases remains unclear, particularly concerning the risk of interstitial lung disease (ILD). ObjectiveTo evaluate the risk of developing ILD among COVID-19 patients with autoimmune diseases treated with Paxlovid or Molnupiravir. DesignRetrospective cohort study. SettingData were Based on data from the US Collaborative Network in TriNetX Patients: 18,384 COVID-19 patients with pre-existing autoimmune diseases. InterventionsTreatment with Paxlovid or Molnupiravir within five days of COVID-19 diagnosis. MeasurementsILD diagnosis confirmed by ICD-10-CM codes and radiographic evidence. ResultsILD occurred in 54 patients in the Paxlovid group and 79 patients in the Molnupiravir group (HR: 0.73, 95% CI: 0.52-1.03), indicating no statistically significant difference. Subgroup analyses by age, sex, and race showed consistent results. LimitationsObservational design limits causal inference; potential residual confounding. ConclusionTreatment with Paxlovid or Molnupiravir does not significantly increase ILD risk in COVID-19 patients with autoimmune diseases. Primary Funding SourceChung Shan Medical University Hospital. RegistrationNot applicable. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIThe safety of COVID-19 antiviral treatments, particularly nirmatrelvir-ritonavir (Paxlovid) and Molnupiravir, in patients with autoimmune diseases has been poorly understood. Patients with autoimmune conditions are considered high-risk due to compromised immune systems and potential susceptibility to complications like interstitial lung disease (interstitial lung disease). C_LIO_LIPrevious studies have generally excluded or underrepresented patients with autoimmune diseases, creating a significant knowledge gap regarding the safety of these treatments for this vulnerable population. C_LI What this study addsO_LIThis study provides evidence that there is no statistically significant difference in the risk of developing interstitial lung disease between COVID-19 patients with autoimmune diseases treated with nirmatrelvir-ritonavir or Molnupiravir. C_LIO_LIIt reinforces that both antiviral treatments can be used safely regarding the risk of interstitial lung disease in patients with pre-existing autoimmune conditions, addressing an important gap in the literature. C_LI How this study might affect research, practice, or policyO_LIThe findings could influence clinical guidelines and policy decisions regarding the management of COVID-19 in patients with autoimmune diseases, suggesting that healthcare providers can use either nirmatrelvir-ritonavir or Molnupiravir without an increased risk of interstitial lung disease. C_LIO_LIThis study might prompt further research into the long-term effects of COVID-19 treatments on different subpopulations, particularly those with chronic underlying conditions. C_LIO_LIPolicymakers might consider these results when developing targeted recommendations for COVID-19 treatment in populations at increased risk for severe outcomes. C_LI