Sustained mTOR inhibition with sirolimus improves respiratory outcomes in LAM patients with COVID-19

Abstract Background Lymphangioleiomyomatosis (LAM) is a rare lung disease that predominantly affects women and can lead to severe respiratory complications. The impact of COVID-19 on LAM patients, particularly regarding the use of mammalian target of rapamycin (mTOR) inhibitors, remains poorly understood. This study investigates the clinical outcomes of LAM patients with COVID-19 and evaluates the role of sustained mTOR inhibition in respiratory outcomes. Results Our cohort included 186 LAM patients with COVID-19. Prior to infection, 72.6% were on mTOR inhibitors, with 29.6% discontinuing therapy due to infection. The hospitalization rate was 1.1%, with no reported need for invasive ventilation or fatalities. Patients with FEV1 less than 70% predicted had a higher risk of dyspnea exacerbation and supplemental oxygen requirement. Continuation of mTOR inhibitor therapy was associated with a lower risk of SpO₂ decline, especially among patients with impaired lung function. Vaccination status did not significantly affect the prognosis. Conclusions LAM patients with COVID-19 showed a low rate of severe illness and mortality, with impaired lung function correlating with worse respiratory outcomes. Continued mTOR inhibitor therapy during COVID-19 infection may improve respiratory outcomes, suggesting the importance of maintaining treatment during viral pandemics.