Sustained mTOR inhibition with sirolimus improves respiratory outcomes in LAM patients with COVID-19: a single-center retrospective study

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 mechanistic target of rapamycin (mTOR) inhibitors, remains poorly understood. This study investigated the clinical outcomes of LAM patients with COVID-19 and evaluated the effect of sustained mTOR inhibition on respiratory outcomes. Results Our cohort included 186 LAM patients with COVID-19. Prior to infection, 72.6% of the patients were on sirolimus, 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 a FEV1 less than 70% predicted had a greater risk of dyspnea exacerbation and supplemental oxygen requirement. The continuation of mTOR inhibitor therapy was associated with a lower risk of decreased SpO2 levels. Multivariate logistic regression analysis including age, baseline FEV1%, baseline DLCO%, baseline SpO2, vaccination status, and mTOR inhibitor discontinuation revealed that only the discontinuation of mTOR inhibitors was an independent predictor of decreased SpO2 levels in this patient cohort (OR: 5.000, 95% CI: 1.830–14.81, P = 0.002). Conclusions LAM patients with COVID-19 had a low rate of severe illness and mortality. Continued mTOR inhibitor therapy during COVID-19 infection may improve respiratory outcomes, suggesting the importance of maintaining treatment of mTOR inhibitors during COVID-19 infection.