Tuberous sclerosis complex (TSC), lymphangioleiomyomatosis, and COVID‐19: The experience of a TSC clinic in Italy

Abstract

Individuals with comorbidities are at higher risk of coronavirus disease 2019 (COVID-19) and worse outcome, but little information has been available about patients with genetic diseases and COVID-19. This study aims at evaluating the presence and outcome of COVID-19 in a cohort of Italian patients with tuberous sclerosis complex (TSC) and/or lymphangioleiomyomatosis (LAM), and at reviewing the possible effects of mTOR inhibitors on SARS-CoV-2 infection. We included 102 unselected individuals with a diagnosis of TSC and/or LAM assessed between January 1, 2020 and April 24, 2020 (29% children, 71% adults). Twenty-six patients were on mTOR inhibitors. Demographic data, TSC manifestations, presence, and outcomes in individuals with confirmed or suspected SARS-CoV-2 infection were evaluated. Health status and outcomes of all patients on mTOR inhibitors were assessed. One patient with severe TSC had polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection, was admitted to ICU, and died. Nine additional patients either met the definition of suspect case or presented with at least two of the most common symptoms of SARS-CoV-2 infection. All recovered fully. None of the patients treated with mTOR inhibitors for their underlying comorbidities was diagnosed with COVID-19, and those who showed suspicious respiratory symptoms recovered fully. This cohort study provides preliminary information on COVID-19 in people with TSC in Italy and suggests feasibility to systematically evaluate the role of mTOR inhibitors in SARS-CoV-2 infection.

COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

“… 130 In agreement with this hypothesis, hospitalized patients with critical COVID-19 treated with NAC showed significant clinical improvement and reduction of inflammation markers, suggesting a beneficial effect of NAC in COVID-19, possibly mediated by mTOR inhibition. 131 Limited observational studies of patients with tuberous sclerosis complex (TSC) and/or lymphangioleiomyomatosis (LAM) on long-term mTOR inhibitors (sirolimus or everolimus) have not identified an increased risk of COVID-19 or poor outcomes of the infection 132 , 133 and clinical trials of mTOR inhibitors in COVID-19 are ongoing. However, whether activation of the mTOR pathway plays a role in SARS-CoV-2-infected patients with SLE remains to be elucidated.…”

Recommended measures for the efficient care of patients with genetic disorders during the COVID‐19 pandemic in low and middle income countries

“…Similarly, some patients could have been asymptomatic at the time of the study but were unaccounted for due to limited RT-PCR testing. As such, these patients may still have a higher risk of COVID-19 infection (Peron et al, 2020). (Ramos, Pilewski, Faro, & Marshall, 2020).…”

COVID‐19 and lymphangioleiomyomatosis: Experience at a reference center and the potential impact of the use of mTOR inhibitors

“…We read with great interest the article entitled "Tuberous sclerosis complex (TSC), lymphangioleiomyomatosis, and COVID-19: The experience of a TSC clinic in Italy" by Peron et al (2020), which described the features and outcomes of coronavirus in patients with tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) in Italy, and the potential role of mTOR inhibitors in such infection. Here, we present our experience of patients with LAM and COVID-19, with an emphasis on the potential influence of the use of mTOR inhibitors.…”

“…investigate the occurrence of COVID-19 specifically in a sample of patients with LAM. Peron et al suggested that TSC and LAM patients do not have an increased risk of developing COVID-19 and discussed the potential risks and benefits of maintaining the use of mTOR inhibitors regarding such infection(Peron et al, 2020). A relevant limitation raised by the authors was the lack of confirmation of the COVID-19 diagnosis by PCR in most of the patients(Peron et al, 2020).…”

“…Peron et al suggested that TSC and LAM patients do not have an increased risk of developing COVID-19 and discussed the potential risks and benefits of maintaining the use of mTOR inhibitors regarding such infection(Peron et al, 2020). A relevant limitation raised by the authors was the lack of confirmation of the COVID-19 diagnosis by PCR in most of the patients(Peron et al, 2020). Recent studies speculate that mTOR inhibitors may have a potential benefit in reducing the viral replication, inflammatory response, and severity associated with COVID-19 beyond their immunosuppressant action(Terrazzano et al, 2020;Zheng, Li, & Liu, 2020).…”