This retrospective study explored the clinical characteristics and outcomes of LAM patients with COVID-19 during Omicron variant epidemic. We observed a low rate of severe illness and mortality in LAM patients with COVID-19. Impaired lung function was associated with adverse outcome, including exacerbated dyspnea, decreased SpO2 levels, and increased supplemental oxygen needs. Adherence to mTOR inhibitor treatment may improve respiratory outcomes, especially among patients with impaired lung function. On the other hand, vaccination status did not significantly affect the prognosis
Our study suggested that only 2 out of 186 (1.1%) patients with LAM infected with Omicron strain were hospitalized, which is much lower than previously reported 31% hospitalization rate in 2020.[3] Meanwhile, no fatalities or severe respiratory interventions were reported during the study period. However, 2 out of 20 hospitalised patients in the 2020 cohort needed mechanical ventilation and 1 death was reported. This disparity may be attributed to the potentially lower virulence of the Omicron variant compared to earlier strains. Our findings are reassuring, as they suggest that LAM patients with COVID-19 may not face a markedly increased risk of severe disease or mortality.
Our study investigated the association between impaired lung function (FEV1 less than 70% predicted) and clinical outcomes. Impaired lung function was identified as a significant risk factor for worsening dyspnea, decreased SpO2 levels, and increased need for supplementary oxygen, consistent with the broader impact of COVID-19 on individuals with pre-existing pulmonary conditions.[5] This highlights the importance of vigilant monitoring of LAM patients with compromised baseline lung function, especially during COVID-19 infection.
mTOR inhibitors play a crucial role in LAM treatment by suppressing mTOR signaling,[6] leading to a halt in lung function deterioration, a reduction in lymphangioleiomyoma burden, and amelioration of pulmonary and extra-pulmonary complications.[7, 8] Current guidelines from the American Thoracic Society and the Japanese Respiratory Society recommend sirolimus as the first-line treatment for LAM patients with an FEV1 of 70% or less. [2] Previous studies suggested that the use of mTOR inhibitors in LAM patients would not affect the outcomes of SARS-CoV-2 infection. [3, 9] But since mTOR inhibitors are mainly used by patients with impaired lung function, who are prone to worse outcomes during the infection, the observation by previous studies [3, 9] might be biased. Therefore, our study focused on the group of patients already taking these medications and analyzed the impact of drug discontinuation during active infection. A substantial proportion of our cohort (40.7%) chose to suspend mTOR inhibitors due to active infection. Our results indicate that maintaining mTOR inhibitor therapy during COVID-19 was associated with a reduced risk of SpO2 decline. In patients with impaired lung function, continuing mTOR inhibitor therapy was linked to a decreased risk of both SpO2 decline and the need for supplemental oxygen. This observation underscores the importance of maintaining regular LAM treatment including sirolimus even in the face of COVID-19 pandemics. Discontinuation of mTOR inhibitors, as noted in some patients due to infection, may need to be carefully weighed against the potential benefits of ongoing therapy. This may also reflect the protective effect of mTOR inhibitors, which are postulated to modulate immune responses, potentially mitigate the cytokine storm associated with severe COVID-19 cases, and might inhibit SARS-CoV-2 replication. [10, 11]
Vaccination in China primarily consists of inactivated, Ad5-vectored, and recombinant protein vaccines. Studies by Huang et al. suggested that these vaccines were effective in preventing severe illness and death during the Omicron BA.2 variant’s dominant period.[12] And study by Cheng et al. demonstrated that neutralizing antibody response of inactivated SARS-CoV-2 vaccine was unchanged in LAM patients on sirolimus.[13] Meanwhile, our study did not observe a significant impact of vaccination on the prognosis of patients with LAM and COVID-19. This finding must be interpreted cautiously due to potential confounders such as vaccine timing, type, prevalent SARS-CoV-2 variant, and the low incidence of severe disease and mortality. Further research is warranted to elucidate the immunological dynamics and assess the long-term vaccine efficacy in LAM.
Our study’s limitations include its retrospective design, potential biases from self-reported questionnaire data, and the possibility that the findings may not extend beyond the Chinese population and the Omicron variant. A more extensive, multicenter, prospective study would yield more conclusive evidence. Future research should also examine the long-term outcomes of COVID-19 in LAM patients, the impact of different SARS-CoV-2 variants, and the potential benefits of various vaccine types and doses in this distinct patient population.