An Open Question: Is It Rational to Inhibit the mTor-Dependent Pathway as COVID-19 Therapy?

Terrazzano, Giuseppe; Rubino, Valentina; Palatucci, Anna Teresa; Giovazzino, Angela; Carriero, Flavia; Ruggiero, Giuseppina

doi:10.3389/fphar.2020.00856

Cited by 53 publications

(59 citation statements)

References 41 publications

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“…As everolimus can both cause pneumonitis and is an effective immunosuppressant, this likely caused the fear in using this treatment during the pandemic. Nevertheless, there are opinion reports speculating on a potential benefit of mTOR inhibition in suppressing the overwhelming immune response in severe COVID-19 disease [19]. The highest risk for a severe course of SARS-COV-2 infection was attributed to systemic chemotherapy treatment.…”

Section: Discussionmentioning

confidence: 99%

Professional Assessment of the Impact of COVID-19 on Handling NET Patients

Krug

Garbe

König

et al. 2020

JCM

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The treatment and monitoring of patients with neuroendocrine tumors (NET) has been a major challenge during the COVID-19 pandemic. In a survey, we investigated the influence of COVID-19 on the care of NET patients in the German speaking countries Germany, Austria and Switzerland. The multidisciplinarity of all treating physicians in the outpatient and inpatient sector was reflected in our survey. Furthermore, we were able to present findings pertaining to the university and non-university medical care. Overall, only a minority of appointments were cancelled, mostly as a result of medical prioritization and less for fear of infection by patients. In the university sector, longer delays for diagnostic measures were observed in comparison to non-university care. During the COVID-19 crisis, NET patients rarely changed their current therapy, but the pandemic impacted the assessment of the different treatment modalities at risk of developing severe COVID-19 disease. This survey provides the first real-world data on the treatment of NET patients from the physicians’ perspective during the COVID-19 crisis. Despite delays in diagnostic procedures and outpatient appointments, only a minority of physicians foresee a major impact of COVID-19 on NET patient care.

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Section: Discussionmentioning

confidence: 99%

Professional Assessment of the Impact of COVID-19 on Handling NET Patients

Krug

Garbe

König

et al. 2020

JCM

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“…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). Recently, LAM Foundation published recommendations based on expert opinion for LAM patients regarding COVID-19, and stated that the risk of complications was associated with the degree of lung function impairment (The LAM Foundation COVID-19 Statement, 2020).…”

mentioning

confidence: 99%

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

Baldi

Colares

Kairalla

et al. 2020

American J of Med Genetics Pt A

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“…The mammalian or mechanistic target of rapamycin complex (mTORC) is a nutrient sensor within multiprotein complexes that control the cell cycle. Dysfunction in mTOR signaling is involved in many pathological states such as cancer and especially autoimmunity, as mTORC has important roles in the activation and polarization of naive T cells (48,56,57). In several studies, mTORC was shown to promote Th0 divergence into Th1 and Th17 lymphocytes, and in vivo inhibition of mTORC reduces the proportion of these cell types in the lamina propria and lymph nodes.…”

Section: T Cell Responsementioning

confidence: 99%

COVID-19 and Systemic Lupus Erythematosus: Focus on Immune Response and Therapeutics

Spihlman

Gadi

et al. 2020

Front. Immunol.

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The SARS-CoV-2 novel coronavirus has caused the COVID-19 pandemic with over 35 million cases and over a million deaths worldwide as of early October 2020. The populations most affected are the elderly and especially those with underlying comorbidities. In terms of race and ethnicity, black and hispanic populations are affected at disproportionately higher rates. Individuals with underlying conditions that cause an immune-compromised state are considered vulnerable to this infection. The immune response is an important determinant in viral infections including coronaviruses, not only in the antiviral defense but also in the disease progression, severity, and clinical outcomes of COVID-19. Systemic lupus erythematosus is a chronic autoimmune disease which also disproportionately afflicts black and hispanic populations. In lupus patients, an aberrant immune response is characterized by the presence of circulating autoantibodies, lymphopenia, aberrant T cells, and proinflammatory cytokines along with defective regulatory mechanisms, leading to immune-mediated damage to tissues. Lupus patients are often treated with immune-suppressants and therefore are immunecompromised and more susceptible to infections and may be vulnerable to coronavirus infection. While the anti-viral immune response is important to protect from coronavirus infection, an uncontrolled proinflammatory cytokine response can lead to cytokine storm which causes damage to the lungs and other organs, causing significant morbidity and mortality. Better understanding of the underlying immune response and therapeutic strategies in lupus and COVID-19 is important to guide management of this deadly infectious disease in the context of lupus and vice-versa.

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An Open Question: Is It Rational to Inhibit the mTor-Dependent Pathway as COVID-19 Therapy?

Cited by 53 publications

References 41 publications

Professional Assessment of the Impact of COVID-19 on Handling NET Patients

Professional Assessment of the Impact of COVID-19 on Handling NET Patients

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

COVID-19 and Systemic Lupus Erythematosus: Focus on Immune Response and Therapeutics

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