mTORC inhibitor Sirolimus deprograms monocytes in “cytokine storm” in SARS-CoV2 secondary hemophagocytic lymphohistiocytosis- like syndrome

Karsulovic, Claudio; López, Mercedes; Tempio, Fabián; Guerrero, Julia; Goecke, Annelise

doi:10.1016/j.clim.2020.108539

Cited by 9 publications

(7 citation statements)

References 13 publications

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“…Rapamycin inhibits the mTOR, protein synthesis and prevents the activation of lymphocytes by blocking mTOR enzyme [ 12 , 13 ]. It also inhibits the expression of proinflammatory cytokines, such as IL-2, IL-6 and IL-10 and suppresses cytokine storm [ 14 ]. Rapamycin interrupts the T cell cycle during their transition from G1 to S phase by inhibiting the interleukin-mediated signal [ 1 ].…”

Section: Resultsmentioning

confidence: 99%

“…RdRp is the core component and plays a central role in COVID-19 replication and transcription cycle. Two nucleoside analogs targeting this protein (the influenza drug favipiravir and the experimental Ebola virus drug remdesivir) are currently being evaluated in clinical trials for the treatment of COVID-19 [ 13 , 14 , 15 ]. The nucleocapsid (N) protein of coronavirus is a multifunctional RNA-binding protein and forms a helical filament structure that is required for the assembly of viral genomic RNA into a ribonucleoprotein complex.…”

Section: Introductionmentioning

confidence: 99%

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Rapamycin: Drug Repurposing in SARS-CoV-2 Infection

et al. 2021

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Since December 2019, SARS-CoV-2 (COVID-19) has been a worldwide pandemic with enormous consequences for human health and the world economy. Remdesivir is the only drug in the world that has been approved for the treating of COVID-19. This drug, as well as vaccination, still has uncertain effectiveness. Drug repurposing could be a promising strategy how to find an appropriate molecule: rapamycin could be one of them. The authors performed a systematic literature review of available studies on the research describing rapamycin in association with COVID-19 infection. Only peer-reviewed English-written articles from the world’s acknowledged databases Web of Science, PubMed, Springer and Scopus were involved. Five articles were eventually included in the final analysis. The findings indicate that rapamycin seems to be a suitable candidate for drug repurposing. In addition, it may represent a better candidate for COVID-19 therapy than commonly tested antivirals. It is also likely that its efficiency will not be reduced by the high rate of viral RNA mutation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rapamycin: Drug Repurposing in SARS-CoV-2 Infection

et al. 2021

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“…COVID-19 been associated with macrophage activation syndrome and hemophagocytic lymphohistiocytosis during the acute phase [ 15 ]. Macrophages and circulating monocytes are essential for T and B lymphocyte recruiting and activation in lymph tissue [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Diffuse Lymphadenopathy Syndrome as a Flare-Up Manifestation in Lupus and Mixed Connective Tissue Disease Following Mild COVID-19

et al. 2021

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Case series Patients: Male, 28-year-old • Female, 25-year-old • Female, 68-year-old Final Diagnosis: Lupus Symptoms: COVID-19 pneumonia with deteriration of clinical symptoms • lymphadenopathy Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Rare coexistence of disease or pathology Background: Manifestations of Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, are highly variable among healthy populations. In connective tissue disease patients, the spectrum of clinical manifestations is even broader. In mild COVID-19 patients, diffuse lymphadenopathy (DL) has not been described as a late manifestation, and only severe COVID-19 has been associated with lupus flare-ups. Herein, we report 3 cases of connective tissue disease patients that presented with DL after diagnosis and complete resolution of mild COVID-19 disease. Case Reports: Case 1. A 28-year-old man with inactive lupus, mixed connective tissue disease (MCTD), and a history of lung and cutaneous involvement. He presented with fever, polyarthralgia, and multiple lymphadenopathies 3 weeks after COVID-19 disease resolution. After evaluation, immunosuppressive treatment was initiated, with rapid response. Case 2. A 25-year-old woman with inactive lupus with a history of articular, hematologic, and cutaneous involvement. Four weeks after resolution of COVID-19 disease, she presented with malaise and cervical lymph-adenopathies. After laboratory testing and imaging, she was treated for lupus flare-up, with rapid response. Case 3. A 68-year-old woman with inactive lupus with a history of articular and cutaneous involvement. Four weeks after COVID-19 resolution, she presented with malaise and cervical and axillary lymphadenopathies. After extensive evaluation, immunosuppressive treatment resulted in a rapid response. Conclusions: After 3 to 4 weeks of mild, outpatient-treated COVID-19 and complete resolution of symptoms, 3 patients with connective tissue disease presented diffuse lymphadenopathy associated with inflammatory and constitutional symptoms. Infectious and neoplastic causes were thoroughly ruled out. All patients responded to reintroduction of or an increase in immunosuppressive therapy. We recommend considering the diffuse lymphadenopathy as a possible post-acute COVID-19 syndrome (PACS) manifestation in these patients, mainly when they are in the inactive phase.

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“…Since ADAMTS7 has been described as an emerging factor in an accelerated atheromatous, measuring its levels in psoriatic patients is of great interest [ 9 ]. On the other hand, activation of the mTORC1 pathway, which targets the phosphorylation of multiple proteins, plays a critical part in monocyte/macrophage inflammatory phenotyping [ 10 ]. These cells actively participate in the atheromatous plaque formation and expansion [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

New Markers for Cardiovascular Disease in Psoriatic Patients: Preliminary Study on Monocyte Phenotype, ADAMTS7, and mTOR Activity

et al. 2023

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Psoriasis is a skin disease with occasional involvement of non-cutaneous territories. Beyond the usual, cardiovascular events are more frequent in these patients and correlate only partially with disease activity, suggesting the presence of other unknown factors. We selected ten psoriatic patients without treatment in the last year and matched them for age and gender with eleven healthy subjects. Ficoll-extracted mononuclear cells were analyzed with flow cytometry for monocyte surface phenotype markers, intracellular NFκB/inflammasome-dependent interleukins, and chemotaxis receptor CXCR3. Using ELISA, patient serum was evaluated for ADAMTS7 and CXCL10. Inflammatory M1 monocytes showed higher levels of IL-1β and IL-6 in psoriatic patients. M2 monocytes also showed higher levels of intracellular inflammatory cytokines. Nevertheless, IL-6 values were higher compared to other monocytes and IL-1β. The mTORC activation markers ADAMTS7 and S6Rp were higher in psoriatic patients than in healthy controls. In psoriatic patients, serum levels of ADAMTS7 were elevated, and M2 monocytes showed a distinct inflammatory response with higher relative levels of NFκB-dependent IL-6 and less activity of the CXCR3–CXCL10 chemotactic pathway. These data suggest pathways with potential markers for prediction and early detection of cardiovascular risk in psoriatic patients.

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mTORC inhibitor Sirolimus deprograms monocytes in “cytokine storm” in SARS-CoV2 secondary hemophagocytic lymphohistiocytosis- like syndrome

Cited by 9 publications

References 13 publications

Rapamycin: Drug Repurposing in SARS-CoV-2 Infection

Rapamycin: Drug Repurposing in SARS-CoV-2 Infection

Diffuse Lymphadenopathy Syndrome as a Flare-Up Manifestation in Lupus and Mixed Connective Tissue Disease Following Mild COVID-19

New Markers for Cardiovascular Disease in Psoriatic Patients: Preliminary Study on Monocyte Phenotype, ADAMTS7, and mTOR Activity

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