Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study

Generali, Daniele; Bosio, Giancarlo; Malberti, Fabio; Antonio, Cuzzoli; Testa, Sophie; Romanini, Laura; Fioravanti, Antonio; Morandini, Alessandro; Pianta, Luca; Giannotti, Guglielmo; Viola, Erika Maria; Giorgi‐Pierfranceschi, Matteo; Foramitti, Marina; Tira, Rosa Angela; Zangrandi, Ilaria; Chiodelli, Giulia; Machiavelli, Andrea; Cappelletti, Maria Rosa; Giossi, Alessia; Giuli, Valeria De; Costanzi, Chiara; Campana, Chiara; Bernocchi, Ottavia; Sirico, Marianna; Zoncada, Alessia; Molteni, Alfredo; Venturini, Sergio; Giudici, Fabiola; Scaltriti, Maurizio; Pan, Angelo

doi:10.1016/j.ijid.2020.12.073

Cited by 56 publications

(32 citation statements)

References 18 publications

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“…In a recent study, mortality risk from COVID-19 was significantly reduced among the patients treated with IL-1 inhibitor [ 103 ], hence, rilonacept should further be assessed for its anti-COVID-19 action. Another identified drug is canakinumab, which restored normal oxygen level in patients suffering from COVID-19-related pneumonia [ 104 ]. Therefore, the identified drug candidates should be evaluated for their protective effect on COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic studies revealed pathophysiological impact of COVID-19 to predominant health conditions

Nain

Barman

Sheam

et al. 2021

Briefings in Bioinformatics

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Despite the association of prevalent health conditions with coronavirus disease 2019 (COVID-19) severity, the disease-modifying biomolecules and their pathogenetic mechanisms remain unclear. This study aimed to understand the influences of COVID-19 on different comorbidities and vice versa through network-based gene expression analyses. Using the shared dysregulated genes, we identified key genetic determinants and signaling pathways that may involve in their shared pathogenesis. The COVID-19 showed significant upregulation of 93 genes and downregulation of 15 genes. Interestingly, it shares 28, 17, 6 and 7 genes with diabetes mellitus (DM), lung cancer (LC), myocardial infarction and hypertension, respectively. Importantly, COVID-19 shared three upregulated genes (i.e. MX2, IRF7 and ADAM8) with DM and LC. Conversely, downregulation of two genes (i.e. PPARGC1A and METTL7A) was found in COVID-19 and LC. Besides, most of the shared pathways were related to inflammatory responses. Furthermore, we identified six potential biomarkers and several important regulatory factors, e.g. transcription factors and microRNAs, while notable drug candidates included captopril, rilonacept and canakinumab. Moreover, prognostic analysis suggests concomitant COVID-19 may result in poor outcome of LC patients. This study provides the molecular basis and routes of the COVID-19 progression due to comorbidities. We believe these findings might be useful to further understand the intricate association of these diseases as well as for the therapeutic development.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic studies revealed pathophysiological impact of COVID-19 to predominant health conditions

Nain

Barman

Sheam

et al. 2021

Briefings in Bioinformatics

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“…Severely ill patients with COVID-19 infection had severe lymphocytopenia, higher NLR ratio (≥ 5-7), lower platelet counts, higher erythro-cyte sedimentation rate (ESR), mildly to moderately increased Creactive protein and procalcitonin, and elevated LDH, whereas the cytokines such as IL-2, IL4, IL-6, IL-10 and IFN-gamma were not increased or only moderately increased (Song et al, 2020). NLR can be used as an objective parameter for the purpose of stratification of patients with COVID-19 infection (Ma et al, 2020), as well as for monitoring the response to the systemic therapy with IL-1beta antibody -Canakinumab; (Generali et al, 2021). Not only the initial value of NLR and D-dimer levels are important for stratifi cation, the dynamic changes of NLR values during hospital stay are of importance too.…”

Section: Nlr For Stratifi Cation Of Covid-19 Pneumonia and Acute Respiratory Failurementioning

confidence: 99%

Neutrophil-to-lymphocyte ratio, past, present and future perspectives

Záhorec¹

2021

BLL

356

286

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In the review we analyzed short history of the establishment of a novel hematological parameter for systemic infl ammation and stress coined as a neutrophil to lymphocyte ratio (NLR). Today NLR is widely used across almost all medical disciplines as a reliable and easy available marker of immune response to various infectious and non-infectious stimuli. We analyzed the immunological and biological aspects of dynamic changes of neutrophil granulocytes and lymphocytes in circulating blood during endocrine stress, dysbalance of autonomic nervous system and systemic infl ammation. NLR refl ects online dynamic relationship between innate (neutrophils) and adaptive cellular immune response (lymphocytes) during illness and various pathological states. NLR is infl uenced by many conditions including age, rice, medication, chronic disease like coronary heart disease, stroke, diabetes, obesity, psychiatric diagnosis, cancer of solid organs, anemia and stress. A normal range of NLR is between 1-2, the values higher than 3.0 and below 0.7 in adults are pathological. NLR in a grey zone between 2.3-3.0 may serve as early warning of pathological state or process such like cancer, atherosclerosis, infection, infl ammation, psychiatric disorders and stress. NLR is used as a reliable and cheap marker of ongoing cancerrelated infl ammation and a valid indicator of prognosis of solid tumors. Majority of meta-analyses have explored the prognostic value of NLR in various solid tumors and have found out the cut-off value of NLR above 3.0 (IQR 2.5-5.0). We summarized its privilege in oncology: NLR may be used for stratifi cation of cancer, correlates with the tumor size, stage of tumors, metastatic potential and lymphatic invasion. NLR has independent prognostic role regarding overall, cancer free and cancer-specifi c survival. It is useful for monitoring oncological therapy, including biological and immune check point inhibitors treatment. NLR is a very sensitive indicator of infection, infl ammation and sepsis, validated in numerous studies. Clinical research confi rmed the sensitivity of NLR for diagnosis/stratifi cation of systemic infection, sepsis, bacteremia as well as its robust predictive and prognostic value. NLR should be investigated daily, and follow-up its absolute values and dynamic course in acute disease or critical illness. The severity of critical illness, the level of stress and serious infl ammation is expressed by dramatic increasing of NLR values above 11 ≥ 17, or even higher than 30. Improving the clinical course of sepsis, critical illness, lower risk of mortality are associated with decline of NLR values below 7. NLR is helpful in differentiating more severe disease versus milder one. NLR is cheap, simple, fast responding and easy available parameter of stress and infl ammation with high sensitivity and low specifi city, it should be used routinely in emergency departments, ICUs, in acute medicine including surgery, orthopedics, traumatology, cardiology, neurology, psychiatry and even oncology. Dynamic changes ...

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“…Currently, a Phase I randomized placebocontrolled trial is underway to evaluate the efficacy of anakinra for the treatment of sHLH by comparing the number of acquired infections or deaths in the treatment and placebo groups (primary outcome) (NCT02780583) iv [137]. Canakinumab and anakinra are also being studied for treatment of COVID-19-induced ARDS and CSS [138]; for instance, a Phase III randomized placebo controlled study is evaluating canakinumab in patients hospitalized with COVID-19 with the primary outcome being the number of patients with clinical response (NCT04362813) v , and a Phase II/III two-arm study is investigating anakinra versus standard of care in patients with CSS secondary to SARS-CoV-2 infection with a primary outcome of treatment success (NCT04443881) vi . In addition, anakinra has abolished CSs and neurotoxicity in humanized mice with high leukemia burden (recapitulating key features of a CS); this approach might offer a therapeutic strategy to tackle neurotoxicity associated with CAR-T cell therapy [139].…”

Section: Autoinflammatorymentioning

confidence: 99%