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Immunobiology and immunotherapy of COVID-19: A clinically updated overview.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new member of the coronavirus family that can cause coronavirus disease 2019 (COVID-19). COVID-9 has become a global pandemic with severe health issues around the world. Identifying the accurate immunopathogenesis of the COVID-19 and the immune response against SARS-CoV-2 is necessary for the development of therapeutic approaches and rational drug design. This paper aims to overview the updated clinical data on the immunopathogenesis of the COVID-19 and review the innate and adaptive immune response to SARS-CoV-2. Also, challenges of the immune response to SARS-CoV-2 leading to dysfunctional immune response and their contribution to the progression of the disease have been discussed. To achieve a more efficient immune response, multiple methods could be applied, including regulation of the immune response, augmentation of the immune system against the virus, inhibition of the dysfunctional immune checkpoints, and inhibition of the viral replication/infection. Based on the immune response against SARS-CoV-2 and its dysfunction, we introduce potential immunotherapies as well as reviewing recruiting/completed clinical trials of COVID-19.

SUBMITTER: Esmaeilzadeh A

PROVIDER: S-EPMC7675260 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Immunobiology and immunotherapy of COVID-19: A clinically updated overview.

Esmaeilzadeh Abdolreza A Elahi Reza R

Journal of cellular physiology 20201006 4

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new member of the coronavirus family that can cause coronavirus disease 2019 (COVID-19). COVID-9 has become a global pandemic with severe health issues around the world. Identifying the accurate immunopathogenesis of the COVID-19 and the immune response against SARS-CoV-2 is necessary for the development of therapeutic approaches and rational drug design. This paper aims to overview the updated clinical data on the immunopathogene ...[more]

PMID: 33022076

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Project description:Immunotherapy has traditionally been a critical component of the cancer treatment armamentarium in genitourinary (GU) cancers. It has an established role in the management of carefully selected patients with metastatic renal cell carcinoma (RCC) [e.g., high dose interleukin-2 (IL-2)] and non-muscle invasive bladder cancer (NMIBC) [e.g., intravesical Bacillus Calmette-Guérin (BCG)]. In 2010, the sipuleucel-T vaccine was approved by the FDA for the management of metastatic castration-resistant prostate cancer (mCRPC), based on a phase III trial showing overall survival (OS) benefit compared to placebo. The immune checkpoint inhibitor nivolumab (anti-PD-1) recently received FDA approval for the management of patients with advanced RCC patients previously treated with anti-angiogenic therapy, based on OS benefit compared to everolimus. Recently, large clinical trials demonstrated meaningful clinical benefit, including durable responses, as well as a good tolerability/safety profile with the use of immune checkpoint inhibitors in advanced RCC and chemotherapy-resistant advanced urothelial carcinoma (UC), while FDA just approved atezolizumab for platinum-treated advanced UC. Numerous interesting trials in different cancers are ongoing. Several combinations of immune checkpoint blockade with chemotherapeutics, vaccines, targeted tyrosine kinase inhibitors & monoclonal antibodies, epigenetic modifiers, anti-angiogenic agents, tumor microenvironment & myeloid cell targeting therapies, metabolic modification strategies, radiation, and others, are being tested in clinical trials. Comprehensive understanding of the factors underlying antitumor immune responses in physiologically relevant animal models and humans will refine further the clinical benefit of immunotherapy. Discovery and validation of appropriate molecular biomarkers via coordinated translational research efforts, rational clinical trial designs with suitable endpoints and well-defined eligibility criteria, prospective registries/databases, careful evaluation of cost-effectiveness and safety/tolerability, adequate funding and open continuous discussions among all stakeholders will support the revolutionary nature of immunotherapy in GU cancers.

Project description:Backgroundclozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused.Objectiveto examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic.Data sourcesa search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia", "side effects", "agranulocytosis", "TRS", or "bipolar affective disorder (BAF)" for the last ten years.Study eligibility criteriaclinical trials on adults with acute symptoms of schizophrenia or related disorders.Resultswe selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection.Limitationswe considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) a CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with the proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.

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Immunobiology and immunotherapy of COVID-19: A clinically updated overview.

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Immunobiology and immunotherapy of COVID-19: A clinically updated overview.

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