Immunopathology and Immunopathogenesis of COVID-19, what we know and what we should learn

Shahgolzari, Mehdi; Yavari, Afagh; Arjeini, Yaser; Miri, Seyed Mohammad; Darabi, Amirhossein; Nejad, Amir Sasan Mozaffari; Keshavarz, Mohsen

doi:10.1016/j.genrep.2021.101417

Cited by 29 publications

(14 citation statements)

References 184 publications

(187 reference statements)

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“…Furthermore, the enrichment analysis of the downregulated DEGs mainly concentrated in the cellular response to stress, lysosome, mature lymphocyte differentiation, negative regulation of protein modification, glycosaminoglycan catabolic pathway, response to hyperoxia, and adaptive immune response. Numerous studies have shown that impaired lymphocyte differentiation and adaptive immune activation are found in severe COVID-19, resulting in delayed viral clearance and persistent proinflammatory cytokine release [ 108 , 109 , 110 , 111 , 112 ]. ARDS and severe pneumonia are also found in severe COVID-19, causing hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Multi-Level Biological Network Analysis and Drug Repurposing Based on Leukocyte Transcriptomics in Severe COVID-19: In Silico Systems Biology to Precision Medicine

Sagulkoo

Chuntakaruk

Rungrotmongkol

et al. 2022

JPM

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The coronavirus disease 2019 (COVID-19) pandemic causes many morbidity and mortality cases. Despite several developed vaccines and antiviral therapies, some patients experience severe conditions that need intensive care units (ICU); therefore, precision medicine is necessary to predict and treat these patients using novel biomarkers and targeted drugs. In this study, we proposed a multi-level biological network analysis framework to identify key genes via protein–protein interaction (PPI) network analysis as well as survival analysis based on differentially expressed genes (DEGs) in leukocyte transcriptomic profiles, discover novel biomarkers using microRNAs (miRNA) from regulatory network analysis, and provide candidate drugs targeting the key genes using drug–gene interaction network and structural analysis. The results show that upregulated DEGs were mainly enriched in cell division, cell cycle, and innate immune signaling pathways. Downregulated DEGs were primarily concentrated in the cellular response to stress, lysosome, glycosaminoglycan catabolic process, and mature B cell differentiation. Regulatory network analysis revealed that hsa-miR-6792-5p, hsa-let-7b-5p, hsa-miR-34a-5p, hsa-miR-92a-3p, and hsa-miR-146a-5p were predicted biomarkers. CDC25A, GUSB, MYBL2, and SDAD1 were identified as key genes in severe COVID-19. In addition, drug repurposing from drug–gene and drug–protein database searching and molecular docking showed that camptothecin and doxorubicin were candidate drugs interacting with the key genes. In conclusion, multi-level systems biology analysis plays an important role in precision medicine by finding novel biomarkers and targeted drugs based on key gene identification.

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Section: Discussionmentioning

confidence: 99%

Multi-Level Biological Network Analysis and Drug Repurposing Based on Leukocyte Transcriptomics in Severe COVID-19: In Silico Systems Biology to Precision Medicine

Sagulkoo

Chuntakaruk

Rungrotmongkol

et al. 2022

JPM

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“…Development of vaccines and immune-based therapeutics against SARS-CoV-2 are based on the understanding of the immunopathogenic basis of human immune responses against SARS-CoV-2. 34 Spike specific CD19+IgG+ memory B cells were detected in the blood samples of eight COVID-19 patients around the time of 9 to 28 days since the onset of symptoms. Monoclonal antibodies were separated from single B cells from 8 COVID-19 patients, some with the capacity to neutralize SARS-CoV-2.…”

Section: Methodsmentioning

confidence: 94%

Immunotherapy and CRISPR Cas Systems: Potential Cure of COVID-19?

Zeng

2022

DDDT

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The COVID-19 has plunged the world into a pandemic that affected millions. The continually emerging new variants of concern raise the question as to whether the existing vaccines will continue to provide sufficient protection for individuals from SARS-CoV-2 during natural infection. This narrative review aims to briefly outline various immunotherapeutic options and discuss the potential of clustered regularly interspaced short palindromic repeat (CRISPR Cas system technology against COVID-19 treatment as specific cure. As the development of vaccine, convalescent plasma, neutralizing antibodies are based on the understanding of human immune responses against SARS-CoV-2, boosting human body immune responses in case of SARS-CoV-2 infection, immunotherapeutics seem feasible as specific cure against COVID-19 if the present challenges are overcome. In cell based therapeutics, apart from the high costs, risks and side effects, there are technical problems such as the production of sufficient potent immune cells and antibodies under limited time to treat the COVID-19 patients in mild conditions prior to progression into a more severe case. The CRISPR Cas technology could be utilized to refine the specificity and safety of CAR-T cells, CAR-NK cells and neutralizing antibodies against SARS-CoV-2 during various stages of the COVID-19 disease progression in infected individuals. Moreover, CRISPR Cas technology are proposed in hypotheses to degrade the viral RNA in order to terminate the infection caused by SARS-CoV-2. Thus personalized cocktails of immunotherapeutics and CRISPR Cas systems against COVID-19 as a strategy might prevent further disease progression and circumvent immunity escape.

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“…Cellular antiviral response to HSV is initiated by host cellular proteins called PRR (C-type lectin receptors, NOD-like receptors, RIG-I-like receptors, and Toll-like receptors), which recognize molecular signatures of viral particles, known as pathogen-associated molecular patterns (PAMPs), and orchestrate the subsequent cellular responses [ 30 ]. After PAMP recognition, PRR activates downstream signaling cascades, production of type I (IFN-α and IFN-β) and III (IFN-λ) interferons, and secretion of other proinflammatory cytokines by multiple myeloid lineages and plasmacytoid dendritic cells [ 5 ]. Then, autocrine IFN-I via IFNα/β receptor (IFNAR) activates the Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

Herpes Simplex Virus 1 (HSV-1) Reactivation in Critically Ill COVID-19 Patients: A Brief Narrative Review

et al. 2022

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Systemic or pulmonary reactivations of herpes simplex virus 1 (HSV-1) have been reported in critically ill patients with COVID-19, posing a dilemma for clinicians in terms of their diagnostic and clinical relevance. Prevalence of HSV-1 reactivation may be as high as [ 40% in this population, but with large heterogeneity across studies, likely reflecting the different samples and/or cut-offs for defining reactivation. There is frequently agreement on the clinical significance of HSV-1 reactivation in the presence of severe manifestations clearly attributable to the virus. However, the clinical implications of HSV-1 reactivations in the absence of manifest signs and symptoms remain controversial. Our review aims at providing immunological background and at reviewing clinical findings on HSV-1 reactivations in critically ill patients with COVID-19.

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Immunopathology and Immunopathogenesis of COVID-19, what we know and what we should learn

Cited by 29 publications

References 184 publications

Multi-Level Biological Network Analysis and Drug Repurposing Based on Leukocyte Transcriptomics in Severe COVID-19: In Silico Systems Biology to Precision Medicine

Multi-Level Biological Network Analysis and Drug Repurposing Based on Leukocyte Transcriptomics in Severe COVID-19: In Silico Systems Biology to Precision Medicine

Immunotherapy and CRISPR Cas Systems: Potential Cure of COVID-19?

Herpes Simplex Virus 1 (HSV-1) Reactivation in Critically Ill COVID-19 Patients: A Brief Narrative Review

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