Urine Proteome of COVID-19 Patients

Li, Yanchang; Wang, Yihao; Liu, Huiying; Sun, Wei; Ding, Baoqing; Zhao, Yinghua; Chen, Peiru; Zhu, Li; Li, Zhaodi; Li, Naikang; Chang, Lei; Wang, Hengliang; Bai, Chunmei; Xu, Ping

doi:10.1101/2020.05.02.20088666

Cited by 24 publications

(40 citation statements)

References 42 publications

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“…Moreover, alteration of the MASP-2-binding motif, either via Masp2 deletion or blocking the MASP-2-N protein interaction, attenuated lung injury. These data, along with human proteomic studies (15,16), suggest that coronavirus infections involve the activation of multiple complement pathways.…”

Section: Introductionmentioning

confidence: 84%

“…Additionally, a subset of those developing COVID-19 have evidence of ongoing clinical and laboratory evidence of ongoing thromboses, confirmed in multiple autopsy reports, with features that overlap with thrombotic microangiopathies (TMAs) (12)(13)(14). These reports, in combination with results from both targeted and unbiased proteomic studies, have increased the likelihood that complement activation is a key contributor to the COVID-19 pathogenesis (12)(13)(14)(15)(16)(17). In this Review, we summarize interactions between coronaviruses and the complement system, with a specific focus on SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 87%

See 1 more Smart Citation

The complement system in COVID-19: friend and foe?

Java¹,

Apicelli²,

Liszewski³

et al. 2020

JCI Insight

331

387

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Interplay between SARS-CoV-2 and the complement system Antiviral strategies. The complement system traces its origins to more than a billion years ago when primitive proteins evolved to protect cells from pathogens and to engage in intracellular metabolic processes (18, 19) (Figure 1A). The contemporary complement system lies at the interface between innate and adaptive immunity (20). It efficiently recognizes and eliminates viral pathogens via several mechanisms: opsonizing viruses and virus-infected cells (including lysing them), inducing an antiviral immunoinflammatory state, boosting virus-specific immune responses, and directly neutralizing cell-free viruses (21) (reviewed in ref. 22). Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19-related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19; (d) a subset of patients with COVID-19 may have a genetic predisposition associated with complement dysregulation; and (e) these observations create a basis for clinical trials of complement inhibitors in life-threatening illness.

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Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 87%

The complement system in COVID-19: friend and foe?

Java¹,

Apicelli²,

Liszewski³

et al. 2020

JCI Insight

331

387

View full text Add to dashboard Cite

show abstract

“… 38 Li et al analyzed urine samples and detected 1008 proteins that were common to both COVID-19 patients and healthy controls. 40 The main drawbacks of DDA stem from its inability to capture all of the incoming precursor ions.…”

Section: How Do We Comprehensively Assess Protein Biomarkers Of Valuementioning

confidence: 99%

“…These and other authors have highlighted a possible impact of COVID-19 on the number of detectable proteins. 39 , 40 …”

Section: How Do We Comprehensively Assess Protein Biomarkers Of Valuementioning

confidence: 99%

Proteomics and Informatics for Understanding Phases and Identifying Biomarkers in COVID-19 Disease

et al. 2020

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The emergence of novel coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 coronavirus, has necessitated the urgent development of new diagnostic and therapeutic strategies. Rapid research and development, on an international scale, has already generated assays for detecting SARS-CoV-2 RNA and host immunoglobulins. However, the complexities of COVID-19 are such that fuller definitions of patient status, trajectory, sequelae, and responses to therapy are now required. There is accumulating evidence—from studies of both COVID-19 and the related disease SARS—that protein biomarkers could help to provide this definition. Proteins associated with blood coagulation (D-dimer), cell damage (lactate dehydrogenase), and the inflammatory response (e.g., C-reactive protein) have already been identified as possible predictors of COVID-19 severity or mortality. Proteomics technologies, with their ability to detect many proteins per analysis, have begun to extend these early findings. To be effective, proteomics strategies must include not only methods for comprehensive data acquisition (e.g., using mass spectrometry) but also informatics approaches via which to derive actionable information from large data sets. Here we review applications of proteomics to COVID-19 and SARS and outline how pipelines involving technologies such as artificial intelligence could be of value for research on these diseases.

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“… 39 Using LC–MS/MS-based proteomics of urine specimens from COVID-19 patients, Li et al found mild and severe COVID-19 patients with comorbidities were clearly differentiated from healthy patients. 40 This study identified that intracellular cholesterol transporter 2 (NPC2), APOA1, and cubilin (CUBN) were downregulated in severe COVID-19 patients, but cyclic AMP-responsive element-binding protein 3, like protein 3 (CREB3L3), hypoxia up-regulated protein 1 (HYOU1), heparin cofactor 2 (SERPIND1), and complement 3 (C3), were upregulated in mild or severe COVID-19 patients. Using orbitrap MS-based targeted proteomics, Bezstarosti et al detected tryptic peptides of SARS-CoV-2 proteins (NCAP, VME1) that could be utilized as a diagnostic of COVID-19.…”

Section: Mass Spectrometry-based Proteomics In Covid-19mentioning

confidence: 99%

Mass Spectrometry Techniques in Emerging Pathogens Studies: COVID-19 Perspectives

Mahmud

Garrett

2020

J. Am. Soc. Mass Spectrom.

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As corona virus disease 2019 (COVID-19) is a rapidly growing public health crisis across the world, our knowledge of meaningful diagnostic tests and treatment for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is still evolving. This novel coronavirus disease COVID-19 can be diagnosed using RT-PCR, but inadequate access to reagents, equipment, and a nonspecific target has slowed disease detection and management. Precision medicine, individualized patient care, requires suitable diagnostics approaches to tackle the challenging aspects of viral outbreaks where many tests are needed in a rapid and deployable approach. Mass spectrometry (MS)-based technologies such as proteomics, glycomics, lipidomics, and metabolomics have been applied in disease outbreaks for identification of infectious disease agents such as virus and bacteria and the molecular phenomena associated with pathogenesis. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is widely used in clinical diagnostics in the United States and Europe for bacterial pathogen identification. Paper spray ionization mass spectrometry (PSI-MS), a rapid ambient MS technique, has recently open a new opportunity for future clinical investigation to diagnose pathogens. Ultra-high-pressure liquid chromatography coupled high-resolution mass spectrometry (UHPLC–HRMS)-based metabolomics and lipidomics have been employed in large-scale biomedical research to discriminate infectious pathogens and uncover biomarkers associated with pathogenesis. PCR-MS has emerged as a new technology with the capability to directly identify known pathogens from the clinical specimens and the potential to identify genetic evidence of undiscovered pathogens. Moreover, miniaturized MS offers possible applications with relatively fast, highly sensitive, and potentially portable ways to analyze for viral compounds. However, beneficial aspects of these rapidly growing MS technologies in pandemics like COVID-19 outbreaks has been limited. Hence, this perspective gives a brief of the existing knowledge, current challenges, and opportunities for MS-based techniques as a promising avenue in studying emerging pathogen outbreaks such as COVID-19.

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Urine Proteome of COVID-19 Patients

Cited by 24 publications

References 42 publications

The complement system in COVID-19: friend and foe?

The complement system in COVID-19: friend and foe?

Proteomics and Informatics for Understanding Phases and Identifying Biomarkers in COVID-19 Disease

Mass Spectrometry Techniques in Emerging Pathogens Studies: COVID-19 Perspectives

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