Proteomic and Metabolomic Characterization of COVID-19 Patient Sera

Shen, Bo; Yi, Xiao; Sun, Yaoting; Bi, Xiaojie; Du, Juping; Zhang, Chao; Quan, Sheng; Zhang, Fangfei; Sun, Rui; Qian, Liujia; Ge, Weigang; Liu, Wei; Liang, Shuang; Chen, Hao; Zhang, Ying; Li, Jun; Xu, Jiaqin; He, Zhike; Chen, Baofu; Wang, Jing; Yan, Haixi; Zheng, Yufen; Wang, Donglian; Zhu, Jiansheng; Kong, Ziqing; Kang, Zhouyang; Liang, Xiao; Ding, Xuan; Ruan, Guan; Xiang, Nan; Cai, Xue; Gao, Huanhuan; Li, Lü; Li, Sainan; Xiao, Qin; Tian, Li; Zhu, Yi; Liu, Huafen; Chen, Haixiao; Guo, Tiannan

doi:10.2139/ssrn.3570565

Cited by 129 publications

(312 citation statements)

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“…Many of the proteins that differentiate the groups in both studies belong to the complement system, acute phase and inflammatory response. For example, both studies agree with independently conducted clinical investigations on a number of differentially expressed proteins, in particular, albumin, the complement factors, Serum Amyloid proteins, ITIH3 and ITIH4 (Nie et al, 2020;Shen et al, 2020) . Despite these similarities, we note important differences.…”

Section: Proteome Signatures Of Inflammation and Acute-phase Responsesupporting

confidence: 81%

Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

Messner

Demichev

Wendisch

et al. 2020

Preprint

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The COVID-19 pandemic is an unprecedented global challenge. Highly variable in its presentation, spread and clinical outcome, novel point-of-care diagnostic classifiers are urgently required. Here, we describe a set of COVID-19 clinical classifiers discovered using a newly designed low-cost high-throughput mass spectrometry-based platform. Introducing a new sample preparation pipeline coupled with short-gradient high-flow liquid chromatography and mass spectrometry, our methodology facilitates clinical implementation and increases sample throughput and quantification precision. Providing a rapid assessment of serum or plasma samples at scale, we report 27 biomarkers that distinguish mild and severe forms of COVID-19, of which some may have potential as therapeutic targets. These proteins highlight the role of complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling upstream and downstream of Interleukin 6. Application of novel methodologies hence transforms proteomics from a research tool into a rapid-response, clinically actionable technology adaptable to infectious outbreaks. Highlights-A completely redesigned clinical proteomics platform increases throughput and precision while reducing costs.-27 biomarkers are differentially expressed between WHO severity grades for COVID-19.-The study highlights potential therapeutic targets that include complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling both upstream and downstream of interleukin 6.

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Section: Proteome Signatures Of Inflammation and Acute-phase Responsesupporting

confidence: 81%

Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

Messner

Demichev

Wendisch

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…These proteins were highly associated with the complement activation, regulation of immune response, cellular oxidant detoxification, cellular response to hypoxia and oxidative stressinduced apoptosis, which might reflect the pathogenesis of the severe COVID-19. These results are consistent with the recent reported sera proteomics [20].…”

Section: Covid-19 Patientssupporting

confidence: 94%

“…For the down-regulated molecular clusters, the proteins related with platelet degranulation was also reported in the sera proteomics recently [20].…”

Section: Covid-19 Patientsmentioning

confidence: 97%

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Urine Proteome of COVID-19 Patients

Wang

Liu

et al. 2020

Preprint

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The atypical pneumonia caused by SARS-CoV-2 is an ongoing pandemic and a serious threat to global public health. The COVID-19 patients with severe symptoms account for a majority of mortality of this disease. However, early detection and effective prediction of patients with mild to severe symptoms remains challenging. In this study, we performed proteomic profiling of urine samples from 32 healthy control individuals and 6 COVID-19 positive patients (3 mild and 3 severe). We found that urine proteome samples from the mild and severe COVID-19 patients with comorbidities can be clearly differentiated from healthy proteome samples based on the clustering analysis.Multiple pathways have been compromised after the COVID-19 infection, including the dysregulation of immune response, complement activation, platelet degranulation, lipoprotein metabolic process and response to hypoxia.We further validated our finding by directly comparing the same patients' urine proteome after recovery. This study demonstrates the COVID-19 pathophysiology related molecular alterations could be detected in the urine and the potential application of urinary proteome in auxiliary diagnosis, severity determination and therapy development of COVID-19.

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“…A recent proteomic and metabolomic study of COVID-19 patient sera evidenced continuous decrease of FFAs including LA (26). Lipid metabolome remodeling is a common element of 10 viral infection (27,28), including by the baculovirus (29) used here to express S. For coronaviruses, the LA to arachidonic acid (AA) metabolic pathway was identified as the epicentre of lipid remodeling (9).…”

Section: Main Textmentioning

confidence: 99%

Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein

Toelzer

Gupta

Yadav

et al. 2020

Preprint

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COVID-19, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms driving high infectivity, broad tissue tropism and severe pathology. Our cryo-EM structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains 5 (RBDs) tightly and specifically bind the essential free fatty acid (FFA) linoleic acid (LA) in three composite binding pockets. The pocket also appears to be present in the highly pathogenic coronaviruses SARS-CoV and MERS-CoV. Lipid metabolome remodeling is a key feature of coronavirus infection, with LA at its core. LA metabolic pathways are central to inflammation, immune modulation and membrane fluidity. Our structure directly links LA and S, setting the 10 stage for interventions targeting LA binding and metabolic remodeling by SARS-CoV-2. One Sentence Summary:A direct structural link between SARS-CoV-2 spike and linoleic acid, a key molecule in inflammation, immune modulation and membrane fluidity. 15 20

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Proteomic and Metabolomic Characterization of COVID-19 Patient Sera

Cited by 129 publications

References 0 publications

Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

Urine Proteome of COVID-19 Patients

Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein

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