scholarly journals Identification of serum prognostic biomarkers of severe COVID-19 using a quantitative proteomic approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yayoi Kimura ◽  
Yusuke Nakai ◽  
Jihye Shin ◽  
Miyui Hara ◽  
Yuriko Takeda ◽  
...  

AbstractThe COVID-19 pandemic is an unprecedented threat to humanity that has provoked global health concerns. Since the etiopathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. Accurately predicting the progression of the disease would aid in appropriate patient categorization and thus help determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins that are closely associated with COVID-19 prognosis. Twenty-seven proteins were differentially expressed between severely ill COVID-19 patients with an adverse or favorable prognosis. Ingenuity Pathway Analysis revealed that 15 of the 27 proteins might be regulated by cytokine signaling relevant to interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF), and their differential expression was implicated in the systemic inflammatory response and in cardiovascular disorders. We further evaluated practical predictors of the clinical prognosis of severe COVID-19 patients. Subsequent ELISA assays revealed that CHI3L1 and IGFALS may serve as highly sensitive prognostic markers. Our findings can help formulate a diagnostic approach for accurately identifying COVID-19 patients with severe disease and for providing appropriate treatment based on their predicted prognosis.

2021 ◽  
Author(s):  
Yayoi Kimura ◽  
Yusuke Nakai ◽  
Jihey Shin ◽  
Miyui Hara ◽  
Yuriko Takeda ◽  
...  

Abstract The COVID-19 pandemic is an unprecedented threat to humanity provoking global health concerns. Since the etio-pathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. An accurate prediction of the disease progression can aid in appropriate patient categorization to determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins closely associated with the prognosis of COVID-19. We observed 27 proteins to be differentially expressed between the cohorts of severely ill COVID-19 patients with adverse and favorable prognosis. Ingenuity pathway analysis revealed that 15 out of the 27 proteins might be regulated by cytokine signalling relevant to interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNF), and their differential expression was possibly implicated in the systemic inflammatory response and cardiovascular disorders. We further evaluated the practical prognosticators for the clinical prognosis of severe COVID-19 patients. Subsequent ELISA analyses further uncovered that CHI3L1 and IGFALS could be potent prognostic markers with a high sensitivity. Our findings can help in formulating a diagnostic approach for accurately discriminating severe COVID-19 patients and provide appropriate treatment based on their predicted prognosis.


2020 ◽  
Vol 17 ◽  
Author(s):  
Perumal Subramaniana ◽  
Jaime Jacqueline Jayapalan ◽  
Puteri Shafinaz Abdul-Rahmanb

A proteome is an efficient rendition of a genome, unswervingly controlling various cancer processes. Molecular mechanisms of several cancer processes have been unraveled by proteomic approach. Thus far, numerous tumors of diverse status have been investigated by two-dimensional electrophoresis. Numerous biomarkers have been recognized and precise categorization of apparent lesions has led to the timely detection of various cancers in persons at peril. Currently used pioneering approaches and technologies in proteomics have led to highly sensitive assays of cancer biomarkers and improved the early diagnosis of various cancers. The discovery of novel and definite biomarker signatures further widened our perceptive of the disease and novel potent drugs for efficient and aimed therapeutic outcomes in persistent cancers have emerged. However, a major limitation, even today, of proteomics is resolving and quantifying the proteins of low abundance. Despite the rapid development of proteomic technologies and their applications in cancer management, annulling the shortcomings of present proteomic technologies and development of better methods are still desirable. The main objectives of this review are to discuss the developing aspects, merits and demerits of pharmacoproteomics, redox proteomics, novel approaches and therapies being used for various types of cancer based on proteome studies.


Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1221
Author(s):  
Alvaro Martinez Mesa ◽  
Eva Cabrera César ◽  
Elisa Martín-Montañez ◽  
Esther Sanchez Alvarez ◽  
Pilar Martinez Lopez ◽  
...  

Introduction: SARS-CoV-2 (COVID-19) patients who develop acute respiratory distress syndrome (ARDS) can suffer acute lung injury, or even death. Early identification of severe disease is essential in order to control COVID-19 and improve prognosis. Oxidative stress (OS) appears to play an important role in COVID-19 pathogenesis; we therefore conceived a study of the potential discriminative ability of serum biomarkers in patients with ARDS and those with mild to moderate disease (non-ARDS). Method: 60 subjects were enrolled in a single-centre, prospective cohort study of consecutively admitted patients: 29 ARDS/31 non-ARDS. Blood samples were drawn and marker levels analysed by spectrophotometry and immunoassay techniques. Results: C-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin were significantly higher in ARDS versus non-ARDS cases at hospital admission. Leukocytes, LDH, ferritin, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were also significantly elevated in ARDS compared to non-ARDS patients during the hospital stay. Total thiol (TT) was found to be significantly lower in ARDS. Conversely, D-dimer, matrix metalloproteinase-9 (MMP-9) and advanced glycosylated end products (AGE) were elevated. Leukocytes, LDH, CRP, ferritin and IL-6 were found to be significantly higher in non-survivors. However, lymphocyte, tumour necrosis factor beta (TGF-β), and TT were lower. Conclusion: In summary, our results support the potential value of TT, ferritin and LDH as prognostic biomarkers for ARDS development in COVID-19 patients, distinguishing non-ARDS from ARDS (AUCs = 0.92; 0.91; 0.89) in a fast and cost-effective manner. These oxidative/inflammatory parameters appear to play an important role in COVID-19 monitoring and can be used in the clinical management of patients.


2008 ◽  
Vol 36 (2) ◽  
pp. 221-228 ◽  
Author(s):  
Srabasti J. Chakravorty ◽  
Katie R. Hughes ◽  
Alister G. Craig

Cytoadherence of PRBCs (Plasmodium falciparum-infected red blood cells) to host endothelium has been associated with pathology in severe malaria, but, despite extensive information on the primary processes involved in the adhesive interactions, the mechanisms underlying the disease are poorly understood. Endothelial cells have the ability to mobilize immune and pro-adhesive responses when exposed to both PRBCs and TNF (tumour necrosis factor). In addition, there is also an up-regulation by PRBCs and TNF and a concurrent down-regulation of a range of genes involved in inflammation and cell death, by PRBCs and TNF. We propose that the balance between positive and negative regulation will contribute to endothelial pathology during malarial infection. Apposition of PRBCs has been shown by a number of groups to activate signalling pathways. This is dependent, at least in part, on the cytoadherence characteristics of the invading isolate, such that the avidity of the PRBC for the receptor on host endothelium is proportional to the level of activation of the signalling pathways. An understanding of the post-adhesive processes produced by cytoadherence may help us to understand the variable pathology seen in malaria and to design appropriate therapies to alleviate severe disease.


2011 ◽  
Vol 110 (1) ◽  
pp. 149-156 ◽  
Author(s):  
Britt Christensen ◽  
Lucila Sackmann-Sala ◽  
Diana Cruz-Topete ◽  
Jens Otto L. Jørgensen ◽  
Niels Jessen ◽  
...  

Erythropoietin (Epo) is produced primarily in the kidneys upon low blood oxygen availability and stimulates erythropoiesis in the bone marrow. Recombinant human Epo (rHuEpo), a drug developed to increase arterial oxygen content in patients, is also illicitly used by athletes to improve their endurance performance. Therefore, a robust and sensitive test to detect its abuse is needed. The aim of the present study was to investigate potential human serum biomarkers of Epo abuse employing a proteomic approach. Eight healthy male subjects were injected subcutaneously with rHuEpo (5,000 IU) every second day for a 16-day period. Serum was collected before starting the treatment regime and again at days 8 and 16 during the treatment period. Samples were homogenized and proteins separated by two-dimensional gel electrophoresis (2DE). Spots that changed significantly in response to rHuEpo treatment were identified by mass spectrometry. Both the number of reticulocytes and erythrocytes increased throughout the study, leading to a significant increase in hematocrit and hemoglobin content. In addition, transferrin levels increased but the percentage of iron bound to transferrin and ferritin levels decreased. Out of 97 serum proteins, seven were found to decrease significantly at day 16 compared with pre-Epo administration, and were identified as four isoforms of haptoglobin, two isoforms of transferrin, and a mixture of hemopexin and albumin. In support, total serum haptoglobin levels were found to be significantly decreased at both days 8 and 16. Thus a 2DE proteomic approach for discovery of novel markers of Epo action appears feasible.


2020 ◽  
Vol 19 (11) ◽  
pp. 1749-1759 ◽  
Author(s):  
Xin Hou ◽  
Xiaomei Zhang ◽  
Xian Wu ◽  
Minya Lu ◽  
Dan Wang ◽  
...  

Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.


Author(s):  
Nadia Mulyanti Gunawan ◽  
Raden Mohammad Budiarto ◽  
Andriati Andriati

Introduction: The most common valvular heart disease is mitral stenosis. Mitral stenosis is an abnormality of the heart valve which causes reduced blood flow from the left atria to the left ventricle due to narrowing of mitral valve orifice during its opening motion. If the condition continues, it will result in complications. The most common complications are pulmonary hypertension, atrial fibrillation, heart failure, and stroke. Appropriate treatment for mitral stenosis may produce more favorable prognosis in these patients. Therefore, the aim of this study was to describe the profile of patients with mitral stenosis in Department of Cardiology and Vascular Medicine, Dr. Soetomo General Hospital, Surabaya from January 2015 to December 2017. It is expected that mitral stenosis can be detected earlier, thus the appropriate treatment can be administered promptly and further complications can be prevented. Methods: This study was a descriptive retrospective study with cross-sectional approach and accidental sampling method obtained from the inpatients medical records of patients diagnosed with mitral stenosis from echocardiography in Department of Cardiology and Vascular Medicine Dr. Soetomo General Hospital, Surabaya from January 2015 to December 2017. The variables were age, gender, disease severity, and the patient’s educational background. The data was processed using Microsoft Excel and IBM SPSS version 20. Results:  This study obtained 41 patients who met the inclusion criteria, then the patients were categorized according to their age, gender, disease severity, and educational background. The results of the study showed that the subjects were dominated by those of productive age at 30-39 years old (39%), the most prevalent gender was female (85.4%), severe disease severity (85.4%), and educational level was from high school (85.4%). Conclusion: The majority of the patients with mitral stenosis were from productive age, female, with severe disease severity, and educational background from middle educational level (high school). 


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