Early prediction of COVID‐19 severity using extracellular vesicle COPB2
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Abstract
The clinical manifestations of COVID‐19 vary broadly, ranging from asymptomatic infection to acute respiratory failure and death. But the predictive biomarkers for characterizing the variability are still lacking. Since emerging evidence indicates that extracellular vesicles (EVs) and extracellular RNAs (exRNAs) are functionally involved in a number of pathological processes, we hypothesize that these extracellular components may be key determinants and/or predictors of COVID‐19 severity. To test our hypothesis, we collected serum samples from 31 patients with mild COVID‐19 symptoms at the time of their admission for discovery cohort. After symptomatic treatment without corticosteroids, 9 of the 31 patients developed severe/critical COVID‐19 symptoms. We analyzed EV protein and exRNA profiles to look for correlations between these profiles and COVID‐19 severity. Strikingly, we identified three distinct groups of markers (antiviral response‐related EV proteins, coagulation‐related markers, and liver damage‐related exRNAs) with the potential to serve as early predictive biomarkers for COVID‐19 severity. As the best predictive marker, EV COPB2 protein, a subunit of the Golgi coatomer complex, exhibited significantly higher abundance in patients remained mild than developed severe/critical COVID‐19 and healthy controls in discovery cohort (AUC 1.00 (95% CI: 1.00‐1.00)). The validation set included 40 COVID‐19 patients and 39 healthy controls, and showed exactly the same trend between the three groups with excellent predictive value (AUC 0.85 (95% CI: 0.73‐0.97)). These findings highlight the potential of EV COPB2 expression for patient stratification and for making early clinical decisions about strategies for COVID‐19 therapy.
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SciScore for 10.1101/2020.10.14.20212340: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Study approval: This retrospective study involving collection of COVID-19 serum samples was approved by the Institutional Review Board at The Jikei University School of Medicine (Number: 32-055(10130)).
Consent: The protocol did not require informed consent, and patients were given the choice of opting out of the study.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from Limitation…SciScore for 10.1101/2020.10.14.20212340: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Study approval: This retrospective study involving collection of COVID-19 serum samples was approved by the Institutional Review Board at The Jikei University School of Medicine (Number: 32-055(10130)).
Consent: The protocol did not require informed consent, and patients were given the choice of opting out of the study.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:As a single center study with a small sample size, our work has several limitations, and caution should be exercised in utilizing the predictive value of the markers we have identified. An expanded random sample across all genders and ages should be more representative of the general population, and larger clinical studies are required to validate the potential of these biomarkers for predicting the severity of COVID-19 progression. Nevertheless, our research has implications that go beyond the simple investigation of biomarkers, since the results also provide important clues regarding the pathogenesis of COVID-19 and the development of therapies for the disease. Indeed, biomarkers such as PRKCB, COPB2, and CD147 may be involved in SARS-CoV-2 infection or replication. Furthermore, 6 markers (MFAP4, ECM1, CDKN2B.AS1, CAPN2, FGG, and CD147) and 2 exRNAs (SNORD33 and miR-122-5p) are involved in thrombosis or liver injury, which are serious complications in patients with severe COVID-19. These findings indicate that the profiles of EV proteins and exRNAs in patient sera clearly reflect specific host reactions to SARS-CoV-2 infection and progression of the disease. Although the pathological significance of some markers is unknown, understanding the profiles of functional extracellular components in patient sera may help clarify various aspects of COVID-19 pathogenesis. With regard to therapy, biomarkers may provide information concerning potential therapeutic targets for mitigatin...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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