Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19
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Abstract
The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUC training = 0.799, p-value = 4.2e-6; multi-class AUC validation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression.
Summary
Feyaerts et al. demonstrate that an integrated analysis of plasma and single-cell proteomics differentiates COVID-19 severity and reveals severity-specific biological signatures associated with the dysregulation of the JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks and the mobilization of the renin-angiotensin and hemostasis systems.
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SciScore for 10.1101/2021.02.09.430269: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. 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: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has certain limitations. First, in this cohort, we only assessed peripheral blood samples of patients affected by COVID-19. It would be of great interest to assess the local immune and proteome perturbations in parallel by analyzing lung biopsies or bronchoalveolar lavage fluid to investigate whether the same trends …
SciScore for 10.1101/2021.02.09.430269: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. 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: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has certain limitations. First, in this cohort, we only assessed peripheral blood samples of patients affected by COVID-19. It would be of great interest to assess the local immune and proteome perturbations in parallel by analyzing lung biopsies or bronchoalveolar lavage fluid to investigate whether the same trends and dampened immune cell responses are observed locally in the lung as well. Second, this is a single-center study with samples collected from patients at Stanford University Medical Center. Most of the patients that were encountered during the study period had mild symptoms. Future studies including patients with different ethnicity, socio-economic status, and co-morbidities will be important to test the boundary of generalizability of our findings. Similarly, we recognize that the severity model is independently validated as a high-dimensional model. Additional testing in larger and more diverse patient cohorts is necessary to determine whether individual model features can serve as clinical biomarkers of disease severity. Finally, this is a cross-sectional study --longitudinal monitoring of plasma and single-cell proteomic features will give increased insight into the fluctuation of these features over time and lead to new insights into patients with COVID-19 “long-hauler” status. Determining the underlying immune pathogenesis across the spectrum of COVID-19 severity remains an important clinical challenge. Our integrated analysis of plasma and singl...
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 scite Reference Check: We found no unreliable references.
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