SARS-CoV-2 Causes a Different Cytokine Response Compared to Other Cytokine Storm-Causing Respiratory Viruses in Severely Ill Patients
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Abstract
Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with coronavirus 2019 (COVID-19) for a subgroup of patients. CRS is not unique to the SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, and H7N9). With a comprehensive literature search, we collected changing the cytokine levels from patients upon infection with the viral pathogens mentioned above. We analyzed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. Our curation indicates that the cytokine response induced by SARS-CoV-2 is different compared to other CRS-causing respiratory viruses, as SARS-CoV-2 does not always induce specific cytokines like other coronaviruses or influenza do, such as IL-2, IL-10, IL-4, or IL-5. Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.
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SciScore for 10.1101/2020.11.14.20231878: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources 3.1 Literature search: A mass literature search of 98 cytokines (48) was performed in PubMed using PubTator, and in bioRxiv1 and medRxiv2 non-peer reviewed pre-publication repositories (49). PubMedsuggested: (PubMed, RRID:SCR_004846)PubTatorsuggested: None3.2 Hierarchical clustering: We clustered our data using the clustermap function from the python package seaborn with Jaccard distance and complete linkage method (50). pythonsuggested: (IPython, RRID:SCR_001658)Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences …SciScore for 10.1101/2020.11.14.20231878: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources 3.1 Literature search: A mass literature search of 98 cytokines (48) was performed in PubMed using PubTator, and in bioRxiv1 and medRxiv2 non-peer reviewed pre-publication repositories (49). PubMedsuggested: (PubMed, RRID:SCR_004846)PubTatorsuggested: None3.2 Hierarchical clustering: We clustered our data using the clustermap function from the python package seaborn with Jaccard distance and complete linkage method (50). pythonsuggested: (IPython, RRID:SCR_001658)Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:One limitation of this study is the lack of anatomical and dynamic dimensions of the cytokine response. Firstly, the set of cytokines measured in the peripheral blood of each patient across the entire disease course or following recovery varied across the studies analysed. Patients were sampled at different stages of the disease, which further adds to the noise observed in the data. Finally, systematic patient-based studies matching our strict curation criteria could not be collected, leaving many gaps in our comparisons (Figure 3, white cells). While confirming many already reported disease traits, our analysis has highlighted several new features that are shared or different between the viral diseases analysed, contributing to filling the gap in the understanding of SARS-CoV2 and other CRS-causing viruses. Blockage of the cytokine response in SARS-CoV2 infection through IL-6 specific antibody has failed during Phase 3 randomised clinical trial (NCT04320615), even with promising results in earlier stages (76), suggesting that further mechanistic investigation of the cytokine storms during SARS-CoV-2 infection will be needed. The ongoing accumulation of patient-derived large data sets will inform the research community and clinicians of the intricacy of host/virus interactions (77). Here we provided a literature curation of patient-derived data and a comparative map across CRS-causing β-coronaviruses and influenza A viruses, linking shared or specific changing cytokines and i...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04320615 Completed A Study to Evaluate the Safety and Efficacy of Tocilizumab i… 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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