Complement activation induces excessive T cell cytotoxicity in severe COVID-19
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SciScore for 10.1101/2021.06.08.21258481: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Remaining PBMCs were subjected to flow-cytometric sorting based on DAPI, CD3 (clone UCHT1), CD4 (clone RPA-T4), CD8 (RPA-T8) and CD38 (clone HB7) antibody staining and simultaneously hashtagged as described above. CD3suggested: NoneCD4suggested: (RayBiotech Cat# CS-11-0132, RRID:AB_1228050)CD8suggested: NoneCD38suggested: NoneScRNA-seq data analysis of Rhapsody data (cohort 2): Detection of SARS-CoV-2-specific IgG and IgA antibodies: Detection of IgG and IgA to the S1 domain of the SARS-CoV-2 spike (S) protein were … SciScore for 10.1101/2021.06.08.21258481: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Remaining PBMCs were subjected to flow-cytometric sorting based on DAPI, CD3 (clone UCHT1), CD4 (clone RPA-T4), CD8 (RPA-T8) and CD38 (clone HB7) antibody staining and simultaneously hashtagged as described above. CD3suggested: NoneCD4suggested: (RayBiotech Cat# CS-11-0132, RRID:AB_1228050)CD8suggested: NoneCD38suggested: NoneScRNA-seq data analysis of Rhapsody data (cohort 2): Detection of SARS-CoV-2-specific IgG and IgA antibodies: Detection of IgG and IgA to the S1 domain of the SARS-CoV-2 spike (S) protein were assessed by anti-SARS-CoV-2 S1 IgG ELISAs (Euroimmun AG, Germany), as described elsewhere (Schlickeiser et al., 2020). anti-SARS-CoV-2suggested: NoneTherefore, the calculated OD ratios can be used as a relative measure for the concentration of IgA and IgG antibodies in the tested sample. IgGsuggested: NoneSoftware and Algorithms Sentences Resources 10x Genomics Chromium single-cell RNA-seq (cohort 1): Approximately 2-3 x105 PBMCs were resuspended in staining buffer (DPBS, Gibco; 0,5% BSA, Miltenyi Biotec, Germany; 2 mM EDTA, Gibco, Thermo Fisher Scientific, USA) and hashtagged with 0.5 µg Total-Seq-C™ Hashtag antibodies for 30 min at 4°C. Gibcosuggested: NoneScRNA-seq data analysis of 10x Chromium data (cohort 1): Gene Set Enrichment Analysis (GSEA): The log2-fold change of differentially expressed genes (with high counts, i.e., “baseMean” > 100) from DESeq2 was used to define the ranked gene list used for GSEA. DESeq2suggested: (DESeq, RRID:SCR_000154)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of the study and future directions: The relatively low number of matched acute and convalescent samples for scRNA-seq analysis limited the comparisons regarding differences in clonal persistence and phenotype between mild and severe COVID-19 patients. Thus, larger studies are needed to confirm the observed increased persistence of late differentiated, CD16 expressing, highly cytotoxic CTLs upon an acute severe disease course. Also, the limited number of convalescent samples did not allow us to perform correlations with patient recovery. Here, our major focus was to reveal immunopathogenic functions of severity-associated T cell populations during acute COVID-19 and to identify driving signals. In this context, it will be of great interest to see whether application of the C3 inhibitor AMY-101 in COVID-19 patients with ARDS will ameliorate differentiation of CD16 expressing, cytotoxic T cells and thus endothelial cell injury and lymphocytic endotheliitis. Taken together, particularly severe COVID-19 leads to an elevation of activated CD16+ T cells that link the elevated complement cascade via TCR-independent cytotoxic T cell functionality to endothelial damage and patient survival, thereby establishing a novel immunopathological link between the innate immune system, the adaptive immune compartment, and endothelial injury, which might constitute an important molecular axis explaining the vast spectrum of organ damage observed in COVID-19.
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.
- Thank you for including a protocol registration statement.
Results from scite Reference Check: We found no unreliable references.
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