Autoimmunity to annexin A2 predicts mortality among hospitalised COVID-19 patients
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SciScore for 10.1101/2020.12.28.20248807: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Patients had consented to use of their biospecimens for COVID-19 research through a central biorepository with de-identified clinical data and a protocol approved by the Institutional Review Board at NYU Langone Health. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources After washing, bound antibody was detected with anti-human IgG-HRP (Invitrogen). anti-human IgG-HRPsuggested: NoneA control ELISA using E. coli-derived human Annexin A2 (R&D Systems) was performed as above to confirm that the observed anti-Annexin … SciScore for 10.1101/2020.12.28.20248807: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Patients had consented to use of their biospecimens for COVID-19 research through a central biorepository with de-identified clinical data and a protocol approved by the Institutional Review Board at NYU Langone Health. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources After washing, bound antibody was detected with anti-human IgG-HRP (Invitrogen). anti-human IgG-HRPsuggested: NoneA control ELISA using E. coli-derived human Annexin A2 (R&D Systems) was performed as above to confirm that the observed anti-Annexin A2 antibody levels were not due to binding to other human antigens. anti-Annexin A2suggested: NoneThis analysis was performed in order to determine whether the anti-Annexin A2 or A5 antibody levels were an independent predictor of inpatient mortality. A5suggested: NonePrediction of Mortality Based on Anti-Annexin A2 Antibody Levels After Adjustment for Age, Sex, Race and Comorbidities Prediction of Mortality Based on Anti-Annexin A2 Antibody Levels After Additional Adjustment for Maximum Lab Values Prediction of Mortality Based on Anti-Annexin A5 Antibody Levels After Adjustment for Age, Sex, Race and Comorbidities Prediction of Mortality Based on Anti-Annexin A5 Antibody Levels After Additional Adjustment for Maximum Lab Values Anti-Annexinsuggested: NoneExperimental Models: Cell Lines Sentences Resources Testing of 39 patient samples from different severity groups in parallel in E.coli or HEK293 cells produced Annexin A2 ELISAs that showed similar results, with an average variation between groups of only 0.17 RU. HEK293suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)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:This finding may be due to the inherent limitations of plasma determinations, which only measure circulating antibody levels and may underestimate the amount of antibody bound to tissues.(37) Cross-reactive binding of SARS-CoV-2 antibodies to self-antigens may also be relatively weak and difficult to measure. Furthermore, patient factors such as age and medical comorbidities may determine which patients are able to survive an autoimmune insult.(38) In our regression analyses, we found that anti-Annexin A2 antibody levels were strongly associated with mortality after controlling for patient factors. Even when we included the maximum laboratory abnormalities during the hospitalization of these COVID-19 patients, we found that anti-Annexin A2 antibody levels were an independent predictor of death. Though we do not present direct evidence of the pathogenicity of these anti-Annexin A2 antibodies in severe COVID-19, our study should spur further investigation into the role of autoimmunity induced by the SARS-CoV-2 virus. The presence of these autoantibodies has often thought to be non-pathogenic given that some patients may have high levels of circulating autoantibodies without any evidence of disease.(39, 40) Another explanation may be that these autoantibodies are only markers of some other underlying disease process that occurs in COVID-19. However, a failure of immune tolerance may in part explain the substantial variation in outcomes after exposure to SARS-CoV-2.(38) Like many...
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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SciScore for 10.1101/2020.12.28.20248807: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Patients had consented to use of their biospecimens for COVID-19 research through a central biorepository with de-identified clinical data and a protocol approved by the Institutional Review Board at NYU Langone Health. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources ELISA Antibody Testing Anti-Annexin A2 and anti-Annexin A5 antibodies were measured by ELISA as follows. anti-Annexinsuggested: NoneA… SciScore for 10.1101/2020.12.28.20248807: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Patients had consented to use of their biospecimens for COVID-19 research through a central biorepository with de-identified clinical data and a protocol approved by the Institutional Review Board at NYU Langone Health. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources ELISA Antibody Testing Anti-Annexin A2 and anti-Annexin A5 antibodies were measured by ELISA as follows. anti-Annexinsuggested: NoneAfter washing, bound antibody was detected with anti-human IgG-HRP (Invitrogen). anti-human IgG-HRPsuggested: NoneTo analyze the maximum laboratory values and the anti-Annexin A2 and A5 antibody levels as stratified by disease severity, we used ANOVA to test for differences in the average values. A5suggested: NoneAntibody Levels at Initial Hospitalization Correlate with Maximum Abnormalities of Key Laboratory Markers of Severe COVID-19 We also analyzed which of the maximum laboratory values during the hospitalization of COVID19 patients were associated with the anti-Annexin A2 or A5 IgG antibody levels as measured at hospital day 0 or 1. anti-Annexin A2suggested: NoneA5 IgGsuggested: None10.18849 Diabetes | .9988619 .6814375 -0.00 0.999 .2623034 3.803707 Obesity | 2.463447 1.709163 1.30 0.194 .6323705 9.596547 | AntiA2 | 9.278525 7.429331 2.78 0.005 1.931614 44.56947 | Constant | .0009595 .0025489 -2.62 0.009 5.26e-06 .1750888 Prediction of Mortality Based on Anti-Annexin A2 Antibody Levels After Additional Adjustment for Maximum Lab Values Logistic regression Log likelihood = -24.823063 Number of obs LR chi2(16) Prob > chi2 Pseudo R2 = = = = 80 42.46 0.0003 0.4610 Died | Odds Ratio Std. AntiA2suggested: (Dr. Judith Grinspan Lab, Children's Hospital of Philadelphia Cat# anti-A2B5+, RRID:AB_2827951)Obesity | 3.496549 2.272455 1.93 0.054 .9782097 12.49819 | AntiA5 | 2.875708 2.447485 1.24 0.215 .5423702 15.24733 | Constant | .0067489 .0150132 -2.25 0.025 .0000862 .5281582 Prediction of Mortality Based on Anti-Annexin A5 Antibody Levels After Additional Adjustment for Maximum Lab Values Logistic regression Log likelihood = -27.473712 Number of obs LR chi2(16) Prob > chi2 Pseudo R2 = = = = 80 37.16 0.0020 0.4034 Died AntiA5suggested: NoneExperimental Models: Cell Lines Sentences Resources High binding microwell plates (Immulon 2HB, Thermo Fisher Scientific) were coated overnight at 4ºC with 10 µg/mL of human recombinant Annexin A2 or A5 produced in HEK293 cells (Ray Biotech) in phosphate-buffered saline (PBS). HEK293suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)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:
This finding may be due to the inherent limitations of plasma determinations, which only measure circulating antibody levels and may underestimate the amount of antibody bound to tissues.(37) Cross-reactive binding of SARS-CoV-2 antibodies to self-antigens may also be relatively weak and difficult to measure. Furthermore, patient factors such as age and medical comorbidities may determine which patients are able to survive an autoimmune insult.(38) In our regression analyses, we found that anti-Annexin A2 antibody levels were strongly associated with mortality after controlling for patient factors. Even when we included the maximum laboratory abnormalities during the hospitalization of these COVID-19 patients, we found that anti-Annexin A2 antibody levels were an independent predictor of death. Though we do not present direct evidence of the pathogenicity of these anti-Annexin A2 antibodies in severe COVID-19, our study should spur further investigation into the role of autoimmunity induced by the SARS-CoV-2 virus. The presence of these autoantibodies has often thought to be non-pathogenic given that some patients may have high levels of circulating autoantibodies without any evidence of disease.(39, 40) Another explanation may be that these autoantibodies are only markers of some other underlying disease process that occurs in COVID-19. However, a failure of immune tolerance may in part explain the substantial variation in outcomes after exposure to SARS-CoV-2.(38) Like many...
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.
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