Role of IgG against N-protein of SARS-CoV2 in COVID19 clinical outcomes
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Abstract
The Nucleocapsid Protein (N Protein) of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) is located in the viral core. Immunoglobulin G (IgG) targeting N protein is detectable in the serum of infected patients. The effect of high titers of IgG against N-protein on clinical outcomes of SARS-CoV2 disease has not been described. We studied 400 RT-PCR confirmed SARS-CoV2 patients to determine independent factors associated with poor outcomes, including Medical Intensive Care Unit (MICU) admission, prolonged MICU stay and hospital admissions, and in-hospital mortality. We also measured serum IgG against the N protein and correlated its concentrations with clinical outcomes. We found that several factors, including Charlson comorbidity Index (CCI), high levels of IL6, and presentation with dyspnea were associated with poor clinical outcomes. It was shown that higher CCI and higher IL6 levels were independently associated with in-hospital mortality. Anti-N protein IgG was detected in the serum of 55 (55%) patients at the time of admission. A high concentration of antibodies, defined as signal to cut off ratio (S/Co) > 1.5 (75 percentile of all measurements), was found in 25 (25%) patients. The multivariable logistic regression models showed that between being an African American, higher CCI, lymphocyte counts, and S/Co ratio > 1.5, only S/Co ratio were independently associated with MICU admission and longer length of stay in hospital. This study recommends that titers of IgG targeting N-protein of SARS-CoV2 at admission is a prognostic factor for the clinical course of disease and should be measured in all patients with SARS-CoV2 infection.
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SciScore for 10.1101/2020.09.23.20197251: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics Statement: This study was approved by the Institutional Review Board (IRB) of the University of Miami. Randomization Fifteen patients were randomly selected for whole blood RNA extraction. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources ELISA test: Serum samples were processed and analyzed for SARS-CoV-2 IgG antibodies and anti N-protein IgG levels using an ELISA kit for IgG by Epitope Diagnostics 16 according to manufacturer’s protocol. SARS-CoV-2 IgGsuggested: Noneanti N-proteinsuggested: NoneSoftware and Algorithms Sentences Resources Statistical analysis was … SciScore for 10.1101/2020.09.23.20197251: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics Statement: This study was approved by the Institutional Review Board (IRB) of the University of Miami. Randomization Fifteen patients were randomly selected for whole blood RNA extraction. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources ELISA test: Serum samples were processed and analyzed for SARS-CoV-2 IgG antibodies and anti N-protein IgG levels using an ELISA kit for IgG by Epitope Diagnostics 16 according to manufacturer’s protocol. SARS-CoV-2 IgGsuggested: Noneanti N-proteinsuggested: NoneSoftware and Algorithms Sentences Resources Statistical analysis was performed using IBM SPSS version 26. SPSSsuggested: (SPSS, RRID:SCR_002865)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:The major limitation of our study is that we did not measure total non-neutralizing IgG and non-neutralizing anti-S and other proteins. In addition, we were unable to show the effect of IgG targeting N protein on mortality of COVID19 patients in the multivariable analysis due to sample size limitations. This study has not yet been validated in another cohort of COVID19 patients. Further investigation is urgently needed to assess the pathologic mechanisms of IgG for N-protein in severe COVID19. In particular, a larger multicentric study should be conducted to investigate the role of IgG targeting N protein on COVID19 mortality. A better understanding of the role of ADE in platelet activation may shed light on the hypercoagulable state in COVID19 and generate new therapeutic modalities. In summary, this study recommends that during the initial assessment of patients with COVID19, IgG targeting N-protein of SARS-CoV2 should be included among the measures. The high concentration of this immunoglobulin may predict poor outcomes, although further validation is needed.
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 10.1101/2020.09.23.20197251: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Fifteen patients were randomly selected for whole blood RNA extraction. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources ELISA test Serum samples were processed and analyzed for SARS-CoV-2 IgG antibodies and anti Nprotein IgG levels using an ELISA kit for IgG by Epitope Diagnostics 16 according to manufacturer’s protocol. SARS-CoV-2 IgGsuggested: Noneanti Nprotein IgG…SciScore for 10.1101/2020.09.23.20197251: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Fifteen patients were randomly selected for whole blood RNA extraction. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources ELISA test Serum samples were processed and analyzed for SARS-CoV-2 IgG antibodies and anti Nprotein IgG levels using an ELISA kit for IgG by Epitope Diagnostics 16 according to manufacturer’s protocol. SARS-CoV-2 IgGsuggested: Noneanti Nprotein IgGsuggested: NoneSoftware and Algorithms Sentences Resources Statistical analysis was performed using IBM SPSS version 26. SPSSsuggested: (SPSS, RRID:SCR_002865)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:
The major limitation of our study is that we did not measure total non-neutralizing IgG and nonneutralizing anti-S and other proteins. In addition, we were unable to show the effect of IgG targeting N protein on mortality of COVID19 patients in the multivariable analysis due to sample size limitations. This study has not yet been validated in another cohort of COVID19 patients. Further investigation is urgently needed to assess the pathologic mechanisms of IgG for Nprotein in severe COVID19. In particular, a larger multicentric study should be conducted to investigate the role of IgG targeting N protein on COVID19 mortality. A better understanding of the role of ADE in platelet activation may shed light on the hypercoagulable state in COVID19 and generate new therapeutic modalities. In summary, this study recommends that during the initial assessment of patients with COVID19, IgG targeting N-protein of SARS-CoV2 should be included among the measures. The high concentration of this immunoglobulin may predict poor outcomes, although further validation is needed.
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.
About SciScore
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