SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike
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Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity and kinetics of the antibody response mounted against this novel virus are not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and non-structural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.
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SciScore for 10.1101/2020.09.12.294066: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Study cohorts: All studies were performed with the approval of the University of Chicago institutional review board and University of Chicago and University of Wisconsin-Madison institutional biosafety 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 Horseradish peroxidase (HRP)-conjugated goat anti-human Ig secondary antibody diluted in PBS 0.1% Tween + 1% milk powder was used to detect binding of antibodies, and after a 1-hour incubation, plates were developed with 100 μl SigmaFast OPD solution … SciScore for 10.1101/2020.09.12.294066: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Study cohorts: All studies were performed with the approval of the University of Chicago institutional review board and University of Chicago and University of Wisconsin-Madison institutional biosafety 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 Horseradish peroxidase (HRP)-conjugated goat anti-human Ig secondary antibody diluted in PBS 0.1% Tween + 1% milk powder was used to detect binding of antibodies, and after a 1-hour incubation, plates were developed with 100 μl SigmaFast OPD solution (Sigma-Aldrich), with development reaction stopped after 10 minutes using 50 μl 3M HCl. goat anti-human Ig secondary antibodysuggested: Noneanti-human Ig secondarysuggested: NoneExperimental Models: Cell Lines Sentences Resources D614G spike protein, SARS-CoV-1 RBD, and MERS-CoV RBD were generated in-house and expressed in HEK293F cells. HEK293Fsuggested: RRID:CVCL_6642)The plasma/virus mixture was incubated for 30 minutes at 37°C and added to TMPRSS2-expressing Vero E6 cells grown in 1x minimum essential medium (MEM) supplemented with 5% FCS. Vero E6suggested: RRID:CVCL_XD71)Experimental Models: Organisms/Strains Sentences Resources ORF7a, ORF8, and full-length N proteins were cloned from the 2019-nCoV/USA-WA1/2020 SARS-CoV-2 strain at Washington University. SARS-CoV-2suggested: NoneSoftware and Algorithms Sentences Resources All statistical analysis was performed using Prism software (Graphpad Version 8), JMP Prismsuggested: (PRISM, RRID:SCR_005375)Graphpadsuggested: (GraphPad, RRID:SCR_000306)(SAS Institute Version 15) SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04340050 Completed COVID-19 Convalescent Plasma 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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