Can we predict antibody responses in SARS-CoV-2? A cohort analysis
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Abstract
Background
After infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2), Immunoglobulin G (IgG) antibodies and virus-specific neutralizing antibodies (nAbs) develop. This study describes antibody responses in a cohort of recovered COVID-19 patients to identify predictors.
Methods
We recruited patients with confirmed SARS-CoV-2 infection from Heidelberg, Germany. Blood samples were collected three weeks after COVID-19 symptoms ended. Participants with high antibody titers were invited for follow-up visits. IgG titers were measured by the Euroimmun Assay, and nAbs titers in a SARS-CoV-2 infection-based assay.
Results
281 participants were enrolled between April and August 2020 with IgG testing, 145 (51.6%) had nAbs, and 35 (12.5%) had follow-up. The median IgG optical density (OD) ratio was 3.1 (Interquartile range (IQR) 1.6-5.1), and 24.1% (35/145) had a nAb titer>1:80. Higher IgG titers were associated with increased age and more severe disease, and higher nAbs were associated with male gender and CT-value of 25-30 on RT-PCR at diagnosis. The median IgG OD ratio on follow-up was 3.7 (IQR 2.9-5.9), a median increase of 0.5 (IQR −0.3-1.7). Six participants with follow-up nAbs all had titers ≤ 1:80.
Conclusions
While age and disease severity were correlated with IgG responses, predictive factors for nAbs in convalescent patients remain unclear.
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SciScore for 10.1101/2021.03.15.21253267: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: All procedures were performed in accordance with the ethical standards of the institutional research committee of Heidelberg University (study approval number S686/2018).
Consent: Written informed consent was obtained from each participant.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 At 20 hours post-infection, cells were fixed with 5% formaldehyde and immune-stained using a primary mouse antiserum binding to double-stranded RNA, a viral replication intermediate (J2 mouse antibody; Scicons, Szirák, … SciScore for 10.1101/2021.03.15.21253267: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: All procedures were performed in accordance with the ethical standards of the institutional research committee of Heidelberg University (study approval number S686/2018).
Consent: Written informed consent was obtained from each participant.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 At 20 hours post-infection, cells were fixed with 5% formaldehyde and immune-stained using a primary mouse antiserum binding to double-stranded RNA, a viral replication intermediate (J2 mouse antibody; Scicons, Szirák, Hungary) and a secondary anti-mouse horseradish peroxidase-coupled antibody (Merck, Darmstadt, Germany). anti-mouse horseradish peroxidase-coupled antibody ( Merck , Darmstadt , Germany) .suggested: NoneExperimental Models: Cell Lines Sentences Resources Neutralization assay: VeroE6 cells were seeded into 96-well plates one day before the assay. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Software and Algorithms Sentences Resources LightMix (TIB Molbiol, Berlin, Germany) for viral RNA using reverse-transcriptase polymerase chain reaction (RT-PCR) designed to detect RdRP and N genes specific for SARS-CoV-2 and the E gene for all of Sarbecovirus including SARS-CoV-2. SARS-CoV-2suggested: (Active Motif Cat# 91351, RRID:AB_2847848)1 (StataCorp LLC. StataCorpsuggested: (Stata, RRID:SCR_012763)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 study has several limitations. The criteria for plasma donation restricted participation to healthy people under 60 years of age. Further, the survey responses showed that most participants had relatively mild COVID-19 disease, although asymptomatic participants were underrepresented and very few were hospitalized. These factors indicate that the results may not be generalizable to populations who are older than 60, have severe disease, have comorbidities, or to asymptomatic patients. Most participants only had one serum sample collected, so there is limited data on the change in antibody titers over time. The variability in the nAb response would require evaluation of larger numbers of convalescent patients in order to yield a better understanding of predictive factors. This study also has several strengths. We present the IgG response in over 200 participants and nAbs in 145 participants. We also collected follow-up data for those participants who had a strong IgG and nAbs response at baseline. The information on illness severity and PCR results from both diagnosis and convalescent time-points provided a fuller clinical picture.
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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