The serological diversity of serum IgG/IgA/IgM against SARS‐CoV‐2 nucleoprotein, spike, and receptor‐binding domain and neutralizing antibodies in patients with COVID‐19 in Japan
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Abstract
Background
We compared the temporal changes of immunoglobulin M (IgM), IgG, and IgA antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleoprotein (N), spike 1 subunit (S1), and receptor‐binding domain (RBD), and neutralizing antibodies (NAbs) against SARS‐CoV‐2 in patients with coronavirus disease 2019 (COVID‐19) to understand the humoral immunity in COVID‐19 patients for developing drugs and vaccines for COVID‐19.
Methods
A total of five confirmed COVID‐19 cases in Nissan Tamagawa Hospital in early August 2020 were recruited in this study. Using a fully automated chemiluminescence immunoassay analyzer, we measured the levels of IgG, IgA, and IgM against SARS‐CoV‐2 N, S1, and RBD and NAbs against SARS‐CoV‐2 in COVID‐19 patients' sera acquired multiple times in individuals from 0 to 76 days after symptom onset.
Results
IgG levels against SARS‐CoV‐2 structural proteins increased over time in all cases but IgM and IgA levels against SARS‐CoV‐2 showed different increasing trends among individuals in the early stage. In particular, we observed IgA increasing before IgG and IgM in some cases. The NAb levels were more than cut‐off value in 4/5 COVID‐19 patients some of whose antibodies against RBD did not exceed the cut‐off value in the early stage. Furthermore, NAb levels against SARS‐CoV‐2 increased and kept above cut‐off value more than around 70 days after symptom onset in all cases.
Conclusion
Our findings indicate COVID‐19 patients should be examined for IgG, IgA, and IgM against SARS‐CoV‐2 structural proteins and NAbs against SARS‐CoV‐2 to analyze the diversity of patients' immune mechanisms.
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SciScore for 10.1101/2021.06.17.21258858: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was performed at the University of Tokyo and Nissan Tamagawa Hospital approved by their ethics committee (protocol number R2-05 and Tama2020-003). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources : Levels of IgG, IgA, and IgM against SARS-CoV-2 N, S1, and RBD and neutralizing antibody (NAb) against SARS-CoV-2 were measured using a fully automatic CLIA analyzer (iFlash3000). IgM against SARS-CoV-2 Nsuggested: NoneSARS-CoV-2suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data …
SciScore for 10.1101/2021.06.17.21258858: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was performed at the University of Tokyo and Nissan Tamagawa Hospital approved by their ethics committee (protocol number R2-05 and Tama2020-003). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources : Levels of IgG, IgA, and IgM against SARS-CoV-2 N, S1, and RBD and neutralizing antibody (NAb) against SARS-CoV-2 were measured using a fully automatic CLIA analyzer (iFlash3000). IgM against SARS-CoV-2 Nsuggested: NoneSARS-CoV-2suggested: NoneResults 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:However, there are some limitations in this study. First, the number of patients is the relatively small this study. It is necessary for us to measure antibody levels in many COVID-19 patients’ sera for a more accurate statistical significance regarding the correlations between antibody isotypes and the severity of symptoms. Second, we didn’t detect neutralizing activity of each isotype against SARS-CoV-2 by the methods considering the bias of different affinities of antibody isotypes as explained above. Furthermore, each antibody isotype affects the total NAb levels at different times after infection because of different seroconversion. We observed IgA levels against S1 and RBD declining followed by rise and below 10AU/mL around day 70 in all cases and a recent study also reported that IgA levels in serum decreased notably 1 month after symptom onset, being more potent than IgG in neutralizing activity for SARS-CoV-2 [17]. We need assess neutralizing activity of IgG, IgA, and IgM against SARS-CoV-2, using the assay which can measure each isotype for understanding the role of these isotype against SARS-CoV-2. Third, we detected NAbs against only RBD of SARS-CoV-2 in serum samples. Antibodies against S1 region except for RBD of SARS-CoV-2 were reported to have neutralizing activity [18, 19]. We should detect NAbs by using S1-coated particles, including RBD region for analyzing neutralization antibody. Last, we found the persistence of NAbs in patients with COVID-19 around 70 d...
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.
Results from scite Reference Check: We found no unreliable references.
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