SARS-CoV-2 mucosal antibody development and persistence and their relation to viral load and COVID-19 symptoms
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Abstract
Although serological studies have shown that antibodies against SARS-CoV-2 play an important role in protection against (re)infection, the dynamics of mucosal antibodies during primary infection and their potential impact on viral load and the resolution of disease symptoms remain unclear. During the first pandemic wave, we assessed the longitudinal nasal antibody response in index cases with mild COVID-19 and their household contacts. Nasal and serum antibody responses were analysed for up to nine months. Higher nasal receptor binding domain and spike protein-specific antibody levels at study inclusion were associated with lower viral load. Older age was correlated with more frequent COVID-19 related symptoms. Receptor binding domain and spike protein-specific mucosal antibodies were associated with the resolution of systemic, but not respiratory symptoms. Finally, receptor binding domain and spike protein-specific mucosal antibodies remained elevated up to nine months after symptom onset.
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      SciScore for 10.1101/2021.02.02.21250910: (What is this?) Please note, not all rigor criteria are appropriate for all manuscripts. Table 1: Rigor Institutional Review Board Statement IRB: The study was approved by the local medical research ethics committee and is registered with ClinicalTrials.gov (NCT04590352; ethical committee reference NL73418.091.20). 
 Consent: Following informed consent, nasopharyngeal and oropharyngeal swabs were taken for viral PCR, as per diagnostic guidelines53.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources Antibodies Sentences Resources Additionally, we used a Naïve Bayesian probabilistic model (R-package “naivebayes”, with prior probabilities derived as the class proportions for the training set, and Laplace smoothing set at 1) to … SciScore for 10.1101/2021.02.02.21250910: (What is this?) Please note, not all rigor criteria are appropriate for all manuscripts. Table 1: Rigor Institutional Review Board Statement IRB: The study was approved by the local medical research ethics committee and is registered with ClinicalTrials.gov (NCT04590352; ethical committee reference NL73418.091.20). 
 Consent: Following informed consent, nasopharyngeal and oropharyngeal swabs were taken for viral PCR, as per diagnostic guidelines53.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources Antibodies Sentences Resources Additionally, we used a Naïve Bayesian probabilistic model (R-package “naivebayes”, with prior probabilities derived as the class proportions for the training set, and Laplace smoothing set at 1) to identify cases within the PCR/seronegative contacts by the anti-S MLF antibody response on day 28. anti-S MLFsuggested: NoneSoftware and Algorithms Sentences Resources Statistical analyses: Analysis of Luminex data was performed with Bio-Plex 200 in combination with Bio-Plex manager software (Bio-Rad Laboratories, Hercules, CA). Bio-Rad Laboratoriessuggested: (Bio-Rad Laboratories, RRID:SCR_008426)All statistical analyses were performed using the Rstudio environment, with libraries ‘stats’ (hypothesis tests and correlations), “naivebayes” for the naïve Bayes classification, “lme4” 56, “lmerTest” 57 for mixed-effects modelling and associated p-values, and “survival” 58 for Kaplan-Meier survival analysis. Rstudiosuggested: (RStudio, RRID:SCR_000432)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:Our study has several limitations. First, the starting point for our study was the inclusion of healthcare workers, most of whom were female, and not entirely representative for the larger population. It should be noted that this study was performed during the first wave in March-April of 2020, when all schools in the Netherlands were closed (Figure 1b), minimizing contacts between children and thus making it hard to study the role of child-child contacts in the transmission of SARS-CoV-2. Lastly, additional mucosal lining fluid measurements would have enabled more advanced modelling of the mucosal antibody trajectories, especially in the household contacts. This study provides an example of the unique possibilities of studying mucosal antibody trajectories. It provides essential new insights into the mucosal antibody kinetics after a SARS-CoV-2 infection, and uncovers novel relations with viral load and symptom resolution. Furthermore, the study design and analysis strategy presented here can be used as a blueprint for follow-up investigations not only for COVID-19, but also for other infectious diseases. The ability to collect repetitive mucosal antibody samples in a non-invasive manner removes an important obstacle for use in age groups that are normally difficult to sample, such as children. Results from TrialIdentifier: We found the following clinical trial numbers in your paper: Identifier Status Title NCT04590352 Completed Mucosal Immunity Against SARS-CoV-2 Infection in COVID-19 Pa… 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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