Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection
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Abstract
Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.
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SciScore for 10.1101/2020.10.13.20211763: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics statement: The COVIDsortium Healthcare Workers bioresource was approved by the ethical committee of UK National Research Ethics Service (20/SC/0149) and registered on ClinicalTrials.gov (NCT04318314).
Consent: The study conformed to the principles of the Helsinki Declaration, and all subjects gave written informed consent.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mean age of the cohort (n=731) was 38±11 years; 33% are male, 31% nurses, 20% doctors, and 19% work in intensive care units. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources SARS-CoV-2 test; Ab … SciScore for 10.1101/2020.10.13.20211763: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics statement: The COVIDsortium Healthcare Workers bioresource was approved by the ethical committee of UK National Research Ethics Service (20/SC/0149) and registered on ClinicalTrials.gov (NCT04318314).
Consent: The study conformed to the principles of the Helsinki Declaration, and all subjects gave written informed consent.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mean age of the cohort (n=731) was 38±11 years; 33% are male, 31% nurses, 20% doctors, and 19% work in intensive care units. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources SARS-CoV-2 test; Ab testing baseline and weekly: IgG Ab assay to spike protein S1 antigen, (EUROIMMUN Anti-SARS-CoV-2 enzyme-linked immunosorbent assay [ELISA]); and anti-nucleocapsid total antibody assay (ROCHE Elecsys Anti-SARS-CoV-2 electrochemiluminescence immunoassay [ECLIA]) anti-nucleocapsid totalsuggested: NoneAntibody ratios ≥ 1.1 were considered test positive for the EUROIMMUN SARS-CoV-2 ELISA and >1 was considered test positive for the ROCHE Elecsys anti-SARS-CoV-2 ECLIA following published Public Health England (PHE) evaluations. Evaluation of Roche Elecsys Anti-SARS-CoV-2 serology assay for the detection of anti-SARS-CoV-2 antibodies. anti-SARS-CoV-2suggested: None[https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/891598/Evaluation_of_Roche_Elecsys_anti_SARS_CoV_2_PHE_200610_v8.1_FINAL.pdf] Evaluation of Euroimmun Anti-SARS-CoV-2 ELISA (IgG) serology assay for the detection of antibodies. Anti-SARS-CoV-2 ELISA ( IgGsuggested: NoneThe cross-sectional case controlled sub-study included 76 HCW (mean age 41y, 36% male) with laboratory defined evidence of SARS-CoV-2 either by SARS-CoV-2 positive PCR and/or positive for spike IgG (Euroimmun ELISA)/ NP IgG/IgM antibody (Roche Elecsys). NP IgG/IgMsuggested: NoneAn OD ratio of ≥1.1 was interpreted as positive for S1 antibodies by manufacturer’s recommendation. S1suggested: NoneELISpot plates were developed with human biotinylated IFN-γ detection antibody (7-B6-1, Mabtech; 1µg/ml) for 3h at room temperature, followed by incubation with goat anti-biotin alkaline phosphatase (Vector Laboratories; 1:1000) for 2h at room temperature, both diluted in PBS with 0.5% BSA by volume (Sigma-Aldrich), and finally with 50µl/well of sterile filtered BCIP/NBT Phosphatase Substrate (ThermoFisher) for 7 minutes at room temperature. anti-biotin alkaline phosphatasesuggested: NoneWhite ELISA plates were pre-coated with 5µg/ml sheep anti-HIV-1 p24 antibody (Aalto Bio Reagents) at 4°C overnight. anti-HIV-1suggested: NoneExperimental Models: Cell Lines Sentences Resources Cell Lines: HEK-293T and Huh7 (both ATCC) were cultured and maintained in high glucose Dulbecco’s Modified Eagle’s Medium and supplemented with GlutaMAX, 10% (v/v) heat-inactivated foetal bovine serum (FBS, 56°C for 30 minutes), 100IU/ml penicillin and 100µg/ml streptomycin. HEK-293Tsuggested: NoneTCID assays were performed by transduction of Huh7 cells to calculate the viral titre and infectious dose for neutralisation assays. Huh7suggested: CLS Cat# 300156/p7178_HuH7, RRID:CVCL_0336)Software and Algorithms Sentences Resources Ethics statement: The COVIDsortium Healthcare Workers bioresource was approved by the ethical committee of UK National Research Ethics Service (20/SC/0149) and registered on ClinicalTrials.gov (NCT04318314). COVIDsortium Healthcaresuggested: NoneCytokine levels in cell culture supernatants in response to PBMC stimulation with Spike or NP protein were calculated in Microsoft Excel by subtracting values obtained for media only controls. Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)Standard curves were plotted using Prism 8.0 for Mac OS (GraphPad). Prismsuggested: (PRISM, RRID:SCR_005375)The curves of relative infection rates (in %) versus the serum dilutions (log10 values) against a negative control of pooled sera collected prior to 2016 (Sigma) and a positive neutraliser were plotted using Prism 8 (GraphPad). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)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 NCT04318314 Recruiting COVID-19: Healthcare Worker Bioresource: Immune Protection a… 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 10.1101/2020.10.13.20211763: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
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 NCT04318314 Recruiting COVID-19: … SciScore for 10.1101/2020.10.13.20211763: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
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 NCT04318314 Recruiting COVID-19: Healthcare Worker Bioresource: Immune Protection a... 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
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
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