Immunological memory to SARS-CoV-2 assessed for up to eight months after infection
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- Evaluated articles (Rapid Reviews Infectious Diseases)
Abstract
Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4 + T cells and CD8 + T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4 + T cell, and CD8 + T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
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Claude-Agnès Reynaud
Review 1: "Immunological memory to SARS-CoV-2 assessed for greater than six months after infection"
Reviewers: Claude-Agnès Reynaud (Institut Necker-Enfants Malades) | 📘📘📘📘📘
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Claude-Agnès Reynaud
Review of "Immunological memory to SARS-CoV-2 assessed for greater than six months after infection"
Reviewers: Claude-Agnès Reynaud (Institut Necker-Enfants Malades) | 📘📘📘📘📘
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SciScore for 10.1101/2020.11.15.383323: (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
Software and Algorithms Sentences Resources Materials and Methods Figures S1-S10 Tables S1-S2 Data File Materials and Methods: Methodssuggested: NoneResults from OddPub: Thank you for sharing your data.
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: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage …
SciScore for 10.1101/2020.11.15.383323: (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
Software and Algorithms Sentences Resources Materials and Methods Figures S1-S10 Tables S1-S2 Data File Materials and Methods: Methodssuggested: NoneResults from OddPub: Thank you for sharing your data.
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: 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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SciScore for 10.1101/2020.11.15.383323: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement METHODS Human Subjects The Institutional Review Boards of the University of California, San Diego (UCSD; 200236X) and the La Jolla Institute for Immunology (LJI; VD-214) approved the protocols used for blood collection for subjects with COVID-19 who donated at all sites other than Mt. Sinai. The Icahn School of Medicine at Mt. Sinai IRB approved the samples collected at this institution in New York City ( Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Subjects (43% male, 57% female) represented a range of asymptomatic, mild, moderate, and severe COVID-19 cases (Table S1), and were recruited from multiple sites … SciScore for 10.1101/2020.11.15.383323: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement METHODS Human Subjects The Institutional Review Boards of the University of California, San Diego (UCSD; 200236X) and the La Jolla Institute for Immunology (LJI; VD-214) approved the protocols used for blood collection for subjects with COVID-19 who donated at all sites other than Mt. Sinai. The Icahn School of Medicine at Mt. Sinai IRB approved the samples collected at this institution in New York City ( Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Subjects (43% male, 57% female) represented a range of asymptomatic, mild, moderate, and severe COVID-19 cases (Table S1), and were recruited from multiple sites throughout the United States. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The percentage of subjects seropositive for SARS-CoV-2 neutralizing antibodies (titer > 20) at 6 to 8 months PSO was 90% (36/40). SARS-CoV-2 neutralizing antibodies (titer > 20suggested: NoneFor IgG, anti-human IgG peroxidase antibody produced in goat (Sigma A6029) was used at a 1:5,000 dilution. anti-human IgG peroxidase antibodysuggested: (Sigma-Aldrich Cat# A6029, RRID:AB_258272)anti-human IgGsuggested: (Sigma-Aldrich Cat# A6029, RRID:AB_258272)For IgA, anti-human IgA horseradish peroxidase antibody (Hybridoma Reagent Laboratory HP6123-HRP) was used at a 1:1,000 dilution. anti-human IgAsuggested: NoneBiotinylated spike was mixed with streptavidin BV421 (BioLegend, Cat# 405225) and streptavidin Alexa Fluor 647 (Thermo Fisher Scientific, Cat# S21374) at 20:1 ratio (~6:1 molar ratio). ~107 previously frozen PBMC samples were prepared in U-bottom 96-well plates and stained with 50µL antigen probe cocktail containing 100ng spike per probe (total 200ng), 27.5ng RBD, 40ng nucleocapsid per probe (total 80ng) and 20ng streptavidin PECy5.5 at 4°C for one hour to ensure maximal staining quality before surface staining with antibodies as listed in Table S2 was performed in Brilliant Buffer at 4°C for 30min. 30minsuggested: NoneAntibodies utilized in the CD8+ and CD4+ T cell activation induced markers (AIM) assays Membrane Antibody Fluorochrome Clone/vendor/catalog Dilution CD45RA BV421 HI100/BioLegend/304130 1:50 CD14 BUV563 M5E2/BD/741360 1:100 CD19 BUV805 HIB19/BD/742007 1:100 Live/Dead ef506/Aqua Thermo Fisher/65-0866-18 1:200 CD8 BV650 RPA-T8/BioLegend/301042 1:50 CD4 BV605 RPA-T4/BD/562658 1:25 CCR7 FITC G043H7/BioLegend/353216 1:50 CD69 PE FN50/BD/555531 1:10 OX40 PE-Cy7 Ber-ACT35/BioLegend/350012 1:50 CD137 APC 4B4-1/BioLegend/309810 1:25 CD3 AF700 UCHT1/Thermo Fisher/56-0038-42 1:25 SUPPLEMENTARY FIGURE LEGENDS Figure S1. CD14suggested: (BD Biosciences Cat# 741360, RRID:AB_2870860)Ber-ACT35/BioLegend/350012suggested: NoneCD3suggested: (Thermo Fisher Scientific Cat# 56-0038-42, RRID:AB_10597906)Three data points are outside the axis limits (C) The ratio of RBD-specific memory B cell frequency (percentage) relative to RBD IgA antibodies (pseudo-first order kinetic model, R2 = 0.3804). RBD IgAsuggested: NoneR2suggested: None( D) The ratio of SARS-CoV-2 specific CD4+ T cell frequency relative to RBD IgG antibodies (best-fit simple linear regression line, R2 = 0.0003891). RBD IgGsuggested: (Thermo Fisher Scientific Cat# 703971, RRID:AB_2866480)Experimental Models: Cell Lines Sentences Resources Briefly, Vero cells were seeded in 96 well plates to produce a monolayer at the time of infection. Verosuggested: NonePre-titrated amounts of rVSV-SARS-Cov-2 (phCMV3-SARS-CoV-2 spike SARS-CoV-2-pseduotyped VSV-ΔG-GFP were generated by transfecting 293T cells) were incubated with serially diluted human plasma at 37°C for hour before addition to confluent Vero monolayers in 96-well plates. 293Tsuggested: NoneSoftware and Algorithms Sentences Resources For gender analyses, modeling and t1/2 was performed similar to cross-sectional analyses; ANCOVA (VassarStats or GraphPad Prism 8.4) was then performed between male and female data sets. VassarStatssuggested: (VassarStats, RRID:SCR_010263)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Neutralization IC50 titers were calculated using One-Site Fit LogIC50 regression in GraphPad Prism 8.0. GraphPad Prismsuggested: (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: 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.
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