Durability of SARS-CoV-2-specific T cell responses at 12-months post-infection
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Abstract
Background
Characterizing the longevity and quality of cellular immune responses to SARS-CoV-2 is critical to understanding immunologic approaches to protection against COVID-19. Prior studies suggest SARS-CoV-2-specific T cells are present in peripheral blood 10 months after infection. Further analysis of the function, durability, and diversity of the cellular response long after natural infection, over a wider range of ages and disease phenotypes, is needed to further identify preventative and therapeutic interventions.
Methods
We identified participants in our multi-site longitudinal, prospective cohort study 12-months post SARS-CoV-2 infection representing a range of disease severity. We investigated the function, phenotypes, and frequency of T cells specific for SARS-CoV-2 using intracellular cytokine staining and spectral flow cytometry. In parallel, the magnitude of SARS-CoV-2-specific antibodies was compared.
Results
SARS-CoV-2-specific antibodies and T cells were detected at 12-months post-infection. Severity of acute illness was associated with higher frequencies of SARS-CoV-2-specific CD4 T cells and antibodies at 12-months. In contrast, polyfunctional and cytotoxic T cells responsive to SARS-CoV-2 were identified in participants over a wide spectrum of disease severity.
Conclusions
Our data show that SARS-CoV-2 infection induces polyfunctional memory T cells detectable at 12-months post-infection, with higher frequency noted in those who originally experienced severe disease.
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SciScore for 10.1101/2021.08.11.455984: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The protocol was approved by the Uniformed Services University Institutional Review Board (IDCRP-085), and all subjects or their legally authorized representative provided informed consent to participate.
Consent: The protocol was approved by the Uniformed Services University Institutional Review Board (IDCRP-085), and all subjects or their legally authorized representative provided informed consent to participate.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Ten minutes after addition of the peptide pools, CD107a antibody (BioLegend, CA) was added. CD107asuggested: None… SciScore for 10.1101/2021.08.11.455984: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The protocol was approved by the Uniformed Services University Institutional Review Board (IDCRP-085), and all subjects or their legally authorized representative provided informed consent to participate.
Consent: The protocol was approved by the Uniformed Services University Institutional Review Board (IDCRP-085), and all subjects or their legally authorized representative provided informed consent to participate.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Ten minutes after addition of the peptide pools, CD107a antibody (BioLegend, CA) was added. CD107asuggested: NoneSoftware and Algorithms Sentences Resources All cytometric data were analyzed using FlowJo software (BD Biosciences, CA). FlowJosuggested: (FlowJo, RRID:SCR_008520)A final wash was performed after 45 minutes of incubation, and antigen-antibody complexes were analyzed on BioPlex 200 multiplexing systems (Bio-Rad) for IgG binding, and median fluorescence intensity (MFI) values were reported for specificity to SARS-CoV-2 S and N protein. BioPlexsuggested: (BioPlex, RRID:SCR_016144)Statistical analysis: Data were analyzed using GraphPad Prism 9 (GraphPad Software Inc, CA). 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: We detected the following sentences addressing limitations in the study:Limitations to our study include the challenge of obtaining biological samples at 12-months PSO prior to vaccination in our MHS cohort, which had timely and reliable access to vaccines. Fifty percent of individuals in our cohort were vaccinated prior to a 12-month draw (Table 1). For these individuals we did not include their S-specific T cell or antibody responses, but did include their N, M and E humoral or cellular responses since these are not components of the mRNA-based vaccines (the vaccines primarily available to our study population). A strength of our cohort is that study participants are followed within the MHS and their epidemiologic, clinical and COVID-19 testing records, and vaccination status are maintained primarily from electronic health record. In addition, sera were analyzed longitudinally to avoid re-infected participants for 12-months T cell analysis. In summary, our data show that both SARS-CoV-2 humoral and cellular responses are measurable 12-months PSO in individuals across a spectrum of disease phenotypes. The magnitude of the CD4 T cell and antibody responses more closely correlated with acute disease severity. Importantly, the memory phenotype and polyfunctional response of the SARS-CoV-2 specific T cells did not differ by disease severity. The breadth of T cell epitope recognition by these memory T cells may provide more durable protection against emerging SARS-CoV-2 variants.
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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