SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2
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Abstract
As of January 2022, at least 60 million individuals are estimated to develop post-acute sequelae of SARS-CoV-2 (PASC) after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While elevated levels of SARS-CoV-2-specific T cells have been observed in non-specific PASC, little is known about their impact on pulmonary function which is compromised in the majority of these individuals. This study compares frequencies of SARS-CoV-2-specific T cells and inflammatory markers with lung function in participants with pulmonary PASC and resolved COVID-19 (RC). Compared to RC, participants with respiratory PASC had between 6- and 105-fold higher frequencies of IFN-γ- and TNF-α-producing SARS-CoV-2-specific CD4 + and CD8 + T cells in peripheral blood, and elevated levels of plasma CRP and IL-6. Importantly, in PASC participants the frequency of TNF-α-producing SARS-CoV-2-specific CD4 + and CD8 + T cells, which exhibited the highest levels of Ki67 indicating they were activity dividing, correlated positively with plasma IL-6 and negatively with measures of lung function, including forced expiratory volume in one second (FEV 1 ), while increased frequencies of IFN-γ-producing SARS-CoV-2-specific T cells associated with prolonged dyspnea. Statistical analyses stratified by age, number of comorbidities and hospitalization status demonstrated that none of these factors affect differences in the frequency of SARS-CoV-2 T cells and plasma IL-6 levels measured between PASC and RC cohorts. Taken together, these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms. These findings also provide mechanistic insight on the pathophysiology of PASC that can inform development of potential treatments to reduce symptom burden.
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SciScore for 10.1101/2022.02.14.480317: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Study approval: This study was approved by the Colorado Multiple Institutional Review Board (COMIRB# 20-1219) at the University of Colorado Anschutz Medical Campus.
Consent: All participants provided written informed consent prior to any study procedures.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Flow cytometry: Cells were analyzed using a LSRII flow cytometer (BD Immunocytometry Systems). BD Immunocytometry Systemssuggested: (South Florida University College of Medicine Fred Wright Jr Flow Cytometry Core Facility, RRID:SCR_017901)To ensure accuracy and … SciScore for 10.1101/2022.02.14.480317: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Study approval: This study was approved by the Colorado Multiple Institutional Review Board (COMIRB# 20-1219) at the University of Colorado Anschutz Medical Campus.
Consent: All participants provided written informed consent prior to any study procedures.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Flow cytometry: Cells were analyzed using a LSRII flow cytometer (BD Immunocytometry Systems). BD Immunocytometry Systemssuggested: (South Florida University College of Medicine Fred Wright Jr Flow Cytometry Core Facility, RRID:SCR_017901)To ensure accuracy and precision of the measurements taken from day-to-day, quality control was performed on the LSRII daily using the Cytometer Setup & Tracking (CS&T) feature of the BD FACSDiva software. BD FACSDivasuggested: (BD FACSDiva Software, RRID:SCR_001456)A manual quality control (QC) using rainbow beads was also performed daily to verify the laser delay and area scaling determined by CS&T. Statistics: Statistical analyses were performed using GraphPad-Prism (Graphpad, San Diego, CA). Graphpadsuggested: (GraphPad, RRID:SCR_000306)Both of these student T and permutation tests of the SPICE analysis were corrected for 21 concurrent comparisons(54). SPICEsuggested: (SPICE, RRID:SCR_016603)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: Please consider improving the rainbow (“jet”) colormap(s) used on page 31. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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