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Department of Clinical Medicine

Stine Sofie Frank Lende

SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses

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SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses. / Vibholm, Line K; Nielsen, Stine Sf ; Pahus, Marie H et al.

In: EBioMedicine, Vol. 64, 103230, 02.2021.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Vancouver

Vibholm LK, Nielsen SS , Pahus MH, Frattari GS, Olesen R, Andersen R et al. SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses. EBioMedicine. 2021 Feb;64:103230. Epub 2021 Jan 30. doi: 10.1016/j.ebiom.2021.103230

Author

Vibholm, Line K ; Nielsen, Stine Sf ; Pahus, Marie H et al. / SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses. In: EBioMedicine. 2021 ; Vol. 64.

Bibtex

@article{f1006a1094254765b70f8cf80aca747d,

title = "SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses",

abstract = "BACKGROUND: Upon SARS-CoV-2 infection, most individuals develop neutralizing antibodies and T-cell immunity. However, some individuals reportedly remain SARS-CoV-2 PCR positive by pharyngeal swabs weeks after recovery. Whether viral RNA in these persistent carriers is contagious and stimulates SARS-CoV-2-specific immune responses is unknown.METHODS: This cohort study was conducted between April 3rd-July 9th 2020, recruiting COVID-19 recovered individuals that were symptom-free for at least 14 days. We collected serum for SARS-CoV-2-specific total Ig, IgA and IgM detection by ELISA, pharyngeal swabs (two time points) for ddPCR and PBMCs for anti-SARS-CoV-2 CD8 T-cell dextramer analyses.FINDINGS: We enrolled 203 post-symptomatic participants with a previous RT-PCR-verified SARS-CoV-2 infection. At time point 1, a median of 23 days (range 15-44) after recovery, 26 individuals (12⋅8%) were PCR positive. At time point 2, 90 days (median, range 85-105) after recovery, 5 (5⋅3%) were positive. There was no difference in SARS-CoV-2 antibody levels between the PCR negative and positive group. The persistent PCR positive group however, had SARS-CoV-2-specific CD8 T-cell responses of significantly increased breadth and magnitude. Assisted contact tracing among persistent PCR positive individuals revealed zero new COVID-19 diagnoses among 757 close contacts.INTERPRETATION: Persistent pharyngeal SARS-CoV-2 PCR positivity in post-symptomatic individuals is associated with elevated cellular immune responses and thus, the viral RNA may represent replicating virus. However, transmission to close contacts was not observed indicating that persistent PCR positive individuals are not contagious at the post-symptomatic stage of the infection.",

author = "Vibholm, {Line K} and Nielsen, {Stine Sf} and Pahus, {Marie H} and Frattari, {Giacomo S} and Rikke Olesen and Rebecca Andersen and Ida Monrad and Andersen, {Anna H.F.} and Thomsen, {Michelle M} and Konrad, {Christina V} and Andersen, {Sidsel D} and H{\o}jen, {Jesper F} and Gunst, {Jesper D} and Lars {\O}stergaard and S{\o}gaard, {Ole S} and Schleimann, {Mariane H} and Martin Tolstrup",

year = "2021",

month = feb,

doi = "10.1016/j.ebiom.2021.103230",

language = "English",

volume = "64",

journal = "EBioMedicine",

issn = "2352-3964",

publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses

AU - Vibholm, Line K

AU - Nielsen, Stine Sf

AU - Pahus, Marie H

AU - Frattari, Giacomo S

AU - Olesen, Rikke

AU - Andersen, Rebecca

AU - Monrad, Ida

AU - Andersen, Anna H.F.

AU - Thomsen, Michelle M

AU - Konrad, Christina V

AU - Andersen, Sidsel D

AU - Højen, Jesper F

AU - Gunst, Jesper D

AU - Østergaard, Lars

AU - Søgaard, Ole S

AU - Schleimann, Mariane H

AU - Tolstrup, Martin

PY - 2021/2

Y1 - 2021/2

N2 - BACKGROUND: Upon SARS-CoV-2 infection, most individuals develop neutralizing antibodies and T-cell immunity. However, some individuals reportedly remain SARS-CoV-2 PCR positive by pharyngeal swabs weeks after recovery. Whether viral RNA in these persistent carriers is contagious and stimulates SARS-CoV-2-specific immune responses is unknown.METHODS: This cohort study was conducted between April 3rd-July 9th 2020, recruiting COVID-19 recovered individuals that were symptom-free for at least 14 days. We collected serum for SARS-CoV-2-specific total Ig, IgA and IgM detection by ELISA, pharyngeal swabs (two time points) for ddPCR and PBMCs for anti-SARS-CoV-2 CD8 T-cell dextramer analyses.FINDINGS: We enrolled 203 post-symptomatic participants with a previous RT-PCR-verified SARS-CoV-2 infection. At time point 1, a median of 23 days (range 15-44) after recovery, 26 individuals (12⋅8%) were PCR positive. At time point 2, 90 days (median, range 85-105) after recovery, 5 (5⋅3%) were positive. There was no difference in SARS-CoV-2 antibody levels between the PCR negative and positive group. The persistent PCR positive group however, had SARS-CoV-2-specific CD8 T-cell responses of significantly increased breadth and magnitude. Assisted contact tracing among persistent PCR positive individuals revealed zero new COVID-19 diagnoses among 757 close contacts.INTERPRETATION: Persistent pharyngeal SARS-CoV-2 PCR positivity in post-symptomatic individuals is associated with elevated cellular immune responses and thus, the viral RNA may represent replicating virus. However, transmission to close contacts was not observed indicating that persistent PCR positive individuals are not contagious at the post-symptomatic stage of the infection.

AB - BACKGROUND: Upon SARS-CoV-2 infection, most individuals develop neutralizing antibodies and T-cell immunity. However, some individuals reportedly remain SARS-CoV-2 PCR positive by pharyngeal swabs weeks after recovery. Whether viral RNA in these persistent carriers is contagious and stimulates SARS-CoV-2-specific immune responses is unknown.METHODS: This cohort study was conducted between April 3rd-July 9th 2020, recruiting COVID-19 recovered individuals that were symptom-free for at least 14 days. We collected serum for SARS-CoV-2-specific total Ig, IgA and IgM detection by ELISA, pharyngeal swabs (two time points) for ddPCR and PBMCs for anti-SARS-CoV-2 CD8 T-cell dextramer analyses.FINDINGS: We enrolled 203 post-symptomatic participants with a previous RT-PCR-verified SARS-CoV-2 infection. At time point 1, a median of 23 days (range 15-44) after recovery, 26 individuals (12⋅8%) were PCR positive. At time point 2, 90 days (median, range 85-105) after recovery, 5 (5⋅3%) were positive. There was no difference in SARS-CoV-2 antibody levels between the PCR negative and positive group. The persistent PCR positive group however, had SARS-CoV-2-specific CD8 T-cell responses of significantly increased breadth and magnitude. Assisted contact tracing among persistent PCR positive individuals revealed zero new COVID-19 diagnoses among 757 close contacts.INTERPRETATION: Persistent pharyngeal SARS-CoV-2 PCR positivity in post-symptomatic individuals is associated with elevated cellular immune responses and thus, the viral RNA may represent replicating virus. However, transmission to close contacts was not observed indicating that persistent PCR positive individuals are not contagious at the post-symptomatic stage of the infection.

U2 - 10.1016/j.ebiom.2021.103230

DO - 10.1016/j.ebiom.2021.103230

M3 - Journal article

C2 - 33530000

VL - 64

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

M1 - 103230

ER -