Neutralisation titres against SARS-CoV-2 are sustained 6 months after onset of symptoms in individuals with mild COVID-19

Alexander P Underwood; Christina Sølund; Carlota Fernandez-Antunez; Signe Lysemose Villadsen; Anni Assing Winckelmann; Signe Bollerup; Lotte S Mikkelsen; Anna-Louise Sørensen; Shan Feng; Ulrik Fahnøe; Ria Lassauniere; Anders Fomsgaard; Santseharay Ramirez; Nina Weis; Jens Bukh

doi:10.1016/j.ebiom.2021.103519

Neutralisation titres against SARS-CoV-2 are sustained 6 months after onset of symptoms in individuals with mild COVID-19

Alexander P Underwood, Christina Sølund, Carlota Fernandez-Antunez, Signe Lysemose Villadsen, Anni Assing Winckelmann, Signe Bollerup, Lotte S Mikkelsen, Anna-Louise Sørensen, Shan Feng, Ulrik Fahnøe, Ria Lassauniere, Anders Fomsgaard, Santseharay Ramirez, Nina Weis, Jens Bukh

Department of Infectious Diseases

11 Citations (Scopus)

Abstract

BACKGROUND: Given the importance of neutralising antibodies in protection against SARS-CoV-2 infection, it is critical to assess neutralisation persistence long-term following recovery. This study investigated neutralisation titres against SARS-CoV-2 up to 6 months post-symptom onset in individuals with mild COVID-19.

METHODS: Plasma neutralisation titres in convalescent COVID-19 individuals were determined at baseline and 6 months post-symptom onset using a cell culture infectious SARS-CoV-2 assay. Total SARS-CoV-2 spike-specific IgG and IgA binding was measured using a lectin capture ELISA and compared between timepoints and correlated to neutralising titres.

FINDINGS: All 48 convalescent COVID-19 individuals were found to have detectable SARS-CoV-2 50% inhibitory dilution neutralisation titres (ID50) at baseline and 6 months post-symptom onset with mean ID50 of 1/943 and 1/411, respectively. SARS-CoV-2 neutralisation titres peaked within 1-2 months post-symptom onset. However, 50% of individuals showed comparable ID50 at baseline and 6 months post-symptom onset. Both SARS-CoV-2 spike-specific IgG and IgA levels correlated well with neutralising titres. IgG binding was found to be sustained up to 6 months post-symptom onset, whereas IgA levels declined.

INTERPRETATION: This study demonstrates durability of SARS-CoV-2 spike-specific IgG and neutralisation responses following recovery from mild COVID-19. Thus, all subjects included in this study might potentially have protective levels of neutralising antibodies 6 months post-symptom onset. This study also demonstrates a relationship between spike-specific IgA and neutralisation decline, with implications for long-term protection against SARS-CoV-2 infection.

FUNDING: Novo Nordisk Foundation, Independent Research Fund Denmark and Danish Agency for Science and Higher Education.

Original language	English
Article number	103519
Journal	EBioMedicine
Volume	71
Pages (from-to)	1-10
Number of pages	10
DOIs	https://doi.org/10.1016/j.ebiom.2021.103519
Publication status	Published - Sep 2021

Keywords

COVID-19
IgA
IgG
neutralisation
neutralising antibodies
SARS-CoV-2

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10.1016/j.ebiom.2021.103519

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Underwood, A. P., Sølund, C., Fernandez-Antunez, C., Villadsen, S. L., Winckelmann, A. A., Bollerup, S., Mikkelsen, L. S., Sørensen, A-L., Feng, S., Fahnøe, U., Lassauniere, R., Fomsgaard, A., Ramirez, S., Weis, N., & Bukh, J. (2021). Neutralisation titres against SARS-CoV-2 are sustained 6 months after onset of symptoms in individuals with mild COVID-19. EBioMedicine, 71, 1-10. [103519]. https://doi.org/10.1016/j.ebiom.2021.103519

Underwood, AP , Sølund, C , Fernandez-Antunez, C , Villadsen, SL , Winckelmann, AA , Bollerup, S , Mikkelsen, LS , Sørensen, A-L , Feng, S , Fahnøe, U, Lassauniere, R, Fomsgaard, A, Ramirez, S , Weis, N & Bukh, J 2021, 'Neutralisation titres against SARS-CoV-2 are sustained 6 months after onset of symptoms in individuals with mild COVID-19', EBioMedicine, vol. 71, 103519, pp. 1-10. https://doi.org/10.1016/j.ebiom.2021.103519

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title = "Neutralisation titres against SARS-CoV-2 are sustained 6 months after onset of symptoms in individuals with mild COVID-19",

abstract = "BACKGROUND: Given the importance of neutralising antibodies in protection against SARS-CoV-2 infection, it is critical to assess neutralisation persistence long-term following recovery. This study investigated neutralisation titres against SARS-CoV-2 up to 6 months post-symptom onset in individuals with mild COVID-19.METHODS: Plasma neutralisation titres in convalescent COVID-19 individuals were determined at baseline and 6 months post-symptom onset using a cell culture infectious SARS-CoV-2 assay. Total SARS-CoV-2 spike-specific IgG and IgA binding was measured using a lectin capture ELISA and compared between timepoints and correlated to neutralising titres.FINDINGS: All 48 convalescent COVID-19 individuals were found to have detectable SARS-CoV-2 50% inhibitory dilution neutralisation titres (ID50) at baseline and 6 months post-symptom onset with mean ID50 of 1/943 and 1/411, respectively. SARS-CoV-2 neutralisation titres peaked within 1-2 months post-symptom onset. However, 50% of individuals showed comparable ID50 at baseline and 6 months post-symptom onset. Both SARS-CoV-2 spike-specific IgG and IgA levels correlated well with neutralising titres. IgG binding was found to be sustained up to 6 months post-symptom onset, whereas IgA levels declined.INTERPRETATION: This study demonstrates durability of SARS-CoV-2 spike-specific IgG and neutralisation responses following recovery from mild COVID-19. Thus, all subjects included in this study might potentially have protective levels of neutralising antibodies 6 months post-symptom onset. This study also demonstrates a relationship between spike-specific IgA and neutralisation decline, with implications for long-term protection against SARS-CoV-2 infection.FUNDING: Novo Nordisk Foundation, Independent Research Fund Denmark and Danish Agency for Science and Higher Education.",

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author = "Underwood, {Alexander P} and Christina S{\o}lund and Carlota Fernandez-Antunez and Villadsen, {Signe Lysemose} and Winckelmann, {Anni Assing} and Signe Bollerup and Mikkelsen, {Lotte S} and Anna-Louise S{\o}rensen and Shan Feng and Ulrik Fahn{\o}e and Ria Lassauniere and Anders Fomsgaard and Santseharay Ramirez and Nina Weis and Jens Bukh",

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year = "2021",

month = sep,

doi = "10.1016/j.ebiom.2021.103519",

language = "English",

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T1 - Neutralisation titres against SARS-CoV-2 are sustained 6 months after onset of symptoms in individuals with mild COVID-19

AU - Underwood, Alexander P

AU - Sølund, Christina

AU - Fernandez-Antunez, Carlota

AU - Villadsen, Signe Lysemose

AU - Winckelmann, Anni Assing

AU - Bollerup, Signe

AU - Mikkelsen, Lotte S

AU - Sørensen, Anna-Louise

AU - Feng, Shan

AU - Fahnøe, Ulrik

AU - Lassauniere, Ria

AU - Fomsgaard, Anders

AU - Ramirez, Santseharay

AU - Weis, Nina

AU - Bukh, Jens

PY - 2021/9

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N2 - BACKGROUND: Given the importance of neutralising antibodies in protection against SARS-CoV-2 infection, it is critical to assess neutralisation persistence long-term following recovery. This study investigated neutralisation titres against SARS-CoV-2 up to 6 months post-symptom onset in individuals with mild COVID-19.METHODS: Plasma neutralisation titres in convalescent COVID-19 individuals were determined at baseline and 6 months post-symptom onset using a cell culture infectious SARS-CoV-2 assay. Total SARS-CoV-2 spike-specific IgG and IgA binding was measured using a lectin capture ELISA and compared between timepoints and correlated to neutralising titres.FINDINGS: All 48 convalescent COVID-19 individuals were found to have detectable SARS-CoV-2 50% inhibitory dilution neutralisation titres (ID50) at baseline and 6 months post-symptom onset with mean ID50 of 1/943 and 1/411, respectively. SARS-CoV-2 neutralisation titres peaked within 1-2 months post-symptom onset. However, 50% of individuals showed comparable ID50 at baseline and 6 months post-symptom onset. Both SARS-CoV-2 spike-specific IgG and IgA levels correlated well with neutralising titres. IgG binding was found to be sustained up to 6 months post-symptom onset, whereas IgA levels declined.INTERPRETATION: This study demonstrates durability of SARS-CoV-2 spike-specific IgG and neutralisation responses following recovery from mild COVID-19. Thus, all subjects included in this study might potentially have protective levels of neutralising antibodies 6 months post-symptom onset. This study also demonstrates a relationship between spike-specific IgA and neutralisation decline, with implications for long-term protection against SARS-CoV-2 infection.FUNDING: Novo Nordisk Foundation, Independent Research Fund Denmark and Danish Agency for Science and Higher Education.

AB - BACKGROUND: Given the importance of neutralising antibodies in protection against SARS-CoV-2 infection, it is critical to assess neutralisation persistence long-term following recovery. This study investigated neutralisation titres against SARS-CoV-2 up to 6 months post-symptom onset in individuals with mild COVID-19.METHODS: Plasma neutralisation titres in convalescent COVID-19 individuals were determined at baseline and 6 months post-symptom onset using a cell culture infectious SARS-CoV-2 assay. Total SARS-CoV-2 spike-specific IgG and IgA binding was measured using a lectin capture ELISA and compared between timepoints and correlated to neutralising titres.FINDINGS: All 48 convalescent COVID-19 individuals were found to have detectable SARS-CoV-2 50% inhibitory dilution neutralisation titres (ID50) at baseline and 6 months post-symptom onset with mean ID50 of 1/943 and 1/411, respectively. SARS-CoV-2 neutralisation titres peaked within 1-2 months post-symptom onset. However, 50% of individuals showed comparable ID50 at baseline and 6 months post-symptom onset. Both SARS-CoV-2 spike-specific IgG and IgA levels correlated well with neutralising titres. IgG binding was found to be sustained up to 6 months post-symptom onset, whereas IgA levels declined.INTERPRETATION: This study demonstrates durability of SARS-CoV-2 spike-specific IgG and neutralisation responses following recovery from mild COVID-19. Thus, all subjects included in this study might potentially have protective levels of neutralising antibodies 6 months post-symptom onset. This study also demonstrates a relationship between spike-specific IgA and neutralisation decline, with implications for long-term protection against SARS-CoV-2 infection.FUNDING: Novo Nordisk Foundation, Independent Research Fund Denmark and Danish Agency for Science and Higher Education.

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KW - IgG

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KW - neutralising antibodies

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DO - 10.1016/j.ebiom.2021.103519

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JO - EBioMedicine

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Neutralisation titres against SARS-CoV-2 are sustained 6 months after onset of symptoms in individuals with mild COVID-19

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