Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients

María Martin-Vicente; Raquel Almansa; Isidoro Martínez; Ana P. Tedim; Elena Bustamante; Luis Tamayo; César Aldecoa; José Manuel Gómez; Gloria Renedo; Jose Ángel Berezo; Jamil Antonio Cedeño; Nuria Mamolar; Pablo García Olivares; Rubén Herrán-Monge; Ramón Cicuendez; Pedro Enríquez; Alicia Ortega; Noelia Jorge; Cristina Doncel; Amanda de la Fuente; Juan Bustamante-Munguira; María José Muñoz-Gómez; Milagros González-Rivera; Carolina Puertas; Vicente Más; Mónica Vázquez; Felipe Pérez-García; Jesús Rico-Feijoo; Silvia Martín; Anna Motos; Laia Fernandez-Barat; Jose María Eiros; Marta Dominguez-Gil; Ricard Ferrer; Ferrán Barbé; Wysali Trapiello; David J. Kelvin; Jesús F. Bermejo-Martin; Salvador Resino; Antoni Torres

doi:10.1111/joim.13386

Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients

María Martin-Vicente, Raquel Almansa, Isidoro Martínez, Ana P. Tedim, Elena Bustamante, Luis Tamayo, César Aldecoa, José Manuel Gómez, Gloria Renedo, Jose Ángel Berezo, Jamil Antonio Cedeño, Nuria Mamolar, Pablo García Olivares, Rubén Herrán-Monge, Ramón Cicuendez, Pedro Enríquez, Alicia Ortega, Noelia Jorge, Cristina Doncel, Amanda de la FuenteJuan Bustamante-Munguira, María José Muñoz-Gómez, Milagros González-Rivera, Carolina Puertas, Vicente Más, Mónica Vázquez, Felipe Pérez-García, Jesús Rico-Feijoo, Silvia Martín, Anna Motos, Laia Fernandez-Barat, Jose María Eiros, Marta Dominguez-Gil, Ricard Ferrer, Ferrán Barbé, Wysali Trapiello, David J. Kelvin, Jesús F. Bermejo-Martin, Salvador Resino, Antoni Torres

Medicine

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

Background: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. Patients/Methods: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. Results: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). Conclusions: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.

Original language	English
Pages (from-to)	232-240
Number of pages	9
Journal	Journal of Internal Medicine
Volume	291
Issue number	2
DOIs	https://doi.org/10.1111/joim.13386
Publication status	Published - Feb 2022

Bibliographical note

Funding Information:
We would like to thank the IBSAL and CIBER for administrative support to perform this study.

Funding Information:
This work was supported by awards from the Canadian Institutes of Health Research, (CIHR OV2 – 170357), Research Nova Scotia, Atlantic Genome/Genome Canada, Li‐Ka Shing Foundation, Dalhousie Medical Research Foundation (David J. Kelvin), David J. Kelvin is a recipient of the Canada Research Chair in Translational Vaccinology and Inflammation, and the “Subvenciones de concesión directa para proyectos y programas de investigación del virus SARS‐CoV2, causante del COVID‐19”, FONDO ‐ COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (Antoni Torres) and finally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la financiación de proyectos de investigación en enfermedad COVID‐19” (GRS COVID 53/A/20) (CA). Ana P. Tedim was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co‐financed by the European Development Regional Fund (A Way to Achieve Europe programme). The funding sources did not play any role neither in the design of the study and collection, not in the analysis, in the interpretation of data or in writing the manuscript.

Publisher Copyright:
© 2021 The Association for the Publication of the Journal of Internal Medicine

ASJC Scopus Subject Areas

Internal Medicine

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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10.1111/joim.13386

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Martin-Vicente, M., Almansa, R., Martínez, I., Tedim, A. P., Bustamante, E., Tamayo, L., Aldecoa, C., Gómez, J. M., Renedo, G., Berezo, J. Á., Cedeño, J. A., Mamolar, N., García Olivares, P., Herrán-Monge, R., Cicuendez, R., Enríquez, P., Ortega, A., Jorge, N., Doncel, C., ... Torres, A. (2022). Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients. Journal of Internal Medicine, 291(2), 232-240. https://doi.org/10.1111/joim.13386

Martin-Vicente, M, Almansa, R, Martínez, I, Tedim, AP, Bustamante, E, Tamayo, L, Aldecoa, C, Gómez, JM, Renedo, G, Berezo, JÁ, Cedeño, JA, Mamolar, N, García Olivares, P, Herrán-Monge, R, Cicuendez, R, Enríquez, P, Ortega, A, Jorge, N, Doncel, C, de la Fuente, A, Bustamante-Munguira, J, Muñoz-Gómez, MJ, González-Rivera, M, Puertas, C, Más, V, Vázquez, M, Pérez-García, F, Rico-Feijoo, J, Martín, S, Motos, A, Fernandez-Barat, L, Eiros, JM, Dominguez-Gil, M, Ferrer, R, Barbé, F, Trapiello, W, Kelvin, DJ, Bermejo-Martin, JF, Resino, S & Torres, A 2022, 'Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients', Journal of Internal Medicine, vol. 291, no. 2, pp. 232-240. https://doi.org/10.1111/joim.13386

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title = "Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients",

abstract = "Background: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. Patients/Methods: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. Results: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). Conclusions: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.",

author = "Mar{\'i}a Martin-Vicente and Raquel Almansa and Isidoro Mart{\'i}nez and Tedim, {Ana P.} and Elena Bustamante and Luis Tamayo and C{\'e}sar Aldecoa and G{\'o}mez, {Jos{\'e} Manuel} and Gloria Renedo and Berezo, {Jose {\'A}ngel} and Cede{\~n}o, {Jamil Antonio} and Nuria Mamolar and {Garc{\'i}a Olivares}, Pablo and Rub{\'e}n Herr{\'a}n-Monge and Ram{\'o}n Cicuendez and Pedro Enr{\'i}quez and Alicia Ortega and Noelia Jorge and Cristina Doncel and {de la Fuente}, Amanda and Juan Bustamante-Munguira and Mu{\~n}oz-G{\'o}mez, {Mar{\'i}a Jos{\'e}} and Milagros Gonz{\'a}lez-Rivera and Carolina Puertas and Vicente M{\'a}s and M{\'o}nica V{\'a}zquez and Felipe P{\'e}rez-Garc{\'i}a and Jes{\'u}s Rico-Feijoo and Silvia Mart{\'i}n and Anna Motos and Laia Fernandez-Barat and Eiros, {Jose Mar{\'i}a} and Marta Dominguez-Gil and Ricard Ferrer and Ferr{\'a}n Barb{\'e} and Wysali Trapiello and Kelvin, {David J.} and Bermejo-Martin, {Jes{\'u}s F.} and Salvador Resino and Antoni Torres",

note = "Funding Information: We would like to thank the IBSAL and CIBER for administrative support to perform this study. Funding Information: This work was supported by awards from the Canadian Institutes of Health Research, (CIHR OV2 – 170357), Research Nova Scotia, Atlantic Genome/Genome Canada, Li‐Ka Shing Foundation, Dalhousie Medical Research Foundation (David J. Kelvin), David J. Kelvin is a recipient of the Canada Research Chair in Translational Vaccinology and Inflammation, and the “Subvenciones de concesi{\'o}n directa para proyectos y programas de investigaci{\'o}n del virus SARS‐CoV2, causante del COVID‐19”, FONDO ‐ COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (Antoni Torres) and finally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y Le{\'o}n, para la financiaci{\'o}n de proyectos de investigaci{\'o}n en enfermedad COVID‐19” (GRS COVID 53/A/20) (CA). Ana P. Tedim was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co‐financed by the European Development Regional Fund (A Way to Achieve Europe programme). The funding sources did not play any role neither in the design of the study and collection, not in the analysis, in the interpretation of data or in writing the manuscript. Publisher Copyright: {\textcopyright} 2021 The Association for the Publication of the Journal of Internal Medicine",

year = "2022",

month = feb,

doi = "10.1111/joim.13386",

language = "English",

volume = "291",

pages = "232--240",

journal = "Journal of Internal Medicine",

issn = "0954-6820",

publisher = "Wiley-Blackwell",

number = "2",

}

TY - JOUR

T1 - Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients

AU - Martin-Vicente, María

AU - Almansa, Raquel

AU - Martínez, Isidoro

AU - Tedim, Ana P.

AU - Bustamante, Elena

AU - Tamayo, Luis

AU - Aldecoa, César

AU - Gómez, José Manuel

AU - Renedo, Gloria

AU - Berezo, Jose Ángel

AU - Cedeño, Jamil Antonio

AU - Mamolar, Nuria

AU - García Olivares, Pablo

AU - Herrán-Monge, Rubén

AU - Cicuendez, Ramón

AU - Enríquez, Pedro

AU - Ortega, Alicia

AU - Jorge, Noelia

AU - Doncel, Cristina

AU - de la Fuente, Amanda

AU - Bustamante-Munguira, Juan

AU - Muñoz-Gómez, María José

AU - González-Rivera, Milagros

AU - Puertas, Carolina

AU - Más, Vicente

AU - Vázquez, Mónica

AU - Pérez-García, Felipe

AU - Rico-Feijoo, Jesús

AU - Martín, Silvia

AU - Motos, Anna

AU - Fernandez-Barat, Laia

AU - Eiros, Jose María

AU - Dominguez-Gil, Marta

AU - Ferrer, Ricard

AU - Barbé, Ferrán

AU - Trapiello, Wysali

AU - Kelvin, David J.

AU - Bermejo-Martin, Jesús F.

AU - Resino, Salvador

AU - Torres, Antoni

N1 - Funding Information: We would like to thank the IBSAL and CIBER for administrative support to perform this study. Funding Information: This work was supported by awards from the Canadian Institutes of Health Research, (CIHR OV2 – 170357), Research Nova Scotia, Atlantic Genome/Genome Canada, Li‐Ka Shing Foundation, Dalhousie Medical Research Foundation (David J. Kelvin), David J. Kelvin is a recipient of the Canada Research Chair in Translational Vaccinology and Inflammation, and the “Subvenciones de concesión directa para proyectos y programas de investigación del virus SARS‐CoV2, causante del COVID‐19”, FONDO ‐ COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (Antoni Torres) and finally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la financiación de proyectos de investigación en enfermedad COVID‐19” (GRS COVID 53/A/20) (CA). Ana P. Tedim was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co‐financed by the European Development Regional Fund (A Way to Achieve Europe programme). The funding sources did not play any role neither in the design of the study and collection, not in the analysis, in the interpretation of data or in writing the manuscript. Publisher Copyright: © 2021 The Association for the Publication of the Journal of Internal Medicine

PY - 2022/2

Y1 - 2022/2

N2 - Background: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. Patients/Methods: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. Results: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). Conclusions: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.

AB - Background: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. Patients/Methods: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. Results: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). Conclusions: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.

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Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients

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