TY - JOUR
T1 - Sustained Antibody-Dependent NK Cell Functions in Mild COVID-19 Outpatients During Convalescence
AU - COVID-19 South Chile Group
AU - Fuentes-Villalobos, Francisco
AU - Garrido, Jose L.
AU - Medina, Matías A.
AU - Zambrano, Nicole
AU - Ross, Natalia
AU - Bravo, Felipe
AU - Gaete-Argel, Aracelly
AU - Oyarzún-Arrau, Aarón
AU - Amanat, Fatima
AU - Soto-Rifo, Ricardo
AU - Valiente-Echeverría, Fernando
AU - Ocampo, Renato
AU - Esveile, Christian
AU - Ferreira, Leonila
AU - Cabrera, Johanna
AU - Torres, Vivianne
AU - Rioseco, Maria L.
AU - Riquelme, Raúl
AU - Barría, Sebastián
AU - Alvarez, Raymond
AU - Pinos, Yazmín
AU - Krammer, Florian
AU - Calvo, Mario
AU - Barria, Maria I.
N1 - Funding Information:
This work was supported by National Agency of Research and Development (ANID) projects COVID0422 (to MB), FONDEF ID20I10192 and ID18I10261 (to MB). FONDECYT 1190156 (to RS-R), 1180798 (to FV-E) and 3200913 (to FF-V). Proyecto FIC20-10 Gobierno Regional de Los Rıós (to VT). We also thank FONDEQUIP EQM150061. Reagents in the Krammer laboratory were generated with support of the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051, NIAID Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), generous support of the JPB Foundation and the Open Philanthropy Project (research grant 2020-215611) (5384); and by anonymous donors.
Funding Information:
We especially thank all blood donors who participate in this study. COVID-19 South Chile Group: Gerardo Sol?s, Marcelo Pozas, Equipo de enfermer?a Servicio de Medicina Interna Hospital Base Osorno, Mar?a Paz Contreras, Equipo de enfermer?a de la Universidad de Los Lagos Osorno, Catherine Fern?ndez, Camila Rojas, Paulina Lagos, Roc?o Mej?as, Melissa Canales, Patricio Suazo, Pamela ?ngel, Romina Inostroza, Pamela Silva, Felipe Collao, Vanina Cuevas, Rodrigo O?ate, Daniel Salamanca, Javier Briones, Vanessa Villagr?n, Diana Bocaz, Andr?s Umanzor.
Funding Information:
Conflict of Interest: Authors JLG and RA were employed by company Ichor Biologics LLC. JLG and RA were partially supported by Ichor Biologics LLC.
Publisher Copyright:
Copyright © 2022 Fuentes-Villalobos, Garrido, Medina, Zambrano, Ross, Bravo, Gaete-Argel, Oyarzún-Arrau, Amanat, Soto-Rifo, Valiente-Echeverría, Ocampo, Esveile, Ferreira, Cabrera, Torres, Rioseco, Riquelme, Barría, Alvarez, Pinos, Krammer, Calvo, Barria and COVID-19 South Chile Group.
PY - 2022/2/7
Y1 - 2022/2/7
N2 - The coronavirus disease 2019 (COVID19) pandemic has left researchers scrambling to identify the humoral immune correlates of protection from COVID-19. To date, the antibody mediated correlates of virus neutralization have been extensively studied. However, the extent that non-neutralizing functions contribute to anti-viral responses are ill defined. In this study, we profiled the anti-spike antibody subtype/subclass responses, along with neutralization and antibody-dependent natural killer cell functions in 83 blood samples collected between 4 and 201 days post-symptoms onset from a cohort of COVID-19 outpatients. We observed heterogeneous humoral responses against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Overall, anti-spike profiles were characterized by a rapid rise of IgA and sustained IgG titers. In addition, strong antibody-mediated natural killer effector responses correlated with milder disease and being female. While higher neutralization profiles were observed in males along with increased severity. These results give an insight into the underlying function of antibodies beyond neutralization and suggest that antibody-mediated natural killer cell activity is a key function of the humoral response against the SARS-CoV-2 spike protein.
AB - The coronavirus disease 2019 (COVID19) pandemic has left researchers scrambling to identify the humoral immune correlates of protection from COVID-19. To date, the antibody mediated correlates of virus neutralization have been extensively studied. However, the extent that non-neutralizing functions contribute to anti-viral responses are ill defined. In this study, we profiled the anti-spike antibody subtype/subclass responses, along with neutralization and antibody-dependent natural killer cell functions in 83 blood samples collected between 4 and 201 days post-symptoms onset from a cohort of COVID-19 outpatients. We observed heterogeneous humoral responses against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Overall, anti-spike profiles were characterized by a rapid rise of IgA and sustained IgG titers. In addition, strong antibody-mediated natural killer effector responses correlated with milder disease and being female. While higher neutralization profiles were observed in males along with increased severity. These results give an insight into the underlying function of antibodies beyond neutralization and suggest that antibody-mediated natural killer cell activity is a key function of the humoral response against the SARS-CoV-2 spike protein.
KW - COVID-19
KW - Fc-effector functions
KW - NK cells activity
KW - SARS-CoV-2
KW - outpatients
KW - spike (S) glycoprotein
UR - http://www.scopus.com/inward/record.url?scp=85125105786&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.796481
DO - 10.3389/fimmu.2022.796481
M3 - Article
C2 - 35197972
AN - SCOPUS:85125105786
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 796481
ER -