TY - JOUR
T1 - COVID-19 survival associates with the immunoglobulin response to the SARS-cov-2 spike receptor binding domain
AU - Secchi, Massimiliano
AU - Bazzigaluppi, Elena
AU - Brigatti, Cristina
AU - Marzinotto, Ilaria
AU - Tresoldi, Cristina
AU - Rovere-Querini, Patrizia
AU - Poli, Andrea
AU - Castagna, Antonella
AU - Scarlatti, Gabriella
AU - Zangrillo, Alberto
AU - Ciceri, Fabio
AU - Piemonti, Lorenzo
AU - Lampasona, Vito
N1 - Funding Information:
We wish to thank Ezio Bonifacio, Anette Ziegler, William Hagopian, Alistair Williams, and Ake Lernmark for useful discussions. We also wish to acknowledge the contribution of Alexander Lindt to the validation of the flu HA LIPS. We are indebted to Florian Krammer for his generous sharing of the SARS-CoV-2 spike S1+S2 coding sequence. This study was supported by the IRCCS Ospedale San Raffaele and Universit? Vita Salute San Raffaele grant Program Project COVID-19 OSR-UniSR
Funding Information:
We wish to thank Ezio Bonifacio, Anette Ziegler, William Hago-pian, Alistair Williams, and Ake Lernmark for useful discussions. We also wish to acknowledge the contribution of Alexander Lindt to the validation of the flu HA LIPS. We are indebted to Florian Krammer for his generous sharing of the SARS-CoV-2 spike S1+S2 coding sequence. This study was supported by the IRCCS Osped-ale San Raffaele and Università Vita Salute San Raffaele grant Program Project COVID-19 OSR-UniSR Address correspondence to: Vito Lampasona or Lorenzo Piemon-ti, Diabetes Research Institute, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. Phone: 39.02.26432540; Email: lampasona.vito@hsr.it (VL). Phone: 39.02.26432706; Email: piemonti.lorenzo@hsr.it (LP).
Publisher Copyright:
© 2020, American Society for Clinical Investigation.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - BACKGROUND. Serological assays are of critical importance to investigate correlates of response and protection in coronavirus disease 2019 (COVID-19), to define previous exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations, and to verify the development of an adaptive immune response in infected individuals. METHODS. We studied 509 patients confirmed to have COVID-19 from the San Raffaele Hospital of Milan and 480 samples of prepandemic organ donor sera collected in 2010–2012. Using fluid-phase luciferase immune precipitation (LIPS) assays, we characterized IgG, IgM, and IgA antibodies to the spike receptor binding domain (RBD), S1+S2, nucleocapsid, and ORF6 to ORF10 of SARS-CoV-2, to the HCoV-OC43 and HCoV-HKU1 betacoronaviruses spike S2, and the H1N1Ca2009 flu virus hemagglutinin. Sequential samples at 1 and 3 months after hospital discharge were also tested for SARS-CoV-2 RBD antibodies in 95 patients. RESULTS. Antibodies developed rapidly against multiple SARS-CoV-2 antigens in 95% of patients by 4 weeks after symptom onset and IgG to the RBD increased until the third month of follow-up. We observed a major synchronous expansion of antibodies to the HCoV-OC43 and HCoV-HKU1 spike S2. A likely coinfection with influenza was neither linked to a more severe presentation of the disease nor to a worse outcome. Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival. CONCLUSION. The measurement of antibodies to selected epitopes of SARS-CoV-2 antigens can offer a more accurate assessment of the humoral response in patients and its impact on survival. The presence of partially cross-reactive antibodies with other betacoronaviruses is likely to impact on serological assay specificity and interpretation.
AB - BACKGROUND. Serological assays are of critical importance to investigate correlates of response and protection in coronavirus disease 2019 (COVID-19), to define previous exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations, and to verify the development of an adaptive immune response in infected individuals. METHODS. We studied 509 patients confirmed to have COVID-19 from the San Raffaele Hospital of Milan and 480 samples of prepandemic organ donor sera collected in 2010–2012. Using fluid-phase luciferase immune precipitation (LIPS) assays, we characterized IgG, IgM, and IgA antibodies to the spike receptor binding domain (RBD), S1+S2, nucleocapsid, and ORF6 to ORF10 of SARS-CoV-2, to the HCoV-OC43 and HCoV-HKU1 betacoronaviruses spike S2, and the H1N1Ca2009 flu virus hemagglutinin. Sequential samples at 1 and 3 months after hospital discharge were also tested for SARS-CoV-2 RBD antibodies in 95 patients. RESULTS. Antibodies developed rapidly against multiple SARS-CoV-2 antigens in 95% of patients by 4 weeks after symptom onset and IgG to the RBD increased until the third month of follow-up. We observed a major synchronous expansion of antibodies to the HCoV-OC43 and HCoV-HKU1 spike S2. A likely coinfection with influenza was neither linked to a more severe presentation of the disease nor to a worse outcome. Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival. CONCLUSION. The measurement of antibodies to selected epitopes of SARS-CoV-2 antigens can offer a more accurate assessment of the humoral response in patients and its impact on survival. The presence of partially cross-reactive antibodies with other betacoronaviruses is likely to impact on serological assay specificity and interpretation.
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U2 - 10.1172/JCI142804
DO - 10.1172/JCI142804
M3 - Article
C2 - 32991329
AN - SCOPUS:85092251177
VL - 130
SP - 6366
EP - 6378
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 12
ER -