COVID-19 survival associates with the immunoglobulin response to the SARS-CoV-2 spike receptor binding domain

BACKGROUNDSerological 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 adaptiv...

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Published in:The Journal of clinical investigation 2020-12, Vol.130 (12), p.6366-6378
Main Authors: Secchi, Massimiliano, Bazzigaluppi, Elena, Brigatti, Cristina, Marzinotto, Ilaria, Tresoldi, Cristina, Rovere-Querini, Patrizia, Poli, Andrea, Castagna, Antonella, Scarlatti, Gabriella, Zangrillo, Alberto, Ciceri, Fabio, Piemonti, Lorenzo, Lampasona, Vito
Format: Article
Language:English
Subjects:
Aged
Antibodies, Viral - immunology
Antigens, Viral - immunology
Care and treatment
Clinical Medicine
Coronaviruses
COVID-19
COVID-19 - immunology
COVID-19 - mortality
Epitopes - immunology
Female
Follow-Up Studies
Health aspects
Humans
Immunoglobulins
Male
Middle Aged
Patient outcomes
Physiological aspects
Protein binding
Protein Domains
SARS-CoV-2 - immunology
Spike Glycoprotein, Coronavirus
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Summary:BACKGROUNDSerological 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.METHODSWe 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.RESULTSAntibodies 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.CONCLUSIONThe 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.TRIAL REGISTRATIONCOVID-19 Patients Characterization, Biobank, Treatment Response and Outcome Predictor (COVID-BioB). ClinicalTrials.gov identifier: NCT04318366.FUNDINGIRCCS Ospedale San Raffaele and Università Vita Salute San Raffaele.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI142804