COVID-19 survival associates with the immunoglobulin response to the SARS-CoV-2 spike receptor binding domain
Massimiliano Secchi, … , Lorenzo Piemonti, Vito Lampasona
Massimiliano Secchi, … , Lorenzo Piemonti, Vito Lampasona
Published September 29, 2020
Citation Information: J Clin Invest. 2020;130(12):6366-6378. https://doi.org/10.1172/JCI142804.
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Clinical Research and Public Health Immunology

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

Abstract

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.TRIAL REGISTRATION COVID-19 Patients Characterization, Biobank, Treatment Response and Outcome Predictor (COVID-BioB). ClinicalTrials.gov identifier: NCT04318366.FUNDING IRCCS Ospedale San Raffaele and Università Vita Salute San Raffaele.

Authors

Massimiliano Secchi, Elena Bazzigaluppi, Cristina Brigatti, Ilaria Marzinotto, Cristina Tresoldi, Patrizia Rovere-Querini, Andrea Poli, Antonella Castagna, Gabriella Scarlatti, Alberto Zangrillo, Fabio Ciceri, Lorenzo Piemonti, Vito Lampasona

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Figure 7

HCoV-OC43 and HUK1 S2 IgG antibodies in patients with COVID-19.

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HCoV-OC43 and HUK1 S2 IgG antibodies in patients with COVID-19. (A, B) K...
(A, B) Kinetics of HCoV-OC43 and HKU1 S2 IgG expansion in COVID-19 (n = 575) and control (n = 480) sera stratified by the duration of symptoms at serum sampling. For each sample are shown the measured arbitrary units (circles), the probability density estimate (with the half violin plot upscaled to maximum width for better visualization), box plot displaying median, IQR, and whiskers extending to 1.96 times the IQR. Fill colors correspond to AU greater than 66th (light blue), greater than 33rd (purple), or less than 33rd (orange) percentile in patients with COVID-19. Shown are the percentages and count of subjects with AU greater than the 66th percentile. (C) Correlation of SARS-CoV-2, HCoV-OC43, and HCoV-HKU1 spike IgG in symptomatic COVID-19 sera. Shown are the linear regression (black lines) of log-transformed AU (circles), its 95% CI (gray areas), and its coefficients. (D) Dumbbell plot of IgG binding reduction in a selection of symptomatic and paucisymptomatic patients with COVID-19. LIPS using the indicated HCoV-OC43 and SARS-CoV-2 antigens were performed with (orange fill) or without (light blue fill) competition with untagged SARS-CoV-2 S1+S2 protein.