Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19 - 04/02/21

Doi : 10.1016/j.jaci.2020.10.040

Carlo Cervia, MMed ^a,^{^{∗
These authors contributed equally to this work.}}, Jakob Nilsson, MD, PhD ^a,^{^{∗
These authors contributed equally to this work.}}, Yves Zurbuchen, MMed ^a, Alan Valaperti, PhD ^a, Jens Schreiner, PhD ^a, Aline Wolfensberger, MD ^b, Miro E. Raeber, MMed ^a, Sarah Adamo, MMed ^a, Sebastian Weigang, MSc ^c, Marc Emmenegger, MSc ^d, Sara Hasler ^a, Philipp P. Bosshard, PhD ^e, Elena De Cecco, PhD ^d, Esther Bächli, MD ^f, Alain Rudiger, MD ^g, Melina Stüssi-Helbling, MD ^h, Lars C. Huber, MD ^h, Annelies S. Zinkernagel, MD, PhD ^b, Dominik J. Schaer, MD ⁱ, Adriano Aguzzi, MD ^d, Georg Kochs, PhD ^c,^j, Ulrike Held, PhD ^k, Elsbeth Probst-Müller, MD, PhD ^a, Silvana K. Rampini, MD ⁱ, Onur Boyman, MD ^a,^l,^⁎
^a Department of Immunology, University Hospital Zurich, Zurich, Switzerland
^b Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
^c Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany
^d Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland
^e Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
^f Clinic for Internal Medicine, Uster Hospital, Uster, Switzerland
^g Department of Medicine, Limmattal Hospital, Schlieren, Switzerland
^h Clinic for Internal Medicine, City Hospital Triemli Zurich, Zurich, Switzerland
ⁱ Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland
^j Faculty of Medicine, University of Freiburg, Freiburg, Germany
^k Department of Biostatistics, at Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
^l Faculty of Medicine, University of Zurich, Zurich, Switzerland

^∗Corresponding author: Onur Boyman, MD, Department of Immunology, University Hospital Zurich, Gloriastrasse 23, 8091 Zurich.Department of ImmunologyUniversity Hospital ZurichGloriastrasse 23Zurich8091

connectez-vous ou créez un compte

Bienvenue sur EM-consulte, la référence des professionnels de santé.
Article gratuit.

Connectez-vous pour en bénéficier!

Abstract

Background

Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly being used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear.

Objectives

Our aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases.

Methods

Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2–specific IgA and IgG in sera and mucosal fluids of 2 cohorts, including SARS-CoV-2 PCR-positive patients (n = 64) and PCR-positive and PCR-negtive health care workers (n = 109).

Results

SARS-CoV-2–specific serum IgA titers in patients with mild COVID-19 were often transiently positive, whereas serum IgG titers remained negative or became positive 12 to 14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2–specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2–specific serum IgA were correlated with severe acute respiratory distress syndrome. Interestingly, some health care workers with negative SARS-CoV-2–specific serum antibody titers showed SARS-CoV-2–specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2–specific IgA titers in nasal fluids were inversely correlated with age.

Conclusions

Systemic antibody production against SARS-CoV-2 develops mainly in patients with severe COVID-19, with very high IgA titers seen in patients with severe acute respiratory distress syndrome, whereas mild disease may be associated with transient production of SARS-CoV-2–specific antibodies but may stimulate mucosal SARS-CoV-2–specific IgA secretion.

Le texte complet de cet article est disponible en PDF.

Graphical abstract

Le texte complet de cet article est disponible en PDF.

Key words : COVID-19, SARS-CoV-2, SARS-CoV-2–specific antibodies, SARS-CoV-2–specific IgA, SARS-CoV-2–specific IgG, humoral immune response, mucosal immune response, COVID-19 severity, COVID-19 seroprevalence

Abbreviations used : ACE2, ARDS, COVID-19, Ct, ECD, HCW, IQR, RBD, RT-qPCR, S, SARS-CoV, SARS-CoV-2

Plan

Methods

Human subjects and patient characteristics

Collection of serum, tears, nasal fluid, and saliva

IgA and IgG immunoassays

RT-qPCR

SARS-CoV-2 microneutralization assay

Statistics

Results

COVID-19 severity, disease duration, and patient age influence SARS-CoV-2–specific serum IgA and IgG secretion

S1-specific antibody responses can be transient and delayed in patients with mild COVID-19

Some seronegative HCWs show SARS-CoV-2–specific IgA at mucosal sites

Discussion

This work was funded by the Swiss National Science Foundation (grant 4078P0-198431 [to O.B. and J.N.] and grant 310030-172978 [to O.B.]), Swiss Academy of Medical Sciences fellowships (No. 323530-191220 [to C.C.], No. 323530-191230 [to Y.Z.], and No. 323530-177975 [to S.A.]), a Young Talents in Clinical Research Fellowship by the Swiss Academy of Medical Sciences and Bangerter Foundation (No. YTCR 32/18 [to M.R.]), the Bundesministerium für Bildung und Forschung through Deutsches Zentrum für Luft- und Raumfahrt (No. 01KI2077 [to G.K.]), the Clinical Research Priority Program of University of Zurich for CRPP CYTIMM-Z (to O.B.), the Pandemic Fund of University of Zurich (to O.B.), and an Innovation Grant of University Hospital Zurich (to O.B.).

Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

Export

Vol 147 - N° 2

P. 545 - février 2021 Retour au numéro

Article précédent

Severe SARS-CoV-2 disease in the context of a NF-?B2 loss-of-function pathogenic variant
Roshini S. Abraham, Joanna M. Marshall, Hye Sun Kuehn, Cesar M. Rueda, Amber Gibbs, Will Guider, Claire Stewart, Sergio D. Rosenzweig, Huanyu Wang, Sophonie Jean, Mark Peeples, Tiffany King, W. Garrett Hunt, Jonathan R. Honegger, Octavio Ramilo, Peter J. Mustillo, Asuncion Mejias, Monica I. Ardura, Masako Shimamura

| Article suivant

Incidence rates of hospitalization and death from COVID-19 in patients with psoriasis receiving biological treatment: A Northern Italy experience
Paolo Gisondi, Stefano Piaserico, Luigi Naldi, Paolo Dapavo, Andrea Conti, Piergiorgio Malagoli, Angelo Valerio Marzano, Federico Bardazzi, Massimo Gasperini, Simone Cazzaniga, Antonio Costanzo, collaborators in the studies of COVID-19 pandemic, Lidia Sacchelli, Elena Pezzolo, Francesco Messina, Claudia Lasagni, Laura Bigi, Angelo Cattaneo, Carlo Giovanni Carrera, Luisa Arancio, Simone Ribero, Giulia Rozzo, Giovanni Damiani, Paola Facheris

Bienvenue sur EM-consulte, la référence des professionnels de santé.

connectez-vous ou créez un compte

Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19 - 04/02/21

Abstract

Background

Objectives

Methods

Results

Conclusions

Graphical abstract

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL