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

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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.

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Graphical abstract

Il testo completo di questo articolo è disponibile in 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

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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.

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Vol 147 - N° 2

P. 545 - Febbraio 2021 Ritorno al numero

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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

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