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Multiple Routes of Antibody-Dependent Enhancement of SARS-CoV-2 Infection

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Title: Multiple Routes of Antibody-Dependent Enhancement of SARS-CoV-2 Infection
Authors: Okuya, Kosuke Browse this author
Hattori, Takanari Browse this author
Saito, Takeshi Browse this author
Takadate, Yoshihiro Browse this author
Sasaki, Michihito Browse this author
Furuyama, Wakako Browse this author
Marzi, Andrea Browse this author
Ohiro, Yoichi Browse this author
Konno, Satoshi Browse this author
Hattori, Takeshi Browse this author
Takada, Ayato Browse this author →KAKEN DB
Keywords: ADE
antibody-dependent enhancement
C1q
COVID-19
complement
Fc receptor
FcR
SARS-CoV-2
Issue Date: 23-Mar-2022
Publisher: American Society for Microbiology
Journal Title: Microbiology Spectrum
Volume: 10
Issue: 2
Start Page: e01553-21
Publisher DOI: 10.1128/spectrum.01553-21
Abstract: Antibody-dependent enhancement (ADE) of infection is generally known for many viruses. A potential risk of ADE in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has also been discussed since the beginning of the coronavirus disease 2019 (COVID-19) pandemic; however, clinical evidence of the presence of antibodies with ADE potential is limited. Here, we show that ADE antibodies are produced by SARS-CoV-2 infection and the ADE process can be mediated by at least two different host factors, Fcg receptor (Fcg R) and complement component C1q. Of 89 serum samples collected from acute or convalescent COVID-19 patients, 62.9% were found to be positive for SARS-CoV-2-specific IgG. Fcg R- and/or C1q-mediated ADE were detected in 50% of the IgG-positive sera, whereas most of them showed neutralizing activity in the absence of Fcg R and C1q. Importantly, ADE antibodies were found in 41.4% of the acute COVID-19 patients. Neutralizing activity was also detected in most of the IgG-positive sera, but it was counteracted by ADE in subneutralizing conditions in the presence of Fcg R or C1q. Although the clinical importance of ADE needs to be further investigated with larger numbers of COVID-19 patient samples, our data suggest that SARS-CoV-2 utilizes multiple mechanisms of ADE. C1q-mediated ADE may particularly have a clinical impact since C1q is present at high concentrations in plasma and its receptors are ubiquitously expressed on the surfaces of many types of cells, including respiratory epithelial cells, which SARS-CoV-2 primarily infects. IMPORTANCE Potential risks of antibody-dependent enhancement (ADE) in the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been discussed and the proposed mechanism mostly depends on the Fc gamma receptor (Fcg R). However, since Fcg Rs are exclusively expressed on immune cells, which are not primary targets of SARS-CoV-2, the clinical importance of ADE of SARS-CoV-2 infection remains controversial. Our study demonstrates that SARS-CoV-2 infection induces antibodies that increase SARS-CoV-2 infection through another ADE mechanism in which complement component C1q mediates the enhancement. Although neutralizing activity was also detected in the serum samples, it was counteracted by ADE in the presence of Fcg R or C1q. Considering the ubiquity of C1q and its cellular receptors, C1q-mediated ADE may more likely occur in respiratory epithelial cells, which SARS-CoV-2 primarily infects. Our data highlight the importance of careful monitoring of the antibody properties in COVID-19 convalescent and vaccinated individuals.
Type: article
URI: http://hdl.handle.net/2115/86595
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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