EClinicalMedicine (Feb 2021)
Antibody titers against SARS-CoV-2 decline, but do not disappear for several months
- Seiya Yamayoshi,
- Atsuhiro Yasuhara,
- Mutsumi Ito,
- Osamu Akasaka,
- Morio Nakamura,
- Ichiro Nakachi,
- Michiko Koga,
- Keiko Mitamura,
- Kazuma Yagi,
- Kenji Maeda,
- Hideaki Kato,
- Masanori Nojima,
- David Pattinson,
- Takayuki Ogura,
- Rie Baba,
- Kensuke Fujita,
- Hiroyuki Nagai,
- Shinya Yamamoto,
- Makoto Saito,
- Eisuke Adachi,
- Junichi Ochi,
- Shin-ichiro Hattori,
- Tetsuya Suzuki,
- Yusuke Miyazato,
- Shiho Chiba,
- Moe Okuda,
- Jurika Murakami,
- Taiki Hamabata,
- Kiyoko Iwatsuki-Horimoto,
- Hideaki Nakajima,
- Hiroaki Mitsuya,
- Norio Omagari,
- Norio Sugaya,
- Hiroshi Yotsuyanagi,
- Yoshihiro Kawaoka
Affiliations
- Seiya Yamayoshi
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan; Correspondence authors at: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan.
- Atsuhiro Yasuhara
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan
- Mutsumi Ito
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan
- Osamu Akasaka
- Emergency Medical Center, Fujisawa City Hospital, Japan
- Morio Nakamura
- Department of Pulmonary Medicine, Tokyo Saiseikai Central Hospital, Japan
- Ichiro Nakachi
- Pulmonary division, Department of Internal Medicine, Saiseikai Utsunomiya Hospital, Japan
- Michiko Koga
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan; Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, the University of Tokyo, Japan
- Keiko Mitamura
- Division of Infection Control, Eiju General Hospital, Japan
- Kazuma Yagi
- Department of Pulmonary Medicine, Department of Medicine, Keiyu Hospital, Japan
- Kenji Maeda
- Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Japan
- Hideaki Kato
- Infection Prevention and Control Department, Yokohama City University Hospital, Japan; Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Japan
- Masanori Nojima
- Center for Translational Research, Institute of Medical Science Hospital, University of Tokyo, Japan
- David Pattinson
- Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA
- Takayuki Ogura
- Department of Emergency Medicine and Critical Care Medicine, Saiseikai Utsunomiya Hospital, Japan
- Rie Baba
- Pulmonary division, Department of Internal Medicine, Saiseikai Utsunomiya Hospital, Japan
- Kensuke Fujita
- Department of Emergency Medicine and Critical Care Medicine, Saiseikai Utsunomiya Hospital, Japan
- Hiroyuki Nagai
- Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, the University of Tokyo, Japan
- Shinya Yamamoto
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan; Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, the University of Tokyo, Japan
- Makoto Saito
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan; Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, the University of Tokyo, Japan
- Eisuke Adachi
- Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, the University of Tokyo, Japan
- Junichi Ochi
- Department of Respiratory Medicine, Eiju General Hospital, Japan
- Shin-ichiro Hattori
- Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Japan
- Tetsuya Suzuki
- Disease Control and Prevention Center, National Center for Global Health and Medicine Hospital, Japan
- Yusuke Miyazato
- Disease Control and Prevention Center, National Center for Global Health and Medicine Hospital, Japan
- Shiho Chiba
- Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA
- Moe Okuda
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan
- Jurika Murakami
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan
- Taiki Hamabata
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan
- Kiyoko Iwatsuki-Horimoto
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan
- Hideaki Nakajima
- Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Japan
- Hiroaki Mitsuya
- Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Japan
- Norio Omagari
- Disease Control and Prevention Center, National Center for Global Health and Medicine Hospital, Japan
- Norio Sugaya
- Department of Pediatrics, Keiyu Hospital, Japan
- Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan; Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, the University of Tokyo, Japan
- Yoshihiro Kawaoka
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA; Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Japan; Correspondence authors at: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan.
- Journal volume & issue
-
Vol. 32
p. 100734
Abstract
Background: To develop an effective vaccine against a novel viral pathogen, it is important to understand the longitudinal antibody responses against its first infection. Here we performed a longitudinal study of antibody responses against SARS-CoV-2 in symptomatic patients. Methods: Sequential blood samples were collected from 39 individuals at various timepoints between 0 and 154 days after onset. IgG or IgM titers to the receptor binding domain (RBD) of the S protein, the ectodomain of the S protein, and the N protein were determined by using an ELISA. Neutralizing antibody titers were measured by using a plaque reduction assay. Findings: The IgG titers to the RBD of the S protein, the ectodomain of the S protein, and the N protein peaked at about 20 days after onset, gradually decreased thereafter, and were maintained for several months after onset. Extrapolation modeling analysis suggested that the IgG antibodies were maintained for this amount of time because the rate of reduction slowed after 30 days post-onset. IgM titers to the RBD decreased rapidly and disappeared in some individuals after 90 days post-onset. All patients, except one, possessed neutralizing antibodies against authentic SARS-CoV-2, which they retained at 90 days after onset. The highest antibody titers in patients with severe infections were higher than those in patients with mild or moderate infections, but the decrease in antibody titer in the severe infection cohort was more remarkable than that in the mild or moderate infection cohort. Interpretation: Although the number of patients is limited, our results show that the antibody response against the first SARS-CoV-2 infection in symptomatic patients is typical of that observed in an acute viral infection. Funding: The Japan Agency for Medical Research and Development and the National Institutes of Allergy and Infectious Diseases.