Preinfection Neutralizing Antibodies, Omicron BA.5 Breakthrough Infection, and Long COVID: A Propensity Score-Matched Analysis

• Published in: The Journal of infectious diseases 2023-12, Vol.228 (12), p.1652-1661
• Main Authors: Yamamoto, Shohei, Matsuda, Kouki, Maeda, Kenji, Horii, Kumi, Okudera, Kaori, Oshiro, Yusuke, Inamura, Natsumi, Nemoto, Takashi, Takeuchi, Junko S, Li, Yunfei, Konishi, Maki, Tsuchiya, Kiyoto, Gatanaga, Hiroyuki, Oka, Shinichi, Mizoue, Tetsuya, Sugiyama, Haruhito, Aoyanagi, Nobuyoshi, Mitsuya, Hiroaki, Sugiura, Wataru, Ohmagari, Norio
• Format: Article
• Language: English
• Subjects: Antibodies, Neutralizing; Antibodies, Viral; Breakthrough Infections; COVID-19; COVID-19 Vaccines; Humans; Post-Acute COVID-19 Syndrome; Propensity Score; SARS-CoV-2
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiad317

Abstract Background Data are limited on the role of preinfection humoral immunity protection against Omicron BA.5 infection and long coronavirus disease (COVID) development. Methods We conducted nested case-control analysis among tertiary hospital staff in Tokyo who donated blood samples in June 2022 (1 month before Omicron BA.5 wave), approximately 6 months after receiving a third dose of COVID-19 mRNA vaccine. We measured live virus-neutralizing antibody titers against wild type and Omicron BA.5, and anti–receptor-binding domain (RBD) antibody titers at preinfection, and compared them between cases and propensity-matched controls. Among the breakthrough cases, we examined association between preinfection antibody titers and incidence of long COVID. Results Preinfection anti-RBD and neutralizing antibody titers were lower in cases than controls. Neutralizing titers against wild type and Omicron BA.5 were 64% (95% confidence interval [CI], 42%–77%) and 72% (95% CI, 53%–83%) lower, respectively, in cases than controls. Individuals with previous Omicron BA.1/BA.2 infections were more frequent among controls than cases (10.3% vs 0.8%), and their Omicron BA.5 neutralizing titers were 12.8-fold higher than infection-naive individuals. Among cases, preinfection antibody titers were not associated with incidence of long COVID. Conclusions Preinfection immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may play a role in protecting against the Omicron BA.5 infection but not preventing long COVID. Preinfection neutralizing antibody titers against Omicron BA.5 approximately 6 months after the third vaccination was correlated with protection against Omicron BA.5 infection but not against long COVID development.