Coronavirus Disease 2019 (COVID-19) Breakthrough Infection and Post-Vaccination Neutralizing Antibodies Among Healthcare Workers in a Referral Hospital in Tokyo: A Case-Control Matching Study

Abstract

Background While increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infection. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity. Methods We described incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo. During the predominantly Delta epidemic, we followed 2,415 fully vaccinated staff (BNT162b2) for breakthrough infection and selected three matched controls. We measured post-vaccination neutralizing antibodies against the wild-type, Alpha (B.1.1.7), and Delta (B.1.617.2) strains using live viruses and anti-spike antibodies using quantitative assays, and compared them using the generalized estimating equation model between the two groups. Results No COVID-19 cases occurred 1–2 months after the vaccination program during the fourth epidemic wave in Japan, dominated by the Alpha variant, while 22 cases emerged 2–4 months after the vaccination program during the fifth wave, dominated by the Delta variant. In the vaccinated cohort, all 17 cases of breakthrough infection were mild or asymptomatic and had returned to work early. There was no measurable difference between cases and controls in post-vaccination neutralizing antibody titers against the wild-type, Alpha, and Delta, and anti-spike antibody titers, while neutralizing titers against the variants were considerably lower than those against the wild-type. Conclusions Post-vaccination neutralizing antibody titers were not decreased among patients with breakthrough infection relative to their controls under the Delta variant rampage. The result points to the importance of infection control measures in the post-vaccination era, irrespective of immunogenicity profile.

Sex‐associated differences between BMI and SARS‐CoV‐2 antibody titers following the BNT162b2 vaccine

“…As of October 2021, we have completed three surveys, in each of which we measured anti‐SARS‐CoV‐2 nucleocapsid (all surveys) and spike (from the second survey onward) protein antibodies. The details of the study design are available elsewhere ( 9 ). For the present analysis, we used the data of the third survey (June 2021), 2 months after the in‐house vaccination program (COVID‐19 mRNA‐lipid nanoparticle BNT162b2; BioNTech, Pfizer [BioNTech SE, Mainz, Germany; Pfizer Inc., New York, New York]).…”

Vaccination for SARS-CoV-2 in Hematological Patients

“…In general, it is not recommended to perform serological tests in order to determine whether the patient is protected [ 18 ]. Nevertheless, antibody levels are often used both in research and in clinical practice, and a correlation between higher antibody levels and neutralization of virus has been shown, though not in all studies [ 19 , 20 ]. We cannot provide any recommendation regarding use of serology to guide vaccination schedule in this review, and local guidelines on vaccination schedule should be followed.…”

Breakthrough SARS-CoV-2 infections with the delta (B.1.617.2) variant in vaccinated patients with immune-mediated inflammatory diseases using immunosuppressants: a substudy of two prospective cohort studies

“… 6 However, severity of disease due to SARS-CoV-2 breakthrough infections and confounding risk factors for breakthrough infections were not compared between patients and controls. Other studies in healthy individuals observed associations between reduced humoral responses after SARS-CoV-2 vaccination and an increased incidence of SARS-CoV-2 breakthrough infections and possibly more severe disease, 7 , 8 , 9 but there is a paucity of data from patients with immune-mediated inflammatory diseases.…”