If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
Seroepidemiological data are useful to estimate the spread of SARS-CoV-2 infection, which can contribute to the planning and evaluation of measures against coronavirus disease 2019 (COVID-19). As the target of mRNA vaccine is spike protein, anti-nucleocapsid antibody (Ig-N) has been used to monitor natural infection after vaccine rollout.
Despite high vaccine uptake, we are facing a marked increase of milder forms of COVID-19, characterized by lower levels of and faster waning of antibodies over time.
Serological markers of SARS-CoV-2 infection; anti-nucleocapsid antibody positivity may not be the ideal marker of natural infection in vaccinated individuals.
COVID-19 breakthrough infection and post-vaccination neutralizing antibody among healthcare workers in a referral hospital in Tokyo: a case-control matching study.
we compared the proportion of Ig-N positives among the patients with PCR or
antigen-confirmed COVID-19 (sensitivity) across different periods and vaccine doses. We measured Ig-N (total Ig) using the Roche Elecsys® Anti-SARS-CoV-2 N assay, which can reliably detect mature Ig-N over 6 months.
In this cohort, we identified 224 patients who were infected for the first time after the second or third dose of mRNA vaccine, mainly BNT162b2 (Pfizer-BioNTech), and subsequently attended a serosurvey without receiving the additional dose. All the infections were mild or asymptomatic.
Patients who were infected within 2 months after the booster (during Omicron BA.1 epidemic) showed a higher proportion of asymptomatic infection (14%) and significantly lower Ig-N index (median, 7.4) and sensitivity (78%), as compared with other groups (sensitivity, 94–100%) (Fig. 1). In contrast, patients who were infected 4 to 5 months after the booster (during Omicron BA.2 epidemic) had Ig-N index (median, 18.6) and sensitivity (97%) comparable to those who were infected before vaccination rollout or after the second dose (during Delta or Omicron BA.1 epidemic). Similarly, patients who were infected 5 to 8 months after the second vaccine had high index (median, 15.1) and sensitivity (96%). These results support that the level of immunity (largely determined by vaccine dose and time since vaccination), rather than Omicron sub-variant, accounts for the discrepancy in test performance.
Fig. 1Roche anti-SARS-CoV-2 nucleocapsid index (Left) and the proportion of seropositive among those with previously confirmed COVID-19 (Right) according to epidemic phase and vaccine status Timing of infection (dominant virus type): Unvaccinated: before vaccination rollout (Wild-type, Japan-specific B.1.1.214), n = 18 2-dose (3–4 m): 3–4 months after the second dose (Alpha, Delta), n = 13 2-dose (5–8 m): 5–8 months after the second dose (Omicron BA.1), n = 25 3-dose (1–2 m): 1–2 months after the third dose (Omicron BA.1), n = 114 3-dose (4–5 m): 4–5 months after the third dose (Omicron BA.2), n = 72
For the Left panel, the bars indicate the median value, and I-shaped bars indicate its interquartile range. The dushed horizontal line in the Left panel indicates the threshold of the seropositive (≥1.0 COI).
For the Right panel, the sensitivity with 95% confidence intervals is calculated using the exact binomial technique.
Statistical significance was tested using Kruskal–Wallis test (Left) and chi-squared test (Right). *** p < 0.001, * p < 0.05, ns P > 0.1.
Earlier serological studies in the pre-vaccine era showed that anti-SARS-CoV-2 Ig-N detection rate is higher among symptomatic patients than asymptomatic patients.
COVID-19 breakthrough infection and post-vaccination neutralizing antibody among healthcare workers in a referral hospital in Tokyo: a case-control matching study.
In the present analysis among patients who were infected within 2 months after the booster, however, the sensitivity did not change (78%) after excluding asymptomatic cases. Among vaccine recipients who might have acquired strong immunity during short period after the booster, the presence of symptoms may not reflect SARS-CoV-2 Ig-N production.
In this well-defined cohort with repeat serological assessments and rigorous registration of COVID-19, the performance of the Roche Ig-N assay was decreased by approximately 20-percentage points for the breakthrough infections occurred within 2 months after the booster dose, whereas it performed well for those occurred 3 months or more after the second or third dose. The decreased performance observed shortly after the booster needs to be considered in the planning of seroepidemiological study and interpretation of the results.
Ethical approval
Written informed consent was obtained from all participants, and the study procedure was approved by the NCGM Ethics Committee (approval number: NCGM-G-003598).
Financial support
This work was supported by the NCGM COVID-19 Gift Fund (grant number 19K059) and the Japan Health Research Promotion Bureau Research Fund (grant number 2020-B-09). Roche Diagnostics provided reagents for anti-SARS-CoV-2 antibody assays.
Declaration of Competing Interest
All authors: No reported conflicts of interest.
Acknowledgment
We thank Mika Shichishima for her contribution to data collection and the staff of the Laboratory Testing Department for their contribution to measuring antibody testing.
References
Jones J.M.
Opsomer J.D.
Stone M.
et al.
Updated US infection- and vaccine-induced SARS-CoV-2 seroprevalence estimates based on blood donations, July 2020-December 2021.
Serological markers of SARS-CoV-2 infection; anti-nucleocapsid antibody positivity may not be the ideal marker of natural infection in vaccinated individuals.
COVID-19 breakthrough infection and post-vaccination neutralizing antibody among healthcare workers in a referral hospital in Tokyo: a case-control matching study.
00480-7&id=gr1.jpg){kind=link}