Seroepidemiologic surveys for assessment of the COVID-19 pandemic in Japan

Seroepidemiologic surveys for assessment of the COVID-19 pandemic in Japan


In a recent study posted to the medRxiv* pre-print server, a team of researchers demonstrated that between August and December 2021, Japan had witnessed a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant-induced endemic.

Study: Large-scale cross-sectional seroepidemiologic study of COVID-19 in Japan: Acquisition of herd immunity and the vaccines’ efficacy. Image Credit: Wirestock Creators/Shutterstock

Earlier serosurveillance in Hyogo Prefecture, a region located in southern-central Japan with a population of 5.4 million, in October 2020, showed a neutralizing activity of 0.15% against SARS-CoV-2.

The seroepidemiologic surveillance conducted during August and December 2021 showed neutralizing activity higher than that estimated by polymerase chain reaction (PCR) analysis, highlighting that, combined with the PCR-based diagnosis, this is a powerful approach in determining the COVID-19 situation at any given time.

About the study

In the present study, researchers collected sera of individuals who went for a health check-up at the clinics of Hyogo Prefecture in Kobe, Japan, between August and December 2021. There were two study cohorts, the August 2021 cohort and the December 2021 cohort, from which the researchers collected 1,000 sera samples each.

The cohorts had people of several age groups, including 20–29, 30-39, 40-49, and 70-79 years, with test subjects falling majorly in the 20-69-year age group. A few test subjects were in the 70–80-year age group, fewer were under 20 years, and none were under 18 years.

Electrochemiluminescence immunoassay (ECLIA) and enzyme-linked immunosorbent assay (ELISA) measured antibody titers against SARS-CoV-2 N and spike (S) antigens, respectively.


ECLIA detected an anti-N positivity rate of 2.1% and 3.9% in the August 2021 and the December 2021 cohorts, respectively. In the August 2021 cohort, with respective anti-N positivity rates of 3.4%, and 4.1% among the individuals of the 30–39 and 40–49 years age groups, this rate was relatively high, whereas no positive cases occurred in the age groups of 18–19 and 70–83 years. In the December 2021 cohort, the anti-N positivity rate for the 20-29 age group was 10.6%, and that in the oldest age group of 70–79-year-olds was 5.0%, suggesting that the infections increased in the younger and the older groups during this time.

The anti-S positivity rates, estimated by ELISA, considered the vaccination and infection history of the test subjects. The anti-S positivity rate for the August and the December 2021 cohorts were 38.7% and 90.8%, respectively, at the cut-off index (COI) of 0.3 for the 40-fold serum dilution.

In the August cohort, the anti-S positivity rates for the 60–69 and 70–83 years age groups were relatively high at 70.7% and 90.2%, respectively. Contrastingly, in the December 2021 cohort, a flattened positive rate between 87.2% and 100% was observed across all the tested age groups. Notably, all the anti-N-positive sera were also anti-S-positive, with only one exception in both the cohorts.

Kruskal-Wallis test estimations showed no significant difference in the distribution of anti-S antibody titers among different age groups in the August 2021 cohort, while the distribution decreased in the 70-79 years age group of the December 2021 cohort.

In the August 2021 cohort, the anti-S-positive subset of 387 individuals showed neutralizing titers of 85.5% against the WT strain, compared to 77.3% against the Delta variant. The Mann-Whitney U-test estimations, thus, indicated the effectiveness of two doses of COVID-19 vaccination.

The December 2021 cohort, which represents the vaccinated population, had a high neutralization-positivity rate of 78.7% against the Delta variant, indicating effective social immunity. In striking contrast, this cohort was vulnerable to Omicron infection, as suggested by a low neutralization rate of 36.6%. Overall, these findings demonstrated that the two-dose vaccination suppressed the spread of the Delta variant, resulting in a relatively lowered infection rate of 3.9% during the study period.

Examining these cohorts segregated based on age groups revealed that in the 70-79 years age group, the neutralization-positivity rate was lower against both the Delta and the Omicron variant, with only 15% sera having neutralization activity against Omicron.

Both Delta and Omicron cases had higher anti-S antibody titers, suggesting that the neutralization activity is largely attributed to the presence of anti-S antibodies.


Between August and December 2021, PCR-based infection rates were approx. two-fold lower than the infection rate revealed by the serosurveillance of the present study, thus suggesting that periodic cross-sectional seroepidemiologic surveillance is a powerful approach in interpreting the COVID-19-induced pandemic situation combined with PCR-based diagnosis and antigen tests.

As of January 6, 2022, 74% population of Japan had received two doses of COVID-19 vaccination, which helped build social immunity among 38.7% of individuals of the August 2021 cohort, as demonstrated by their anti-S seroprevalence results. These results also correlated with Hyogo prefecture's single and two-dose vaccination rates of 32.79% and 42.05%, respectively.

By December 2021, the vaccination rate plateaued in Japan, and the serosurveillance survey revealed a high seropositive rate of 90.8%. Furthermore, this survey revealed a high seropositive rate of 78.7% against the Delta variant but a much lower rate of 36.6% against the Omicron. Overall, these results suggested that the vaccinations in Japan established herd immunity and contributed to bringing down the severity of the COVID-19 situation by December 2021.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Zhenxiao Ren, et al. (2022). Large-scale cross-sectional seroepidemiologic study of COVID-19 in Japan: Acquisition of herd immunity and the vaccines' efficacy. medRxivdoi:

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Antibodies, Antibody, Antigen, Assay, Coronavirus, Coronavirus Disease COVID-19, covid-19, Enzyme, immunity, Immunoassay, Omicron, Pandemic, Polymerase, Polymerase Chain Reaction, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome

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Neha Mathur

Neha Mathur has a Master’s degree in Biotechnology and extensive experience in digital marketing. She is passionate about reading and music. When she is not working, Neha likes to cook and travel.

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