Correlation between asymptomatic cases and the incidence of COVID-19 in Japan

Moto Kimura¹, Yukari Uemura¹, Norio Ohmagari¹, Masato Ikeda³, Wataru Sugiura^1*

¹Center for Clinical Sciences, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan
²Disease Control Center, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan
³SB Coronavirus Inspection Center Corp, Tokyo, Japan

^*Correspondence: Wataru Sugiura, Center for Clinical Sciences, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan, E-mail: wsugiura@hosp.ncgm.go.jp

Abstract

Objective: A better understanding of epidemiology is crucial when developing preventive measures against COVID-19. We aimed to investigate the incidence of asymptomatic COVID-19 positive cases among the office workers in Japan and thus help formulate preventive measures against COVID-19.

Method: RT-PCR screening tests were performed for office workers who agreed to participate in the study for nine (9) months, from September 2020 to June 2021. We compared our study’s COVID-19 test results among asymptomatic individuals and published data from the Ministry of Health, Labour, and Welfare. All statistical analyses were conducted using R, version 4.1.0 (R Foundation for Statistical Computing, Vienna, Austria).

Result: In total, we performed 1.2 million tests and found the incidence of asymptomatic COVID-19 cases as 0.076% on average. Further, the weekly incidence of asymptomatic COVID-19 cases was consistent with the incidence of COVID-19 cases over time.

Conclusion: Our findings highlight the potential role of asymptomatic patients in the transmission network of SARS-CoV-2. Further multicentric investigations might help clarify the relationship between asymptomatic cases and symptomatic hospitalizations and their role in disease transmission.

Short Communication 

Coronavirus disease-2019 (COVID-19) has various clinical manifestations, from mild flu-like symptoms to severe conditions. Asymptomatic COVID-19 cases were less frequently reported than symptomatic cases [1], comprising only 1.2–12.9% of patients [2]. Thus, it is crucial to understand epidemiology when developing preventive measures against COVID-19.

Screening by polymerase chain reaction (PCR) has been conducted to provide a safe working environment since July 27, 2020. Healthy individuals, including those who requested to be screened to identify asymptomatic infection in each business location, underwent RT-PCR tests. Self-collected saliva was sent to our laboratory through express delivery service, using a special canister containing inactivating solution. The “SARS-CoV-2 Direct Detection RT-qPCR Kit” (Takara Bio Inc.) was used for the testing [3]. A comparison between the number of COVID-19 tests in asymptomatic people in our study and published data from the Ministry of Health, Labour, and Welfare (MHLW) is shown in Figure 1. In the MHLW data, 567,460 tests were conducted in September 2020 [4]. In contrast, 14,092 tests were conducted among asymptomatic individuals in September 2020 [4]. It is possible that a single person underwent more than one test. The highest number of tests were performed in January and May 2021, during the outbreak, with numbers as high as 513,832 and 647,289 tests, respectively. As of May 30, 2021, a total of 1,222,638 tests have been conducted, and 926 (0.076%) tests returned positive. According to the MHLW (2021), the overall frequency of COVID-19-reported cases in Japan was 0.51%.

Furthermore, the incidence of COVID-19 positivity among asymptomatic individuals was positively correlated with the incidence of COVID-19 cases (Spearman correlation coefficient, 0.60; 95% confidence interval, 0.35–0.77, P<0.001, Figure 2). There was a strong positive correlation in 2021, when the infections had increased compared to 2020 (Spearman correlation coefficient, 0.11; 95% confidence interval, 0.41–0.57, P=0.696, Figure 3 and Spearman correlation coefficient, 0.86; 95% confidence interval, 0.68–0.95, P<0.001, Figure 4). Consequently, the general trend of asymptomatic cases was synchronous with the incidence of COVID−19 cases. However, several infected cases remain undetected.

The Ministry of Health of Israel has developed a virtual cohort of newly vaccinated individuals between December 20, 2020, and February 1, 2021, to rapidly assess the new COVID-19 vaccine BNT162b2 (Pfizer/BioNTech) [5]. In their analysis, among 596,618 individuals who received their second doses, 4,460 were COVID-19-positive. Of the 4,460 cases diagnosed with COVID-19 starting from the day of receiving their second dose, 2071 (46.4%) were asymptomatic. The status of breakthrough infections in Japan remains unknown. However, considering the data from Israel, numbers suggest that COVID-19 screening should be continued irrespective of the decline in incidence rates since the large proportion of asymptomatic infected patients cannot be ignored. Considering the relatively large proportion of asymptomatic COVID-19 cases, further studies should explore their relationship with symptomatic hospitalized cases and their role in COVID-19 transmission.

Acknowledgement

We thank all individuals who participated in the screening tests. We thank Mr. Yukumasa Kazuyama, Director of the SB Coronavirus Inspection Center Corp, and the members for testing the enormous number of specimens since last summer. Moreover, we thank Yosuke Shimizu for supporting us with the data analysis and statistics of the study. Finally, we greatly appreciate Mr. Masayoshi Son for his volunteerism and headstrong resolve to confront COVID-19 and for backing the foundation of SB Coronavirus Inspection Center Corp.

Declarations

Ethical approval

All saliva samples were anonymized post-collection to protect the identities of specific individuals. Although written consent was not obtained for this study, information about the study was made available on the National Center for Global Health and Medicine website, and patients were allowed to decline from participating in the study. Opt-out consent was approved for this study by the Institutional Review Board of the National Center for Global Health and Medicine (approval no. NCGM-G-004225-01). 

Funding

This research was supported by SB Coronavirus Inspection Center Corp.

Conflict of interest

Moto Kimura and Wataru Sugiura have received research grants from SB Coronavirus Inspection Center Corp. Masato Ikeda is an employee of SB Coronavirus Inspection Center Corp.