A Genome Epidemiological Study of SARS-CoV-2 Introduction into Japan

Abstract

After the first case of coronavirus disease 2019 (COVID-19) in Japan on 15 January 2020, multiple nationwide COVID-19 clusters were identified by the end of February. The Japanese government focused on mitigating the emerging COVID-19 clusters by conducting active nationwide epidemiological surveillance. However, an increasing number of cases continued to appear until early April 2020, many with unclear infection routes and no recent history of travel outside Japan. We aimed to evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences from the COVID-19 cases that appeared until early April 2020 and to characterize their genealogical networks in order to demonstrate possible routes of spread in Japan. Nasopharyngeal specimens were collected from patients, and reverse transcription-quantitative PCR tests for SARS-CoV-2 were performed. Positive RNA samples were subjected to whole-genome sequencing, and a haplotype network analysis was performed. Some of the primary clusters identified during January and February 2020 in Japan descended directly from the Wuhan-Hu-1-related isolates from China and other distinct clusters. Clusters were almost contained until mid-March; the haplotype network analysis demonstrated that the COVID-19 cases from late March through early April may have created an additional large cluster related to the outbreak in Europe, leading to additional spread within Japan. In conclusion, genome surveillance has suggested that there were at least two distinct SARS-CoV-2 introductions into Japan from China and other countries. IMPORTANCE This study aimed to evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences from COVID-19 cases and to characterize their genealogical networks to demonstrate possible routes of spread in Japan. We found that there were at least two distinct SARS-CoV-2 introductions into Japan, initially from China and subsequently from other countries, including Europe. Our findings can help understand how SARS-CoV-2 entered Japan and contribute to increased knowledge of SARS-CoV-2 in Asia and its association with implemented stay-at-home/shelter-in-place/self-restraint/lockdown measures. This study suggested that it is necessary to formulate a more efficient containment strategy using real-time genome surveillance to support epidemiological field investigations in order to highlight potential infection linkages and mitigate the next wave of COVID-19 in Japan.

Introductions and evolutions of SARS-CoV-2 strains in Japan

“…It is quite intriguing that D614G_KR is dominant despite the fact that comparable numbers of D614G and D614G_Q57H strains were introduced into Japan. For unknown reasons, strains other than D614G_KR have not been able to establish and propagate in Japan 21 .…”

Genomic Epidemiology Reveals Multiple Introductions of Severe Acute Respiratory Syndrome Coronavirus 2 in Niigata City, Japan, Between February and May 2020

“…Interestingly, the first wave was characterized by a local epidemic that occurred in a closed environment, namely a sports facility, which resulted in a chain of cluster-mediated infections, as described above. On the other hand, the second wave was characterized by the clade GR (20B) virus from Europe, which was prevalent in Japan since mid-March (Sekizuka et al, 2020a), with an increased number of cases with unknown routes of infection compared to the first wave. There was no commonality in age, sex, or behavior of the patients in the second wave, indicative of multiple routes of entry.…”

Identification of B.1.346 Lineage of SARS-CoV-2 in Japan: Genomic Evidence of Re-entry of Clade 20C

“…3,4 In Japan, five laboratories (including our group) have deposited whole viral genome data in the public sequence database GISAID (https://www.gisaid.org/): a total of 9943 sequences have been deposited, and some results of national surveys have been summarized. 5,6 These studies indicated the importance of SARS-CoV-2 genome sequencing analysis for the prevention of outbreaks during the early pandemic period (March to April 2020). SARS-CoV-2 whole-genome data was generated using specimens from 198 patients with COVID-19 admitted to 13 collaborating hospitals located in the Tokyo metropolitan area.…”