As the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to take its toll on human life and activity, new mutations and variants have emerged in different populations and regions. As scientists struggle to keep pace with these new strains, the enormous value of genomic sequencing of the viral RNA, and of sharing such data internationally, is becoming clear.
A new preprint that appeared on the medRxiv* preprint server recently describes the outcome of such sequencing efforts in Japan as an important tool towards containing the spread of the infection. The researchers used whole genome sequencing of samples from COVID-19 patients to identify a new clade that appeared to have been imported, rather than spreading from the cases already existing in the community.
The need for molecular genomic surveillance
Infection control demands that cases arising during the same short period of time in a hospital be distinguished as being of nosocomial origin or derived from the community. If the former, it becomes necessary to trace the contacts of both inpatients and healthcare workers, which is not always essential in the community setting.
Secondly, the direction in which the virus is adapting and changing in a given region or country is also signaled by the whole genome sequences obtained from COVID-19 patients in multiple hospitals. Such datasets as the national surveillance system in use in the UK have revealed that during the period of high national and international mobility, over a thousand viral lineages spread freely throughout the population.
Recently, this system rapidly identified two variants of concern (VOCs), the UK and South African variants – 501Y.V1 (B.1.1.7) and 501Y.V2 (B.1.351), respectively. These have been found to have greater infectivity and transmissibility due to the array of mutations found in each of them.
Two dominant lineages in Japan
In Japan, eight laboratories are engaged in whole genome sequencing of the virus, uploading the new sequences to the Global Initiative for Sharing All Influenza Data public database. However, the date of collection or the regional origin of many samples sequenced in Japan is missing.
The current study focuses on the lineage summary of the sequencing data from 13 hospitals in the Kanto region of Japan, including 198 specimens. The researchers show that most of the strains belong to two closely related lineages, namely, B.1.1.284 and B.1.1.214.
This is in contrast to other countries, such as the UK, already cited above, with over 1,000 lineages of the virus. The very restricted number of lineages seems to indicate the ability of Japan’s strict quarantine system to keep out new lineages from other countries. The researchers recommend that this system be continued to be enforced, as more virulent and highly infectious strains have emerged in the UK and South Africa.
Of the 198 strains, 96% came from clade 20B, which comprised 52% from the B.1.1.284 lineage, and 32% classified as B.1.1.214 lineage. These two lineages have six nucleotide differences, and are found to make up over 4,000 and 1,000 of the more than 9,900 sequences from Japan on GISAID.
These lineages are exclusive to Japan, for the most part, with only eight and three samples of B.1.1.284 and B.1.214, respectively, having been sequenced from other parts of the world. A few other lineages of clade 20B have also been found in Japan.
Single case of clade 20C infection
Strangely, however, a single patient with nosocomial COVID-19 infection was found to harbor a strain belonging to the B.1.346 lineage, belonging to clade 20C. The researchers found 159 sequences belonging to this lineage on the GISAID database, most being from the western part of the USA.
Available data shows that clade 20C was last seen in Japan in March and May 2020, fading out thereafter unless in individuals under quarantine. This appears to be the result of undetected importations of the infection at the border between the two countries, evading the stringent quarantine barrier.
This strain had 18 nucleotide mutations from the original Wuhan SARS-CoV-2 sequence. However, it does not appear to be associated with either altered transmissibility or increased virulence.
What are the implications?
The researchers conclude that genomic surveillance is essential to detect breaches in quarantine policy. Due to the surprisingly small number of lineages circulating in Japan, unlike almost any other country in the world, it may be relatively easy to pick up a foreign strain near the point of introduction.
Secondly, even if such an introduction does occur, identifying the region or country of origin of the imported strain should be easy by a comparison of genomic sequences and mutations.
The researchers also point out the value of decentralized sequencing efforts with common sharing of molecular data, in addition to the single national surveillance system comprising the National Institute of Infectious Diseases in Tokyo and Public Health Centers and Public Health Institutes.
The advantage of the former is its agility in identifying and following up new trends as soon as they are noticed, with appropriate national policies responding to quarantine breaches or containing areas where VOCs are detected, for instance.
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.