Delays and shortages plague SARS-CoV-2 genomic surveillance program

Shortly after the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) began to spread around the world, leading to the devastating 2019 coronavirus disease (COVID-19) pandemic, the first sequences have been published. Since then, virus genomic surveillance has been a critical tool in keeping track of new and possibly more virulent or transmissible variants as they emerge and spread.

A new study from the Institute of Bioinformatics and Applied Biotechnology (IBAB), Bengaluru, India, provides insight into how this important oversight mechanism works around the world. The team published their findings as a pre-publication on the bioRxiv* server.

Good viral surveillance practices through genomic sequencing depend on the existence of a common open access platform that makes all genomes sequenced so far freely accessible to researchers around the world.

At the very beginning, COVID-19 researchers co-opted the Global Initiative on Sharing All Influenza Data (GISAID) genome sharing platform to deposit the new SARS-CoV-2 sequences.

It is now the largest open access platform in use, storing genomic sequences with clinical and epidemiological correlates of over 1.7 million strains of SARS-CoV-2, making it the organism the most studied of all time.

This facilitated the identification of several new variants, including variant B.1.1.7 (Alpha), first identified in the UK; B.1.351 (Beta, first seen in South Africa); B.1.1.28 or P.1 (Gamma; first in Brazil); B.1.617.2 (Delta) and B.1.617.1 (Kappa), both first in India; P.3 (Theta; first in the Philippines); and B.1.427 and B.1.429 (Epsilon; first in the United States).

This platform has helped analyze sequences, identify emerging variants in a timely manner, and provide useful information to governments at risk in shaping their policies. In response, there has been a concerted chorus of scientists urging an increase in sequencing around the world. However, there is an observable delay in submitting footage to these portals, hampering their usefulness.

The scientists in this study therefore proposed a measure of this delay, called the collection delay on submission (CSTlag) per strain.

Significant delays in downloading footage

The median / mean values ​​of the CSTlag vary from country to country, from one day to one year (or even more).

Among countries that have submitted 1,000 genomes or more, the UK has the least delay (16 days) with around 420,000 genomes submitted.

For other European countries, around 590,000 genomes were deposited with a 25-day lag. The United States follows closely behind, contributing nearly 500,000 genomes 26 days behind schedule.

In Asia, Japan took 79 days (median) for more than 37,000 genomes. India’s CSTlag was 72 days for approximately 16,000 genomes. Qatar in the Middle East uploaded around 2,200 genomes with a median lag of almost 290 days. Conversely, Singapore has a median lag of 26 days for around 2,500 genomes.

In the southern hemisphere, Australia and New Zealand have a lag of 40 and 51 days for 17,000 and 1,000 genomes, respectively. South America downloaded over 18,000 genomes, at 61 days, and Africa 7,000 with a median lag of 50 days.

Sequencing rate

Scientists also assessed the rate of genome sequencing per total number of COVID-19 cases and per million population, respectively.

As a proportion of the number of reported cases, Iceland has sequenced an impressive 77% of all positive cases, compared to ~ 60% in Australia. New Zealand and Denmark sequenced around 40% and 35%, respectively.

The greatest number of genomes come from the United States, as seen above, and the United Kingdom. Although India has a very large population of over a billion people and was hit hard by the second wave, it only sequenced 0.05%.

This corresponds to the pattern observed in Asia, Africa and South America, where sequencing covers less than 0.1% to 0.4% of cases. Europe sequenced ~ 2%, North America 1.4%, but Oceania 37% of cases.

Population-based sequencing rates

When it comes to the sequencing rate per million inhabitants, the First World countries in the West (Europe and the United States) lead the pack, along with Israel and Reunion, with more than 1,000 per million inhabitants. . The North American average is 600, against 1000 for Europe, but 600 for Oceania.

In fact, the United States and Japan are the only countries with more than 100 million inhabitants to have sequencing rates greater than 100 people per million inhabitants. Brazil is next in this group, at 50, comparable to the whole of South America. Conversely, India has a meager 11, about half of the Asian average of 21, and closer to the African value of 14.

What are the implications?

The CSTlag reflects the strength of the local public health infrastructure, reflecting the general functioning of the public health system. Efficient sample collection and recording of metadata, as well as smooth delivery to RNA isolation and genome sequencing centers, are therefore essential to increase genomic sequencing capabilities.

Second, the absence or failure of such systems in low-resource or low-efficiency environments is exacerbated by the dearth of biosecurity facilities capable of handling highly infectious pathogens such as COVID-19 or may not have any. only a few, which again contributes to the delays.

Third, funding is often affected during situations such as a pandemic as resources are diverted to urgent and essential care. Fourth, restrictions on the import of reagents and equipment necessary for RNA sequencing may further hamper this area of ​​research.

Finally, resorting to possibly outdated and more expensive processes can further exacerbate the delay. Many of these factors are known to work in India, for example, and will need to be corrected.

An alternative solution may be institutional-level partnerships covering new ground, rather than relying on local and national governments for infrastructure facilities. This means an inevitable lag before these systems are operational.

Beyond the actual sequencing, downloads are often delayed. “It is likely that many more samples were sequenced than what is shown in GISAID. “

This may be due to a desire to keep research a secret until articles or patents are ready for publication, an initial lack of understanding of the importance of sequencing, or even because of the pervasive stigma associated with variant names named after the countries that first reported them.

Political interference may also have contributed to a large extent, although this is, of course, murky water.

Whatever the cause, a delay in notification gives the variant time to spread across national borders and even to undergo further mutations and emerge as another strain. In order to mitigate this phenomenon, it is crucial to identify and remove these obstacles, to sequence a higher proportion of positive cases and to quickly upload the sequences to open access platforms.

The researchers write:

This will allow researchers around the world to track evolved variants, their mutations, epidemiology and biological consequences, which will provide crucial information for appropriate and effective public health policies.. “

*Important Notice

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

About Warren Dockery

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