The hunt for coronavirus genomes that could exacerbate the pandemic

The extremely contagious new type of COVID-19 that is spreadingout the UK is now possibly running through the US

The challenge is to find it.

Unlike the United Kingdom, America has not yet fully utilized the power of genomics to quickly detect significant changes in the virus that could change the course of the pandemic that is devastating the country.

“We work blindly,” with insufficient selection to know how common the tension is, Dr. Charles Chiu of UC San Francisco, whose laboratory is collaborating with the Department of Public Health for the new variant, called B.1.1, said. .7., In viral samples among recent travelers in the UK in many provinces in California.

On Friday, on December 20, Chiu’s laboratory discovered two new cases of the variant virus from samples collected from members of a household in the Big Bear area. One member of the household had contact with a traveler who returned from the UK on 11 December. The finding follows news of two cases in San Diego and two cases in Denver, all of which were confirmed Wednesday. As of Saturday, the variant has been reported in 33 other countries.

Because none of the people involved in US affairs have traveled while traveling, experts fear unnoticed community distribution.

Like all viruses, the COVID-19 pathogen makes small changes in its genome as it reproduces. Understanding this evolution – and especially what mutations can change its behavior – is essential to estimating the threat of new strains.

The genetic composition of the virus, which is stored in a single strand of RNA, determines whether it can suddenly become resistant to drugs, and whether a vaccine is protective or useless.

But of the more than 19 million COVID-19 cases officially reported in the United States, only 58,500 or 0.3 percent were genetically analyzed for variants, according to the latest data from a centralized database.

And most of these analyzes are catchy cases. The average delay time between sample collection and sequence sharing in the US is 96.6 days – compared to 38.5 days in the UK. While more than half of the samples in the country are sequenced within a month, only 14.7% of U.S. samples are.

It is no coincidence that the country’s first case was found in Colorado. Unlike California and most other states, Colorado’s state laboratory follows all COVID-19 samples for the British variant, according to health officials. The laboratory also follows the sequence of suspicious samples sent by commercial laboratories.

California follows an example of people who meet at least one of the following criteria: Recent trip to the UK or Europe; exposure to persons who have recently traveled to the United Kingdom or Europe; or a diagnostic test with mutations indicating that it may be related to the British strain. These samples are sent to a network of laboratories – including the California Department of Public Health and local public health laboratories, diagnostic laboratories, Chan Zuckerberg Biohub, Invitae Corporation, UCSF and the Scripps Institute – collectively referred to as “COVIDNet”.

SAN FRANCISCO, CA. – DES. 30: Dr Charles Chiu of UCSF follows hundreds of viruses in Northern California from recent travelers in the UK to understand the latest mutations. A device capable of generating 400 million series per operation runs on Wednesday, December 30, 2020 in San Francisco, California (Karl Mondon / Bay Area News Group)

The state’s discovery of the variant is a wake-up call, says Stacia Wyman, a scientist at the Berkeley-based Innovative Genomics Institute, whose team sequences the genomes of 700 COVID-19 virus samples from the East Bay.

“I deeply suspect it’s in many other places,” she said. With more universal order, “we would have known it.”

Until now, California has largely focused its sequencing efforts on specific incidents, such as outbreaks at nursing homes, correctional facilities, hospitals, and other group settings. When there is a so-called ‘superspreader’ opportunity, laboratories for laboratories and public health rush to examine the viral genomes to detect the transmission patterns.

This strategy, for example, revealed that one person infected 52 others during a fraternity party at UC Berkeley last year. Three specific mutations defined the group, says Wyman, whose team led the investigation. Her team searched for the pattern in the genetic sequences of many samples – and to their relief found no evidence that the virus had jumped into the wider community.

“It’s just turned off,” she said. “The whole tribe that determined the group just disappeared, because the university responds very well to it.”

The two San Diego cases were discovered because of the close relationship between the country and Scripps Research, which has a well-known genome sequencing program. The initial illness was detected during UCSD’s mandatory testing program, and within just 17 hours, Scripps had an answer.

It is unclear how and where this disturbing new variant originated.

Although this virus is usually fairly stable and accumulates only one or two mutations per month, there have been several notable changes during the pandemic, according to the World Health Organization.

One of the first variants, a mutation called D614G, which increases infectivity and transmission, appeared in China last winter; by June it was the dominant form of the virus. Another new strain, possibly reducing immune protection, was spotted in Denmark in August; fortunately it does not appear to be widespread.

The worrying new UK variant has 23 different differences compared to what is currently being distributed. One of these changes seems to be easier to transfer. Although this virus is not more deadly than the existing strain, it can be more difficult to contain.

Another variant, announced by South Africa on 18 December, also appears to increase portability and has since spread from two provinces to four other countries.

A powerful computer browser at UC Santa Cruz helps scientists compare hundreds of viral sequences simultaneously, revealing where these new mutations are located and how common they are. This so-called SARS-CoV-2 Genome Browser also shows which parts of the genome are being studied by different teams, and provides information on the mutations. Based on the computer code written by the postdoc scholar Yatish Turakhia, the browser is much faster than the existing tools.

“We absolutely must increase our oversight of what the virus does and how it transmits it,” said David Haussler, professor of biomolecular engineering at the UCSC. “We need to keep up with how the virus is exploiting us.”

The two largest sequencing centers in California are Chan Zuckerberg Biohub in San Francisco, which sequenced and published 2,817 COVID-19 virus genomes, and the Anderson Lab at Scripps Research, based in La Jolla, which published and published 2,374 genomes.

A federal infrastructure of ‘sequencing centers’ will create more consistent, representative and thoughtful analyzes, says IGman’s Wyman. “Right now, every state is doing its own thing.”

This is the challenge: sequencing is expensive. It requires manpower. It takes time. And it diverts attention away from more urgent public health needs.

Unlike the United Kingdom, whose national strategy of so-called ‘genomic surveillance’ is run by a handful of large laboratories, US efforts fall on the tired shoulders of many state and local health departments, already highlighted by the pandemic. . There is no federal funding for a coordinated and real-time effort. And because our healthcare system is fragmented, there is no single pipeline that will yield all positive samples for sequencing.

There is a new federal initiative called SPHERES (Sequencing for Public Health Emergency Response, Epidemiology and Surveillance), but it mostly serves as a central repository of data. It does not pay for the actual laboratory work.

“We can not even do enough diagnostic tests. How, then, would you have the resources needed for sequencing? ‘says dr. Omai Garner, co-director of clinical microbiology for the UCLA health system. “It’s extremely expensive and technically very, very challenging.”

With the pressure on current affairs, it is understandable that the country is focused on testing, vaccinations and reducing the burden on hospitals, experts agreed.

But the arrival of the British tribe warns us of what may come more, they said. Even after everyone has been vaccinated, the country needs to be vigilant for the surprising emergence of dangerous new tribes.

“The idea is to identify local outbreaks of these new varieties before they get a chance to spread so that they are contained,” Chiu said.

” A strong surveillance system will help control not only the pandemic now, ” he said, ” but also in the future. ‘ ‘


How to do COVID-19 “whole genome sequence”:

  • Scientists take infected cells and treat them with chemicals that break them open, releasing the viral RNA. The RNA is then purified.
  • RNA is cut using short enzymes into known fragments of known length.
  • Scientists make many copies of each RNA fragment using a process called polymerase chain
    reaction (PCR). The pool of fragments generated in a PCR machine is called an ‘RNA library’.
  • The RNA library is placed on a sequencer. The combination of nucleotides (A, U, C and G) that each fragment of RNA consists of is determined and each result is called an ‘RNA reading’.
  • The sequencer produces millions of RNA reads and specialized computer programs are used to put them in the correct order, like pieces of a puzzle.
  • Upon completion, the genome sequence containing millions of nucleotides – including any surprising changes in the usual sequence called mutations – is ready for further analysis.

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