Diagnostic test from Berlin in demand worldwide

The Wuhan virus continues to spread. In order to slow down the advance of the pathogen causing respiratory diseases, precise diagnostic procedures are important to quickly identify infected persons. Researchers at the Charité hospital in Berlin have developed such a virus test in record time.

By Volkart Wildermuth - 23.01.2020

Pipettes suck, centrifuges rush, cell sorters click in the laboratory at the Berlin University Hospital Charité. But the most important laboratory device for developing the test for the new corona virus 2019-nCoV was simply a refrigerator, explains Professor Christian Drosten. This is where the head of the Institute of Virology at Charité University Hospital keeps samples of viruses from past outbreaks. Christian Drosten has already co-discovered the SARS virus; he is a renowned expert on corona viruses and learned about the new virus early on through contacts with researchers in China.

"Already between Christmas and New Year, the first informal information arrived here. And of course we immediately set about doing what we are particularly good at: Developing diagnostic test procedures in a very short time. And then, above all, make them available worldwide."

Renowned virologist with early suspicion

In the beginning it was not clear what kind of pathogen it is. But the experienced virologist had a suspicion: "Yes, we did indeed rely on a few pieces of evidence. We had information from social media that this could be a SARS-like virus and we put one and one together."

The computer in Berlin stores the sequence data of numerous corona viruses. With their help, the Berlin researchers designed virtual tests for a virus they hardly knew anything about: 

"And when, some time later, the colleagues from China made the first genome sequence of this new virus public, we compared it with all our candidate tests, selected the best ones and continued working with them."

Christian Drosten boots up the computer and searches for the appropriate files. The Gs, As, Ts, and Cs - the abbreviations for the DNA building blocks of the viral genomes - are arranged exactly one above the other.

"What you see here in the top line are the very large matches between the SARS corona virus and this new virus at the sites where the molecules we use in the test dock. And you can see the differences here: These are also just letters that are entered here, in related viruses from bats. Partly from Europe and partly from China."

The test was further refined with DNA data from China

Bats are among the natural hosts of the corona viruses. The researchers first looked for sequences that are typical of already known corona viruses that infect humans, such as SARS and MERS. They constructed suitable probes for two of these specific DNA sections. When these bind to a viral genome, the piece in between can be massively multiplied using the polymerase chain reaction and then detected. If there is no corresponding virus genome in the patient sample, nothing happens. Thanks to the new sequence from China, the test could be further refined. As with the pregnancy test, there are now two strips, or in this case two colors, which the PCR machine displays.

Charité researcher: "With the Wuhan virus it glows in two colors at the same time."

Christian Drosten: "In principle, we have a gray box that stands on the laboratory bench, in which the reaction takes place in very, very small volumes, about a quarter of a drop of water. And then we see the results on the computer. It's like this: if the positive control has worked, it only glows in one color. If the Wuhan virus is in it, then it glows in two colors at the same time."

At least that was the plan for the test, because it was still virtual. Because everything was based exclusively on information, on DNA sequences. Not a single virus particle came to Berlin from China. But even a test developed in the virtual world must prove itself in reality. And that is where the refrigerator came into play. The researchers from Berlin - together with colleagues from Rotterdam and London - took old samples from patients with known respiratory diseases and tried out the new virus test on them. As expected, it did not react to influenza viruses, adenoviruses, enteroviruses or other pathogens. So it was clear: the new test does not raise false alarms. This is the first important criterion for a good test. The second is of course: Does the test really detect the pathogen you are looking for?

Litmus test was conducted in China - and convinced the WHO

"We have made this test available to colleagues in China, whose names I cannot give you now. And they tested it for us and told us that it worked well."

This has also convinced the World Health Organization, which was the first to present the Berlin test on its website. In China itself, a test was also developed and distributed in the country at the same time, but there is great interest in Christian Drosten's test among the Southeast Asian nations. And there are also many inquiries from Europe. More than eighty orders have been received, and padded envelopes containing the reagents are piled up in the corridor - financed by EU subsidies. Wherever a traveler from Wuhan with breathing difficulties and high fever arrives, the new test can be used. In Europe and Germany, Christian Drosten suspects that the diagnostic tool will primarily help to calm down.

"Well, we are in the northern hemisphere during the influenza season. This means that all these patients who come now and say: 'I was in Wuhan and I'm not feeling well' - they still have a higher probability of having an influenza virus or a different respiratory virus than this new virus. You have to distinguish between them. And you can't do that with a clinical eye diagnosis - but with a laboratory test."

In Southeast Asia, however, the test will help to track the spread of the infection. The number of cases continues to rise - and it is difficult to estimate how great the threat actually is.

Translated & reblogged Version - Original here