Detection Of New Crown Pneumonia Virus: From Insufficient Capacity To Speed Debate

Since the outbreak of the COVID-19, we have experienced a test of speed, capacity and quality in terms of diagnosis and means from China to the world.

An endless stream of ways and means has almost reached the speed of updating every day. Saliva has also been used as a new sampling method after nasopharyngeal swabs, bronchoalveolar lavage fluid, serum and plasma.

In April 13th, RUCDR Infinite Biologics announced that it received FDA's emergency use authorization (EUA), a new collection method, that is, using saliva as the main test biomaterial for the new crown virus. This is the first approval granted by FDA, which will be able to conduct a wider population screening than the current nasal and throat swab methods.

This is the thirty-fourth emergency use authorization issued by FDA for diagnostic testing. It is not yet known whether the method is more efficient and accurate. FDA said it has worked with more than 300 test development institutions and personnel, and more than 180 laboratories in the United States have begun testing their policies.

In the early days of the outbreak, China's State Food and drug administration also used 4 days to test several kits to cope with the shortage at that time. By the end of March, the State Food and drug administration has approved 25 new coronavirus products, including 17 new nucleic acid reagents and 8 antibody detection kits.

With the spread of the epidemic, the supply of testing products in China has shifted from internal to external. On April 5th, at the press conference held by the joint defense and joint control mechanism of the State Council, Zhang Qi, deputy director of the instrument Supervision Department of the State Administration of drug control, gave the present situation of China's capacity: the nucleic acid test reagent production capacity reached 3 million 60 thousand per person / day, the antibody detection reagent production capacity reached 1 million 200 thousand per person / day, and the total capacity reached 4 million 260 thousand per person / day.

However, according to Dongxing securities research data, the total number of test kits needed for overseas effective control is about 65 million 720 thousand, and the actual cumulative number is about 8 million 27 thousand.

By the end of March, the State Food and drug administration has approved 25 new coronavirus detection products. - Xinhua News Agency

Testing institutions: more and more

Nucleic acid detection, antibody detection and CT detection of "three swordsman" diagnostic new crown virus have been widely known in the epidemic. In the latest version of the National Health Council's new version of the new coronavirus pneumonia treatment plan (Trial Seventh Edition), three ways are included.

On the basis of the original nucleic acid detection and sequencing, the serological test can also be used as a basis for the diagnosis, that is, "new coronavirus specific IgM antibody and IgG positive" or "new coronavirus specific IgG antibody" is positive from negative to 4 times higher than that in the acute phase.

There are two kinds of testing reagent products for emergency examination and approval by the State Administration of drug administration. They are nucleic acid detection reagents and antibody detection reagents. The antibody detection reagent is used as a supplementary test for suspected cases of negative detection of new crown virus, or in conjunction with nucleic acid detection in suspected case diagnosis, not as a basis for diagnosis and exclusion of new crown virus infection, nor for ordinary people. Group screening, antibody detection reagent only for medical institutions.

Nucleic acid detection is still the "gold standard" for diagnosis in China. On the other side of the ocean, the United States has also urgently authorized dozens of nucleic acid and blood antibody testing companies in the early years after it experienced high test threshold, inadequate reagent kit, uneven quality and high price. In mid March, manufacturers were allowed to conduct tests without the need for a review or emergency permit: FDA director Stephen M. Hahn said in March 16th's announcement that "FDA does not intend to oppose the use of new commercial development tests for distribution and laboratory tests before EUA is granted to EUA."

The US Centers for Disease Control and Prevention (CDC) did not let go of all tests at the beginning. In February 5th, the first data reported by public health laboratories outside the CDC laboratory came into existence. Until February 26th, the daily number of non CDC laboratories was still less than three digits. Since February 27th, the number of reported data has started to break 100. In March 4th, CDC released standards everywhere, and the number of reported tests began to surge to four digits until subsequent outbreaks.

FDA approved in vitro diagnosis of EUA was only two in February, respectively, CDC and New York public health ministry testing agency. On March 12th and 13, FDA authorized two diagnostic giants Roche Diagnostics and SEM Fisher virus tests. In March 24th, Roche said it could provide millions of tests per month at the current highest productivity. SEM Fisher said its authorized testing technology could provide results within four hours after receiving the samples in the laboratory, and it is expected that the weekly production scale will be expanded to 5 million tests in April.

In the United States, more and more institutions and laboratories gradually joined. In March 30th, the Jennifer Doudna team, known for its CRISPR gene editing research, also announced that it had transformed its laboratory into providing COVID-19 virus services, and that it could handle more than 1000 patients in 24 hours with a maximum of 3000.

On the other side of the ocean, in April 8th, although the diagnosis itself was not one of its core businesses, two British pharmaceutical giants AstraZeneca and GlaxoSmithKline also announced that they would assist the British government in conducting the COVID-19 test by establishing a joint laboratory at University of Cambridge. Pascal Soirot, chief executive of AstraZeneca, said the goal of the lab is to conduct 30000 tests a day in the first week of next month.

In addition, after questioning the cost of early detection, in April 11th, the medical insurance and Medicaid service (CMS), the Ministry of labour and the Ministry of Finance issued new guidelines to ensure that Americans with private health insurance are free to detect.

As of Beijing time April 14th, statistics from Johns Hopkins University in the United States showed that the number of confirmed COVID-19 in the world was 1925811, and the United States had diagnosed 582594 people. According to CDC data, as of April 12th, the total number of public health laboratories completed and tested in the United States was 95, and the number of samples tested was 298499. Because FDA no longer requires the public health laboratory using CDC analysis to submit samples to CDC for confirmation, there is a big discrepancy between data and reality.

Speed of detection: the sooner, the better?

In April 12th, Stephen Hahn admitted that it was necessary to step up the test. "The United States has conducted more than 2 million checks. There is no doubt that we need to do more." But he also said, "inaccurate testing is worse than not testing at all." The pressure on the supply chain is the reason for testing differences across the country. No test is 100% perfect, but we do not want extremely inaccurate testing. Testing must be effective, accurate and reliable, which is very important. "

But no matter whether nucleic acids or antibodies are tested faster, officials and manufacturers seem to be selling more and more testing methods together.

In March 27th, BOSCH said it developed a rapid test method that could detect new crown viruses within 2.5 hours. It could be carried out directly at the nursing point without the need to transport samples. Then, in March 28th, Abbott released the test plan that came out in 5 minutes.

Trump then introduced the rapid test plan in a press conference, but he placed the instrument in reverse when he demonstrated it. But according to a document issued by the Ministry of health and public service and the federal emergency administration a week later, the state and local public health laboratories only tested a total of 5500 times, much less than Abbott coordinator Deborah Birx said, "Abbott has about 500 thousand testing capabilities". These tests seem to have not been fully utilized in the states of the United States, and there is no large sample size for accuracy at present.

It is also small and convenient, which is also suitable for small medical institutions. But the industry also has doubts about its cost, throughput and sensitivity. A 1 test of 5 samples for 5 minutes has no obvious advantage over high throughput; if the viral load is too low, the risk of omission will increase.

No test can be 100% accurate. Fan Jianbing, the founder of benchmark medicine, said in an interview with the twenty-first Century economic news reporter that evaluating the effectiveness of a test should depend on sensitivity, specificity and other targets as well as testing purposes, not just speed.

"Detection time is related to what objects you test. If you want to test whether the body is infected with a new crown virus, nucleic acid testing, throat swabs, nasopharyngeal swabs and other means of sampling, that is, the use of PCR platform also takes a few hours. Some blood antibody tests are very simple and fast, but this kind of detection is more supplementary. Because there are individual differences, each person has different reaction time to the virus and the time to produce antibodies. Positive and negative results need further confirmation and careful interpretation. There may be a virus but no pathological symptoms. It is also possible that the virus is too low to detect. Fan Jianbing said, "not a few minutes is better than a few hours of wisdom." this is a comparison between apples and oranges. It depends on the actual situation that needs to be tested. But I am skeptical about using saliva samples to detect the new crown RNA virus, and not to mention the stability of RNA virus in saliva. It is hard to say that the amount of virus contained in saliva is far away from the lesion. The sensitivity of detection will be lower, and the corresponding relationship with pneumonia should be asked.

?