WHO reports China making 1.6M COVID-19 diagnostic kits per week, describes therapy and vaccine R&D priorities

WHO: China makes and deploys 1.6 million COVID-19 tests/week; the U.S. is just starting to ramp up capacity

A WHO report on a Feb. 16-24 mission to China to assess the COVID-19 outbreak summarizes the situation on the ground, highlights countermeasure R&D initiatives, challenges and needs, and identifies critical knowledge gaps.

What stands out is the dramatic speed with which China has developed and deployed diagnostic tests -- and the contrast with the U.S.

Manufacturers in China “have the capacity to produce and distribute as many as 1,650,000 tests/week,” the WHO reported.

Manufacturing capacity in the U.S. is about 3,150 tests per week, according to Robert Redfield, director of the CDC. U.S. capacity is set to expand in the coming weeks as FDA plans to authorize labs to conduct testing.

The first RT-PCR assays for COVID-19 were distributed to Hubei province on Jan.16, nine days after the virus that causes the disease was first isolated.

“By 23 February, there were 10 kits for detection of COVID-19 approved in China by the NMPA, including 6RT-PCR kits, 1 isothermal amplification kit, 1 virus sequencing product and 2 colloidal gold antibody detection kits,” the WHO reported. “Several other tests are entered in the emergency approval procedure” and “other tests are close to approval.”

However, the rush to deploy tests has led to concerns about the quality of testing and reliability of results (see “Plotting a Scientific Path to Counter COVID-19”).

WHO said it “will be important to compare the sensitivities and specificities of [the tests in use now in China] and future serologic tests" and called for initiatives to “consistently evaluate existing and future diagnostic tests for detection of COVID-19 using a harmonized set of standards for laboratory tests and a biorepository that can be used for evaluating these tests.”

The U.S. CDC has a capacity to test about 450 samples per day for the virus that causes COVID-19, CDC director Robert Redfield told a congressional committee on Feb. 28.

Problems with one of three reagents in a CDC-developed test led CDC to postpone the nationwide rollout of its COVID-19 test. Capacity could increase after CDC’s Feb. 27 decision to give some state labs the green light to run the test using two reagents.

The Association of Public Health Laboratories (APHL) asked FDA on Feb. 24 to allow hospitals to run laboratory developed tests (LDTs) for COVID-19, which could also increase testing capacity.

FDA is in the process of “increasing flexibility to allow private sector labs to develop coronavirus testing on an accelerated basis, and a combined CDC-FDA guidance will be out soon with specifics on that,” HHS Secretary Alex Azar told reporters Friday.

The guidance will create a “streamlined, expedited process [to conduct] testing in labs across America,” he said. “We hope within a fairly short period of time to have a vast increase in the capacity of testing here in the United States.”

In addition, several Emergency Use Authorization requests from diagnostics companies for COVID-19 tests are pending at FDA and could be approved soon.

Increased testing will almost certainly reveal new cases of COVID-19 in the U.S., informing public health interventions and adding to pressure to rapidly develop and test therapies and vaccines.

Research priorities and challenges

The WHO report lists as immediate "priority research areas" remdesivir, chloroquine, favipiravir, convalescent plasma and traditional Chinese medicine (TCM), and noted that hundreds of clinical trials of these potential COVID-19 therapies are under way or planned in China.

WHO also identified intraveneous immunoglobulin (IVIG) as an intermediate research goal, and "innovative approaches (CRISPR-CAS; RNAi; cell-based; positive hits from screening)" as long-term priority research areas.

Two companies, Mammoth Biosciences and Sherlock Biosciences Inc., are developing CRISPR-based diagnostic tests for COVID-19, and Sherlock hopes to submit its test for FDA clearance this season (see “CRISPR-based Diagnostics Poised to Make An Early Debut”).

The report does not mention the active search for mAbs that could be used as treatments or prophylactics. At least four companies, including AbCellera Biologics Inc., Regeneron Pharmaceuticals Inc. (NASDAQ:REGN), Vir Biotechnology Inc. (NASDAQ:VIR) and WuXi Biologics Inc. (HKEX:2269) are attempting to discover and develop mAbs that could treat or prevent COVID-19 infections (see “COVID-19 mAb Menagerie”).

“It is important for there to be a degree of coordination between those conducting studies within and beyond China.”

WHO

WHO hints at concerns that the most promising agents are not being prioritized and that some trials are being conducted in a manner that isn’t likely to yield actionable information. “Evaluation of investigational agents requires adequately powered, randomized, controlled trials with realistic eligibility criteria and appropriate stratification of patients. It is important for there to be a degree of coordination between those conducting studies within and beyond China.”

WHO also highlighted concerns about the potential for a COVID-19 vaccine to enhance the severity of infections caused by other coronaviruses, including viruses that are likely to emerge in the future. “Vaccine safety is of prime concern in the area of coronavirus infection in view of the past experience of disease enhancement by inactivated whole virus measles vaccine and similar reports in animal experiments with SARS coronavirus vaccines,” the report stated.

Several COVID-19 vaccine development projects have been launched based on recombinant protein, mRNA, DNA, inactivated whole virus and recombinant adenovirus technologies and some are now entering animal studies. BioCentury has identified 39 COVID-19 vaccine development programs (see “COVID-19: A Growing List of New Vaccines and Therapies in Development”).

“Too many clinical studies are designed in ways that won’t be informative.”

David Ho, Aaron Diamond AIDS Research Center,

David Ho, director of the Aaron Diamond AIDS Research Center, has also raised concerns about uncontrolled COVID-19 studies.

Speaking on Feb. 25 during an online forum organized by WuXi Apptec Co. Ltd. (Shanghai:603259; HKEX:2359), Ho said that “at the present time too many clinical studies are designed in ways that won’t be informative.” He noted that a high percentage of COVID-19 patients recover without treatment, so uncontrolled studies are likely to produce only anecdotes. A lack of controls in studies of agents used in SARS trials created little valuable data.

The WHO report suggests that the Chinese government consider establishing a centralized program to oversee the COVID-19 research portfolio and ensure that the most promising vaccines, treatments and fundamental research is adequately supported and prioritized. Program staff from a centralized program could work at clinical research sites to reduce the burden on clinicians.

Scientific gaps

In the report, WHO identifies a number of gaps that should be filled quickly to advance the development of therapies and vaccines.

“The ideal animal model for studying routes of virus transmission, pathogenesis, antiviral therapy, vaccine and immune responses has yet to be found,” the report notes. “The ACE2 transgenic mouse model and Macaca Rhesus model are already used in research laboratories. Systematically addressing which models can accurately mimic human infection is required.”

The WHO report also flags fundamental uncertainties about COVID-19, including the clinical course, factors that influence susceptibility, and long-term effects of the disease, and calls for an observational study to provide answers. “An observational cohort study of patients with COVID-19 enrolled from the time of diagnosis (with appropriate controls) could provide in-depth information about clinical, virologic and immunologic characteristics of COVID-19.”

Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus. The COVID-19 content is free to all who visit the site.

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