LONDON – As the death toll passed 1,000 and the number of confirmed cases reached 42,000, the World Health Organization on Feb. 11 convened 400 scientists at a global research and innovation forum to draw up an R&D blueprint for “pathogen X,” now officially named COVID-19.

“We hope that one of the outcomes of this meeting will be an agreed roadmap around which researchers and donors will align,” said WHO Director General Tedros Adhanom Ghebreyesus, opening the forum at WHO headquarters in Geneva.

A research roadmap is important for organizations that fund research to have a clear sense of what the public health priorities are, so they can make investments that deliver the biggest public health impact, Ghebreyesus said.

There are still huge gaps in understanding the epidemiology of the novel coronavirus and a lack of diagnostics, vaccines and therapeutics that are needed to bring the outbreak under control.

But it’s also the case that the research effort to date has amassed a significant body of knowledge about COVID-19, and jumpstarted work on the development of tools to prevent and treat the infection it causes.

As Ghebreyesus said, “it’s hard to believe” that just two months ago, COVID-19 was “completely unknown to us.”

One of the keys to tackling the epidemic has been the DNA sequence, which has made it possible to diagnose the infection using traditional central laboratory PCR testing. Now, companies and academic researchers around the world are pitching in and applying their own technologies to develop more rapid and flexible diagnostics.

Similarly, having the sequence of COVID-19 in hand made it possible to identify the surface proteins of the virus and to generate vaccine constructs. Two such vaccines that have been developed by academic groups in the U.K. are ready for animal testing and expected to enter human trials in the summer.

And while there are no approved drugs for treating COVID-19, a number of countries, including China, have been administering various antivirals under compassionate use protocols, and WHO expects initial data on effectiveness to start rolling in within the next month. Meanwhile, one formal clinical trial is underway in China, of an (unnamed) therapy, and others are planned, to test drugs during the epidemic.

R&D Blueprint

The speed with which projects have got up and running is a reflection of better preparedness following the emergence of two other coronavirus infections, MERs and SARs, and in particular, of the 2013 – 2016 Ebola epidemic in West Africa.

The time taken to coordinate the international response to expedite development and manufacturing of Ebola drugs and vaccines, and to initiate clinical trials in affected areas, led directly to the R&D Blueprint, WHO’s strategy for developing products before epidemics, and accelerating R&D during epidemics.

The West Africa Ebola epidemic also prompted the formation in January 2017 of the Collaboration for Infectious Disease Preparedness (CEPI). COVID-19 is the first new epidemic disease to emerge since, and CEPI was able to rapidly mobilize resources, directing four pre-existing vaccines programs to focus on the novel coronavirus, and also launching a call for proposals for the fast development and manufacture of other vaccines, which closes on Feb 14.

Robin Shattock, head of mucosal infection and immunity at Imperial College London, who is a recipient of CEPI funding, said the availability of COVID-19’s DNA sequence allowed his group to identify the surface proteins of the virus and generate a lipid encapsulated RNA vaccine construct in 14 days. Animal tests are underway.

“We will do the first clinical studies by the summer to test for safety and immunogenicity,” Shattock said. Going from that point to an efficacy trial is not usually a quick process. “The earliest a vaccine could potentially be available for widespread use will depend on the level of funding and commitment,” said Shattock.

Similarly, Sarah Gilbert, professor of vaccinology at Oxford University, expects to conduct the first clinical studies by the summer of an adenovirus-vectored vaccine developed at the university’s Jenner Institute. “We know the doses we need to use from work we have done before,” she said.

In 2014, when WHO moved to fast track clinical trials of Ebola vaccines, four products were put through first-in-human trials at the Jenner Institute. The problem then was to understand if those constructs would work in the context of an ongoing epidemic.

Gilbert, who leads Jenner’s influenza and emerging pathogen program, and who also has CEPI funding, said there needs to be agreement about how to test COVID-19 vaccines in exposed populations. “In 2014, in Ebola, it was efficacy that mattered, to know how to design trials,” she said, adding, “Lots of vaccines are being developed. If many of them work, that’s great.”

Also quick off the mark in response to the online publication of COVID-19’s DNA sequence, in this case to develop a diagnostic, was Novacyt SA, of Paris. Since the launch on Jan 31, the company has sold 33,000 of its research-only tests and had enquiries for a further 32,000.

Next week it will launch a CE-marked version that can be used for clinical diagnosis and has applied for FDA Emergency Approval Use. The diagnostic, which is stable at ambient temperature, produces a result in two hours.

Another diagnostics company, Mobidiag, of Espoo, Finland, said this week that it has started development of a molecular diagnostic for the simultaneous detection of COVID-19 and influenza viruses. That will make it possible to rapidly single out COVID-19 infections in people presenting with flu-like symptoms. The assay, being developed in collaboration with Autobio Diagnostics Co. Ltd., of Zhengzhou, China, will process samples in 30 minutes.

Ghebreyesus said the development of vaccines and therapeutics is one important part of the research agenda. “But it is only one part. They will take time to develop, but in the meantime, we are not defenseless. There are many basic public health interventions that are available to us now, and which can prevent infections now,” he said.

Research ongoing

Central to measures to limit transmission is understanding of the epidemiology of COVID-19. Some original research, albeit not peer-reviewed, has started to be published. Most recently, on Feb. 10, researchers in China published what is known about the clinical characteristics of COVID-19 on the preprint server Medrxiv.

The data, based on 1,099 patients with confirmed COVID-19 infection from 552 hospitals, showed there is a median incubation period of three days, but that in some cases it was as long as 24 days.

Commenting on the paper, Paul Hunter, professor in medicine at the University of East Anglia in the U.K., said the suggestion that the incubation period may extend up to 24 days is definitely worrying. “However, the median incubation period remains very short at three days. This means that a half of people who will get ill will have developed their illness within three days of the initial contact,” Hunter said.

“There is still so much we don’t know,” Ghebreyesus noted on opening the R&D forum. “What are the reservoirs? What are the transmission dynamics? What is the period of infectiousness? Which samples should be used for diagnosis and monitoring of treatment? What is the best way to manage cases of severe disease?

“To defeat this outbreak, we need answers to all those questions, and more.”

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