Enlarge /. This photo, taken on February 4, 2020, shows a medical worker (C) marking a test tube that contains samples taken from a person residing in a quarantine zone in Wuhan, the epicenter of the outbreak, in China's central Hubei Corona virus to be tested province.
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In the quarantined Chinese city of Wuhan, health workers fighting the explosive outbreak of a new corona virus have been improvising for weeks, trying to covid-19 patients with symptoms ranging from cough and fever to severe pneumonia and septic shock possible to supply and organ failure. In addition to treating these symptoms with oxygen therapy, ventilators and antibiotics, the doctors there also resorted to experiments. With no approved treatments for any of the diseases caused by coronaviruses, health workers have tried everything from steroids and antibodies to medications that are normally designed for HIV and influenza. However, since these treatments have been given on a case-by-case basis without strict, centralized tracking of results, it is difficult to know if they are effective against the new disease.
Now researchers in China are trying to start more systematic testing of these reused drugs. Scientists have registered 19 clinical trials in China since January 28, and at least some have already started dosing patients. With the first results expected in April, the rapid leap into clinical research is an important step for front-line health workers who are desperately looking for hard evidence of which therapies work best. The trick will be to make sure that evidence piles up.
"When you have treatment, you can measure different things in a patient," said Marie-Paule Kieny, WHO's director-general for health systems and innovation, at a press conference on Wednesday. "If you want to compare different treatments, it is important that they all measure the same." Her remarks came to the end of a two-day WHO summit, attended by major donors and more than 300 scientists, to identify the most pressing research priorities for the current outbreak.
Chinese scientists who were present in person or practically pushed for two urgent, short-term requests, said Kieny, who led the summit. The first is to create simpler diagnostic tests for Covid-19 that doctors can use as part of community screening programs at the patient's bedside or even on-site. Currently, the only tests available require time-consuming laboratory work, which means that biological samples must be delivered to qualified hospitals where residues can build up quickly. The second is that the global medical community creates standardized treatment plans with a strong data collection component. In other words, they want to know what works for the sickest patients.
WHO Director General Tedros Adhanom Ghebreyesus said on Wednesday that the organization is currently developing a master plan for coordinating clinical trials. The framework is intended to create consistency across studies of different treatments so that the data can be compared as soon as it is received.
A randomized, controlled trial is the gold standard in clinical research. Merging one for Covid-19, however, is complicated by the reality of working in hospital systems that are overwhelmed by the sheer size of the outbreak. One of the biggest problems is ensuring the same level of care wherever the drug is tested, says Nahid Bhadelia, medical director of the Special Pathogens Unit of the National Emerging Infectious Disease Laboratories at Boston University. "You can't tell if a drug is working unless the rest of the treatment that patients receive is the same," Bhadelia says.
It becomes much more difficult in the event of a public health emergency, such as that in Hubei Province, where more than 48,000 people are ill. Reports from the region show that hospitals have been marginalized – long lines, crowded wards, people who have been turned away – as the number of patients has not yet been alleviated by the rapid construction of field hospitals and temporary quarantine structures.
Enlarge /. YANGZHOU, CHINA – On Valentine's Day, some doctors in an isolation ward do a new type of coronavirus pneumonia in Yangzhou Third People's Hospital and make a gesture of love through glass.
Costfoto / Barcroft Media via Getty Images
However, the researchers there have deep and growing expertise in clinical trials. About 20 percent of all clinical trials are now conducted in China, compared to 10 percent five years ago, Thompson Reuters reported recently. This includes nearly 500 ongoing trials in the city of Wuhan, which was hit hardest by Covid-19. The outbreak has disrupted some of these studies as the doctors and institutions that were once dedicated to them have become a frontline of the epidemic. However, there has been no shortage of willing patients to test potential Covid-19 treatments on.
Two studies, the New York Times reported starting patient recruitment last week, will test the effectiveness of Remdesivir, an experimental antiviral drug manufactured by American drug maker Gilead. It blocks the enzyme with which many viruses replicate in human cells. It has not yet been approved for use, but appears to be safe, according to the results of a 2018 clinical study with Ebola patients in the Democratic Republic of the Congo. Although this will be the first human coronavirus test, scientists in China recently reported that remdesivir has been shown to be effective in preventing SARS-nCoV-2 (the virus that causes Covid-19) from infecting primate cells.
The studies conducted by researchers at the China-Japan Hospital compare remdesivir to a placebo. One will enroll patients with severe symptoms, the other with mild to moderate symptoms. According to company spokeswoman Sonia Choi, Gilead has provided enough doses of the drug to treat up to 500 study participants. After the Ebola outbreaks in recent years, Gilead has stocked up to supply medication for the two studies and for requests for compassionate use, Choi wrote in an email. So far, the company has only announced the treatment of one Covid-19 patient in the United States: a 35-year-old man in Washington State.
To date, more than 100 patients have been admitted, with another 660 to be added. (Not all participants receive the medication, some receive the placebo.) "This speaks both for the resource capacity in China and the commitment of its employees there," said Richard T. Davey, medical director of the department for special clinical studies at the National Institute for Allergies and infectious diseases. He led the research team that conducted the 2018 Remdesivir study in Ebola patients, which took place in an active war zone in a healthcare setting that was not used to research. In comparison, China is much better able to act quickly. "They have experts and a lot of people who have done trials before. We are just waiting to hear what, if anything, we can do to help them."
With this quick recruitment, the results of the trials in China are expected in April. If Remdesivir is effective, it is unclear whether Gilead has enough of the drug to treat the thousands of people who are likely to be in need.
According to Choi, the company is taking steps to increase the available offer as quickly as possible. This includes producing more than one formulation of Remdesivir, starting discussions with new production partners in several regions and increasing internal production capacity. "In anticipation of potential future needs, we have shortened manufacturing times to increase our available offer as quickly as possible," Choi wrote. "We do this before we know if remdesivir is considered safe and effective in treating patients with COVID-19."
In addition to remdesivir, researchers have started dosing patients in another study and testing the antiviral drugs lopinavir and ritonavir, which are approved for HIV and are available in generic formulations. These drugs also inhibit viruses by blocking an enzyme that they use to replicate in human cells. Studies are due to begin shortly to test the effectiveness of oseltamivir and arbidol, influenza drugs already approved in China, that fight the flu by preventing them from dropping copies of themselves from the surface of the host cells , The study registry also contains a number of more unconventional – and possibly dubious – approaches, including hormones, stem cell injections, and even vitamin C infusions. And unfortunately, there will be no shortage of patients who want to try something out in the event of an outbreak.
This story originally appeared on wired.com.