Much-Touted Remdesivir Fails To Reduce COVID-19 Deaths; Results Of WHO-Coordinated Solidarity Trial Medical Innovation 16/10/2020 • Elaine Ruth Fletcher & Madeleine Hoecklin Share this:Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to print (Opens in new window) Remdesivir received emergency use approval for COVID-19, only to fall by wayside in WHO Solidarity trial. Two more experimental COVID-19 drugs, including the much-touted Remdesivir, appear to have fallen by the wayside, failing to show significant reductions in mortality among seriously ill patients. Interim results on Remdesivir and three other drug treatments being studied as part of the WHO Solidarity Therapeutics Trial, the world’s largest randomized controlled trial of COVID-19 drugs, were published Friday on the pre-print journal, medRxiv.org. The WHO-coordinated study, covering some 11,266 participants across 30 countries, found that the antiviral Remdesivir, as well as Interferon, had no effect on 28-day mortality among hospitalized COVID-19 patients and little or no effect in reducing the initiation of ventilation or the duration of hospital stay. While the news on Remdesivir was fresh, the study also reported results of treatments with two other drugs, the anti-malarial Hydroxychloroquine, and the HIV/AID drug combination Lopinavir/Ritonavir, which have already been largely disqualified as good treatment options, in light of findings from studies published over the spring and early summer. “These Remdesivir, Hydroxychloroquine, Lopinavir and Interferon regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay,” states the study. “The mortality findings contain most of the randomized evidence on Remdesivir and Interferon, and are consistent with meta-analyses of mortality in all major trials.” Dr Tedros Adhanom Ghebreyesus, WHO Director-General announcing negative Remdesivir results The study includes findings from drug trials covering some 11,266 participants across 30 countries, with 2750 participants administered Remdesivir, 954 Hydroxychloroquine, 1411 Lopinavir, 651 Interferon plus Lopinavir, 1412 Interferon, and 4088 receiving no treatment drug. In a sober announcement of the results at Friday’s WHO press conference, Director General Dr Tedros Adhanom Ghebreyesu made it even more plainly clear: “Interim results from the trial now show that the other two drugs in the trial, Remdesivir and Interferon, have little or no effect in preventing death from COVID-19 or reducing time in hospital. “For the moment, the corticosteroid steroid dexamethasone is still the only therapeutic shown to be effective against COVID-19 for patients with severe disease,” Dr Tedros added. WHO Will Push On To Test Monoclonal Antibodies and Other Antivirals Despite the dead-end reached with the drugs that only a few months ago had seemed to offer potential for improving COVID treatment, Dr Tedros also said that WHO Solidarity Trial would push ahead in coordinating new research to “assess other treatments, including monoclonal antibodies and new antivirals.” The potential of drugs containing controlled portions of anti-SARS-CoV2 monoclonal antibodies have catapulted into the spotlight recently, after US President Donald Trump claimed that such a cocktail by the pharma company Regeneron had virtually “cured’ him of COVID-19. Even so, clinical trials on a similar treatment, under development by Eli Lilly, were halted just this week after an adverse reaction occurred in one trial participant. Despite the lack of evidence about either drug, both Eli Lilly and Regeneron have already filed requests with the United States Food and Drug Administration for Emergency Use Authorizations of their products. Remdesivir had also been approved by the FDA as well as by the European Medicines Agency, under the same EUA process. The WHO Director General said that the global Solidarity Trial also is considering for evaluation other, newer antiviral drugs and immunomodulators – the latter are being studied because of the role they may play in tempering over-reactions by the immune system. Mass Gatherings, Protests, Masks & Travel – WHO Offers Views But Says Decisions Up To Member States With no drugs, or a vaccine, yet in sight, WHO officials are also stressing the importance of using what they call “non-pharma” measures that have been demonstrated to be effective in controlling the virus spread. Key among those strategies are the management of mass gatherings, use of masks, and safety in travel, said WHO Health Emergencies Executive Director Mike Ryan. But he hedged on providing firm advice to countries to mandate masks or ban mass gatherings – saying it is ultimately up to the governments themselves to set out policies based on the local context. Some excerpts: Mike Ryan, Executive Director of WHO Health Emergencies Programme Mass gatherings – Not only the United States, but leading countries around Africa and the Eastern Mediterranean are also entering election season. Ryan repeated comments made earlier this week, saying that the pandemic shouldn’t be used as an excuse to discourage people from coming out to vote – saying rather that mass gatherings can be “managed” to ensure that elections can proceed. Ryan: “In terms of people coming together and gathering, many countries, groups and communities have shown that it is possible for communities to come together to express their views, to vote and to do other things, and that can be done in a safe manner. And therefore we continue to offer advice to countries and to organizations who are planning gatherings, especially important gatherings and elections. They must be associated with good risk management measures.” Protests – Civil disobedience and protests are common occurrences, particularly during the COVID-19 pandemic, which has exacerbated existing inequalities and has strained the relationship between individuals and public authorities and institutions, Ryan acknowledged, adding: “We do call for calm. People are suffering and when people are tired and suffering, there can be a gap in trust that emerges between communities and the people that govern them. But governments don’t govern people, governments are there to serve the people first and foremost…Governments should always encourage the right to protest and express dissatisfaction and we will continue to provide support to countries to ensure that they support their communities in that way.” “Many people in many countries have many issues they want to raise with governments, everything from climate, to social justice, to employment, to COVID-19. It’s an important part of our global approach to democracy to ensure that people always have the right to protest and express their views. But obviously, we hope that can be done safely and in a properly risk managed way and can be done peacefully.” Masks – WHO only belatedly began supporting masks as a public health measure – after considerable evidence showed efficacy. Now that it has become enthusiastic about their use, some countries, such as Sweden, still refrain from mandating masks, even in confined and crowded spaces, like public transport. Ryan: “Each country has had to take a different approach in this response, and each country has had to determine what its social contract is, and what is possible within the context of the relationship that the government has with people.” “We, as WHO, would say that masks are an important part of the strategic, comprehensive approach to stopping the spread of this disease, especially where you have widespread community transmission and where you do not understand fully the chains of transmission…We will continue to work in our European regional office with all countries in the region to optimize their strategies.” Maria Van Kerkhove, WHO Health Emergencies Technical Lead Maria Van Kerkhove, Health Emergencies technical lead adds: “Masks must be used as part of a comprehensive package. It must not be masks alone, because you still need hand hygiene and to use alcohol based rub…When you enter the workplace, avoid crowded settings, enclosed spaces, especially with poor ventilation, open the windows, physical distancing. All of this needs to happen.” Travel precautions – WHO’s Tedros and Mike were adamantly opposed to any travel restrictions in the early months of the COVID-19 epidemic, even as international travel was clearly the vector carrying the infection across the world. After most countries ignored WHO’s advice and unilaterally slapped on their own travel restrictions, sometimes closing their air space altogether and at other times, applying more selective measures, WHO fell silent on the matter and has largely remained so, despite pleas by some member states, such as Austria at last week’s Executive Board meeting, for more targeted and nuanced advice. Says Ryan: “Great strides have been made in ensuring that international travel is safer…De-risking travel is one thing in the sense of ensuring people aren’t exposed to the virus while traveling. “It’s a very different issue when it comes to deciding who can travel from one country to the other. If we’re going to see international travel resume in a meaningful way, we can commend the travel industry for doing all they can to reduce the risk of exposure during travel, but there’s still a way to go to create the confidence and trust between countries, so that travel can be opened between countries.” COVID-19 Soaring, but Restrictions May also Help Reduce Flu in Northern Hemisphere Although COVID cases are rising sharply in 8 out of 10 countries of WHO’s European region after a reprieve over the summer, the spread remains uneven and posing various levels of threat, WHO officials also noted at the briefing. Active cases of COVID-19 around the world and COVID-19 deaths globally (top right) as of 8:00PM CET 16 October 2020. “Within Europe there are about 37 areas in 13 countries that have an increasing incidence and increasing hospitalizations that we’re looking at,” said Van Kerkhove. Meanwhile, Dr Tedros expressed hopes this year’s flu season in the northern hemisphere might at least be lighter as a result of the wave of restrictions and preventive measures that are now being adopted by European countries to combat COVID-19. “Many of the same measures that are effective in preventing COVID-19 are also effective for preventing influenza, including physical distancing, hand hygiene, covering coughs, ventilation, and masks,” said Dr Tedros. “But we cannot assume the same will be true in the Northern Hemisphere flu season,” warned Tedros. Every year there are approximately 3.5 million cases of severe seasonal influenza worldwide, however, during this year’s influenza season in the Southern hemisphere, there were far fewer cases than usual, said Dr Tedros. Influenza coupled with COVID-19 has the potential to overwhelm health systems and facilities. Although vaccines exist for influenza, high demands would stretch supplies, particularly in low-income countries. However, it is hoped that the northern hemisphere countries can replicate the experience in the southern hemisphere, where the flu season was light, presumably because of precautionary COVID-19 measures taken there. Influenza Vaccination May Also Help Protect Against COVID-19 – New Study Finds Meanwhile, several recent epidemiological studies also have suggested that there may be cross-protection between influenza vaccination and COVID-19 during the pandemic. Another preprint study published Friday by a group of Dutch researchers on medriXiv.org even suggested the possibility of using an influenza vaccine against both influenza and COVID-19 for the 2020-2021 influenza season. The study found that the quadrivalent inactivated influenza vaccine used in the 2019-2020 influenza season in the Netherlands induced a trained immune response against SARS-CoV2, in laboratory blood samples, suggesting a possible relative protection against COVID-19. In addition, observational study of 10,000 Dutch health workers found somewhat lower levels of COVID-19 infection among people who had received their flu vaccine for the 2019-20 flu season. In the study group, 1.3% of vaccinated workers came down with test-positive cases of COVID-19, as compared to 2% of those who did not get the vaccine. Image Credits: European Medicines Agency, WHO, Johns Hopkins. 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