Ensuring Universal COVID-19 Vaccine Access Requires Political Will & Scaling Production

29/05/2020 Grace Ren

As the COVID-19 pandemic continues to ravage the world, hope has been pinned on the development and roll-out of an effective vaccine. But in a global crisis where demand for the vaccine will be everywhere, how can fair and equitable distribution be ensured?

Panelists from the World Health Organization; the Coalition for Epidemic Preparedness Innovations (CEPI); Medicines Law and Policy, the Shuttleworth Foundation, and a former Brazilian diplomat tackled this question in the second webinar in the ‘Global Pandemics in an Unequal World’ series, cosponsored by the New School and Health Policy Watch.

“How do we turn the commitment to a universal vaccine from rhetoric to an implementation plan?” posed Sakiko Fukuda Parr, moderator of the discussion and director of the Julien Studley Graduate Programs in International Affairs at the New School.

“What we have now is not only a health crisis, but a crisis that shakes your world order. We can’t separate what is going to happen in health from what happens in the global geopolitical situation,” said Celso Amorim, former Brazilian Minister for External Relations.

In the midst of redefining the world order, a new paradigm for ensuring access must emerge in order to roll-out any successful COVID-19 vaccines in an equitable fashion, said other panelists.

“The supply of any successful and safe and efficient vaccine will be limited for several years…[because] the global demand will be everywhere at the same time,” said Elen Høeg, policy manager at the Coalition for Epidemic Preparedness and Innovation (CEPI), which is supporting the development of at least three different vaccine candidates.

Fair allocation of any vaccine should then be based on public health need, rather than countries’ ability to pay, said Mariângela Simão, assistant director-general for Access to Medicines & Vaccines at the World Health Organization.

“We are bound to establish new [allocation] criteria that are unprecedented in the world, based on ethical and moral values. And then we need to make these products accessible and affordable,” she added.

To do that requires the buy-in of major Heads of States, says Amorim, who proposed a United Nations General Assembly Session to put pandemic preparedness and response on the agenda for all Member States.

“Like it or not, people are represented internationally by governments and I think we have to have a very broad discussion in the United Nations in a political body,” he said.

But another looming issue is the problem of scale – manufacturing capacity will have to ramp up significantly to meet the global demand, even with equitable access conditions in place.

One solution is to tie access requirements into funding agreements for vaccine development, said Achal Prabhala, Shuttleworth Foundation fellow.

“The EU, the US and the UK could attach some access conditions to the billions of dollars being given to vaccine developers,” Prabhala explained. But he also lamented that this is “the solution that will probably not be implemented.”

Here are some key remarks from the featured speakers:

Sakiko Fukuda-Parr, director, Julien J. Studley Graduate Programs in International Affairs, The New School

We need a global public good vaccine for COVID-19 that is effective and safe, but also mass produced, priced affordably and distributed widely and equitably. And that would reach all people, especially vulnerable populations and developing countries. There’s an overwhelming support for this idea as an objective, and it’s been endorsed by political and religious and intellectual leaders around the world such as presidents and prime ministers of France, Germany, Canada, China, China, South Africa and others. And there’s also a broad consensus that this is not only an ethical imperative, but an urgent public health priority and that there is a need for international cooperation and multi stakeholder partnership.

But there is much greater difficulty in achieving agreement on how to get there. How do we go from the business as usual market model upon pharma research and development, financed by charging high prices under 20 year patents and other intellectual property exclusivity with limited distribution focusing on high income countries first, and from that to a people’s vaccine that is patent free mass produced accessible in the global south?

Who will have early priority access to the vaccines or other necessary technologies, who will bear the financial burden, who will benefit from the investments and who will receive the treatments? How can the values of solidarity and multilateralism prevail over nationalism? How can 21st century capitalism address market failures by creating innovative social institutions to protect public health priorities that do not align with just a maximum profit, private profit and revenues? How do we turn the commitment to a universal vaccine from rhetoric to an implementation plan? And in particular, how will low-income people and countries in the Global South have access to vaccines and other treatments so that we can actually end the pandemic?

Mariângela Simão, assistant director-general for Access to Medicines & Vaccines, World Health Organization

First we live in a globalized world, so anything that happens in one country affects others. Secondly, it’s also shown that the countries are not prepared, no matter how many resolutions were approved in the World Health Assembly. On the other hand, this has been a very democratic virus… It raised an enormous, collaborative effort to try to sort it out, because no one is safe as long as someone else is vulnerable to this virus.

We cannot let low and middle income countries end up with an unfair allocation of the leftovers. The market cannot work the same way it worked in the past pandemics and it cannot work the same way. We think we should be all applying at least to five principles; transparency, because we have right now we have a situation where you have companies trying to sell products that we don’t have yet to countries in, we have some countries trying to buy products that are not there yet. We are talking about a new normal, where income should not play a role anymore.

We also need flexible regulatory in procurement approaches, we need collaboration among the different stakeholders to produce a safe and effective product in the shortest time possible. But we also need these products to be allocated to address public health needs, with ethical rules informing the allocation. So it’s really super important that we have agreed criteria to allocate products that will enable equitable access. We’ll need to take into account the vulnerability.

For example, the Bahamas, a high income country. Suddenly last year, they were devastated by a hurricane. And now they get COVID, so their ability to pay is very limited. So income doesn’t play the same role anymore. So we are bound to establish new criteria that are unprecedented in the world, based on ethical and moral values. And then we need to make these products accessible and affordable.

Achal Prabhala, Shuttleworth Fellow in advancing innovation and access to medicines

The thing that strikes me the most over the last 20 years is that access to treatments and vaccines is no longer an afterthought.The model that we followed right through something like one year ago was develop the drug first, get a treatment, and then let’s figure out how to give people access to it. That’s not the model here. But having said that, there are two big threats that confront us. And the first is intellectual property, private monopolies that are owned by corporations. And to provide one quick example of how IP remains a threat, I think one can do no better than to look to Gilead’s license for remdesivir, which is the first US FDA approved emergency use treatment for COVID-19.

They released an access agreement that allows a few production facilities in India to sell generic versions of the drug in 127 countries. But about half the world is left out – every middle income country, so every country in Latin America including Brazil, which is particularly severely hit by the coronavirus. Many of the former Soviet Union countries are completely left out.

The second trait, however, is nationalism. And I think the perfect example of how nationalism is playing out is when the CEO of Sanofi, which is registered in France, suggested that the US would have first dibs on its vaccine. And of course, this raised a fly in France. Since the French President intervened, and then the chairman of Sanofi had to backtrack those comments. When it comes to vaccines, there are very, very few production facilities around the world that can even make a generic vaccine.

There are solutions that countries are advocating for themselves. Brazil, Chile, Germany, Canada, Ecuador, have begun taking actions to suspend monopolies around Coronavirus related treatments, vaccines and diagnostics, should that be necessary. There are multilateral solutions that have been discussed like the WHO COVID-19 Technology pool. And then finally, we have the solution that probably will not be implemented, which is having the EU, the US and the UK attach some access conditions to the billions of dollars being given to vaccine developers.

Elen Høeg, Policy Manager, Coalition for Epidemic Preparedness and Innovation (CEPI)

The challenge of ensuring access in a pandemic is fundamentally different from an epidemic in that the global demand will be everywhere at the same time. Hence, the supply of any successful and safe and efficient vaccine will be limited for several years.

So, as pointed out, then there’s this balance between the national interests and global solidarity, because I do think we all recognize this is a global challenge that requires a global solution. There will be both development challenges and access challenges. One thing that has become evident is the need to step up and very urgently get in place large scale manufacturing across many geographies to cover the global demand.

So we must put in place mechanisms for a global procurement and ordering system, both to give predictability for manufacturing and security of investments as well as addressing the regulatory measures. A fair allocation mechanism, which will be led by the WHO, will be established. We see great will from partners to commit to having doses secured for a global pool of vaccines to serve a fair global allocation model.

Celso Amorim, Minister of External Relations of Brazil (1993-94; 2003-2010), and Minister of Defense of Brazil (2011-2014)

What we have now is the biggest crisis that’s not only a health crisis, but a crisis that shakes your world order. We can’t separate what is going to happen in health from what happens in the global geopolitical situation. I think there are changes that are going to help. I hope it doesn’t lead to conflict at some point; I hope it can lead to new kinds of cooperation in the world which are multipolar in which developing countries can help.

I think this is basically a political question. Even the Doha Provision only was able to pass because rich countries also saw they needed it. Of course, technical expertise has to come from the WHO. But we really need the involvement of the United States. That’s why we have been proposing the idea of a special session of the General Assembly where all countries would participate. Like it or not, people are represented internationally by governments and I think we have to have a very broad discussion in the United Nations in a political body. You need a big, international conference, Heads of State in order to push for better replies to world problems. The WHO simply is not enough. We have to have big political support – the General Assembly of the United Nations is the only place where you can have really a big impulse.

Ellen t’Hoen, director, Medicines, Law & Policy

If a vaccine becomes available, the demand will be immediate, it will be global, and it will be enormous. And we need to plan for this. Now, if there’s one thing that we’ve learned from the HIV crisis, it’s the danger of having no plan. The drugs were developed, but it took about a decade before they became available in low and middle income countries. One lesson-learned from that is that you need to sort out the ownership issue. And this is not only about patterns with HIV, there were barriers to the low cost, generic production of drugs on a large scale, and that was largely solved through the Doha Declaration and the establishment of the Medicines Patent Pool (MPP), where patents for antiretrovirals (ARVS) could be pooled [and licensed to generics manufacturers]. All the patent licenses for all WHO-recommended antiretrovirals are available through the MPP.

In mid-March, Costa Rica, proposed to the WTO to establish a COVID-19 technology pool that brings together all the necessary intellectual property – data, cell lines, know-how, technology – in order for that to be freely shared to advance science and future large scale production of vaccines ,therapeutics and diagnostics. The pooling of such knowledge was endorsed by the World Health Assembly and tomorrow, there will be an announcement with the president of Costa Rica, WHO, and a number of other member states to launch this initiative. What this whole initiative will do, is create a place where the donors funding the research and development of vaccines, drugs, and diagnostics, can put conditions on that spending regarding sharing technologies that are needed to scale up production worldwide.

I hope that this crisis will lead to increased multilateralism and collaboration, and then we can move away from the kind of vaccine nationalism that we now see around the world. The people first in line for a vaccine should be the health care workers of the world, but you need to have agreements for making that happen.

Upcoming Webinars in ‘Global Pandemics in an Unequal World’

The Tuesday event was the second in a series of four webinars, co-sponsored by The New School and Health Policy Watch, with the Centre for Development and Environment at the University of Oslo joining as a partner. Join us in June and July for the next two webinars, covering these themes:

24 June – Digital technology and Inequality in the COVID-19 response

22 July – COVID-19 inequalities and the environment

This story was updated 2 June 2020 to amend a quote by Ellen t’Hoen.

AstraZeneca & Pfizer Announce Plans For Phase III COVID-19 Vaccine Trials

28/05/2020 Svĕt Lustig Vijay

(Top, left-right) Pascal Soriot, CEO AstraZeneca; Emma Walmsley, CEO GSK (Bottom, left-right) Albert Bourla, CEO Pfizer; Paul Stoffels, CSO Johnson&Johnson

The UK-based Pharma firm AstraZeneca and US-based Pfizer announced they are planning to start Phase III trials as early as July for an experimental COVID-19 vaccine in the United States and the United Kingdom. The massive trials would enroll over 30,000 people, and AstraZeneca’s hope is to have an effective vaccine by the end of the year.

Pfizer is aiming for an even more ambitious timeline to have a vaccine ready for approval by the US Food and Drug Administration and European Medical Agency by October, announced Albert Bourla, chairman and CEO of Pfizer.

“If things goes well, and the stars are aligned, we will have conclusive or enough evidence of safety and efficacy so that we can feel comfortable and the FDA will feel comfortable, and EMA will feel comfortable to have a vaccine around the end of October,” said Bourla, speaking at a briefing by pharma industry leaders, hosted by the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA). GlaxoSmithKline (GSK) and Johnson&Johnson were also present at the briefing.

Pfizer’s Phase I clinical trials will conclude in June, Bourla added.

AstraZeneca meanwhile is conducting studies in Kenya, in South Africa, in Brazil, with the hope that trials in many other countries will start “anytime soon.”

“The hope is that we will have a [Covid-19] vaccine, hopefully several, by the end of this year,” said Pascal Soriot, CEO of AstraZeneca.

Not for Profit Approach – But Vaccine Will Likely Be Rolled Out First In Countries With Stronger Infrastructure

Johnson & Johnson, GSK and AstraZeneca executives said that they were taking a “not-for-profit” approach to vaccine development and sale, at least for now.

“We do it not-for-profit for the pandemic period, as we want to [ensure] equitable access over the world…and especially to get vaccines to make sure we get a stop to the pandemic,” said Stoffels of Johnson & Johnson.

“We can actually provide this vaccine in a fairly equitable manner to everybody around the world. And finally, just like everybody else, we do it at no profit,” said Soriot.

Said GSK’s CEO Emma Walmsley: “We’re on record saying we don’t expect to profit during this period because we want to invest in short term profit in pandemic preparedness and in donations.”

While Pfizer’s CEO Albert Bourla did not commit to a ‘not-for-profit’ approach explictly, he acknowledged that vaccine pricing will have to approached differently in times of the pandemic:

“Typically the industry is pricing their product based on the value that they bring. And this is impossible to happen right now. In times of pandemic, you can’t have pricing policies that respect [demand and the rules of an open market]…I don’t know what will be the price reduction because I’ve never thought about it.”

Bourla also stressed that the lack of infrastructure would still be a barrier to global rollout of a new COVID-19 vaccine.

Albert Bourla speaking at a May 28 press briefing

“Technologies [we are developing] right now require -80 °C,” said Bourla. “The technology is not very convenient for Africa because they will likely lack basic infrastructure…[the vaccine] will come to the Western world first but [in the] second wave, we are working on making sure that we can develop and manufacture products that are not requiring [refrigeration in Africa]”.

“Not all vaccine candidates can go all over the world,” agreed Stoffels, saying this will depend on its features.

Even so, Bourla said that Pfizer was “absolutely engaged”’ in joining coalitions like the European Union-led ACT Accelerator to ensure equitable access for COVID-19 health technologies.

Patent Pool Gets Cold Shoulder

Thomas Cueni speaking at a May 28 press briefing

The pharma leaders spoke just a day before the World Health Organization was to launch a new COVID-19 patent pool, which is supposed to group intellectual property of any coronavirus-related technologies – to ensure accessibility in low and middle income countries.

IFPMA head Thomas Cueni said he would not be joining Friday’s ceremony, which followed the announcement two weeks ago Costa Rica, Chile and the WHO.

“I don’t quite see what the new initiative adds [in comparison to existing mechanisms] I’m too busy [to participate],” Cueni said.

Cueni and other industry leaders have said that infrastructure shortcomings, manufacturing challenges and supply chains are likely to be bigger access obstacles than patents in the current race to achieve universal access to a pandemic vaccine.

Distribution Bottlenecks Likely

One of the main issues with mass-producing a vaccine is not necessarily the amount of vaccine itself, but getting enough vials, said Soriot.

“The challenge is not so much to make the vaccine itself, it is to fill the vial. And there’s not enough vials in the world,” he said.

In light of limited vial supplies and the fact that some 15 billion vaccine doses might be needed, said Cueni, pharmaceuticals like AstraZeneca and Johnson & Johnson are trying to squeeze a handful of vaccine doses within each vial to distribute more of the vaccine with less vials:

“Like everybody else, we are looking into five or ten doses per vial,” said Soriot.

And as vial makers scramble to produce more vials, they face an unprecedented challenge as they have never had to produce such quantities – Planning needs to happen ‘now’ to tackle the vaccine distribution issue: “If we go to 15 billion vaccines, that has never been done in history from a filling capacity as well as vials… planning [is not] for next month…we need to start planning now,” he said

Who Gets Priority?

Reports of some countries signing pre-purchase agreements for COVID-19 vaccines have surfaced in the past few weeks, sparking concerns that some countries will jump the line in the queue for an effective vaccine.

Last week, the French-based company Sanofi sparked outrage in Europe when they announced that they would first sell the vaccine in the United States – which had invested heavily in R&D at the company’s US locations as well as making pre-purchase agreements. After protests by French government officials, Sanofi’s CEO retracted the statements.

But so far, the Pfizer CEO said the company had not signed any pre-purchase contracts for their vaccine, currently concluding Phase I clinical studies that will likely yield results by June 2020.

“We haven’t signed contracts and also I think it is known that Pfizer is not taking any money from any government, the US government or any other government to advance our vaccines. We don’t do that,” said Bourla.

France Rolls Back Hydroxychloroquine Recommendations For COVID-19; The United Kingdom Issues Emergency Use Approval For Remdesivir

27/05/2020 Gauri Saxena

France rolled back recommendations on the use of hydroxychloroquine, a malaria drug, for severe COVID-19 patients, just two days after the World Health Organization suspended its large multinational hydroxychloroquine trial.

Meanwhile, the United Kingdom has authorized the use of remdesivir for severe cases of COVID-19. The drug showed modest potential to shorten the length of infection in a large, US study.

France had previously recommended hydroxycholoroquine to be used at providers’ discretion for treating patients with severe COVID-19. However, the French Ministry of Solidarity and Health on Wednesday issued a revised recommendation stating, “whether in town or in hospital, this molecule should not be prescribed for COVID-19 patients.”

The Ministry statement is informed by the High Council for Public Health (HCSP), which earlier in the week also reversed its stance on the drug, no longer recommending it for discretionary use for severe COVID-19 patients.

“The working group concluded in a collegial manner that there was no sufficiently robust clinical study demonstrating the efficacy of hydroxychloroquine in COVID-19 regardless of the severity of the infection,” stated the HCSP in a notice posted Tuesday.

The moves by the WHO and France were prompted by a massive study published in The Lancet that found a much higher risk of cardiac arrhythmias and mortality among nearly 15,000 COVID-19 patients who were given hydroxychloroquine, chloroquine, or either drug plus a macrolide antibiotic, compared to 81,000 who did not receive any combination of the drugs.

However, the jury is still out on use of hydroxychloroquine as a preventative medicine. India recently expanded its recommendations for prophylactic use of hydroxychloroquine based on early results from a small observational study.

Both President Trump of the United States and Salvadoran president Nayib Bukele have touted the use of a drug as a prophylactic. In a parallel development, Brazil’s Jair Bolsonaro has also unveiled plans to expand the prescription of chloroquine, a predecessor of the drug, while acknowledging that there is no scientific evidence of its efficacy, however, the situation continues to be monitored in Brazil and globally.

UK Issues Emergency Use Guidelines for Remdesivir

Hope is turning more towards remdesivir, an antiviral originally developed by Gilead Sciences for treating Ebola, which has shown modest positive effects on speeding recovery.

“This shows fantastic progress. As we navigate this unprecedented period, we must be on the front foot of the latest medical advancements, while always ensuring patient safety remains a top priority,” said Minister for Innovation Lord Bethell of the UK’s recent remdesivir approval.

However, the drug is still being studied in ongoing clinical trials, and some experts warn against pinning all hopes on remdesivir.

“Whilst this is clearly the most ethically sound approach, it also means that we ought not to expect the drug to immediately act as a magic bullet. We can instead hope for improved recovery rates and a reduction in patient mortality, which we hope will benefit as many patients as possible,” Stephen Griffin, a professor from the University of Leeds Medical School told BBC.

Thus, countries like the UK, which just released a package of guidance for emergency use of remdesivir, are approaching the rollout of the drug carefully, limiting it to use only to patients with severe disease.

Merck Joins The COVID-19 Vaccine Race

Merck, one of the largest pharmaceutical companies in the world, has announced deals to develop and manufacture two different COVID-19 vaccines as well as an experimental antiviral compound which is already in early clinical trials.

The company will be collaborating with IAVI to develop a vaccine candidate against SARS-CoV-2, the virus that causes COVID-19. This vaccine candidate will use the recombinant vesicular stomatitis virus (rVSV) technology that is the basis for Merck’s Ebola Zaire virus vaccine, ERVEBO®, which was the first rVSV vaccine approved for use in humans. Initial funding support for the initiative comes from the Biomedical Advanced Research and Development Authority (BARDA), part of the office of the Assistant Secretary for Preparedness and Response within an agency of the United States Department of Health and Human Services.

Merck also announced on Tuesday it would be acquiring the small biotech company Themis, which is working with the Institut Pasteur on a COVID-19 vaccine candidate delivered using the same technology used to carry the measles vaccine. The Themis vaccine candidate is still in preclinical trials, and will aim to begin clinical trials by late 2020.

According to the World Health Organization’s latest table of COVID-19 vaccines, 124 candidates are at various stages of development with eight different technologies, or platforms.

Merck has also backed the development of the compound EIDD-2801, which is designed to inhibit viruses with RNA-based genetic material, including SARS-CoV-2. In this regard, the company is collaborating with Ridgeback Biotherapeutics, which has started a safety trial of the compound in healthy patients in the UK.

Image Credits: Jamie.

Bold New WHO Manifesto Calls For Low Carbon COVID-19 Recovery; European Union Unveils €750 Billion Stimulus Package

27/05/2020 Gauri Saxena, Grace Ren & Elaine Ruth Fletcher

WHO Director-General Dr Tedros Adhanom Ghebreyesus unveiled a bold new WHO Healthy Recovery Manifesto – including an unprecedented call to governments to stop subsidizing the fossil fuel industry to the tune of US$ 400 bilion annually – driving both climate change, air pollution, and an epidemic of chronic diseases that also sharply increased mortality risks for people infected with COVID-19.

The move coincided with the European Union;s unveiling of a much anticipated Covid-19 recovery plan with a green investment edge. Named Next Generation EU the €750 billion package aims to address the economic and social fallout of the coronavirus pandemic with direct investments in renewable energy technologies and support to countries to shift to low-carbon economies.

The six WHO-endorsed manifesto principles include oft-repeated calls for healthier cities, food systems, and clean water. However, WHO’s blunt call to governments to “stop using taxpayers money to fund pollution” steps out of the Organization’s traditional comfort zone. The manifesto also calls for an end to biodiversity destruction and the “unsafe management and consumption of wildlife”, noting that it is these activities that lead to the transmission of deadly animal pathogens such as COVID-19 to humans, and “increase the risk of emerging infectious diseases.”

These steps, WHO says, will lead towards healthier societies, more resilient to future outbreaks and epidemics.

“The human cost of COVID-19 has been devastating, & the so-called lockdown measures have turned lives upside down,” said Dr Tedros in a press briefing. “But the pandemic has given us a glimpse of what our world could look like if we took the bold steps that are needed to curb climate change and air pollution. Our air and water can be clearer, our streets can be quieter and safer, and many of us have found new ways to work while spending more time with our families.”

Both the WHO and EU proposals were unveiled just a day after over 40 million healthcare workers issued a call to place climate-friendly initiatives at the heart of COVID-19 economic recovery.

Turn “Immense Challenge into Opportunity”

This is Europe's moment. Together, let's build a green, digital and resilient future for the #NextGenerationEU. pic.twitter.com/sj92YYzeHA

— Ursula von der Leyen (@vonderleyen) May 27, 2020

“The recovery plan turns the immense challenge we face into an opportunity, not only by supporting the recovery but also by investing in our future: the European Green Deal and digitalization will boost jobs and growth, the resilience of our societies and the health of our environment,” European Commission President Ursula von der Leyen said in launching the plan.

The plan would require all 27 EU member states to back it up with concrete investments. It comes as the bloc faces the prospects of a EU-wide recession. However, Member States have remained divided on whether the plan represents the best way forward.

France, Germany, Spain and Italy have welcomed the package, with French President Emmanuel Macron hailing it “a crucial step”. But Austria, Denmark, the Netherlands, and Sweden — known as the “frugal four” — have protested the proposal, saying the aid should instead come in the form of low-interest loans. As such, the plan in its current form is unlikely to pass in its current form, given that it does not have unanimous support.

Climate-Friendly Initiatives Core to in the European Union Plan

Urban pedestrian & green space (Photo: CCAC)

One key pillar of the EU plan is “supporting the green transition to a climate-neutral economy.” A new “Recovery and Resilience Facility” of €560 billion would offer financial support for investments and reforms focusing on green and digital transitions.

The plan also earmarks €91 billion per year in EU grants and loan guarantees to businesses and households that install green technologies such as rooftop solar panels, building insulation and heating systems based on renewable energy.

The facility also sets aside €5 billion in guarantees for “green mortgages”, tying low-carbon renovations into property sales, giving schools, hospitals, and social housing the priority.

Other climate-friendly instruments include a proposal to strengthen an EU Just Transition Fund, with up to €40 billion to assist economically weaker Member States in accelerating the transition towards climate neutrality, and a €15 billion injection of funds into the European Agricultural Fund for Rural Development, to support a trajectory for rural areas to reach climate neutrality.

The plan has been largely praised for centering on climate-friendly initiatives. However, some advocates have criticised the plan for leaving out ocean health initiatives, and other climate NGOs blasted leaked drafts of the plan for being too lenient towards polluting industries such as automakers and fossil fuel.

“The European Commission’s €1.85 trillion recovery plan is contradictory at best and damaging at worst,” said Greenpeace in a statement. “It does not solve the problem of existing support for gas, oil, coal, and industrial farming – some of the main drivers of a mounting climate and environmental emergency. The plan also fails to set strict social or green conditions on access to funding for polluters like airlines or carmakers,” the NGO added.

WHO Manifesto For Green COVID-19 Recovery

The bold new WHO manifesto begins with a comment by Dr Tedros on the intimate links that have been laid bare between viral threats and other emergencies, pollution and climate change and wildlife and biodiversity destruction:

“The pandemic is a reminder of the intimate and delicate relationship between people and planet. Any efforts to make our world safer are doomed to fail unless they address the critical interface between people and pathogens, and the existential threat of climate change, that is making our Earth less habitable,”

The WHO Healthy Recovery Manifesto includes six key principles, described as “prescriptions” for a healthy and green recovery from COVID-19, which include the following key messages:

1) Protect and preserve the source of human health: Nature

“Human pressures, from deforestation, to intensive and polluting agricultural practices, to unsafe management and consumption of wildlife, undermine these services. They also increase the risk of emerging infectious diseases in humans – over 60% of which originate from animals, mainly from wildlife. Overall plans for post-COVID-19 recovery, and specifically plans to reduce the risk of future epidemics, need to go further upstream than early detection and control of disease outbreaks. They also need to lessen our impact on the environment, so as to reduce the risk at source.”

Pangolin, Manis javanica – harbors coronavirus infections, and is hunted for its meat and scales

2) Invest in essential services, from water and sanitation to clean energy in healthcare facilities

“Around the world, billions of people lack access to the most basic services that are required to protect their health, whether from COVID-19, or any other risk. Handwashing facilities are essential for the prevention of infectious disease transmission, but are lacking in 40 % of households. Antimicrobial-resistant pathogens are widespread in water and waste and their sound management is needed to prevent the spread back to humans. In particular it is essential that health care facilities be equipped with water and sanitation services, including the soap and water that constitutes the most basic intervention to cut transmission of SARS-CoV-2 and other infections, access to reliable energy that is necessary to safely carry out most medical procedures, and occupational protection for health workers.”

3) Ensure a quick, healthy energy transition

“Currently, over seven million people a year die from exposure to air pollution – 1 in 8 of all deaths. Over 90% of people breathe outdoor air with pollution levels exceeding WHO air quality guideline values. Two-thirds of this exposure to outdoor pollution results from the burning of the same fossil fuels that are driving climate change. Energy infrastructure decisions taken now will be locked in for decades to come. Factoring in the full economic and social consequences, and taking decisions in the public health interest, will tend to favour renewable energy sources, leading to cleaner environments and healthier people. Several of the countries that were earliest and hardest hit by COVID-19, such as Italy and Spain, and those that were most successful in controlling the disease, such as South Korea and New Zealand, have put green development alongside health at the heart of their COVID-19 recovery strategies.”

Solar panels supply energy for hot water at Bertha Gxowa Hospital in Johannesburg. Photo: Health Care Without Harm

4) Promote healthy, sustainable food systems

Diseases caused by either lack of access to food, or consumption of unhealthy, high calorie diets, are now the single largest cause of global ill health. They also increase vulnerability to other risks – conditions such as obesity and diabetes are among the largest risk factors for illness and death from COVID-19. Agriculture, particularly clearing of land to rear livestock, contributes about ¼ of global greenhouse gas emissions, and land use change is the single biggest environmental driver of new disease outbreaks. There is a need for a rapid transition to healthy, nutritious and sustainable diets. If the world were able to meet WHO’s dietary guidelines, this would save millions of lives, reduce disease risks, and bring major reductions in global greenhouse gas emissions.

5) Build healthy, liveable cities

Cycling in Fortaleza, Brazil – the city strengthened its active transport plans as part of the Healthy Cities Partnership

“As cities have relatively high population densities and are traffic-saturated, many trips can be taken more efficiently by public transport, walking and cycling, than by private cars. This also brings major health benefits through reducing air pollution, road traffic injuries – and the over three million annual deaths from physical inactivity. Many of the largest and most dynamic cities in the world, such as Milan, Paris, and London, have reacted to the COVID-19 crisis by pedestrianizing streets and massively expanding cycle lanes – enabling “physically distant” transport during the crisis, and enhancing economic activity and quality of life afterwards.”

6) Stop using taxpayers’ money to fund pollution – halt US$ 400 billion in fossil fuel industry subsidies

“Financial reform will be unavoidable in recovering from COVID-19, and a good place to start is with fossil fuel subsidies.

Globally, about US$400 billion every year of taxpayers money is spent directly subsidizing the fossil fuels that are driving climate change and causing air pollution. Furthermore, private and social costs generated by health and other impacts from such pollution are generally not built into the price of fuels and energy. Including the damage to health and the environment that they cause, brings the real value of the subsidy to over US$5 trillion per year- more than all governments around the world spend on healthcare – and about 2,000 times the budget of WHO.

Placing a price on polluting fuels in line with the damage they cause would approximately halve outdoor air pollution deaths, cut greenhouse gas emissions by over a quarter, and raise about 4% of global GDP in revenue. We should stop paying the pollution bill, both through our pockets and our lungs.”

New ‘WHO Foundation’ Aims To Raise More Flexible Funding For The World Health Organization

Dr Tedros (left) and Thomas Zeltner (right) sign an MOU between the WHO and the newly established WHO Foundation

Meanwhile, WHO also unveiled a new initiative Wednesday to address some of its own pressing financial problems – triggered by the temporary suspension of funding from the United States as well as by a longer term decline in “assessed contributions” by WHO member states to the Organization.

The WHO Foundation was launched today to raise funding from the general public and other “non-traditional sources” for the Organization. The new foundation will give the agency a source of unearmarked income, providing more flexibility in financing WHO’s General Programme of Work.

“The creation of the foundation represents a truly innovative approach to diversify WHO’s resource mobilization strategy. This new approach is clearly an urgent need,” said WHO Foundation founder and former Swiss Secretary of State for Health Thomas Zeltner.

“One of the greatest threats to WHO success is the fact that less than 20% of our budget comes in the form of flexible assets contributions from Member States,” said Dr Tedros at the press briefing. “For WHO to fulfill its mission and mandate, there is a clear need to broaden our donor base, and to improve both the quantity and quality of funding we receive – meaning more flexibility.”

WHO is one of the few international organizations that, up until now, has no legal channel for receiving donations from the general public, he noted.

The success of the COVID-19 Solidarity Fund, which has raised more than US $241 million in a few short months, served as a good proof-of-concept for the WHO Foundation, which aims to raise money for a broader, more flexible and more long-term portfolio encompassing all of WHO health programmes.

Currently, almost 80% of the funding that WHO receives comes in the form of voluntary contributions earmarked for specific programmes, according to Dr Tedros.

“This means that WHO has little discretion over the way it spends almost 80% of its funds,” he explained.

More flexible funding, channeled through the new WHO Foundation, will allow the organization to address some underfunded programmes that have not caught the eye of other large donors. attention.

“All funding of the WHO Foundation will help implement WHO’s General Programme of Work. On average, between 70-80% of the funds we raise will go directly to the WHO Secretariat. The remaining 20-30% will be used to strengthen public health globally by working with implementing partners of WHO,” said Zeltner.

Still, money raised by the new Foundation is meant to “complement, not supplement” existing resources available to the agency, clarified Zeltner.

The WHO Foundation will be set up as an independent, non-profit organization under Swiss law. A Memorandum of Understanding between the WHO and the WHO Foundation was signed Wednesday by Zeltner and Dr Tedros to set the framework for how the Foundation will collaborate with the agency.

Image Credits: Twitter: @WHO, Wikimedia Commons, Piekfrosch/wikipedia, Health Care Without Harm, FAO/Shutterstock, City of Fortaleza.

As COVID-19 Cases In The Americas Rise; 1-4 People At Higher Risk Of Serious Illness Due To ‘Pervasive’ Incidence Of Underlying Diseases

26/05/2020 Svĕt Lustig Vijay

WHO Regional Director for the Americas Carissa Etienne at a regular press conference

As global COVID-19 cases topped 5 million this past week, Latin America has surpassed Europe and the United States in terms of new cases being reported everyday, said WHO Regional Director for the Americas, Carissa Etienne, at a Pan American Health Organization press conference on Tuesday.

There have been almost 32,000 new cases of COVID-19 in Latin America and the Caribbean over the past 24 hours, as compared to 24,000 in the United States and 18,000 in WHO’s European Region – which includes the recently hard-hit Russian Federation and Turkey as well as western European states, such as Italy, Spain and the United Kingdom, which saw a major wave of infections in March and April.

However, the United States and Brazil are now the two countries with the highest cumulative number of reported cases worldwide, added Etienne. And the Americas region as a whole has seen 2.4 million of the world’s 5.5 million reported cases, as well as 143,000 of the 350,000 deaths. As of Tuesday evening, the United States reached the 100,000 mark for deaths from the novel virus.

The latest data is ‘truly alarming’, Etienne said in light of the fact that non-communicable diseases (NCDs) like diabetes, cancers or other respiratory diseases are “pervasive” throughout the “Americas” region – and those diseases make people more vulnerable to serious illness from Covid-19.

“We have Never Seen Such a Deadly Relationship”

Prior to COVID-19, about 80% of all deaths in the Americas were already due to such non-communicable diseases and almost 40% of these deaths were premature, as they occurred before 70 years of age, said Etienne. The Americas Region, according to World Health Organization’s definitions, includes Latin America and the Caribbean as well as the United States and Canada.

That means one in four people in the Americas is at an increased risk of poor outcomes if they become infected with COVID-19, said Etienne.

“We have never seen such a deadly relationship between an infectious disease and NCDs”, said Etienne. “One of the most concerning aspects of the COVID-19 pandemic in PAHO is the disproportionate impact of the virus on people suffering from non-communicable diseases.”

Latin America has 62 million people living with diabetes and 1.2 million people living with cancer, and these populations are much more vulnerable to COVID-19.

Diabetics are twice as likely to have severe COVID-19 disease, according to a recent review of 16,000 patients with COVID-19. And in one Chinese study, almost 30% of cancer patients died from the virus, as compared to only 2% on average, said Etienne.

Smoking increases vulnerability to COVID-19

Smoking prevalence is another risk factor in the Americas that is exacerbating the current crisis. About 15% of adults in the region still smoke, increasing the likelihood of developing severe illness from COVID-19, as smoking reduces respiratory capacity and promotes cancers, heart and lung disease.

For all of these reasons, she said, health systems need to prioritize prevention and control of non-communicable diseases along with supporting the pandemic response – as treating NCDs can prevent COVID-19 from becoming life-threatening.

“As cases continue to rise in our region, our efforts to protect those with underlying conditions must intensify,” she said. “We must ensure timely access to care for chronic diseases to prevent them from becoming life-threatening.”

“Fighting non-communicable diseases now is integral to our response to COVID-19. We need aggressive preventive measures to protect people with diabetes, respiratory and cardiovascular diseases from the new coronavirus.”

If measures are not taken now to help people with NCDs, health systems will be faced with a “parallel epidemic” of preventable deaths in persons with those conditions.

The New Epicentre Of Infection – Latin America

There can be ‘no doubt’ that Latin America has become the epicenter of the COVID-19 pandemic, said Etienne at Tuesday’s press conference.

And over the past day, the ‘highest increase’ in cases was seen in Latin American countries like Chile, Brazil and Peru.

While Chile has reported almost 5000 new cases in the past day, a 7% increase, Brazil has seen almost 16000 new cases over the past 24 hours, a 5% increase. Meanwhile, Peru and Mexico have each witnessed a 4% increase in cases over the past day, said Etienne.

Some countries in the region have successfully ramped up testing; Chile, for instance, has reached the milestone of 25,000 tests per million people, comparable with the highest range of testing rates in Europe at the height of the pandemic wave there. But testing is still ‘not sufficient’ in most other countries, said Director of PAHO’s Department of Communicable Diseases Marcos Espinal – The majority of South American nations are still only managing to test less than 5000-6000 people per 1 million, a figure that is much lower than most European countries.

The Americas has 40% of the world’s cases and 40% of total deaths

Image Credits: WHO, WHO.

Africa Hosts Just 1.5% Of Global COVID-19 Tally

25/05/2020 Grace Ren, Zixuan Yang & Tsering Lhamo

COVID-19 responders learn how to properly don and doff protective gowns in Kenya

In contrast to Europe and the Americas, Africa has just 1.5 percent of the world’s reported cases of COVID-19, and less than 0.1 percent of the world’s deaths, World Health Organization Director-General Dr Tedros Adhanom Ghebreyesus noted on Africa Day 2020.

“Africa appears to have so far been spared the scale of outbreaks we have seen in other regions,” said Dr Tedros. “Of course, these numbers don’t paint the full picture. Testing capacity in Africa is still being ramped up, and there is a likelihood that some cases may be missed.”

Still, African countries’ histories of facing outbreaks of infectious disease have played in their favor, said the WHO Director-General.

“Africa’s knowledge and experience of suppressing infectious diseases has been critical to rapidly scaling up an agile response to COVID-19,” he said.

For example, a coalition of African leaders, organized through the African Union chaired by South African President Cyril Ramaphosa, was set up early in the global pandemic to coordinate cross-country preparedness efforts. Infrastructure and knowledge from battling previous outbreaks was used to rapidly scale COVID-19 interventions, as seen in South Africa’s rapid deployment of mobile diagnostic teams, and the Democratic Republic of the Congo’s use of Ebola screening infrastructure for COVID-19 temperature screening.

Additionally, citizens across the continent have largely understood the need for strong lockdown measures, taken early by many African nations. WHO Regional Director for Africa Dr Matshidiso Moeti on Monday thanked citizens for abiding by stay-at-home orders where possible, acknowledging the hardships that many were facing.

“I’d like to very much commend and thank [the citizens]… because we think that it’s thanks to these measures that we have not started to see the kind of evolution of the pandemic in Africa that we were projecting,” said Moeti. “They accepted the need for some of these measures, although many of them recognize that it would be very tough on them in the households, particularly if you take into account the proportion of African people that are in a sector where you need to be out, earning your money in order to be able to put food food on the table.”

Japan Lifts State Of Emergency As Other Asian Countries Seesaw On COVID-19 Control

On Monday, Japan officially lifted its state of emergency in all its provinces ahead of the May 31st deadline, regarding the emergency situation as “no longer necessary” according to the Ministry of Health. The country has been largely praised for its efficient coronavirus response, relying almost solely on quick contact tracing, testing, and isolation of cases.

India also lifted its restriction on domestic air travel effective Monday, although there were mixed opinions on the move. Meanwhile, Philippines President Rodrigo Roa Duterte commanded its government agencies to expedite the repatriation of more than 24,000 overseas Filipino workers (OFW) within the week.

In China, clusters of cases in Jilin province in the northeast have led to officials to lockdown cities only a couple weeks after the original pandemic epicentre Wuhan began relaxing lockdown measures.

Tensions between China and the US remain high. China’s Foreign Minister Wang Yi remarked that a “political virus is spreading in the US, with some politicians ignoring facts and promoting conspiracy” at a video press conference on Sunday. Still, Wang expressed hope that there could be future collaboration between China and the U.S. for addressing global challenges.

Park rules in Paterson, New Jersey, USA.

New Death Projections in US Cast Somber Outlook If States Are Too Eager To Reopen

In stark contrast to the Chinese approach, states across the US have begun relaxing social distancing guidance even as new cases continue to appear.

And health experts warn that relaxing COVID-19 measures early could lead to a fresh wave of coronavirus deaths. Some 23,000 more people could die if states failed to reimplement social distancing measures, according to a new analysis by epidemiologists at the Columbia Mailman School of Public Health.

And enacting federal social distancing measures just two weeks earlier could have prevented 83% of the US’ nearly 100,000 coronavirus deaths, according to the same study.

But experts fear that social fatigue from complying with the stringent measures mean that citizens will be loathe to comply with any renewed measures. As such, the importance of scaling up public health measures to rapidly detect and contain the virus, as well as improve health education, is even more important in the next phase of the fight.

“Our results also indicate that without sufficient broader testing and contact tracing capacity, the long lag between infection acquisition and case confirmation will mask the rebound and exponential growth of COVID-19 until it is well underway,” says lead researcher Jeffrey Shaman, professor of environmental health sciences at the Columbia Mailman School of Public Health in a press release. “Efforts raising public awareness of the ongoing high transmissibility and explosive growth potential of COVID-19 are still needed at this critical time.”

A COVID-19 triage tent in Italy

High COVID-19 Death Rates in Italy & Sweden

Sweden had a seven-day rolling average of 6.08 deaths per million between 13 May and 20 May, overtaking the UK, Italy and Belgium to have the highest coronavirus per capita death rate in the world regardless of its low population densities and limits in international travel.

In contrast to countries like France and Germany, social distancing implemented in Sweden depending largely on the discretion of individual Swedes, without harsh controls, fines, or policemen.

However, the high mortality rate has thrown the government’s decision to avoid strict lockdown into further doubt- especially as its neighboring countries such as Norway, Denmark and Finland, where much tighter restrictions are put in place, have seen dramatically lower numbers of deaths over the past month.

Sweden’s decision to keep open schools, bars and restaurants and to continue to allow gatherings of up to 50 people has been praised by many who believe that the country will be better equipped for a “second wave” with certain degree of herd immunity through the relatively relaxed measures. However, WHO experts have repeatedly warned that early antibody surveys are showing that a far higher proportion of the population will remain susceptible to a second wave, casting strong doubt on the ‘herd immunity’ approach.

Meanwhile, a recent analysis of death registry data by two Italian economists shows that Italy had a 40% higher death rate from February to March 2020, as compared to the same time the previous year.

The economists estimated that the virus may have killed 0.1% of the local population in less than 40 days and that its mortality is vastly underreported in official statistics.

But on the bright side, the analysis shows that stringent containment measures were significantly lower in the Veneto region, which has “embraced mass testing, contact tracing and at-home care provision.” Neighboring Emilia-Romagna and Lombardia did not fare as well.

The economists also found that closure of service activities is effective in reducing COVID-19 mortality – a 10% increase in proportion of the service industry closed correlated with a 15% lower death rate in municipalities. In this second paper, the economists draw from daily death registry data on 4,000 Italian municipalities to investigate two policies, namely the shutdown of non-essential businesses and the management of the emergency care system. However, shutting down factories is much less effective. In addition, results also show that morality strongly increases with distance from the intensive care unit (ICU).

Svet Lustig Vijay contributed to this story

Image Credits: Twitter: WHOAFRO, Paterson Great Falls, Servizio Nazionale della Protezione Civile.

WHO Pauses Hydroxychloroquine Arm Of COVID-19 Clinical Trial – After Lancet Study Finds Higher Mortality Rate Among Patients Getting The Drug

25/05/2020 Grace Ren

This story was updated 4 June to reflect the Lancet study’s retraction.

WHO Chief Scientist Soumya Swaminathan provides reasoning behind pausing hydroxychloroquine arm of the Solidarity Trial.

Enrollment of new patients in the hydroxychloroquine (HCQ) arm of the World Health Organization’s Global COVID-19 Solidarity Trial will be put on pause, as the trial’s oversight committee reviews all available data on COVID-19 and hydroxychloroquine, WHO Director-General Dr. Tedros Adhanom Ghebreyesus said on Monday.

The WHO decision on Saturday came just a day after a major observational study published in The Lancet found a higher mortality rate in COVID-19 patients who have received hydroxochloroquine, chloroquine, or a combination of either drug and azithromycin, as compared to COVID-19 patients who did not receive any treatments.

The Lancet paper was later retracted on 4 June by three of the authors due to concerns about the “veracity of the primary data sources.”

“The executive group [composed of experts from 10 countries involved in the trial] has implemented a temporary pause of the hydroxychloroquine arm within the Solidarity trial,” said Dr Tedros speaking at a WHO press conference. “The group has agreed to review a comprehensive analysis and critical reappraisal of all evidence available globally. The review will consider data collected so far in the Solidarity trial, and important, robust randomized available data to evaluate the potential benefits and harms from this drug.”

WHO Experts Clarify Reasoning Behind Hydroxycholoroquine Arm Suspension

Still, WHO experts said that mortality conclusions could not be definitively drawn from an observational study, such as the one reported by The Lancet. WHO’s Chief scientist Soumya Swaminathan acknowledged that unlike randomized controlled trials such as the one WHO is conducting observational studies can yield misleading results.

“We know that the evidence from observational studies, however large they may be, is still subject to inherent bias. What’s really important is to have well-conducted randomised control studies, done in large numbers,” said WHO Chief Scientist Soumya Swaminathan, also speaking at the press briefing.

WHO Emergencies head Mike Ryan also underlined that WHO’s decision to suspend the hydroxychloroquine arm of the WHO Solidarity Trial was not due to any negative preliminary results that had already been flagged in the ongoing WHO study.

Rather, the decision was a “proactive” one made to “err on the side of caution,” said Swaminathan.

“There were also a lot of questions coming from our own principal investigators in countries, and we knew that the regulatory agencies in many countries were also discussing these data…So the steering committee decided that in the light of this uncertainty that we should be proactive, err on the side of caution and suspend enrollment temporarily into the hydroxychloroquine arm,” she told reporters.

As one part of the review, the trial’s independent data safety monitoring board will be analyzing data collected so far to see if there are any “signals” that the drug is failing, and send them to the trial’s advisory committee for further review, said WHO Health Emergencies Executive Director Mike Ryan.

“We will expect that if there is no signal of failing, and we don’t have any problems, we will try to use the drug,” said Ryan.

Dr Tedros highlighted that hydroxychloroquine, which has been widely approved for use for malaria and the autoimmune disease Lupus, is still safe to use in patients with those diseases.

**Researchers Criticise The Lancet Study Design**

Analysis of HCQ studies finds that randomised control studies (green) are more likely to find the drug has a positive effect on COVID-19, compared to observational studies (red)
(Credit: Didier Raoult et al.)

Other researchers have also criticised The Lancet study’s design. While the study had analyzed a large body of data from 671 hospitals in 6 continents, there could still be bias in the analysis that is obscuring the true effects of the drug.

In smaller RCTs for example, positive results for hydroxychloroquine had been found. Treatment failure had so far mainly been identified only in observational studies, according to an analysis by Didier Raoult, director of the Marseille University Hospital Institute for Infectious Diseases ( IHU Méditerranée Infection).

One major critique is that The Lancet study does not adequately adjust for the fact that many of the patients in the study are more likely to be severely ill, and are already at increased risk of death.

Critics contend that The Lancet study primarily observes patients experiencing more severe disease who began receiving HCQ later in disease progression, while the drug has shown promise when given earlier or used as a preventative treatment. For example, India now recommends the prophylactic use of hydroxycholoroquine to protect against COVID-19 infection in all healthcare and frontline workers, following results from a small observation trial that found the likelihood of infection was lower in those who took the drug.

“Another poorly designed interpretation of a hydroxychloroquine data set for COVID-19. A larger poorly designed “trial” only leads to larger erroneous conclusions,” tweeted Steven Phillips, a Yale-educated internal medicine doctor who specializes in zoonotic infectious diseases.

About two-thirds of the patients in The Lancet study were from North America, where delays in testing mean that patients aren’t identified until 5 to 7 days after they begin showing symptoms, says Phillips.

“HCQ early COVID-19 treatment isn’t embraced in the US. It’s given only to the sickest patients, without contrary evidence in this study. To state that the baseline disease severity between treatment & control is equal was incorrect,” he added.

For example, one measure used in The Lancet study to determine baseline disease severity is the “quick sequential organ failure assessment”(qSOFA) score. There is little difference between qSOFA scores across different disease severities, so the score is “proving a bad stratifier for COVID,” tweeted antimalarial pharmacology researcher James Watson, a lead scientist at the Mahidol Oxford Tropical Medicine Research Unit (MORU).

“So a quick conclusion is that they have just inadequately adjusted for disease severity, which is driving the treatment allocation [of HCQ or no HCQ],” added Watson.

“I agree with one thing the authors said: ‘Randomized clinical trials will be required before any conclusion can be reached regarding benefit or harm of these agents in COVID-19 patients,'” Phillips tweeted in conclusion.

Image Credits: Matthieu Million, Yanis Roussel, Didier Raoult.

Two COVID-19 Vaccine Candidates Induce Immune Response In Healthy Volunteers

22/05/2020 Grace Ren & Svĕt Lustig Vijay

Scientist conducting coronavirus vaccine research at NIAID’s Vaccine Research Centre, Moderna’s original collaborator on the SARS-CoV-2 vaccine.

A COVID-19 vaccine candidate made by Chinese researchers successfully induced the development of neutralizing and binding antibodies against SARS-CoV-2, the virus that causes COVID-19, according to early results from a non-randomized phase I clinical trial published Friday in The Lancet.

The trial results follow on to results announced by Moderna earlier this week, which found that their vaccine candidate was able to induce neutralizing antibodies in 8 healthy volunteers. In vaccine trials, the development of neutralizing antibodies is the most sought-after immune response because these antibodies bind to viral particles in a way that immediately blocks infection.

The non-randomized Chinese study, which was published in The Lancet, reported preliminary safety and efficacy results for a vaccine in 108 healthy middle-aged adults at low, medium, and high doses; with 36 participants enrolled in each dosage level. At low dose and middle-doses, about a half of the individuals produced neutralizing antibodies after 28 days. At high doses, some three-quarters (27/36) of volunteers produced neutralizing antibodies. Regardless of vaccine dosage, over 90% of participants showed a four-fold increase in binding antibodies.

“These results represent an important milestone,” said Wei Chen from the Beijing Institute of Biotechnology, who was responsible for the study. “The trial demonstrates that a single dose of the new adenovirus type 5 vectored vaccine produces virus-specific antibodies and T cells in 14 days, making it a potential candidate for further investigation.”

The Ad5-nCoV vaccine also stimulated a rapid T cell response in 83.3% of individuals that received a low dose – and in the medium and high- dose groups, 97% (35/36) of individuals exhibited rapid T cell responses. Certain types of T cells develop responses when exposed to specific antigens, or parts of disease-causing pathogens, and “remember” to attack the same pathogen once exposed to it again. Vaccines, which contain un-infective pieces of viruses or weakened viruses, help activate this immune memory by inducting a T-cell mediated response.

The most common adverse reactions to the vaccine persisted for less than 48 hours, which is usually considered acceptable for a vaccine. Side effects ranged from mild pain at the injection site reported in over half (54%, 58/108) of vaccine recipients, as well as fever (46%, 50/108), fatigue (44%, 47/108), headache (39%, 42/108), and muscle pain (17%, 18/108).

Many Limitations to Chinese Vaccine Study & Concerns with the Adenovirus 5 Vector

Still, “the challenges in the development of a COVD-19 vaccine are unprecedented, and the ability to trigger these immune responses does not necessarily indicate that the vaccine will protect humans from COVID-19,” warned Chen.

Further, randomized trials are needed to tell whether the immune response the vaccine candidate elicits effectively protects against SARS-CoV-2 infection, he added.

And health experts have brought up concerns around the vector used to carry the vaccine, a weakened common cold-causing virus, adenovirus type 5 or Ad5.

“There has been a shadow with the Ad5 as a vaccine vector over the last decade, not seen with other Ad vectors for vaccines. Have these concerns been allayed?” tweeted Jeremy Farrar, director of the research foundation Wellcome Trust, in response to the study.

Farrar referred to a previous case where an HIV-vaccine candidate using the Ad5 vector was found to put study participants who received the vaccine at a higher risk of HIV infection – and further exploration of that vaccine candidate was promptly discontinued. It’s been posited that the T-cells activated by the Ad5-vector HIV vaccine candidate made the cells more vulnerable to infection by HIV-1, which attacks immune cells.

Of the concerns, the study authors write, “although the association between HIV-1 acquisition risk and Ad5 vectored vaccine is controversial and its mechanism is unclear, the potential risks should be taken into account in studies with this viral vector delivery platform.

“We plan to monitor the participants in our upcoming phase 2 and phase 3 studies to assess the indication for any such acquisition.” At least two other vaccine candidates using the Ad5 vector are listed in the World Health Organization’s draft registry of SARS-CoV-2 vaccine candidates, the study authors say.

However, another concern is that half of the participants in the COVID-19 vaccine trial also already had immunity to the Ad5 virus, and these participants showed weaker immune responses to the COVID-19 vaccine.

“Our study found that pre-existing Ad5 immunity could slow down the rapid immune responses to SARS-CoV-2 and also lower the peaking level of the responses,” said Feng-Cai Zhu from Jiangsu Provincial Center for Disease Control and Prevention in China, part of the group that led the study. “Moreover, high pre-existing Ad5 immunity may also have a negative impact on the persistence of the vaccine-elicited immune responses.”

The authors note that the other limitations of the trial are its small sample size, relatively short duration, and most importantly, lack of a randomised control group – which may have biased their results.

To address these limitations, a randomised, double-blinded, placebo-controlled phase 2 trial in 500 healthy adults has been initiated in Wuhan to determine whether the results can be replicated, and if there are any adverse events up to 6 months after vaccination. For the first time, this will include participants over 60 years old, an important target population for the vaccine.

Moderna Vaccine Induces Immune Response In Limited Number Of Healthy Volunteers

In a parallel development, eight people injected with Moderna’s experimental COVID-19 vaccine, mRNA-1273, developed neutralizing antibodies against the virus, announced the US-based pharmaceutical firm on Monday.

Neutralizing antibodies were detected in 4 participants that were given a low vaccine dose of 25 micrograms, and in 4 others that received a higher dose of 100 micrograms, 43 days after receiving the vaccine. At these doses, the vaccine was generally safe and well tolerated, said Moderna in a statement.

Neutralizing antibody titers for the remaining study participants were not yet available. The data were from a Phase I clinical trial conducted in collaboration with the US National Institute for Allergies and Infectious Diseases (NIAID).

“These interim Phase 1 data, while early, demonstrate that vaccination with mRNA-1273 elicits an immune response of the magnitude caused by natural infection starting with a dose as low as 25 micrograms,” said Tal Zaks, M.D., Ph.D., Chief Medical Officer at Moderna.

“When combined with the success in preventing viral replication in the lungs of a pre-clinical challenge model at a dose that elicited similar levels of neutralizing antibodies, these data substantiate our belief that mRNA-1273 has the potential to prevent COVID-19 disease and advance our ability to select a dose for pivotal trials,” added Zaks.

Based on these early results, Phase 2 trials for the Moderna vaccine were amended to include a 50 ug dosage and a 100ug dosage in order to finalize a dosage for Phase 3 studies. A 50ug dosage arm was added to the Phase 1 – NIAID study.

Phase 3 clinical trials could be initiated as soon as July 2020, an unprecedented speedy timeline for vaccine development.

However, similar to the Chinese vaccine study, the initial results don’t necessarily show that the vaccine induces an immune response strong enough to protect against COVID-19, nor do they show how long protection might last.

The concentration of neutralizing antibodies in the 8 participants was similar to the concentration found to be protective against COVID-19 in mouse models, although the results from animal models do not necessarily always correlate directly with humans. The 8 participants with neutralizing antibodies were sampled only two weeks after receiving the second dose of vaccine, and must be followed further in order to determine whether and for how long the neutralizing antibodies could protect against SARS-CoV-2 infection.

Some 45 participants also developed ‘binding antibodies’, which can bind to a virus but do not make it less infectious.

Though Moderna’s vaccine study was led by the US National Institute of Allergy and Infectious Diseases (NIAID), the NIAID did not publish a press release, and declined to comment on Moderna’s announcement. If successful, this would be the first vaccine candidate that Moderna, a company that is experimenting with new, mRNA vectors for carrying vaccines, will bring to market.

In recent months, health experts and government leaders are more and more pinning their hopes to quash the pandemic for good on a successful COVID-19 vaccine, as serological studies are beginning to show that a large proportion of countries’ populations will remain susceptible to the virus after the first wave.

Not everyone that gets infected with COVID-19 develops antibodies, suggest recent European serological surveys. In Switzerland, one of the hardest-hit countries in Europe, only 1 in every 10 people had antibodies against COVID-19 – and older people had about half as many antibodies as young and middle-aged individuals.

Surveys in Spain and France also paint a solemn picture of immunity, as only about 4-5% of the population has detectable antibody levels. Though the number of people with antibodies is growing rapidly as infections increase, herd immunity is far away.

The creation of an effective vaccine is seen as the long-term solution to controlling the COVID-19 pandemic. Currently, there are more than 100 candidate COVID-19 vaccines in development worldwide.

Image Credits: NIAID.

Hydroxychloroquine May Cause More Harm Than Benefit To COVID-19 Patients, Says New Lancet Study

22/05/2020 Svĕt Lustig Vijay & Grace Ren

This story was updated 4 June to reflect the paper’s retraction.

Colorized scanning electron micrograph of a dying cell (blue) heavily infected with SARS-COV-2 (yellow), the virus that causes COVID-19

New research published in The Lancet on Friday found that hydroxychloroquine and chloroquine has ‘no benefit’ for coronavirus patients, and could even increase the risk of heart arrhythmias and mortality.

The study was retracted by three of its authors on June 4, due to the authors own concerns about the “veracity of primary data sources.”

“This is the first large scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with COVID-19,” said lead author of the study and Executive Director of the Brigham and Women’s Hospital Center in Boston Mandeep R. Mehra. “Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death.”

In the worst-case scenario, some 8% of patients in The Lancet study who were given hydroxychloroquine combined with azithromycin developed a heart arrhythmia (502/6,221), compared with 0.3% patients in the control group (226/81144).

Hydroxychloroquine and chloroquine use predicts in-hospital mortality

Treatment with hydroxychloroquine, chloroquine, or either drug in combination with azithromycin was also associated with higher odds of death, even after accounting for age, race, body mass index, and preexisting conditions.

While not a randomized control study, The Lancet article is the largest study to date on the hyped drugs, analyzing data from nearly 15,000 COVID-19 patients who received hydroxychloroquine, chloroquine, or a combination of either drug with a macrolide antibiotic such as azithromycin, and 81,000 COVID-19 patients who did not receive any of those treatments. The data came from 671 hospitals across 6 continents.

In light of mounting evidence that hydroxychloroquine provides little benefit to coronavirus patients, health experts are again repeating calls to take caution in rolling out emergency approval for unproven treatments, even as countries all over the map cautiously begin to authorize the use of hydroxychloroquine for COVID-19. India even issued a revised advisory on Friday expanding the use of hydroxychloroquine as a prophylactic treatment in healthcare workers and contacts of lab-confirmed coronavirus patients.

Experts from the World Health Organization have also been cautioning against widespread, unmonitored use of the drug.

“We do point to the fact that… the current clinical evidence does not support the widespread use of hydroxychloroquine for the treatment of COVID-19, not until the trials are completed and we have clear results,” said WHO’s Executive Director of Emergencies Programme Mike Ryan, at WHO’s press conference on Friday, referring to evidence from clinical and systematic reviews carried out by the WHO Pan American Health Organization (PAHO).

Hydroxychloroquine, and hydroxychloroquine plus azithromycin are two of the drug regimens being tested for COVID-19 patients in WHO’s giant, multicountry Solidarity Trial.

The Lancet results support previous findings from a widely disseminated Brazilian study that found an increased risk of heart arrhythmias in COVID-19 patients receiving high doses of the drug. The study was discontinued shortly after, as subjecting patients to increased risk of death in the trial was deemed unethical by study coordinators.

The Lancet study however, does not explore another use for hydroxychloroquine – taking the drug to prevent onset of COVID-19.

India Revises Hydroxychloroquine Recommendations To Promote Prophylactic Use

Indian Ministry of Health recommends prophylactic use of hydroxychloroquine in revised advisory

On Friday, India’s National Task force (NTF) for COVID-19 issued a revised advisory on prophylactic use of hydroxychloroquine – expanding the recommendation to include all asymptomatic healthcare workers in COVID-19 positive and non-COVID-19 settings, all asymptomatic frontline workers in the COVID-19 response including contact tracers, and all asymptomatic household contacts of laboratory confirmed cases.

The previous advisory, issued on 23 March, restricted the recommendation to healthcare workers who worked directly with confirmed and suspected COVID-19 patients, and asymptomatic household contacts of laboratory confirmed cases.

The revised recommendation was based on a small prospective observational study of 334 healthcare workers. According to the advisory, the incidence of COVID-19 infection in the 248 healthcare workers who took HCQ prophylaxis in New Delhi was lower than the incidence of infection in those who did not take it after following up with the study subjects for a median of 6 weeks, however the exact reduction was not listed.

Still, the revised advisory recommends that the drug has to be given under ‘strict medical supervision with informed consent’ and ‘only on the prescription of a registered medical practitioner’ – noting a number of preexisting conditions that make taking the drug risky.

The advisory also notes that only under ‘rare’ circumstances does hydroxychloroquine lead to the dangerous cardiovascular side effects. Among 1323 healthcare workers who took HCQ prophylaxis, serious side effects were reported in 7. Among those 7, three healthcare workers had a serious cardiac side effect – prolongation of QT interval on ECG.

“Rarely the drug causes cardiovascular side effects such as cardiomyopathy and rhythm (heart rate) disorders. In that situation the drug needs to be discontinued,” said the advisory.

China, Spain, Brazil, and the United States have also issued recommendations for use of hydroxychloroquine in limited populations, largely restricting them to use in clinical trial settings in light of the new reports of serious cardiac side effects.

But the authors of The Lancet study still warn that the overall likelihood that these drugs improve clinical outcomes in COVID-19 patients is quite low, and underline that the medicines should not be recommended by countries for widespread treatment of COVID-19.

“Several countries have advocated use of chloroquine and hydroxychloroquine, either alone or in combination, as potential treatments for COVID-19. Justification for repurposing these medicines in this way is based on a small number of anecdotal experiences that suggest they may have beneficial effects for people infected with the SARS-CoV-2 virus,” said Director of the Heart Center at University Hospital Zurich Frank Ruschitzka, who also co-authored The Lancet study.

Image Credits: NIAID, The Lancet, India Ministry of Health.

New Guidance Helps Governments Estimate True Extent Of COVID-19 Pandemic

21/05/2020 Editorial team

New technical guidance for national governments was released to support the enhanced measurement of two key indicators for the COVID-19 response; the number of cases and the number of deaths, as reported on national and global dashboards. The package was launched by global health NGO Vital Strategies.

Limited COVID-19 testing capacity in low- and middle-income countries makes it especially challenging to use confirmed cases as a measure of epidemic impact and burden.

“In the absence of adequate global testing capacity, measuring cases and deaths specifically due to COVID-19 is not straightforward,” said Dr. Philip Setel, vice president of the Civil Registration and Vital Statistics Program at Vital Strategies in a press release. “Rapid surveillance of total mortality can provide critical data to national leaders and health authorities as they work to temper and control the pandemic within their borders.”

The new guidance, Revealing the Toll of COVID-19: A Technical Package for Rapid Mortality Surveillance, offers a step-by-step manual on ‘rapid mortality surveillance,’ which relies on the key concept of estimating excess deaths due to COVID-19. The technique allows countries to rapidly determine the extent of the epidemic and accordingly plan outbreak responses.

By comparing year-on-year all-cause mortality data from national civil registration and vital statistics (CRVS) systems, countries can see how many more deaths occurred in 2020 compared to previous years, and get a snapshot of how many excess deaths may have been caused by COVID-19, according to the new guidance. The data can then be visualized separately by age group, sex, and location to further identify trends in deaths.

Brazil, Colombia and Peru already began using existing civil registration and vital statistics systems for rapid mortality surveillance through the Bloomberg Philanthropies Data for Health Initiative. Analysis of vital registration data helped identify a sharp increase in total mortality in April 2020 compared to the same time in 2019 in Manaus, Brazil, illustrating the enormous impact the pandemic has had on the city’s death rate.

“All countries need timely and reliable data to inform health planning. This need becomes particularly acute at times like now when they face a swiftly evolving pandemic,” said Dr. Samira Asma, Assistant Director General for Data, Analytics, and Delivery for Impact at the World Health Organization

Rapid mortality surveillance generates daily or weekly counts of total mortality by age, sex, date of death, place of death and place of usual residence, helping to provide a fuller picture of the scale and direction of the pandemic, including estimates of deaths due to COVID-19 that may have been missed by the traditional testing and surveillance system. Data is collected through facility- and community-based surveillance, which helps capture deaths that are also occurring in homes.

The technique also estimates indirect mortality caused by disruptions to health services, and the interaction of the virus with pre-existing conditions such as noncommunicable diseases.

“Governments need timely, reliable data to inform decisions that will ultimately save lives, now more than ever,” said Dr. Kelly Henning, head of Bloomberg Philanthropies’ public health programs. “This new technical package will empower leaders around the world with a faster, more accurate understanding of potential COVID-19 deaths, and allow them to take action to slow the spread of this pandemic.”

The technical package was developed with experts from Vital Strategies and partner organizations that helped shape the package, ensuring clarity, rigor and ease of use: Africa Centers for Disease Control and Prevention, Bloomberg Philanthropies Data for Health Initiative, CDC Foundation, Pan American Health Organization, UN Economic Commission for Africa, UN Economic and Social Commission for Asia and the Pacific, US Centers for Disease Control and Prevention, and the World Health Organization.

Image Credits: Twitter: @WHOKenya.