SARS-CoV-2 (green) attacking a human cell (red)

It is still too early to tell how long immunity to SARS-CoV-2, the virus that causes COVID-19, may last after infection, the World Health Organization’s Technical Lead for COVID-19, Maria Van Kerkhove said at Monday press briefing.

Van Kerkhove’s comments came just after the publication of a new study by researchers from Kings College, London, which found that immunity seemed to peak at three weeks after symptoms first appeared, but then waned rapidly afterward.  Previous studies have also suggested that immunity to SARS-CoV-2 may wane within a few months after infection.

“We do expect that people who are infected with SARS-CoV-2, they do mount some level of an immune response…What we don’t know is how strong that protection is and for how long that protection will last,” said Van Kerkhove. 

While not referring specifically to the recent study, Van Kerkhove added that experience with other coronaviruses indicates that it is possible to become reinfected, and  there is data suggesting that immunity to SARS-CoV-2 could wane: 

“From our experience with MERS and SARS1, the virus that spilled over in 2003, we know that people can have an antibody response for maybe a year or even longer. But with the human coronaviruses that circulate regularly, it’s much shorter than that. So it’s an incomplete answer because we don’t have that answer yet,” said Van Kerkhove.

In the antibody study posted on the preprint server MedRxiv, researchers from King’s College London found that levels of neutralizing antibodies, the type of antibodies that can bind to and neutralize the virus, peaked at three weeks after symptoms appeared. 

However, immunity rapidly waned after the three-week mark. 

“Using sequential samples from SARS-CoV-2 infected individuals collected up to 94 days post-onset of symptoms, we demonstrate declining neutralizing antibody titres [levels] in the majority of individuals,” the authors, a group of researchers from Katie Doore’s lab at Kings College London, wrote. 

Those who survived more severe infection had higher levels of neutralizing antibodies at the three week mark. However the time it took for antibody responses to peak was consistent across all study subjects despite differing levels of disease severity.

The study, Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection, measured antibody levels between March and June in 96 healthcare workers and patients who had laboratory confirmed cases of COVID-19.

Such studies casts further doubt over the potential of populations to develop broad “herd immunity” to the virus, no matter how widely it circulates, in the absence of a vaccine.  It may also prove to be a complicating factor in vaccine research, insofar as a potential vaccine would need to provoke a more long-lasting response to the virus in order to be a viable candidate for distribution on a global scale.

Dutch Study Finds Strong Link Between Air Pollution & More COVID-19 Deaths

A pig pokes his head out of a barn in Oosterhout, North Brabant, The Netherlands – where air pollution produced by livestock in rural areas is linked to higher rates of COVID-19 deaths.

Meanwhile, a Dutch study has yielded what some observers say may be the best study yet linking higher air pollution levels to higher rates of COVID-19 hospitalizations and deaths.

The peer-reviewed Dutch study is particularly noteworthy because it found the correlations in Dutch rural areas, which have some of the country’s highest air pollution levels – due to ammonia particulate emissions produced by livestock waste as well as farm fertilizers.

The Dutch study thus tends to strengthen the emerging evidence about a direct linkage between air pollution and COVID-19 outcomes. While a correlation between higher air pollution levels and higher COVID-19 death rates was previously identified in two previous studies by a group of researchers at Harvard’s School of Public Health, as well as researchers in Italy, critics had said that those findings might be due to other factors related to the urban environment, such as poverty or other health inequalities – and not directly linked to air pollution exposures per se.  

The Harvard study looked county-wide throughout the United States and found an 8% increase in coronavirus deaths for a single-unit rise in fine particle pollution, while controlling for factors such as obesity and smoking incidence. 

However, the Dutch study analyzed data at the municipal level for some 355 Dutch municipalities, averaging 95 km2 in size, as compared to the US county level, which is over 30 times larger.

This means that researchers could look more granularly at pollution exposures and outcomes, said lead author Matt Cole, in a blog in the journal The Conversation. The Dutch study also uses COVID-19 data up to 5 June 2020, allowing it to capture almost the full wave of the epidemic.

“The correlation we found between exposure to air pollution and COVID-19 is not simply a result of disease cases being clustered in large cities where pollution may be higher,” Cole said. “After all, COVID-19 hotspots in the Netherlands were in relatively rural regions.”

COVID-19 cases per 100,000 people and annual concentrations of PM2.5 (averaged over the period 2015-19) in the Netherlands. (Matt Cole, The Conversation)

The study found the highest air pollution concentrations included rural areas in the south-eastern provinces of North Brabant and Limburg, where intensive pig and chicken production produces large amounts of ammonia particles as a byproduct of livestock excrement, which form a significant proportion of fine particulate matter in air pollution. COVID-19 hospitalization and death rates were similarly clustered in those same regions.

The Dutch study found that an increase in fine particulate matter concentrations of 1 microgram per cubic metre was linked with an increase of up to 15 COVID-19 cases, four hospital admissions and three deaths, on average.

While media reports had suggested that some of the excess deaths seen in that region of The Netherlands may have also been due to the mass gatherings in rural areas for carnival season in February and March, the researchers controlled statistically for those gatherings as well as other factors.

“The relationship we found between pollution and COVID-19 exists even after controlling for other contributing factors, such as the carnival, age, health, income, population density and others” Cole observed.

The Dutch study, co-authored by Ceren Ozgen of the University of Birmingham and Eric Strobl of the University of Berne, is also the first study to have been accepted for publication in a peer reviewed journal – Environmental and Resource Economics.

Image Credits: NIAID/NIH, Flickr: Dutchairplaneshooter.

Healthcare workers dons protective equipment

Ibadan, Nigeria – The World Health Organisation (WHO) is advocating for equitable access to effective COVID-19 vaccines but developments surrounding the race to a vaccine suggest this may be extremely difficult. And health policy leaders in Africa and other low and middle-income countries are increasingly worried about their prospects for being pushed to the back of the line queue.   

While it used to be the pharmaceutical companies racing to be the first to have their vaccine candidates approved, the pandemic has also seen countries lobbying to get quick access to the vaccines, even before they become available, with the United States taking the most aggressive lead.

In the US, Operation Warp Speed (OWS) aims to deliver 300 million doses of a safe, effective vaccine for COVID-19 by January 2021. On 30 March 2020, the US Department of Health and Human Services (HHS) announced $456 million funding for Johnson & Johnson’s candidate vaccine, with Phase 1 clinical trials starting in summer. About two weeks later, HHS made up to $483 million in support available for Moderna’s candidate vaccine, which began Phase 1 trials on March 16 and received a fast-track designation from the FDA. Then on May 21, HHS announced up to $1.2 billion in support for AstraZeneca’s candidate vaccine, developed in conjunction with the University of Oxford. 

Under the agreement, at least 300 million doses of the vaccine will be made available for the United States, with the first doses delivered as early as October 2020 and Phase 3 clinical studies beginning this summer with approximately 30,000 volunteers in the United States.

But the US is not the only country that is striving to engage in COVID-19 vaccine nationalism which is an attempt to get as many doses of the vaccine for a country before others. Europe is also 

Late June 2020, Brazil signed a $127 million agreement for local production of AstraZeneca’s experimental vaccine that has shown promise to fight the COVID-19 pandemic. A similar agreement has also been signed by Moderna with Spain’s Rovi.  France, Germany, Italy and Netherlands are also setting up an “Inclusive Vaccine Alliance” through which they will jointly negotiate with COVID-19 vaccine developers and potential producers. For its 27-member states, the European Union is seeking a mandate to negotiate with the companies for advance contracts and reservations for doses of candidate vaccines.

African Countries’ Limited Choices
Shabir Madhi, Principal Investigator of the South African arm of Oxford University’s COVID-19 vaccine trial

With countries in Africa and other low and middle income countries unable to outbid the economic powerhouses, efforts on COVID-19 vaccine development is not on the same level as that of other parts of the world and the possibility of Africa not getting the vaccine as soon as possible is a major concern to the WHO and African leaders – although this is not new.

“Too often, African countries end up at the back of the queue for new technologies, including vaccines. These life-saving products must be available to everyone, not only those who can afford to pay,” said Dr Matshidiso Moeti, WHO Regional Director for Africa, speaking at a press event Thursday on vaccines for Africa, sponsored by the Geneva-based World Economic Forum. 

Currently, there are a total of 152 vaccines in development, and about 20 are in clinical trials. Out of those, only one is currently recruiting volunteers in Africa. 

Prof Shabir Madhi of South Africa’s Wits University is the Principal Investigator of Oxford COVID-19 Vaccine Trial in South Africa. Officially referred to as the South African Ox1Cov-19 Vaccine VIDA-Trial, it aims to involve 2000 volunteers aged 18–65 years, including individuals living with HIV. Clinical trials for the same vaccine are also ongoing in the United Kingdom and Brazil involving thousands of participants.

African Countries Should Support More Clinical Trials Despite Sensitivities

Madhi noted that one of the ways that African countries can accelerate the availability of COVID-19 vaccines for their citizens is for them to actively participate in clinical trials.

“In the past, it usually takes from 5 to 20 years for already approved vaccines to become available in Africa because of the non-existence of local data from clinical trials. We can reduce that by participating in clinical trials,” he told a press conference on Thursday.

According to Gavi, the Vaccine Alliance,  vaccine trials in Africa are a “sensitive and potentially controversial issue”, because of instances of Western researchers conducting unethical trials in African countries, and scientists undertaking medical experiments on people of African origin in the USA.

In April 2020, efforts geared towards encouraging African countries to participate in COVID-19 clinical trials stalled with the emergence of a video in which two French scientists made racist remarks in referring to Africa as the testing ground for new vaccines. Realising this could erode public trust in the science community, the video prompted a direct rebuke from Dr Tedros Adhanom Ghebreyesus, Director-General of the WHO.

Continent has a Long Record of Successful Clinical Trial Research 

Although Africa only accounts for about 2% of the world’s clinical trials, vaccine trials are not new in Africa. Prof. Pontiano Kaleebu, Director MRC/UVRI and LSHTM Uganda Research Unit told the press conference that while French scientists’ gaffe raised concerns about Africans being used as guinea pigs for clinical trials, the continent has been participating in various vaccine trials including trials for HIV and Ebola vaccines.

“There is no advantage in using Africans as guinea pigs and in my experience, we have not seen anyone going below international ethical standards,” he added.

Pontiano Kaleebu

The African Union is also striving to get more African countries involved in COVID-19 vaccine activities. It has endorsed the need for Africa to develop a framework to actively engage in the development and access to COVID-19 vaccines. 

“Success in developing and providing access to a safe vaccine requires an innovative and collaborative approach, with significant local manufacturing in Africa. We need to support the contribution of African scientists and healthcare professionals. We need to act with urgency,” said AU’s Chairperson, President Cyril Ramaphosa of South Africa.

New African CDC Consortium Aims to Develop Vaccine

The African CDC has also launched its Consortium for COVID-19 Vaccine Clinical Trial (CONCVACT) through which it seeks to mobilise academics, researchers and the private sector “to work together and use all available platforms for the development of COVID-19 vaccine”.

The consortium aims to secure more than 10 late stage vaccine clinical trials as early as possible on the continent by bringing together global vaccine developers and funders, as well as African organizations that facilitate clinical trials. 

“The goal is to ensure that sufficient data is generated on the safety and efficacy of the most promising vaccine candidates for the African population so they can be confidently rolled out in Africa once vaccines are approved,” Africa CDC stated.

Other challenges – Vaccine Production Capacity and Coverage 

While the global vaccination target is 90% coverage, Africa has averaged at 76% according to Moeti who described the bottlenecks of Africa’s immunisation efforts as a possible limitation in ensuring many Africans are able to get vaccinated against COVID-19 as soon as the vaccine becomes available. But there is another problem, that of mass production.

Advocates of equitable access to COVID-19 vaccine are asking the pharmaceutical companies with the promising vaccine candidates not to hold on to intellectual properties, but to share such to facilitate mass production of the vaccine in various parts of the world.

In Africa, Moeti noted that vaccine production capabilities are available in several African countries including Senegal (which is already producing the yellow fever vaccine), South Africa, Egypt, Tunisia, Ethiopia, Morocco and Algeria. But Madhi added there is no facility in Africa that has the capability to mass produce gene-based vaccines and such vaccines are the ones that are declared effective, Africa may have to rely on producers elsewhere for the vaccine.

Study volunteer receives inoculation at Redemption Hospital in Monrovia on the opening day in Liberia of PREVAC, a Phase 2 Ebola vaccine trial in West Africa.
China to the Rescue?

While the United States, Europe and several other regions are choosing to prioritise getting COVID-19 vaccines for their citizens ahead of the rest of the world, China has promised to supply any COVID-19 vaccine to Africa first, and at no cost.

China is leading the COVID-19 vaccine race with more vaccine candidates in the late clinical trial phase than any other country. Out of the three vaccines that are in Phase III trials, two are from China – Sinovac Biotech and China National Pharmaceutical Group (Sinopharm).

In June 2020, China’s president, Xi Jinping, told African leaders that participated in the Extraordinary China-Africa Summit On Solidarity Against COVID-19 that the continent will get China-developed COVID-19 vaccine for free. According to him, a China-developed vaccine will serve as a global public good. He added that African countries will be the first to benefit from the Chinese vaccine.

Expanding Vaccine Production Globally Could Avoid Competition
Vaccines have been tested on the continent before. But scaling up production in Africa could help avoid competition

Microsoft’s co-founder and co-chair of the Bill & Melinda Gates Foundation, Bill Gates believes that the only way to avoid countries competing for vials of the COVID-19 vaccine and leaving developing countries behind, will be to expand vaccine production capacity globally.

“There’s a plan to have multiple factories in Asia, multiple factories in the Americas, multiple factories in Europe, and if we can make over 1 to 2 billion doses a year, then the allocation problem is not super-acute,” Gates said. 

But there will be an impossible problem if the maximum annual production capacity is only 100 million doses a year.

Gates and Gavi CEO Seth Berkley put the cost of immunizing the world at tens of billions of dollars, said in an interview last month.

“The costs of some COVID-19 vaccines could end up ranging from about $4 a dose to potentially $15 a dose. While effort will involve making financial commitments to several vaccine programs, it’s worth it,” Gates said.

But with developed countries offering pharmaceutical companies huge sums of money to secure millions of doses of their COVID-19 vaccine candidates, Doctors Without Borders recently warned that there’s no guarantee that pharmaceutical companies will charge affordable prices.

“Everyone seems to agree that we can’t apply business-as-usual principles here, where the highest bidders get to protect their people from this disease first, while the rest of the world is left behind. Governments must ensure any future COVID-19 vaccines are sold at cost and universally accessible to all across the world,” said said Kate Elder, Senior Vaccines Policy Advisor for Doctors Without Borders’s Access Campaign.

Despite their limited capacity to outbid rich countries, Madhi advises African governments not to expect the vaccines to be given for free. Instead, he said they should engage the manufacturers and be actively involved in initiatives to dialogue and ensure that Africans are not totally sidelined or excluded.

Africa’s options are however limited. While the developed countries have the dual option of paying for millions of doses for their citizens or locally producing the vaccines after securing authorization and guideline from the manufacturers, Africa’s highly limited and largely unused vaccine production capacity make the continent to be largely unable to compete with the developed countries who are positioned as the first in line to procure doses for their citizens.

“Expecting African companies that have not produced vaccines in the past 25 years to now start producing COVID-19 vaccine over a 25-week period is overly optimistic. So we need to be guided regarding what to expect in terms of manufacturing on the African continent. It’s still a long path ahead to get to the few vaccines that will be available. In the meantime, the focus can’t be around vaccines, the focus remains trying to slow the rate of transmission of the virus,” Madhi said.

Image Credits: Twitter: @WHOAFRO, NIAID, Twitter: @WHOAFRO.

Photo Credit: Raul Lieberwirth

The World Health Organization announced a new program on Friday to help more than 1 billion tobacco users – a group at high risk for coronavirus complications – quit smoking during the pandemic.

The project, the Access Initiative for Quitting Tobacco, will be first rolled out in Jordan, where 82.5% of men over the age of 18 used tobacco or e-cigarettes, and 60% of young people between the ages of 13 to 15 were addicted to nicotine, according to a 2019 survey.

“COVID-19 has required us all to don masks, and yet it has also unmasked too many uncomfortable truths. One of those glaring truths is that smoking tobacco in all of its forms – electronic and non electronic – has shown no benefits whatsoever to its users,” said Princess Dina Mired of Jordan. “On the contrary it depletes one’s health one’s heart, and money, and now also puts the user in the highest risk group for not only contracting COVID-19, but also in spreading it, as well as not being able potentially to fight and survive the virus due to higher vulnerability to severe complications.”

Princess Dina Mired of Jordan

Even before COVID-19, smoking killed an estimated 8 million people a year. It’s a large risk factor for many deadly non-communicable diseases, such as heart disease, cancer, and chronic obstructive pulmonary disease (COPD). But during a pandemic of a deadly respiratory pathogen, smokers lungs are even more vulnerable.

“But if users need more motivation to kick the habit, the pandemic provides the right incentive,” added WHO Director-General Dr Tedros Adhanom Ghebreyesus.

The initiative aims to help smokers access nicotine replacement therapy, a tactic used to wean off of tobacco products, and other free resources to help quit smoking. WHO is also rolling out its first ever virtual health worker, eponymously named Florence after the world’s first nurse, to help quitters manage their smoking cessation plan.

The project will be led by WHO and the UN Interagency Task Force on Noncommunicable Diseases and brings together the tech industry, pharmaceutical and NGO partners like the Coalition for Access to NCDs Medicines & Products. Amazon Web Apps and Google, along with New Zealand and Australian companies helped develop Florence.

The pharma company Johnson & Johnson has joined to initiative to donate more than 40,000 patches of Nicorette, a line of nicotine infused products used for smoking cessation.

“We know that one simple patch of nicotine replacement therapy can change the trajectory of the health of a smoker. And this is what we are talking about here, one smoker at a time, but with a commitment to a large scale impact,” said Thibaut Mongon, Johnson & Johnson’s Worldwide Chairman for Consumer Health.

The program comes just a few weeks after the World Trade Organization ruled that Australia’s ‘plain-packaging’ laws for tobacco products did not present barriers to international trade – a major win for public health advocates against smoking.

Thibaut Mongon

Image Credits: Flickr: Raul Lieberwirth.

COVID-19 can be transmitted through tiny airborne particles floating in the air called aerosols

Just three days after almost 240 scientists criticized WHO for downplaying the risks of airborne transmission of tiny SARS-CoV-2 particles, or aerosols, the Organization edged closer to its critics point of view.   

WHO’s latest scientific brief, published Thursday, acknowledges that “short-range aerosol transmission cannot be ruled out”.

The tiny virus particles floating through the air may indeed infect some people, especially in poorly ventilated indoor settings. As a result, the donning of masks among groups of people standing one meter or less from each other would be warranted, WHO concluded. 

“WHO, together with the scientific community, has been actively discussing and evaluating whether SARS-CoV-2 may also spread through aerosols… particularly in indoor settings with poor ventilation”, says the new WHO brief. 

“Thus, a susceptible person could inhale aerosols, and could become infected if the aerosols contain the virus in sufficient quantity to cause infection within the recipient….

“Respiratory droplet transmission can occur when a person is in close contact (within 1 metre) with an infected person who has respiratory symptoms (e.g. coughing or sneezing) or who is talking or singing.”

The WHO revisions come as more and more COVID-19 disease outbreaks have been linked to overcrowded indoor spaces that lack effective ventilation such as churches and choirs, restaurants or fitness clubs. Particularly in such settings, critics have said that stronger WHO advice about the wearing of masks is needed.

“I applaud the WHO for the new brief”, said Professor of Epidemiology at Columbia University Stephen S. Morse. “It is an improvement [that suggests] WHO’s willingness to examine our assumptions, and to clarify some of the confusing definitions.  Science adapts to new information, and it’s to everyone’s benefit to re-examine assumptions.”

He also acknowledged that “WHO is in the difficult position that its advice has to be applicable all over the world, including resource limited settings, and that these recommendations often have to address both the general population, as well as healthcare infection prevention and control, where priorities may be different.”

Stephen S. Morse, Professor of Epidemiology at Columbia University

Critics Say Virus Arc of Travel is 10 Meters – Not 1

Geneva’s citizens wear masks in indoor space to prevent infection spread

But some critics immediately said that the WHO advice remained problematic — because the virus aerosols can in fact circulate much more widely, infecting people up to 10 meters away, at least in indoors spaces where it can linger for longer.

“Peer-reviewed scientific publications clearly demonstrate that particles even as large as 30 µm [micrometres] can move on air currents and travel more than 10 meters indoors”, said Donald Milton, professor of Public Health at the University of Maryland and an expert on respiratory virus transmission, in a tweeted response. “Even droplets as large as 100 µm can be inhaled and lodge in the nose.”

The WHO brief also falls far short of the much stronger recommendations that Milton and others were hoping for on the use of masks. 

“First — the good. WHO included the recommendations to “Avoid … enclosed spaces with POOR VENTILATION;” and that we should “ENSURE GOOD VENTILATION in indoor settings, including homes and offices.” I’m really happy to see this.” said Milton, in a detailed tweet chain analysis.

“But… they only recommend face masks when within one meter of other people. This is very bad advice, especially in “enclosed spaces with poor ventilation,” he added.  

“This terrible recommendation comes from the fundamental problem with the new WHO “scientific brief;” they do not use fact-based science to define “respiratory droplets” and “aerosols.” They only cite their own previous statements, not peer-reviewed scientific literature.”

“The extensive research and tremendous progress in the physics and biology of aerosols since 1940 appears to have had no impact. The contention that “respiratory droplets” in the size range of >5 to 10 µm [microns] in diameter only travel up to 1 meter is absolutely wrong,” he said. 

WHO Still Maintains Aerosols Are Secondary Mode of Transmission

Health personnel cleans surfaces aboard a Swiss train

Even with the revised guidance, WHO also continues to maintain that the virus causing COVID-19 is primarily spread through direct contact or larger respiratory droplets contained in coughs and sneezes  – rather than aerosols produced more routinely by speaking and breathing:

“To the best of our understanding, the virus is primarily spread through contact and respiratory droplets…Current evidence suggests that SARS-CoV-2 is primarily transmitted between people via respiratory droplets and contact routes,” the WHO brief states. 

Critics, on the other hand, have said that aerosols are the ‘most likely’ form of transmission of SARS-CoV-2, as was the case for the virus that caused the 2003 SARS epidemic in Asia.  

“Several retrospective studies conducted after the SARS-CoV-1 epidemic demonstrated that airborne transmission was the most likely mechanism explaining the spatial pattern of infections. “Retrospective analysis has shown the same for SARS-CoV-2”, said Lidia Morowska from Queensland University of Technology and Donald K. Milton from the University of Maryland, lead authors of the critical commentary published in the Journal of Clinical Infectious Diseases on Monday.

Other viruses that have been shown to aerosolize include respiratory syncytial virus (RSV), Middle East Respiratory Syndrome coronavirus (MERS-CoV) and influenza. As a a result, There is “every reason to expect that SARS-CoV-2 behaves similarly” to other viruses, stated Monday’s commentary. And with MERS, there’s evidence that aerosols could have been a source of infection in “at least one case”, said Morse. 

If a “significant portion” of COVID-19 transmission turns out to be through aerosols, then current physical distancing precautions of 1-2 metres are likely to be insufficient, he added.

WHO Should Adopt Precautionary Principle On Aerosols Given Current Evidence

Electron microscope image of SARS-CoV-2, the virus that causes COVID-19

WHO’s hesitancy about acknowledging a wider transmission ring of the virus stems from the lack of experience culturing it out of samples in the air, the Organization states, noting: 

“Further studies are needed to determine whether it is possible to detect viable [infectious] SARS-CoV-2 in air samples,” the WHO brief states, adding that transmission in crowded indoor spaces also “could be due” to other routes of transmission, like direct contact between individuals or respiratory droplets from coughing or sneezing.

In the face of unclear data, critics like Milton urged WHO to adopt the ‘precautionary principle’ to save more lives around the world:

“The report points out that SARS-CoV-2 RNA has been detected in air, but that the virus has not been cultured from air – but it ignores that this same argument was made about influenza virus for years – until two groups, one at CDC-NIOSH and one at the University of Maryland demonstrated that influenza virus can be cultured from the air,” he stated.

“It is understood that there is not as yet universal acceptance of airborne transmission of SARS-CoV2; but in our collective assessment there is more than enough supporting evidence so that the precautionary principle should apply.”

“Following the precautionary principle, we must address every potentially important pathway to slow the spread of COVID-19.”

Image Credits: CCO Public Domain, Stephen Morse, HP-Watch/Svet Lustig Vijay, Don Milton, Svĕt Lustig Vijay, National Institute of Allergy and Infectious Diseases, NIH.

WHO experts poised to announce details of independent evaluation of global COVID-19 response

An independent evaluation of the global response to the coronavirus pandemic, including steps taken by the World Health Organization, will be led by former Prime Minister of New Zealand Helen Clark and former President of Liberia Ellen Johnson Sirleaf.

The former world leaders will co-chair and Independent Panel for Pandemic Preparedness and Response (IPPR), the World Health Organization Director-General Dr Tedros Adhanom Ghebreyesus announced Thursday at a virtual meeting of Member States.

The establishment of the panel follows through on a resolution passed at the 73rd World Health Assembly, which called for WHO to initiate an independent and comprehensive evaluation of the international response to COVID-19.

The new IPPR will operate independently of WHO’s Independent Oversight and Advisory Committee for the WHO Health Emergencies programme, which will be continuing its own line of work.

Dr Tedros proposed that the two co-chairs select the other members of the Panel.

A Special Session of the Executive Board be called in September to discuss the Panel’s progress. The Panel will present an interim report at the resumption of the World Health Assembly in November.

In January 2021, the Executive Board will hold its regular session, where the Panel’s work will be further discussed; and in May of next year, at the World Health Assembly, the panel will present its substantive report.

While the IPPR overtakes a comprehensive overview, Dr Tedros said that the agency is already reviewing “low hanging fruit” such as universal peer review, and the binary mechanism for declaring a public health emergency of international concern (PHEIC) under the International Health Regulations.

Critics have claimed that one of WHO’s missteps was declaring a PHEIC days late at the start of the pandemic. the IHR committee had been deadlocked on whether to declare a PHEIC during the first meeting, leading WHO to declare a PHEIC a week later. Even in January, Dr Tedros had proposed moving towards a “stop-light” warning system, rather than maintaining a binary system for declaring a PHEIC.

Testing bacteria for resistance to antibiotics at the Liverpool School of Tropical Medicine

A new Antimicrobial Resistance (AMR) Action Fund will inject nearly US $1 billion into the collapsing antibiotic development pipeline, aiming to bring two to four new antibiotics to patients by 2030.

The investment, organized by the International Federation of Pharmaceutical Manufacturers & Associations and 23 different pharma companies, is the biggest single investment in antibiotic research in four years. It aims to address the rising tide of life threatening infections caused by pathogens that have evolved resistance to antibiotics.

“We must act together to rebuild the pipeline and ensure that the most promising and innovative antibiotics make it from the lab to patients,” said Director General of the IFPMA, Thomas Cueni. “The AMR Action Fund is one of the largest and most ambitious collaborative initiatives ever undertaken by the pharmaceutical industry to respond to a global public health threat.”

AMR infections kill more than 700,000 people every year, a higher death toll than COVID-19 so far, Cueni further added. And the toll of infections extends beyond physical health – AMR could push 28 million more people into poverty at a staggering cost of $ 60-100 trillion, according to the IFPMA.

But investments in antibiotic development are lacking, despite the huge need. New antibiotics are closely rationed to prevent the development of resistance against them, so it is difficult to turn a profit on antimicrobials that have just hit the market.

“Fact of the matter is right now the worst which can happen to somebody who invests in antibiotics is that they succeed, because then they will lose more money than when they just have to write off research expenditure,” said Cueni. Several small biotech firms in antibiotic research have gone bankrupt in the past few years for such reasons.

The investment provides “an urgently needed lifeline for innovators,” said Jeremy Farrar, director of the research foundation the Wellcome Trust, especially for small and medium sized enterprises.

The Fund also “really complements a lot of other initiatives at the European level”, added Nathalie Moll, Director-General of the European Federation of Pharmaceutical Industries and Associations, as she referred to 12 ongoing projects to boost AMR-related R&D in Europe.

The AMR Action Fund synergizes with existing initiatives because it seals the investment vacuum at later stages of R&D, said Denmark-based investor Novo Holdings, which supports early-stage development of AMR therapies through its US $165 million Impact Repair Fund:

“The Impact Repair Fund [of Novo Holdings] is focused on the earlier stages of development”, said Novo Holdings CEO Kasim Kutay. “We were always counting on other investors to take the products into the more complicated and more expensive later stages [of R&D], but with investors having fled the field, we were trying to do both at the same time, which is just not practical.”

COVID-19 Could Exacerbate AMR

electron micrograph of methicillin-resistant Staphylococcus aureus (MRSA, brown), a deadly bacteria resistant to many antibiotics, surrounded by cellular debris

Even before COVID-19, about half of antibiotics were inappropriately prescribed by general practitioners, which either prescribed the wrong antibiotic, or prescribed it unnecessarily, according to the OECD.

But the World Health Organization has warned that the COVID-19 pandemic may even hasten the long looming threat of antimicrobial resistance, as hospitalizations due to the disease ramp up. Healthcare professionals are increasingly likely to prescribe affected patients with antibiotics to ward off secondary bacterial or fungal “co-infections” in hospital settings, which serve as breeding grounds for antimicrobial resistance. 

In one review of 18 studies, over 1450 out of 2010 patients with COVID-19 – or 72% of patients – received antimicrobial treatment although only 10 % had bacterial or fungal co-infections, said researchers from Imperial College London and the UK’s National Health Service in early May.

Over-prescription of antibiotics may be due to some COVID-19 patients presenting with symptoms similar to severe sepsis, a systemic life-threatening bacterial infection, said Priya Nori, Medical Director of the Antimicrobial Stewardship Program (ASP) at New York’s Montefiore Medical Centre.

An increasing appetite for treatments against COVID-19 may also exacerbate AMR, warned Rita Mangione-Smith from Kaiser Permanente Washington, a healthcare and health insurance provider in Washington state. In recent months, both US and Brazil’s political leaders Donald J. Trump and Jair Bolsonaro repeatedly touted the use of an antibiotic, azithromycin, in combination with anti-malarial hydroxychloroquine despite substantial evidence to support their claims.

And as COVID-19 disrupts essential health services all over the world, antimicrobial stewardship programmes – which aim to curb unnecessary use of antimicrobials through routine monitoring – are also likely to be hit, Nori warned, further raising the risk of AMR.

“AMR is a slow tsunami that threatens a century of medical progress,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus, in a video message at the AMR Action Fund Launch. “So game changing investments into biotechnology companies around the world are required now.”

Image Credits: DFID/ Will Crowne, NIAID.

Colorized brain scan (Photo Credit: Florey Institute)

First came the dry cough. Then the shortness of breath and fever.

But what Noely, a 32 year old COVID-19 patient in Lima Peru, hadn’t expected, was her lost sense of taste, worsening anxiety, and impaired motor function.

“At first, I had symptoms of atypical pneumonia, with a lot of chest pain, and I lost my sense of taste. When the disease was really bad, I slept for five consecutive days,” she told Health Policy Watch. 

New symptoms appeared, such as an increased agitation around everyday chores like feeding her dogs or while cooking – so severe she had to escape to her bed to calm down. And Noely found that after her bout of illness, she would frequently burst into tears.

“The doctors gave me a muscle relaxant, as I was tense and agitated. Even before I was infected with COVID-19, I wanted to get tested for ADHD, but now I’m sure I’ve developed some condition I didn’t have before…I can’t function normally,” she said. “I felt overwhelmed, I cried and I prayed to get better.”

Over the past few months, a growing body of evidence has painted an insidious picture of SARS-CoV-2, the virus that causes COVID-19, as much more than a simple acute respiratory pathogen. The virus appears to be able to attack multiple organ systems – and patients can be left with long-lasting lung damage, kidney failure, and cardiovascular damage – especially those who are critically ill.

Now, it is becoming apparent that coronavirus can also hit the brain – even in those experiencing only mild respiratory symptoms. 

“Many elderly patients came in with altered mental status, but instead of being lethargic, they were aggressive or combative, and would have COVID-related encephalopathy [damage to the brain]”, according to one emergency medicine physician who worked in the Bronx, the borough with the highest rate of COVID-19 cases in the United States’ original epicentre – New York City.

A handful of COVID-19 patients presented in the emergency room with classic symptoms of stroke, such as being unable to move one side of the body, the physician, who wished to remain anonymous, told Health Policy Watch.

Young Patients Can Also Experience Severe Neurological Complications

Noely, a 32-year old COVID-19 survivor from Peru

But strikingly, younger patients such as Noely are also reporting neurological and psychiatric complications after their initial infection.

Severe neurological symptoms were reported in patients as young as 16 in a study that followed a cohort of 43 COVID-19 patients from UCL Queen Square National Hospital for Neurology, published 8 July 2020 in the journal Brain. 

And some patients with severe neurological symptoms only had mild respiratory symptoms. The study in Brain found that the severity of the neurological symptoms – which ranged from encephalopathy and psychosis to microbleeds in the brain – did not correlate with the severity of patients’ respiratory symptoms.

“”We should be vigilant and look out for these complications in people who have had Covid-19. Whether we will see an epidemic on a large scale of brain damage linked to the pandemic—perhaps similar to the encephalitis lethargica outbreak in the 1920s and 1930s after the 1918 influenza pandemic—remains to be seen,” joint senior author of the Brain study, Michael Zandi, said in a press release.

Additionally, a UK-wide surveillance study published in the Lancet found that “acute alterations in mental status were disproportionately overrepresented in younger patients in our cohort.

“These early data identify that acute alterations in mental status were disproportionately overrepresented in younger patients in our cohort…this symptom typically predominates in older groups,” the authors, from Universities of Oxford, Cambridge, Edinburgh, and Boston, among others, wrote in Lancet Psychiatry.

An Unpalatable Surprise From COVID-19

In late March and April, leading neurologists were surprised by the fact that an unusually high proportion of patients were experiencing an impaired sense of smell and taste. About 40% of patients with COVID-19 had these symptoms, according to systematic review and meta-analysis analyzing data from over 8000 patients from late May.

But the new paper published in Brain describes more serious neurological symptoms such as hallucinations, encephalitis (or dangerous swelling of the brain), and hemorrhagic changes such as microbleeds in patients who experienced varying symptoms.

Most worryingly, there were nine patients with acute disseminated encephalitis (ADEM), a rare but deadly condition where the body’s own immune system attacks myelin – the protective covering around nerves. 

The team saw an average of one case of ADEM per week during the study period. UCL Queen Square National Hospital of Neurology, where the study was done, normally sees only one case of ADEM per month, and the condition usually affects children. 

Seven of the patients also presented with Guillain-Barré Syndrome (GBS), a rare condition where the body’s own immune system attacks the nerves, causing weakness and muscle paralysis. Two of the patients have yet to recover from GBS at the time of the study’s publication.

Ischaemic stroke, a condition caused by blood clots blocking the delivery of oxygen-rich blood to the brain, causing brain cells to die within minutes, was reported in eight patients. The youngest stroke patient was 27 years old.

In late June, a study  in The Lancet identified a “large group” of patients with “altered mental status”, reflecting both neurological and psychiatric diagnoses, such as encephalitis and psychosis in the United Kingdom. 

Out of 125 patients identified with neurological and psychiatric complications across the UK, 77 (62%) had cerebrovascular events – mainly ischaemic stroke or intracerebral hemorrhage. If these complications aren’t treated in time, patients can die, or be left with permanent brain damage due to lack of oxygen to the organ.

The second most common symptom in about a third of patients (39/125) were ‘acute’ alterations in mental status – or changes in personality, behavior, cognition, or consciousness. Of those 39 patients, 16 had some form of encephalopathy and 23 had psychiatric diagnoses like new-onset psychosis, a neurocognitive ‘dementia-like’ syndrome, and an affective disorder.  

However, the Lancet study may have overrepresented critically ill patients, said the researchers, and it is still unclear how common these symptoms are in COVID-19 patients overall. 

Early Warnings Of SARS-CoV-2’s Effect On The Brain

The first warnings of COVID-19’s potential to cause neurological damage came from the original epicentre – Wuhan, China – where the virus first emerged. Over a third of coronavirus patients in a cohort of 200 had neurological symptoms such as acute cerebrovascular events, impaired consciousness, and muscle injury, according to a retrospective study published in early April. 

Later in May, clinicians from University College London (UCL) and the UK’s National Health Service (NHS) identified six COVID-19 patients suffering from acute ischaemic strokes.

“We now know that COVID-19 is not just a disease of the lungs”, said David Werring, Professor of Clinical Neurology at UCL and corresponding author of a letter published in the Biomedical Journal. “Our findings suggest that blockages of large brain arteries in COVID-19 patients are associated with highly abnormal blood clotting.”

But perhaps SARS-CoV-2’s effects on the brain were truly first hinted at by its deadly sister coronavirus – Middle East respiratory syndrome (MERS), which has a case-fatality rate of 35%. In Saudi Arabia’s MERS epidemic five years ago, scientists documented seizures, confusion and encephalopathy in patients struck by the disease.

SARS-CoV-2 Causes Inflammation & Blood Clotting
SARS-CoV-2 (red) attacking a dying cell (tan)

SARS-CoV-2 has a deadly trick up its sleeve – the ability to make the body turn on itself.

In some severe COVID-19 cases, the patient’s own immune system overreacts to the disease,  unleashing a wave of cytokines and inflammatory cells that damage the lungs and can even lead to death. 

This so-called ‘cytokine storm’ could explain how COVID-19 ravages other organs like the kidneys or the brain. Many of the rare neurological conditions seen in COVID-19 patients, such as GBS and ADEM, are caused by an overreaction of the immune system. 

Excessive inflammation could even be the trigger for blood clots that lead to ischaemic strokes, according to a letter by researchers from UCL and the NHS. 

 “The exaggerated inflammatory immune response known to occur in COVID-19 patients stimulates abnormal blood [clotting], including raised [levels of] D-dimer”, wrote UCL’s researchers.

While clinicians can look for evidence of a clot on brain scans, researchers can also measure the level of D-dimer in patient samples, a blood product that’s associated with blood clotting. All six patients that suffered from strokes in the UCL study had “markedly” high levels of D-dimer.

However, researchers warned that their data is not conclusive, as four out of six patients already had a history of hypertension, and two had atrial fibrillation – predisposing them to blood clots.

Preventing Strokes And Blood Clotting: Blood Thinners & Endovascular Treatment
Excessive blood-clotting, leading to thrombosis and stroke is one of the outcomes of serious COVID-19 cases

If used at an early stage of COVID-19 disease, blood thinners “could reduce” the number of people having strokes or blood clots elsewhere in the body, said UCL’s Werring in a statement:

“Early use of anticoagulant [blood thinners] drugs might be helpful, but this needs to be balanced against their brain bleeding risk, especially soon after an ischaemic stroke,” according to Werring. However, he added that more trials would be needed in order to find the best combination of drugs to treat people with COVID-19 related strokes. 

“Clinical studies (ideally controlled trials) are needed to find out the best treatment to reduce the disability caused by ischaemic stroke in people with COVID-19,” said Werring. 

Some researchers have also pointed to the most common and effective method for treating stroke – endovascular treatment – or the removal of a blood clot. Removing the blood clot works for “most people with acute ischaemic strokes,”  irrespective of patient characteristics or geographical location.

However, time is of the essence for this procedure. The earlier a stroke is treated,the less likely it is to cause severe, long-lasting damage, according a Nature opinion written by Johanna M. Ospel and Mayan Goyal in July. 

But lockdowns, combined with shortage of trained healthcare staff, could prevent patients from receiving treatment in a timely manner. 

“Our findings emphasise that even during the lockdown people with suspected stroke must attend hospital immediately to ensure they get the best treatment,” emphasized Werring.

Image Credits: Flickr: Florey Institute of Neuroscience & Mental Health, Varatharaj et al. 2020, NIAID, Cardiovascular and Interventional Radiological Society of Europe.

Donald Trump gives a speech in Arizona, the state with one of the fastest rising coronavirus caseloads in the US, on 23 June 2020.

BREAKING – The United States on Tuesday gave formal notice to the United Nations and the US Congress that it intends to withdraw from the World Health Organization as of  6 July 2021, following President Donald Trump’s announcement after the World Health Assembly on 18 May.

The administration first notified the United Nations, and sent letter to Congress shortly after. Although some senior legal experts have said the move would still require Congressional approval, others have said the question remains “murky”.

“Congress received notification that POTUS officially withdrew the U.S. from the @WHO in the midst of a pandemic,” said US Senator Bob Menendez in a Tweet. “To call Trump’s response to COVID chaotic & incoherent doesn’t do it justice. This won’t protect American lives or interests—it leaves Americans sick & America alone.”

The move was quickly denounced by political leaders and public health experts.

“US withdrawal from WHO is a setback for international cooperation. Global infection dynamics show that coordinated action is required. We need more international cooperation to fight pandemics, not less,” Jens Spahn, Germany’s Minister of Health, tweeted. Spahn added that European states were looking to “initiate WHO reforms.”

“The president of the United States does not represent the interests of the United States nor the world. He only represents his own personal and political interests. This appeases his base. That is all,” said Howard Forman, a professor of public health at Yale University.

Trump had previously said that he was withdrawing from WHO due to its alleged “China-centric” bias in its responses to the COVID-19 pandemic, as well as its failure to recommend stiff measures such as travel bans, in the early days of the virus’ spread.  But political analysts said that the real motive was to divert attention from the administration’s own botched coronavirus response, leading the US to claim the unenviable title as the country with the most COVID-19 cases and deaths in the world.

It’s Unclear Whether Trump Requires Congressional Approval To Withdraw From The WHO
The United States Capitol Building, seat of the US Congress (Photo: Daniel Mennerich)

If, indeed, the move turns out to require Congressional approval, as some senior legal experts contend, then the withdrawal process could be tied up for many more months in controversy, leading up to the US Presidential elections in November.

Lawrence Gostin, director of the O’Neill Center at Georgetown University School of Law, called the move “unlawful & dangerous” in a tweet from May, when Trump first expressed intentions to withdraw from the WHO.

“Let’s start w/ fact that Secretary of State Mike Pompeo sent [the withdrawal] letter to the UN without first notifying WHO or Congress. They weren’t informed until a day later. No press briefing or media scrutiny. This lack of transparency & accountability is exactly the unfounded charge the President of the US made against Dr Tedros,” Gostin tweeted in recent reaction to the official withdrawal announcement.

“Trump cannot unilaterally withdraw from WHO without Congress,” Gostin further tweeted.

“The US entered WHO under a Joint Congressional resolution. [The president] cannot withdraw without consent of Congress. US also owes all past & current WHO dues through July 2021,” Gostin added.

Gostin, along with 749 other experts in global health law, US Constitutional law, and international relations had submitted a letter to Congress detailing that under the US Constitution’s “mirror principle,” the same process used to ratify an international treaty must be used to withdraw from it. Therefore, because Congress had approved the treaty to join the WHO, it must also approve a withdrawal from the agency.

However, other legal experts say the situation is more unclear.

“Legally it’s murky if the President can withdraw. While [the executive branch] has power to sign treaties, ratification follows advice & consent of Senate. Some argue [the executive branch] thus retains power to exit treaties – Others argue it requires Congress consent,” Alexandra Phelan, global health policy expert at Georgetown Law tweeted.

“Politics likely matter more,” she added.

Impacts on the WHO Operations – Funding and Morale
WHO Director-General Dr Tedros Adhanom Ghebreyesus delivers the closing speech for the World Health Assembly

While the US move cuts off a major source of funding to the Geneva-based Organization, particularly for African emergency disease control activities where much of US funds were traditionally directed, in fact the Trump administration had already begun to close the tap earlier this year. Funding for 2020 was only expected to be about one-half of the estimated US$ 553 milllion contributed in 2019.

Fortunately for the Geneva-based headquarters, Germany last month stepped up to the bat with an unprecedented commitment of € 500 million (US$ 561 million) just last month.  However, WHO’s America’s Regional Office, which operates as an independent legal entity, under the name of the Pan American Health Organization (PAHO), remains in dire financial states – with its budget entirely separate from Geneva’s and heavily dependent on funds from Washington as well as Brazil, another big donor.

While WHO insiders say that the United States appears poised to remain part of the PAHO regional office based in Washington DC, and therefore may eventually resume that line of financial support, monies are likely to come with many strings attached. Potentially, that could translate into demands that the fiercely independent PAHO administration treads more in line with US policies on issues ranging from the treatment of rival states such as Cuba and Venezuela, to controversial US positions on access to sexual and reproductive health services.

Meanwhile, other big countries such as Brazil, today the world’s second-largest centre of the COVID-19 outbreak, are also in arrears on payments, exacerbating PAHO’s financial woes.

The situation in PAHO is so dire that a number of the organization’s senior technical advisors took the highly unusual step of publishing a letter about the crisis in The Lancet.

The letter, entitled Financial Crisis at PAHO in the Time of COVID-19: a Call for Action, said, “Due to non-payment of Member States’ contributions, PAHO stands on the brink of insolvency…Health security in the western hemisphere would be severely threatened without a functioning PAHO. Reserve funds will be exhausted by September, 2020.”

Most of the non-payments, the letter says, are attributable to the United States, which accounts for 67% of missed or late payments to PAHO. Along with Brazil, Venezuela, Mexico, Argentina, Colombia, Chile, and others also have late payments totaling US$164·6 million.

 

Image Credits: WHO / Antoine Tardy, Gage Skidmore, Daniel Mennerich.

WHO experts at a July 7 virtual press briefing

The World Health Organization said Tuesday that it would reconsider its longtime stance that airborne transmission of the SARS-CoV-2 virus occurs only rarely – after a group of over 239 scientists published a commentary on Monday in the Journal of Clinical Infectious Diseases, urging the agency to acknowledge the greater role played by tiny virus particles emitted from route breathing and speech in driving COVID-19’s spread.

Currently, WHO maintains that the main route of virus transmission is via larger droplets – expelled by people coughing and sneezing at close range into the noses, mouths, and eyes of uninfected people nearby.

While the distinction may seem esoteric to some – it is critical to disease control policy decisions. Since most large, liquid droplets fall quickly to the ground, assuming disease spread is via droplets has also precluded a strong WHO position on the usefulness of masks, or on the infection risks within indoor settings, from restaurants to offices.

“We have been engaged with this group since April, when they first wrote to us,” said WHO COVID-19 Technical Lead Maria Van Kerkhove. “We have been talking about the possibility of airborne and aerosol transmission, as one of the modes of transmission of COVID-19, as well as droplets, fomites [surface contamination], fecal-oral, mother-to-child, and animal-to-human transmission. We are producing a scientific brief summarizing where we are… [and] we will be issuing our briefing in the coming days.”

“We acknowledge that there is emerging evidence in this field… regarding the COVID-19 virus and pandemic, and therefore we believe that we have to be open to this evidence, and understand its implications regarding [the virus’] mode of transmission and precautions that need to be taken,”  added Benedetta Allegranzi, Infection Prevention and Control Lead at WHO.

Some of WHO’s recommendations already account for the possibility of airborne spread of the virus, according to WHO Chief Scientist Soumya Swaminathan, speaking at the press event. For example, WHO recommends avoiding crowded settings and ensuring proper ventilation in indoor areas.

Emerging infectious disease epidemiologist Stephen Morse explains ‘social distancing’ in a video produced by Columbia University Mailman School of Public Health

However experts interviewed by Health Policy Watch and other media have complained that WHO’s guidelines are based on out of date evidence, overly rigid and medicalized – thus failing to account for the rapidly evolving evidence about virus transmission via tiny airborne particles that can travel much further than liquid droplets, remain suspended for longer in the air, and spread further over time closed or poorly ventilated rooms.

“The infection control folks sort of helping WHO set their policies think of particles in two ways – Droplets, which are very large, or…. small droplet nuclei, which is their term for particles in air… the can travel far from the source,” said Lisa Brosseau, an industrial hygienist studying aerosol transmission at the Center for Infectious Disease Research and Policy. “What they don’t seem to recognize in that dichotomy, is that when you cough and sneeze and talk and breathe, you actually generate lots of smaller particles.”

“Personally, I think the WHO should stop arguing what looks like semantics to much of the outside world. Science adapts to new information,” Stephen Morse, emerging infectious disease epidemiologist and influenza expert at Columbia University told Health Policy Watch. “The terminology is terribly confused, and therefore unfortunately leads to a great deal of confusion.

“When someone sneezes, coughs, talks loudly, etc., it generates a range of particles. The larger ones are droplets, which are fairly heavy and generally go only a short distance before falling to the ground (hence the “6 ft” rule).  Finer particles can stay in the air longer and go further; some can stay airborne for long periods and go long distances in the wind (remember the Sahara dust that just passed our way?). Unfortunately, the varying definitions give people the wrong impression that there is some sort of dichotomy.  It’s not an ‘either/or’.

“In my opinion (nothing more), infection probably does occur by both droplets and fine particles [that can remain suspended in air], but we don’t know how important each is.  And since there’s a distribution of particle sizes, the answer may not be quite so simple, either.

“The confusion may arise, in part, from the distinction between “droplet” and “airborne” transmission made by infection control practitioners [in hospital settings]. I think the problem is that they didn’t have better words to use when they were developing the guidelines,” said Morse.

Experts Head to China in Quest for Animal Sources of the Virus

In a parallel development, WHO scientists will also be going to China this weekend in order to track down the zoonotic origins of COVID-19, Dr Tedros announced. The WHO team will be collaborating with Chinese counterparts to define a scope of work and terms of reference.

“The mission objective is to advance the understanding of animal hosts for COVID-19 and ascertain how the disease jump between animals and humans,” said Dr Tedros.

Still, hunting down the animal origins of the virus is not as simple as it sounds. The virus may circulate in some host animals in the wild, and then pass through other animals that are more likely to pass the disease onto humans. These so-called ‘intermediate hosts’ can be difficult to identify, according to WHO Executive Director of Health Emergencies, Mike Ryan.

“The narrative of this virus into the human population is extremely important, but it’s not always a straightforward process of being able to get that answer. I know that sounds obtuse, but there are many dead ends to study these things,” said Ryan. “We spent many years trying to look up the source for Ebola and the intermediate host, and we still, even in Ebola, have difficulties with identifying the intermediate hosts.”

Brazilian President Contracts COVID-19 After Months Of Scorning Measures To Slow The Pandemic

Meanwhile, as new COVID-19 cases continued to rise sharply in the Americas and India – the latest global hotspots – WHO  Director General Dr Tedros Adhanom Ghebreyesus told reporters that the world has “not yet reached the peak of the pandemic” .

His dire warning came as Brazil’s President Jair Bolsonaro tested positive for COVID-19 and more than 400,000 new COVID-19 cases were reported worldwide over the past weekend. In comparison, it took 12 weeks for the pandemic to hit the first 400,000 cases.

Cumulative (red) and Active (orange dots) COVID-19 cases around the world as of 7:35PM CET July 7 2020. Numbers change rapidly.

Bolsonaro’s infection came after months in which his government continually downplayed the seriousness of the COVID-19 pandemic, even while Brazil now has the largest number of confirmed cases in the world, second only to the United States, with India trailing in third place.

In a fairly dismissive announcement of his test results, Bolsonaro declared on Brazilian national television Tuesday that “everyone knew that it would reach a considerable part of the population sooner or later.

“On Sunday, I wasn’t feeling very well. On Monday, it got worse when I started feeling tired and some muscle pain. I also had a 38-degree [Celsius] fever. Given those symptoms, the presidential doctor said there was suspicion of COVID-19,” Bolsonaro said.
Bolsonaro’s diagnosis comes as Brazil recorded more than 1.6 million cumulative COVID-19 cases. Like parts of the US, many places in Brazil are operating “business-as-usual,” with retail shops, restaurants, bars, and churches open for public use.
“The number in Brazil has stabilized… and moved down in the past days. However, the hospital system still remains under pressure,” said Ryan.
But Brazil isn’t the only area in trouble – cases are on the rise across Latin America in hotspots like Mexico, Peru, and Chile. The case seems dire in Mexico, which has the eighth highest number of coronavirus cases in the world, but ranks 4th in the highest number of deaths.

“The whole of Latin America doesn’t look good. Cases are on the rise. Deaths are on the rise,” said Dr Tedros, adding that the only country WHO was not concerned about was Canada, where new cases have dropped to a few hundred a day. In one bright spot, the Caribbean countries also appear to be controlling the virus’ spread.

Elsewhere, India and Russia have also seen a surge in cases. India’s number of new cases reported daily is still on the rise, and the country now has over 700,000 cumulative cases. Russia has more than 690,000 cases, but new cases seem to be on the decline. Currently, the US has the most COVID-19 cases in the world with almost 3 million cumulative cases.

Image Credits: Columbia University Mailman School of Public Health, Johns Hopkins CSSE.

Healthcare workers in the Western Cape suit up to take care of COVID-19 patients.

Cape Town, South Africa  – The US government’s recent purchase of almost the entire available stock of Gilead’s remdesivir – a medicine shown to help speed up the recovery of people who are moderately sick with COVID-19 – has raised fears about whether poorer countries will also be left in the dust if a vaccine is developed.

South Africa recently appealed to the World Trade Organisation (WTO) to explore “multilateral cooperation” to find “an innovative solution” in light of such concerns.

“In anticipation that intellectual property may pose a barrier to access, several ad-hoc unilateral initiatives have emerged,” South Africa’s Dr Mustaqeem de Gama told a recent informal meeting of the WTO’s ’s Council on Trade-Related Aspects of Intellectual Property Rights (TRIPS).

“However, these initiatives, while commendable, are simply inadequate to address the intellectual property barriers,” added De Gama.

For example, pharmaceutical companies with patents could opt not to join these mostly voluntary initiatives, or issue licenses for generics of their medicines to manufacturers in only a few select countries, warned De Gama.

In the case of remdesivir, Gilead has issued voluntary licenses to manufacturers to produce the medicine for 127 countries including South Africa – but Brazil, China and Mexico are excluded. A single vial of the generic version will cost US $55 according to South African reports, while the medicine in will cost US $390 per vial in US hospitals.

Taking Concerns About Access Barriers to the WTO
WTO TRIPS Council meeting, pre-pandemic.

Sidwell Medupe, spokesperson for South Africa’s Department of Trade and Industry, said that South Africa aimed to “to encourage a discussion within the WTO TRIPS Council that will promote multilateral cooperation”, including “pooling rights to technologies that are useful for the detection, prevention, control and treatment of the COVID-19 pandemic.”

De Gama stressed that “an effective response to the COVID-19 pandemic requires rapid access to affordable medical products” – but many developing countries faced “legal, technical and institutional challenges in using TRIPS flexibilities.”

A key TRIPS flexibility allows governments to issue compulsory licenses to generic companies to make pharmaceutical products without the permission of patent holders.

But many countries’ own patent laws either don’t allow for compulsory licenses or involve “time-consuming” processes, warned De Gama.

South Africa itself has yet to amend its 1978 patent law to allow for compulsory licensing, despite adopting a national policy committing it to doing so two years ago.

And despite the TRIPS flexibilities, the issuing of compulsory licenses is not common – partly because pharmaceutical companies are often involved in intense lobbying of governments to prevent this.

Brazil and Thailand used compulsory licenses to get access to cheaper antiretroviral medication to address HIV, but South Africa did not take this route despite having the largest HIV positive population in the world.

Instead, South Africa largely imported cheaper ARVs via generic companies in countries such as India with the help of a number of global initiatives. These include  UNITAID’s Medical Patent Pool (MPP). Set up in 2010, the MPP negotiated with pharmaceutical companies to issue voluntary licenses to generic manufacturers to make ARVs for developing countries, particularly sub-Saharan countries.

Compulsory Licenses may be the ‘Most Powerful’ Access Instruments Available to Countries
WTO Headquarters in Geneva

Hu Yuan Qiong, senior legal and policy advisor for Médecins Sans Frontières’ Access Campaign, says that in the context of TRIPS, “compulsory licenses are the most powerful instrument that countries can use right now.”

Even some high-income countries, who don’t normally talk about these licenses, are starting to take notice.

“Many countries have talked about compulsory licenses since the start of the pandemic. We have seen countries like Germany, Canada and Australia changing their laws to make compulsory licenses easier and more automatic and comprehensive so they can quickly issue one to allow for importation, local production or whatever they need to get access to the technology to address COVID-19,” says Hu, who is based in Geneva.

Chile, Ecuador and Brazil are also considering making it easier to issue compulsory licenses.

Still, “we haven’t seen this with developing countries, although it isn’t easy to do a compulsory license in many of these countries, including in South Africa,” says Hu.

She adds that “compulsory licensing is still a territorial response that relies on national laws and how flexible the law is.”

In addition, manufacturing some medical products – such as ventilators – might involve more than one patent, “so more regional and ultimately global flexibility would be more ideal.

“From MSF’s perspective, a better solution would be to suspend the application of intellectual property rights on medical tools related to COVID-19 for the time being,” said Hu

Upfront, Global Agreements Required to Secure Access

Andy Gray, a senior lecturer in pharmaceutical sciences at the University of KwaZulu-Natal in South Africa, agrees with Hu that, in the case of the development of a vaccine or COVID-19 treatment, “country-by-country flexibility isn’t that helpful when what we need is an upfront agreement.”

“With a COVID-19 vaccine, for example, it is unlikely that one company will be able to meet global demand. So if a company develops a vaccine, it should commit to issuing voluntary licenses to other companies before it is even granted a patent,” says Gray. “There has also been a lot of public investment in the development of vaccines. A condition for the investment of public money in vaccine development should be that the company which has benefited commits to issuing voluntary licenses. This should be an upfront agreement as a condition for the use of public money.”

The COVID-19 Vaccine Global Access (COVAX) initiative announced recently by the global vaccine alliance, GAVI, has been criticised for failing to extract upfront access agreements from the pharmaceutical companies that are getting public funds for vaccine development.

In a letter to the GAVI board, 45 civil society organisations criticised COVAX for being based on a “business as usual” approach to intellectual property in which “pharmaceutical  companies are allowed to retain and pursue rights to  vaccines under development, resulting in vaccines that are  proprietary  and  under  the  monopoly  control  of  individual  companies.”

“Since  there  has  been  no  change  in  how  intellectual  property  is  handled  during  the  pandemic,  pharmaceutical  companies  are  able  to  monopolise  future  COVID-19 vaccines and decide who does and does not get access,” the NGOs warned.

A COVID-19 Vaccine Must be a ‘People’s Vaccine’
Shabir Madhi, Principal Investigator of the first Covid-19 vaccine trial in South Africa

South Africa is a key partner in a global lobby for a “people’s vaccine” for COVID-19, and it has united with 139 other countries and prominent leaders to advocate that “all vaccines, treatments and tests be patent-free, mass produced, distributed fairly and made available to all people, in all countries, free of charge.”

Announcing the initiative, South African president Cyril Ramaphosa and head of the African Union said, “As the countries of Africa, we are resolute that the COVID-19 vaccine must be patent-free, rapidly made and distributed, and free for all. All the science must be shared between governments. Nobody should be pushed to the back of the vaccine queue because of where they live or what they earn.”

The “people’s vaccine” initiative advocates for a “global agreement on COVID-19 vaccines, diagnostics and treatments” that “ensures mandatory worldwide sharing of all COVID-19 related knowledge, data and technologies with a pool of COVID-19 licenses freely available to all countries.” The World Health Organization would be responsible for overseeing this agreement.

MSF’s Hu says it cannot be business as usual with COVID-19.

“If we look at the COVID-19 vaccine, there are so many companies involved and so many people are joining clinical trials worldwide trying to find solutions,” she said. “But eventually, governments and global health institutes end up negotiating with the same pharmaceutical companies.

“It’s the same old business model,” she laments. “The vaccine and technologies are held by the same companies. It is a piecemeal solution where different countries have different laws. It’s going to be an endless story unless there is a global agreement.”

 

Image Credits: Government ZA, WTO, Kerry Cullinan.