Center of Excellence for Long-acting Therapeutics launched at the University of Liverpool
Center of Excellence for Long-acting Therapeutics launched at the University of Liverpool

A US$40 million research consortium has been created to repurpose existing medicines for hepatitis, tuberculosis and malaria into long-acting treatments that can benefit low- and middle-income countries (LMICs) where people often have trouble accessing medicine over and over again, Unitaid experts told Health Policy Watch.

The consortium on Tuesday launched the new Centre of Excellence for Long-acting Therapeutics (CELT) at the University of Liverpool, as a first of its kind research center in the world.

Unitaid, a global WHO-hosted partnership of private and public sector actors, is engaged in finding innovative solutions to prevent, diagnose, and treat infectious diseases more quickly, cheaply, and efficiently in LMICs, was the major funder of the cutting-edge Centre and research consortium.

Initially research will focus on developing three long-acting products as part of the Unitaid-funded LONGEVITY project – a single-injection cure for hepatitis C over a treatment period of 12-weeks, and tuberculosis and malaria preventative treatment through one-dose injectables.

“If you can replace [multiple doses] with one single shot injectable that can last for the whole malaria season, you are logistically gaining a lot. [Medicine] will be less costly to distribute, and it is more certain that people will receive treatment because they no longer need to come back [for additional treatment],” said Carmen Perez Casas, Senior Technical Manager at Unitaid, adding that the aim is to cover an individual for an entire malaria season with one injection – making medication cheaper to deliver and easier to use.  

Unitaid-funded CELT is currently working on a malaria injectable that could last a whole malaria season.
Unitaid-funded CELT is currently working on a malaria injectable that could last a whole malaria season.

“We are working to shape the market to ensure that any of the emerging long-acting technologies – whether for HIV, malaria, tuberculosis, are affordable and manufactured in sufficient volumes.” 

Long-acting technology allows the release of medication to be manipulated, with sufficient concentration of the drug to last long periods of time – for months to a year, or even longer. There are various types of long-acting technologies, including implants, oral medicines that dissolve over a period of time, and injectables.

Diverse health fields, from reproductive and mental health have already benefited and continue to benefit from long-acting technology. Patients with schizophrenia and other psychoses who have difficulty accessing therapy and treatment can use long-acting injectables to replace the daily pill. 

“One-fifth of [schizophrenia] patients will have relapses and be admitted into hospitals for emergencies. They can now be stable because of continuous intake,” said Perez Casas. 

Long-Acting Technology: Ease of Access Leads to Increased Uptake of Medicines in LMICs
Long-acting technology eases the complication of difficult and strict dose regimens for oral medication
Long-acting technology eases the complication of difficult and strict dose regimens for oral medication

Perez Casas addressed the complications that exist with traditional oral medications. These medications do not properly tackle chronic diseases or treatments that adhere to a strict dosage regimens. There is also the stigma associated with taking a pill every day, she said. 

Such complications make prevention campaigns difficult to organize in LMICs, given the multiple doses required of certain medicines and the necessary accessibility to healthcare facilities. 

Long-acting technology eases the stigma and increases the uptake and efficacy of the drug, giving it the potential to be applied to other diseases, especially those common in LMICs, by reaching more people with long-acting medications as opposed to oral daily treatments. 

For instance, HIV prevention through pre-exposure prophylaxis (PrEP) typically can only be done through an oral pill, but the efficiency of long-acting PrEP can aid in preventing HIV through increased uptake over a longer period of time. 

Though the research will be conducted primarily at laboratories at the University of Liverpool, there is continual multi-partner collaboration between scientists and global stakeholders, all working with affected communities in mind.

Long-Acting Treatments Are Particularly Suitable To Pandemic Context 

The COVID-19 pandemic has heavily impacted malaria, HIV, and tuberculosis in terms of continuity of treatment through the dependence of health systems and supplies. With CELT, Unitaid is working to urgently address affected treatment and chain of supply issues for those in LMICs impacted by COVID-19. 

Cherise Scott, Technical Manager of Strategy at Unitaid, said: “CELT aims to bring together various parties on the science and global health side. Learnings across various entities are shared, and that’s one way we can get our products to people who need them quickly.” 

Given the current vaccine hesitancy in regards to COVID-19, Unitaid is working with representatives of communities and governments for each stage of project development, as well as community advisory boards to ensure that long acting medicines will be accepted by community members, and will not impose a cost-burden compared to standard treatments.  

Co-director of CELT, Professor Andrew Owen, said: “Long-acting drug delivery promises to transform patient management, with huge potential impact for treatment and prevention of infectious diseases. Benefits for efficacy flow from overcoming issues associated with patients sometimes not taking their medication, which may also help reduce emergence of antimicrobial resistance. CELT harnesses the power of local, national and international collaboration to accelerate understanding of the medicines of the future.”  

Image Credits: Vita Student/Flickr, World Bank/Flickr, AL.Eyad/Flickr.

The Swiss Federal Government has secured 7.5 million doses of the Moderna vaccine with deliveries expected to begin next week.

Switzerland’s drug regulatory agency, Swissmedic, has authorized Moderna’s mRNA COVID-19 vaccine for use – in a move that should helop accelerate its rollout of vaccines against the pandemic,

The Swiss Federal Government has secured 7.5 million doses of the Moderna vaccine, with deliveries expected to begin next week from the Visp-based plant where most of Moderna’s international vaccine stock is being manufactured.

Switzerland’s vaccine drive has so far been slow to get off the ground, hampered by limited access to doses of the Pfizer mRNA vaccine, which was approved by Swissmedic in December,

Critics had bemoaned Switzerland’s slow pace in authorizing Moderna’s comparable product, which was approved by the United States Food and Drug Administration nearly a month ago, and by the European Union last week.

Israel was the first country outside of North America to authorize the Moderna vaccine on 5 January, with the United Kingdom and the granting approval for emergency use separately last week.

Switzerland’s Vaccine Campaign Got Off To A Slow Start – Now It May Speed Up

While Switzerland was in fact the first country in continental Europe to administer a COVID vaccine on 23 December, the motion was largely symbolic. During the Christmas and New Year’s period, only a few more vaccines were administered, with more serious efforts planned for mid-January.

Trailing far behind Israel, the UK, and the United States, Switzerland’s vaccine rollout has also lagged between that of other European Union member states which also began at the end of December, following the European Medical Agency’s approval of the Pfizer vaccine.

Deliveries of the Moderna vaccine to EU countries already began on Monday 11 January, with 160 million doses pre-purchased so far.

“Switzerland has played a critical role in Moderna’s history since our early days,” Stéphane Bancel, Chief Executive Officer of Moderna, said in a statement. “It means a lot to us that we can now provide a highly effective vaccine to help protect the citizens of Switzerland.”

Swiss bankers were among the first to invest in Moderna’s novel mRNA vaccine technology nearly a decade ago, and Bancel hails from the nearby French city of Lyon.

At a J.P. Morgan Healthcare Conference on Monday, company representatives said research so far leads them to estimate that the immunity generated by the vaccine would last for at least a year, and that it felt confident in its ability to develop a vaccine based on the new variants that have emerged in the UK and South Africa. It also confirmed it would examine the vaccine’s response to new strains.

Moderna expects to deliver between 600 million and 1 billion doses of its vaccine globally in 2021, with forecasted sales of $US 11.7 billion, based on advanced purchase agreements.

Speaking  at the JP Morgan conference, Bancel said: “The team feels very comfortable … that we are on track to deliver at least 600 million doses.”

Image Credits: KEYSTONE/Gaetan Bally.

Doctor administering a COVID-19 vaccine in North Carolina, USA.

Governments have spent at least €93 billion on COVID-19 vaccines and therapeutics globally since the beginning of the pandemic, a new study has found.

Research published on Monday by the kENUP Foundation, a European non-profit supporting research-based innovation in health industries, found that in 11 months, the public sector invested heavily in the development of vaccines, with a commitment of 95% – €86.5 billion – of the total spending, while only 5% of the funds were spent on therapeutics. 

Somewhat surprisingly, the majority of the investments made by governments for vaccines was made in Small and Medium Enterprises (SMEs) and corporations with a market value between $2 billion and $10 billion. Only 18% of public COVID-19 funds went to large pharmaceutical manufacturers. 

“Public investments have been instrumental in supporting innovation in the fight against the coronavirus,” said Holm Keller, Chairman of kENUP Foundation. This is particularly the case for SMEs, which have played a large role in driving innovation. 

The new Advance Market Commitment (AMC) mechanism – a legally binding agreement for an amount of funds to subsidize the purchase of vaccine doses prior to availability – was widely utilised by states and supported by the COVAX Facility to speed up the availability of vaccines, especially for low- and middle-income countries. 

93% of funding – €86.5 billion – was committed through AMCs and was carried out through various national, multilateral, and global efforts to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, such as through Operation Warp Speed in the US, the European Commission, and the COVAX Facility. 

The majority of the public funds directed towards vaccine developers originated from high-income countries, with 32% invested by the US, 24% by the EU, and 13% from Japan and South Korea. 

While the investment in COVID-19 vaccines has resulted in unprecedented progress, with over 40 countries vaccinating their populations using five different vaccines a year after the first recorded case of SARS-CoV2, the rollout of vaccines in low- and middle-income countries has not yet begun and the global achievement of herd immunity is still a fairly distant goal. 

The total number of COVID-19 vaccination doses administered per 100 people as of 11 January.

“To bridge the time until broad rollout of vaccines, further investment in therapeutics is especially important,” said Keller. “In parallel, a dedicated public pandemic preparedness scheme that would make vaccines and therapeutics readily available at lower development costs for any kind of pandemic pathogen is needed.”

The conclusion raised by Keller and the kENUP Foundation is supported by several experts. “So important to keep the pipeline of new potential therapeutics against COVID19 flowing,” said Connor Bamford, researcher at the Centre for Experimental Medicine at the Queen’s University Belfast. “With medicines, vaccines and public health measures, we will be able to conquer COVID and prevent the major impacts of ‘the next big one.'”

Additionally, in the context of the emergence of new SARS-CoV2 variants, high rates of infection, and limited supplies of vaccines, COVID-19 treatments could prove to be an important part of tackling the pandemic. With vaccines currently overshadowing therapeutics and drawing away investment, efforts to develop novel, better treatments are struggling.

“The SARS-CoV2 virus has taken advantage of human susceptibility and simultaneously has evolved to evade protective immunity,” said Sir Stephen Holgate, professor of immunopharmacology at the University of Southampton, in an op-ed in the Independent. “It is absolutely essential that…we prioritise research into helping sick people get better, as well as preventing them from getting ill in the first place.”

Image Credits: Flickr – Mecklenburg County, Our World in Data.

WHO has said that its investigation into the origins of the SARS-CoV-2 pandemic – although starting in Wuhan – is not about assigning blame, but rather is about improving global health.

The World Health Organization (WHO) research investigation in China to study the origin of the SARS-CoV2 virus that triggered a worldwide pandemic of COVID-19 is not intended to apportion blame, Executive Director of WHO’s Health Emergencies Programme Michael Ryan stressed in a press briefing on Monday.

The statement was made hours after WHO Executive Director Dr Tedros Adhanom Ghebreyesus confirmed that the international team of 10 would finally be traveling to China on 14 January.

The build-up to this moment has been defined by months of roadblocks, delaying the team’s formation and then it’s dispatch. Most recently, on 5 January, WHO confirmed that two members of its 10-person mission were turned away at China’s doorstep, after official visa approvals that WHO understood to be finalized were held up at the last minute.

China’s state-controlled news channels have meanwhile also been spinning claims that human infections from SARS-CoV2 may not have first originated in the China at all – reflecting the official jitters in Beijing over any research that might clearly pin the virus origins onto China’s map.

But the planned investigation is not a matter of assigning blame, Ryan asserted during Monday’s media briefing. “It is about finding the scientific answers about the very important interface between the animal kingdom and the human kingdom.”

He also stressed that species-jumps to humans from the animal kingdom – like the jump believed to have caused the current pandemic – are “not a new thing,” noting that all influenza pandemics have occurred in similar circumstances.

Dr Michael Ryan, Executive Director of WHO’s Health Emergencies Programme.

“There are a number of aspects that all of us across the world are looking at to really better understand [in] this pandemic,” he said.

“The investigations in China may lead to hypotheses, and may lead to the need to make further inquiries or investigations in other countries. We will go anywhere and everywhere to gather more information around the origins and impact of disease,” added Ryan.

Maria Van Kerkhove, WHO COVID-19 Technical Lead, also confirmed that studies into the virus origins also would take place in Wuhan, something which had previously not been confirmed.

She noted that: “The studies that are commencing in Wuhan – especially looking at those initial patients that were first identified in December – are really, really critical to help us better understand the beginning of this pandemic.”

Meanwhile, Dr Tedros said the global body was “pleased that an international team” of scientists and experts from 10 institutions and countries were travelling to China to engage in and review scientific research on the origins of the virus.

“Studies will begin in Wuhan to identify the potential source of infection of the early cases,” said Dr Tedros. “Scientific evidence will drive hypotheses, which will then be the basis for further long term studies. This is important not just for COVID-19, but for the future of global health security and to manage emerging disease threats with pandemic potential.”

Japan Reports New Variant, as WHO Urges Countries to Genome Sequence

Meanwhile, as yet another new COVID-19 variant was identified in Japan over the weekend, WHO called on all member countries to step up their monitoring of virus mutations. The Organization was also at pains to emphasize that the exponential spread of the virus in many countries was related to the relaxation of social distancing over the holiday period, moreso than than to variants.

“What is most critical is that we sequence the virus effectively, so we know how it’s changing, and how to respond,” said Dr Tedros. “While diagnostics and vaccines still seem to be effective against the current virus, we may need to tweak them in the future.” 

WHO released a comprehensive implementation guide and risk monitoring framework last week to help countries set up high impact sequencing programmes.

“We call on all countries to increase the sequencing of the virus to supplement ongoing surveillance monitoring and testing efforts, and to share that data internationally,” Dr Tedros stressed.

He warned that “the transmissibility” of the virus “appears to be increasing” through its variants, which can “drive a surge of cases and hospitalizations, which is highly problematic for health workers and hospitals already close to breaking point”.

However, Ryan stressed that there “is no evidence that variants are driving any element of severity” but “there is some evidence that variants may be increasing, or adding to transmission, and in some sense, giving them some extra transmissibility to the virus.”

“There were increases in transmission in a number of countries before these variants were circulating, and that was due to increases in the mixing of people. There’s no way around that,” added Dr Maria Van Kerkhove, the WHO’s technical lead on COVID-19. “Variants don’t help in situations where they are now circulating, and now are being identified in other countries, that’s going to make it that much harder, but we have tools in our toolbox that help us be able to break chains of transmission.”

Image Credits: Wikipedia/user: 钉钉.

On 5 January, WHO confirmed that 2 members of its 10 person mission were turned away at China’s doorstep, after official approvals that WHO understood to be finalized were held up at the last minute.

After months of delay, China has confirmed that a WHO research team investigating the origins of the SARS-CoV-2 virus will finally be allowed to enter the country on Thursday, 14 January –  a week after Beijing blocked their entry, leaving two international experts stuck in transit.

Members of the task force will now be able to enter China’s national health authority said on Monday, with Dr Tedros Adhanom Ghebreyesus, WHO Director-General, later confirming this in a tweet.

This is a landmark moment in the ongoing investigation into the origins of the current coronavirus pandemic – setting in motion a mission that was first mandated by the World Health Assembly (WHA) in May 2020.

Since then, however, there have been multiple delays in getting the investigation off of the ground; the ten team members were only named and terms of reference created in the autumn.

In December, when WHO confirmed the organization would be deploying the investigative team to China in January, Wuhan was not specifically mentioned as a place that the team would visit.

Then on 5 January, WHO confirmed that two members of its 10-person mission were turned away at China’s doorstep, after official visa approvals that WHO understood to be finalized were held up at the last minute. China claimed this was a “misunderstanding”.

China Strictly Controlling SARS-CoV-2 Research & Suggesting Alternative Origins Narrative

In the year since the pandemic began, China has strictly controlled domestic research on the sensitive topic of the virus origins, effectively closing off most channels of query or visits by foreign researchers and media. Most recently, that included blocking a BBC crew last month from visiting caves in China’s Yunnan Province, which harbour the species of horshoe bats that carry genetically-similar coronaviruses, where a number of miners also died in 2012 from a mysterious pneumonia-like illness.

China’s state-controlled news channels have meanwhile begun to construct an alternative narrative, claiming that the human infections with SARS-CoV-2 may not have first originated in China at all – even though China is the place where the most genetically comparable strains of coronaviruses have been reported to be circulating in the wild, in bat populations.

Even now, it remains unclear if the investigative team will be able to visit “ground zero” – Wuhan, where the first clusters of human infection emerged in December 2019. WHO has repeatedly insisted that any epidemiological investigation must begin with the first cluster of human cases: and those were found in Wuhan. Those first clusters included employees and shoppers at a Wuhan market where wild animals were sold for slaughter and human consumption.

However, some of the first COVID-19 cases seen in Wuhan or among visitors to the city also could not be traced back the market. This has stirred speculation that the virus could even have escaped from a local bioresearch facility that was doing research into coronaviruses. Other experts have also suggested that people from the rural parts of China where similar strains of the virus circulate the wild could have first become infected – and then carried the infection, or a mutation, to Wuhan, a city of 10 million people that is also a major trade and manufacturing center.

Along with China’s inherent resistance to any independent scrutiny of the virus origins, the US administration of outgoing President Donald Trump has also exacerbated the geopolitical tensions around the investigation, accusing WHO of bias and blaming China for the spread of SARS-CoV-2.

At a November session of the World Health Assembly, the deputy director of the US Department of Health and Human Services, Garrett Grigsby, charged that the just-published terms of reference for the investigative team were “not negotiated in a transparent way with all WHO member states”.

“Understanding the origins of COVID-19 through a transparent and inclusive investigation is what must be done” in order to meet that mandate, he said.

Image Credits: pxfuel.com.

Health care worker taking the temperature of an asymptomatic COVID-19 postive individual in an assisted living facility in Ohio.

Two new studies published this week highlight the challenges to health policy posed by COVID-19 – with seriously ill COVID-19 patients continuing to suffer with “Long COVID”  months after being released from the hospital – while completely asymptomatic cases drive more than half of overall disease transmission.  

More than three quarters of patients diagnosed with COVID-19 have at least one persistent symptom six months after falling ill, finds a new study published Saturday in The Lancet, the largest yet on the long-term effects of the virus.  Some 76% of over 1,700 patients studied reported experiencing at least one symptom half a year after their initial onset of symptoms and hospitalization.

The study found that fatigue or muscle weakness – the most common persistent symptom – was reported by 63% of patients, while a quarter experienced sleep difficulties, and 23% experienced anxiety or depression. 

Researchers from several universities and hospitals in China, including the Jin Yin-tan Hospital in Wuhan and the China-Japan Friendship Hospital in Beijing, examined 1,733 patients discharged from the Jin Yin-tan Hospital with COVID-19. The follow-up study, conducted between June and September, contains the longest follow-up period of a peer-reviewed study on the long term effects of SARS-CoV2 infection. 

“Our analysis indicates that most patients continue to live with at least some of the effects of the virus after leaving the hospital, and highlights a need for post-discharge care, particularly for those who experience severe infections,” said Bin Cao, vice-director of the National Clinical Research Center for Respiratory Diseases and co-author of the study. 

According to the study’s scale of disease severity, the risk of reporting at least one symptom was higher among those hospitalized and requiring ventilation than those hospitalized but not requiring supplemental oxygen. 

Doctor checking on a COVID-19 patient connected to a ventilator in the ICU in Louisiana.

Those higher on the disease severity scale were found to have more problems with mobility, pain and discomfort, as well as reduced lung function – characterized by decreased flow of oxygen from the lungs to the bloodstream – compared to those with a less critical COVID-19 infection. 

Diminished exercise capacity was noted among patients with more severe disease, with 29% of those high on the severity scale walking less in six minutes than the lower limit of the normal range, compared with 24% at the lower end of the scale. 

Age and gender were also risk factors for symptoms. Older age was associated with higher levels of lung diffusion impairment and fatigue or muscle weakness, while being a woman was a risk factor for persistent psychological symptoms, such as higher levels of stress, anxiety and depression. 

The results of the study are consistent with previous data gathered on long term SARS symptoms. In a study from 2007, 33% of patients reported significant reductions in mental health and 18% had lowered exercise capacity a year after their illness. A four year follow-up study found that 40% of patients still had a chronic fatigue problem, along with other psychiatric morbidities.  

Beyond influencing mental health and lung function, COVID-19 has also been linked to adverse impacts on other organs. Approximately 13% of patients with normal kidney function at the time of their hospitalization with COVID-19 had lower levels of kidney function at the follow-up. 

Additionally, six months after COVID-19 infection, the levels of neutralizing antibodies were 52% lower than at the time of infection. The authors warn of the potential implication for re-infection. 

“Our work also underscores the importance of conducting longer follow-up studies in larger populations in order to understand the full spectrum of effects that COVID-19 can have on people,” Bin Cao said. 

COVID-19 Infections Driven By Asymptomatic Carriers

Paradoxically, however, while some people suffer serious long-term impacts, it is asymptompatic individuals who are responsible for more than one-half of all SARS-CoV-2 transmission, according to another study published in the Journal of the American Medical Association on Thursday.

The study reported on the results of a model, developed by the US Centers for Disease Control (CDC), which found that 59% of transmission of SARS-CoV-2 is caused by asymptomatic carriers.

“The bottom line is controlling the COVID-19 pandemic really is going to require controlling the silent pandemic of transmission from persons without symptoms,” Jay Butler, deputy director for infectious diseases at the CDC and co-author of the study, said in an interview with the Washington Post. 

The analytical model is based on a series of assumptions about peak infectiousness, the proportion of individuals that never develop symptoms, and the infectiousness of presymptomatic or asymptomatic individuals. 

The proportion of transmission due to all individuals without symptoms at the time of transmission. For example, peak infectiousness at the same time as median symptom onset (0 days difference) with 10% of transmission from individuals who never have symptoms would mean that approximately 51% of transmission is from asymptomatic individuals.

According to authors of the study, under a range of scenarios and assumptions, the model consistently indicated that at least 50% of transmission is linked to individuals without symptoms at the time of transmission. 

The baseline scenario assumed that asymptomatic individuals are 75% as contagious as those who develop symptoms and established that 35% of asymptomatic transmission originated from presymptomatic individuals and 24% from those who never develop symptoms. 

These findings highlight the importance of wearing masks, hand hygiene, social distancing, and strategic testing in order to slow the spread of COVID-19. 

“The community mitigation tools that we have need to be utilized broadly to be able to slow the spread of SARS-CoV2 from all infected persons, at least until we have those vaccines widely available,” said Butler.

Although the model simplifies the complex phenomenon of transmission and makes several assumptions, the findings could assist in beginning to understand and control asymptomatic transmission. 

This is particularly important in the context of the global spread of two more contagious variants of SARS-CoV2. 

Image Credits: Flickr – The National Guard, Flickr – US Navy, JAMA.

A doctor preparing the Moderna COVID-19 vaccine at the Naval Hospital in Bremerton, Washington, US.

Some 42 countries around the world are now rolling out brand new COVID-19 vaccines to their populations. But 36 of those are high-income countries, 6 are middle-income countries, and none at all are low-income countries, said WHO’s Director General Dr Tedros Adhanom Ghebreyesus at a WHO press briefing on Friday. 

He and other WHO officials at the briefing called upon pharma manufacturers and countries to stop arranging bilateral deals on vaccine supplies – and channel new vaccine procurement through the WHO co-sponsored COVAX facility – In what seemed at times like an almost quixotic vision, in terms of how the real-world rollout is actually proceeding.

Dr Tedros Adhanom Ghebreyesus, WHO Director General, at the press briefing on Friday.

Although the COVAX facility has indeed secured funding and deals to provide at least 2 billion vaccine doses to countries around the world in 2021 – the fact that high and middle income countries, including South Africa and India most recently, are now organizing huge vaccine purchases outside the framework of the global procurement initiative, is a signal of the lack of leverage that the global facility wields to see that vaccines are distributed equitably. 

As more and more countries race ahead with their own deals, WHO officials clearly are concerned that COVAX could languish in the backwaters as a kind of  “poor persons” fund supplying some vaccines to the 92 countries that cannot afford to pay on their own – but in limited quantities and at higher prices to boot.    

“The governments and health systems are on standby for global vaccine rollout. We are ready, COVAX is ready, countries are ready. The time to deliver vaccines equitably is now,” Dr Tedros said. 

COVID-19 vaccine doses administered as of 8 January 2021, since 14 December 2020.

But rather than channel vaccine purchases through the global procurement system, bilateral deals are becoming the norm, he protested, saying:  “Both high and middle income countries that are part of COVAX [are] making additional bilateral deals. This potentially bumps up the price for everyone and means high risk people in the poorest and most marginalized countries don’t get the vaccine,” said Tedros. “I want to see manufacturers prioritize supply and rollout through COVAX.

“I urge countries and manufacturers to stop making bilateral deals at the expense of COVAX. No country is exceptional and should cut the queue and vaccinate all their population while some remain with no supply of the vaccine,” said Tedros, adding.  “Science has delivered, let’s not waste an opportunity to protect the lives of those most at risk and ensure all economies have a fair shot at recovery. Vaccine nationalism hurts us all and is self defeating.” 

On the flip side, he added that “vaccinating equitably would not only save lives and stabilize health systems, but also “lead to a truly global economic recovery that stimulates job creation. 

“Importantly it would also help us limit the virus opportunities to mutate,” he added, referring to evidence that the more SARS-CoV2 infections spread, then the more potential dangerous virus mutations occur, which can make the virus more dangerous, more infectious, or more elusive to vaccines.  

The WHO Director General also urged countries to turn over surplus vaccines to the facility, saying: “I urge countries that have contracted more vaccines than they will need, and are controlling the global supply to also donate and release them to COVAX immediately, which is ready today to roll them out quickly.

Appeal To Pharma – Provide WHO With Data on Safety And Efficacy To Facilitate WHO Global Vaccine Approvals
Dr Mariângela Simão, WHO Assistant-Director General for Access to Medicines and Health Products.

At the briefing, WHO officials also appealed to Pharma manufacturers to supply them with more up-to-date data on the safety and efficacy of vaccines recently approved by national regulatory authorities – or in the final stages of clinical trials, so that WHO can make informed recommendations on vaccines that countries may choose to use.  

WHO’s own “pre-qualification” and “emergency use” approval processes – can help support and  expedite approvals in countries where regulatory authorities are weak – as well as paving the way for acquisition of more vaccines by COVAX. 

“Some companies and countries have not submitted critical data, which we need to issue emergency use listings [and] which blocks the whole system of procurement and delivery,” said Tedros.

Added Dr Mariângela Simão, WHO Assistant-Director General for Access to Medicines and Health Products, WHO has received at least 13 valid proposals for vaccine approvals since October.  

However so far, WHO has only received complete data from one vaccine manufacturer, Pfizer, which it recently approved for emergency use. 

Transparent access to such trial data is necessary as many countries rely on WHO’s assessment prior to authorizing a medical product, such as a COVID-19 vaccine, for emergency use, she underlined: “It helps international procurers, like UNICEF and others, to procure the vaccines that have been assessed by the region.”

Added Bruce Aylward, senior advisor to the Director General: “We are not in a position to provide a perspective on vaccines that are in use that we’ve not seen the data on. And at this point as I say the vaccine that we have seen is the Pfizer vaccine.” 

WHO Received Data From Chinese Sinopharm Phase 3 Trial – Russia’s Sputnik Data Expected Soon

In the case of Chinese and Russian vaccines, which are already being administered in some countries, both products “are currently being assessed by WHO,” Simão confirmed.

WHO had obtained finalized data from the Chinese Sinopharm candidate’s Phase 3 trial, she said.  More data is expected by the end of this month on the results of trials of Russian Sputnik V vaccine, developed by the Gamalaya Research Institute.

That is significant since WHO review and recommendations on Chinese and Russian vaccines could help build confidence in, and speed to market, the more affordable vaccine products being produced by both countries.  Moreover, neither vaccine has been subjected to a transparent review by an independent regulatory agency. 

Call For Countries & Companies To Transparently Report On Vaccine Procurement Deals Being Concluded
Kate O’Brien, WHO’s head of Immunization, Vaccines and Biologicals, at the Friday press briefing.

In a related issue, the WHO officials said that when vaccine deals are concluded bilaterally, then  countries and companies should report on those deals – in order to facilitate tracking that would also ensure more equitable distribution of other available vaccine doses.  

Said Kate O’Brien, WHO’s head of Vaccines, Immunologics and Biologicals, “Our understanding of…what deals are being made is extremely important in order to help with this whole process of equitable allocation and equitable access to vaccines; 

“We’re calling on countries and manufacturers to be clear and transparent about where vaccine deals are being done, the doses that are being arranged for use in various countries, and their actual rollout.

“Having this information over time is really important for WHO and for the world to respond to this crisis in a way that will have its maximum impact,” she said. 

Said Aylward: “This is where we need the manufacturers working with us and we need…the donor countries and others working with us and working together. If a company does not submit the data that we need, it is slowing equitable access to vaccines around the world. If a company doesn’t sign and work the deals through us and if we don’t have the financing to do it, they’re slowing equitable access.” 

Aylward highlighted Tedros’ call to action for “access to the data on all of these products in real time as it is coming out, so that we can ensure that we can provide a perspective on these products as rapidly as possible and get them out equitably around the world.” 

COVAX Provides Flexibility
Bruce Aylward, Senior Advisor to the Director General of the WHO, at the press briefing on Friday.

Despite the lackluster role played by COVAX so far in the initial stages of vaccine rollout, the officials also tried to sound upbeat about the advantages that COVAX could still offer to countries – giving them more flexible access to a wider range of vaccines.

“The importance of having a portfolio of vaccines that serve different needs of different countries and especially serving the different needs of delivery situations. We know from the different products that we have some that require an ultra cold chain…some require refrigeration, so we have a lot of variability of the products in terms of a range of their characteristics,” said O’Brien. 

“The range of needs of countries and choices of countries is served by having this portfolio of vaccines, where there can be matching of vaccines to the delivery needs and the characteristics that countries have for the access to those vaccines,” she added.  

“One of the beauties of the COVAX facility, the way we set it up is we’ve got a very broad portfolio of products. We know we have a broad range of clients that we’re working with,” said Aylward.

“It’s one of the reasons [why] this facility is such an important part of the global solution to equitable access and rollout,” Aylward added. “We’re going to work with [countries] to get that right balance of products.”

Image Credits: Flickr – Official US Navy, WHO, Our World in Data.

The UK is the latest bloc to approve the candidate, but supplies are not expected to be delivered for a short while.

The United Kingdom has approved the mRNA vaccine developed by Moderna, securing an additional 10 million doses to its initial 7 million: but supplies aren’t expected until spring.

Despite procuring 17 million doses of the vaccine, a rollout isn’t anticipated for some time, with Moderna vaguely stating that “deliveries of the COVID-19 Vaccine … from Moderna’s dedicated non-US supply chain are expected to commence early in 2021”.

So far, around 1.5 million people in the UK – including almost a quarter of over-80s in England – have received at least one dose of either the Pfizer/BioNTech or Oxford/AstraZeneca vaccine.

The UK Government has said the current target is to vaccinate 15 million people by mid-February. It is not clear, however, if this means 15 million will have received both doses or a single dose. The country has been criticized by WHO and Pfizer for its decision to delay booster-doses.

Health Policy Watch was told this week that the Moderna vaccine appears to be able to reduce infection and therefore transmission of SARS-CoV-2, based on the limited data available. Both the Moderna and Pfizer candidates appear to share a similar efficacy of around 95%.

The UK is the latest bloc to approve the candidate. On Wednesday, the European Medicines Agency (EMA) recommended a conditional authorization which would mean countries across the European Union (EU) could begin immunizing their populations.

The Moderna vaccine was approved in the United States in December by the Food and Drug Administration (FDA), with its recommendation panel providing no opposition: a stark contrast to the 17-4 vote delivered for the European Pfizer vaccine.

Moderna’s statement can be read here, and the UK Government’s announcement is available here.

Image Credits: Moderna TX.

WHO called on European countries to step up their game to curb the highly contagious COVID-19 variants that are overtaking the region, already straining overstretched health systems.

Meanwhile some researchers were warning that the new virus variants could spell double trouble if the mutation first identified in South Africa, in particular, makes new vaccines just being rolled out less effective.  

WHO European Regional Officials said that so far there was no evidence of that in the case of the UK virus variant that has spread to over 30 countries so far. However, the South African variant, which has a number of additional mutations, is raising far more concern, according to some scientists.

In any case, the surges of infections being seen now constitute an “alarming situation” warned Hans Kluge, head of WHO’s European Regional Office, on Thursday. 

“We need to do more than we have done, to intensify the public health and social measures, … and flatten this steep vertical line.”

He also called on countries to step up “vigilance to identify any variants by first investigating unusually rapid transmission and unexpected disease presentation or severity.” 

Kluge spoke as the region continues to face “extremely” high levels of transmission, with almost a third of the European population under strict lockdowns, and more countries set to announce further restrictions in the coming week. 

Currently, about 25% of European member states are experiencing “very high incidence” and strained health systems, although lower reporting of infections during festivities may have underestimated the true extent of transmission, he added.

Infection trends are at least partially due to the new variant first seen in the UK, also known as “B.1.1.7”, which has potential to become the dominant SARS-CoV-2 lineage in the region. 

So far, B.1.1.7 has been spotted in 22 European countries, said Kluge, and while it doesn’t trigger more severe COVID-19 disease than its predecessors, it appears to be at least 50% more infectious, according to a recent modelling study by the London School of Hygiene and Tropical Medicine.

Kluge also noted that in 2020, the WHO European region saw almost 600,000 deaths as a result of the more than 26 million COVID-19 cases reported. This amounts to a five fold increase in excess deaths from all causes as compared to 2019, he said. 

WHO Says Vaccine Efficacy Should Hold Up To Variant Challenges; Others Not So Sure

Catherine Smallwood, Senior Health Emergency Officer for the European region

Despite the chaos triggered by recent variants of the coronavirus, there is “promising evidence” that the vaccines developed so far will work, said Catherine Smallwood, Senior Health Emergency Officer for the European region, also speaking in Thursday’s press briefing.

“At the moment there is no evidence for any of the variants that have emerged that there would be any decreased effectiveness of the vaccine, but studies are still ongoing,” she said.

But it appeared that the WHO comments were referring largely to the variant first identified in the UK, known as B.1.1.7,. In that case, while the virus has mutations that make it more infectious, none have significantly altered the protein structure of the coronavirus’ characteristic “spike”, which is also the target of most vaccines. 

The UK variant is currently more widespread – it has been reported in over 30 countries; in contrast variants that first were identified in South Africa have been identified in a handful of countries, including Japan, Norway and the United Kingdom, but it could be spreading further under the radar. 

Why South African Variant Could Be More Dangerous

The emerging research is far less reassuring, however, when it comes to the variant first discovered in South Africa, known as 501Y.V2 (or B.1.351).

Some of these variants contain a mutation known as E484K, which changes the protein structure of the “spike” of SARS-Cov-2 – which may make it easier for the virus to elude the body’s antibody defenses.

Earlier this week, researchers at the University of Washington found that this mutation seemed to make it more resilient to attack by the very same “neutralizing antibodies” that are critical to fighting the disease  – and may be naturally produced or stimulated by a vaccine.   

“The South African variant has a number of additional mutations including changes to some of the virus’ spike proteins, which are concerning,” said Simon Clarke, Associate Professor in Cellular Microbiology at the University of Reading in an expert review of the South African variant, published in Science Media Centre.  

“They cause more extensive alteration of the spike protein than the changes in the [British] Kent variant and may make the virus less susceptible to the immune response triggered by the vaccines.“

In a pre-print study mapping antibody responses among eleven patients, the ability of neutralizing antibodies to bind to the virus was reduced by a factor of ten among some of those people infected with the SARS-CoV-2 virus bearing the E484K mutation. 

Those same neutralizing antibodies are critical to the immune response triggered by vaccines. 

“This does not mean that the existing COVID-19 vaccines will not work at all, just that the antibodies induced by the current vaccines may not bind and neutralise the South African variant as well as it would the other circulating viruses – including the UK variant,” said Julian Tang from the University of Leicester. 

https://twitter.com/jbloom_lab/status/1346442049663340544 

Vaccines should still be effective for “quite a while”, even if they turn out to be less effective than previously assumed, emphasized Jesse Bloom, the head of the Seattle-based laboratory that published the study. He said that it could take “years” for current vaccines to become ineffective.

Welcome News From Pfizer, But More Robust Data Needed

Just on Thursday, a study by Pfizer and researchers from the University of Texas Medical Branch revealed that its mRNA vaccine effectively neutralized a virus variant with the N501Y mutation, offering some relief that Pfizer’s vaccine is resilient against an important and increasingly common mutation. The study has not been peer-reviewed yet.

“This is welcome information”, said the World Health Oranization’s director for immunization, vaccines and biologicals Kate O’Brien at a press briefing on Friday. But she said that understanding of the variants remains “dynamic” and the most “powerful information” will be “evidence from efficacy trials that are being conducted in areas where the variants are circulating.”

The N501Y mutation is among several key mutations that have given the British and South African variants a highly infectious edge. Similarly to Bloom’s study, researchers extracted blood samples from two dozen volunteers immunised with the Pfizer-BioNTech vaccine to test how well their antibodies held up against the N501Y mutation. 

While the results were welcomed as “very encouraging news”, the study authors acknowledged they had only tested the effect of one mutation in isolation – rather than the full set of mutations in either of the variants.  Yet, unlike the Bloom lab, Pfizer’s team did not investigate whether the alarming E484K mutation in the South African strain reduced antibody neutralization.

Also, the mutation that was tested was created in a laboratory, and not naturally derived, the authors said in a paper on the preprint server Bioxriv. “A limitation of this finding is that the Y501 virus [variant studied] does not include the full set of spike mutations found on the rapidly spreading strains in the UK or South Africa,” admitted the study authors. 

The preprint study covers just one of the 16 virus mutations that Pfizer has investigated so far, according to a top Pfizer scientist, interviewed by Reuters on Friday.  However that work has still not gone far enough to explore the most dangerous mutations that the variants are displaying, said Lawrence S. Young, a virologist from England’s University of Warwick. 

Other changes which might affect infectivity have not been examined

“For both [British and South African] virus variants there are other changes which might affect infectivity and these have not been examined. This is particularly a concern with the South African variant,” noted Young, referring to the E484K mutation, in an expert reaction published by the Science Media Centre.

 “These changes are very likely to influence the infectiousness of this South African variant and may also impact its ability to be blocked by antibodies,” he said. Additionally, he noted that the blood samples examined in the Pfizer study were those of volunteers who had quickly received the second dose of the vaccine – within three weeks of the first dose, as per Pfizer’s protocol. 

This, he said, “highlights the importance” of quickly receiving the second dose.

His comment came on the heels of the United Kingdom’s controversial move to delay the second dose by as much as 12 weeks – or six weeks longer than the WHO’s recommendations – in a desperate attempt to expand vaccine efforts. Some scientists have warned that delaying the second dose of the vaccine could in fact promote more mutations, lead to poorer immunity, or even exacerbate vaccine hesitancy. 

Still, Pfizer hopes to gather more comprehensive data on the full set of mutations in the British and South African variants “within weeks”.

If any of these mutations turn out to reduce vaccine efficacy, the Pfizer/BioNTech and Moderna vaccines could be “updated” in as little as six weeks, noted experts.  

However, if an updated mRNA vaccine ends up being developed, its soaring price and complex cold-chain requirements suggest that low- and middle-income countries would wait in the queue for a long time before getting their hands on it, in a similar vein to what is happening now. 

 

CAPE TOWN – As South Africa reported its highest COVID-19 cases ever this week – over 20,000 in one day – Health Minister Dr Zweli Mkhize announced that the country had procured 1.5 million doses of the AstraZeneca-Oxford vaccine and would start vaccinating health workers by the end of this month.

The South African government has bought the vaccines directly from the Serum Insitute of India, with one million doses arriving this month and the balance being delivered in February.

The minister said that an estimated 1.25 million health workers are working in both public and private health, and these would get the vaccine first. However, the AstraZeneca vaccine requires two doses so it appears that all health workers will receive one initial dose.

Three doctors died of COVID-19 this week in KwaZulu-Natal, one of the country’s nine provinces worst affected by the pandemic. The SA Medical Association (SAMA), which represents health professionals, says that there is a “dire shortage” of medical staff, oxygen and personal protective equipment (PPE) in the province.

The Western Cape province, which has the highest infection rate per 100,000 (3326), has reported that over 7200 health workers had been infected since March, over 1000 are currently infected and more than 240 have died. 

“As recently as yesterday, our teams from the National Department of Health and the South African Health Products Regulatory Authority (SAHPRA) were fine-tuning and aligning all the regulations processes to ensure that there are no unnecessary delays or regulatory impediments to activate this rollout,” Dr Mkhize told the South African Parliament’s Health Portfolio Committee.

“We are happy that the SII/ AstraZeneca vaccine has already been approved by various regulators and is being rolled out in other countries. Therefore, as part of expediting the regulatory process, SAHPRA is applying reliance on that regulatory work,” said Mkhize.

Just last week, the United Kingdom approved the AstraZeneca vaccine, which was co-developed with Oxford University – followed by Indian approval of the vaccine this week. Unlike the Pfizer and Moderna vaccines, based on cutting edge mRNA technology which requires ultra-cold storage, the AstraZeneca vaccine can be stored in a refrigerator – and while it is also to soon be deployed in Great Britain, it has also been considered one of the best vaccine candidates for large-scale rollout in countries with less cold-chain capacity.  

Announcement Comes as South Africa Battles New Virus Variant 

The announcement came as South Africa battled the highly infectious “501.V2” variant, which, according to preliminary research,  could reduce vaccine efficacy as a result of three mutations in the so-called “receptor-binding domain” of the viral spike protein – including N501Y, K417N and E484K.

Although South Africa’s rate of new infections is still far lower than those being seen in the UK, Europe or the US, rates here are the highest on the continent and they have risen sharply over the past month.  

Mkhize said that Phase 2 of the country’s vaccination rollout “will be the essential workers such as teachers, police, the military and other people who are working in settings where they are serving communities and risk exposure to the virus because of their services to the community”. 

On Sunday, the Health Department also said that South Africans over the age of 60 as well as those living with other chronic medical conditions would be targeted in Phase 2 of the rollout – and that 16 million doses would be needed for those groups. 

South Africa is also a member of the WHO co-sponsored COVAX vaccine procurement facility  – which also aims to distribute at least 2 billion doses this year to countries that have joined. COVAX vaccine doses are expected to arrive by April, but as per the distribution plan, those would only cover 10% of South Africa’s population. 

 As a middle-income country, South Africa also has to buy the COVAX vaccine – while some 92 low-income countries will be able to get donor support for their allocations.  

South Africa is also in bilateral discussions with a range of pharmaceutical companies with the aim of getting vaccines for the rest of the population – around 40 million people – but declined to name these or provide any details.

WHO Warns Against Bilateral Agreements Outside COVAX

Dr Tedros Adhanom Ghebreyesus

However, WHO Director-General Dr Tedros Adhanom Ghebreyesus appealed to member countries not to seek deals outside of COVAX when he addressed them at a briefing on the pandemic today.

“Forty two countries have started vaccinating their high-risk populations with various COVID-19 vaccines. Of the 42, 36 are high-income and six are upper middle-income countries,” said Dr Tedros.

“This is clearly a problem and this problem is getting worse because some countries are pursuing new deals outside of COVAX offering higher prices. This compromises our collective commitment to equitable access.”

He added that 190 countries and economies had committed to COVAX and the WHO expected all stakeholders to ensure vaccines are distributed “as swiftly and equitably as possible to all countries”.

“History will not judge us kindly if we fail the low- and middle-income countries in their hour of need and sharing is in the best interest of each and every country.  We can only recover faster as a global community by sharing.”

Tedros said that wealthier member states could improve vaccine access for low and middle-income countries by subscribing to the new COVAX dose-sharing principles with the goal of having the first donations by the end of January or early-February.

“I challenge each and every one of us to do everything possible to reduce cases as quickly as possible while simultaneously increasing production and rollout of vaccines,” urged Tedros.

 

 

Image Credits: WHO.