AstraZeneca’s multi-stage manufacturing and quality testing process for its COVID-19 vaccine, which was developed with Oxford researchers.

The World Health Organization (WHO)’s expert group on immunisations remains confident in the Oxford/AstraZeneca vaccine’s efficacy against severe SARS-CoV2 disease – despite the enormous worldwide concerns triggered by a small South African study that showed it had little effect in stemming mild disease from the B.1.351 variant first identified in that country.

“It is very clear that the vaccine has efficacy against severe disease, hospitalizations and deaths,” Dr Katherine O’Brien, WHO director of Immunization, told the body’s bi-weekly media briefing on Monday after WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) meeting to decide on whether to grant the vaccine an emergency use license earlier in the day. 

“There is also evidence that the likelihood of meaningful impact against severe disease is a very plausible scenario against the B.1.351 [South African identified] variant,” O’Brien added, explaining that SAGE had met earlier in the day with investigators from Oxford/ AstraZeneca trials in the UK, Brazil and South Africa.

Dr Katherine O’Brien, WHO Director of the Department of Immunization, Vaccines and Biologicals.

Stressing that the situation was dynamic, O’Brien said that evidence unfolding from the trial of people with mild disease, might seem to contradict expert opinions that the vaccine could still prevent  severe illness – but that was because “we’re painting the picture in parts and pieces and bits”.  So  far the ongoing trials have not yielded clear evidence of the AstraZeneca’s efficacy on the South African variant. 

Last Friday, WHO officials said that they would be set to make a decision on approving the AstraZeneca vaccine for widespread rollout by the Global COVAX facility sometime this week.

WHO Director General Dr Tedros Adhanom Ghebreyesus described as “concerning” the news that the AstraZeneca vaccine was “minimally effective at preventing mild to moderate disease caused by a variant first identified in South Africa”.

COVAX Suppliers Need To Be Prepared to Adjust Products To Viral Evolution

Meanwhile, Dr Seth Berkley, CEO of the vaccine alliance, GAVI, stressed that pharma manufacturers supplying vaccines to the global COVAX facility “must be prepared to adjust to COVID-19’s viral evolution, including potentially providing future booster shots and or adaptive vaccines, if found to be scientifically necessary”.

Seth Berkley, CEO of Gavi, the Vaccine Alliance

“COVAX has signed advanced purchase agreements with AstraZeneca and the Serum Institute of India, and we’ve published plans to distribute near nearly 350 million doses in the first half of the year, hopefully starting later this month, should the emergency use listing be forthcoming,” said Berkley, who added that while COVAX was currently dependent on AstraZeneca and Pfizer vaccines, other vaccines would be added to its portfolio later in the year.

Richard Hatchett, CEO of  the Coalition for Epidemic Preparedness Innovations (CEPI) stressed that a diversity of vaccine candidates “provides us with a large number of tools which we need to explore to see which works best against the variants.”

“We can also look potentially at combinations of the vaccines and of course we must accelerate the development of new strain-specific vaccines. A large number of companies have already begun to undertake that work,” said Hatchett.

Image Credits: AstraZeneca, WHO.

Civil society organizations, pharmaceutical industries, and other stakeholders support the ratification of the AMA Treaty.

On the two-year anniversary of the establishment of the African Medicines Agency (AMA) Treaty, over 40 patient and civil society organizations, health and pharmaceutical industries, and product development partnerships called upon African Union member states to ratify the Treaty. 

Rapidly ratifying the Treaty, which was created to provide a unified approach to the approval of new medicines and vaccines, is a “matter of priority” and the failure to do so undermines patients’ access to effective therapies and vaccines, according to the numerous stakeholders representing patients, researchers and industry leaders. 

The Treaty was adopted at the 32nd African Union Assembly to enhance regulatory oversight across the continent’s 54 countries. It has been signed by 19 countries but only ratified by eight out of the required 15. 

“The African Medicines Agency is important for universal health coverage [UHC] in Africa. The 148th World Health Organization’s Executive Board has resolved to ask the 74th World Health Assembly to adopt the WHO Flagship Global Patient Safety Action Plan 2021-2030,” Kawaldip Sehmi, CEO of the International Alliance of Patients Organisations (IAPO), told Health Policy Watch. 

“A cornerstone of this plan is that each Member State must have a competent institutional, legislative, policy, practice and standards framework in place for the regulation of safe and quality innovative medicines, health devices and other health products. The African Union, like the European Union and its European Medicines Agency, can ensure that all 54 African countries can place this cornerstone of their UHC together at the same time,” he added.

The AMA has a critical role to play, particularly in the midst of the COVID-19 pandemic, when a competent and efficient regulatory authority – similar to the European Medicines Agency or the US Food and Drug Administration – is needed to review, approve and monitor vaccines, therapeutics, diagnostics and health technologies. 

“If we had the AMA, it would be working very closely with the WHO and other bodies to facilitate regulatory issues on drugs to help control the COVID-19 pandemic” and to ensure their rapid and streamlined introduction to markets, said John Nkengasong, Director of the Africa Centres for Disease Control and Prevention, at press briefing in October.

As COVAX, the global initiative to procure and equitably distribute COVID-19 vaccines, prepares to start shipping 90 million doses to Africa in February, the continent is almost two months behind vaccine rollouts that began in Europe and the US in December. 

“That is precisely what the AMA’s mission will be: to help African countries fight disease outbreaks by ensuring that only high-quality drugs, vaccines, and other health-related supplies reach the market and health systems from Cape to Cairo,” said Sehmi in a press release. 

Similarly, disruptions in the approval or rollout of vaccines could be investigated and solved by a regional regulatory agency. South Africa’s decision on Sunday to halt its use of the Oxford/AstraZeneca vaccine will have serious implications for massive African vaccine rollouts planned by both the WHO co-sponsored COVAX facility as well as the African Union’s dedicated African Vaccine Acquisition Task Team (AVATT).

“The events this weekend, with South Africa suspending the AstraZeneca vaccinations and seeking new information and advice from the manufacturer and European medicines regulatory agencies, is exactly what we wanted to avoid in our call to action,” Ellos Lodzeni, Treasurer of the IAPO Governing Board and founder of the Patient and Community Welfare Foundation of Malawi, told Health Policy Watch.

“This has left vaccination programmes in the rest of Africa in a limbo. The African Medicines Agency could have been that competent pan-African medicines regulatory agency that could have resolved this matter very early. The African Union must have a competent regional medicines regulatory agency that can help us build back better faster and safer,” Lodzeni said.

Additionally, establishing the AMA could improve country participation in clinical research and scientific innovation, boost manufacturing capacities, and allow for greater collaboration and knowledge sharing.

While progress has been made over the past couple of months on increasing the ratification of the Treaty, less than half of countries that have signed it have ratified it and established it as part of their national law. Only eight countries have ratified the agreement – Rwanda, Mali, Burkina Faso, Ghana, Seychelles, Guinea, Morocco, and Namibia.

Leading southern and eastern African nations, such as South Africa, Kenya, Uganda, and Tanzania, along with Cameroon, Nigeria, and Egypt have yet to sign onto the Treaty. 

Regional Challenges and Aims of the AMA

Over a quarter of the continent’s medicines are substandard or falsified, while only 2% are produced in Africa, according to the African Union Development Agency New Partnership for Africa’s Development (AUDA-NEPAD).

Weak regulatory systems have led to the circulation of falsified or substandard products, which pose a risk to public health and undermine confidence in health systems. The current network of separate national regulatory authorities has resulted in slow processes for new medicines to be approved by each country – time that is severely lacking during a public health emergency.

“No single country has enough resources and capability to efficiently and effectively regulate the whole supply chain system alone in this globalised world,” said Karim Bendhaou, who heads Africa Affairs for Merck and is chair of the IFPMA’s Africa Engagement Committee.

The main aims of the AMA are to:

  • Strengthen and harmonize efforts of regional health organizations and member states;
  • Provide evidence-based scientific regulatory decisions and guidance;
  • Improve patients’ access to effective, safe and quality medicines; 
  • Minimize administrative hurdles; and
  • Manage the prevalence of substandard and falsified medical products. 

A strong, unified regulatory system could coordinate market surveillance for falsified and substandard medical products, centralize information collection and sharing, strengthen national efforts to improve access to safe and innovative products, and optimize healthcare systems. 

“The establishment of the African Medicines Agency is a critical next step to enable all patients in Africa to have timely access to quality medicines that are safe and effective,” said Adam Aspinall, chair of the Fight the Fakes Alliance. 

-Updated on 9 February

Image Credits: Interpol, IFPMA.

CAPE TOWN – The failure of the Oxford/ AstraZeneca SARS-COV2 vaccine to protect against the COVID-19 variant identified in South Africa has serious implications for massive African vaccine rollouts planned by both the WHO co-sponsored COVAX vaccine facility as well as the African Union’s dedicated African Vaccine Acquisition Task Team (AVATT).

The bulk of Africa’s COVAX allocations and a significant proportion of the AVATT acquisitions are for the AstraZeneca vaccine produced by the Serum Institute of India (SII).  Yet most southern African countries neighboring South Africa are almost certain to be dominated by the B.1.351 variant  (also called 501Y-V2) which was first identified in South Africa. The variant has already appeared in Malawi, eSwatini, Lesotho, Mozambique, Zambia and Zimbabwe, experts say, and it could have already spread to East Africa.

South Africa’s health minister, Dr Zweli Mkhize told a media briefing on Sunday night that the country had suspended its planned rollout of the AstraZeneca vaccine – due to the failure of a recent South African trial to show that the vaccine was effective against preventing mild to moderate disease from the B.1.351 variant. The decision came just one week after one million AstraZeneca doses had arrived in the country as a result of a bilateral deal with SII.

SA health minister Dr Zweli Mkhize
South Africa’s Health Minister, Dr Zweli Mkhize

The country now plans to vaccinate its health workers with the Pfizer vaccine, which it will get via COVAX. It is also in negotiations with Johnson & Johnson to purchase its vaccine, which has shown reduced efficacy against the 501Y-V2 variant but was 85% effective in reducing serious illness, although it is not yet approved by the country’s regulator.

Officials also are considering rolling out the AstraZeneca vaccine to 100,000 people and monitoring hospitalisations – to see if the vaccine may still be more effective in reducing serious disease.

“If we are confident that the vaccine is effective in preventing hospitalisation, then we can roll it out,” said South Africa’s co-chair of the Ministerial Advisory Committee on COVID-19, Professor Salim Abdool Karim. “Alternatively, if it’s above that threshold, then we need to look at alternatives.

“So put very simply. We don’t want to end up with a situation where we vaccinated, a million people, or too many people with a vaccine, that may not be effective in preventing hospitalisation and severe disease.”

Vaccine Study Inadvertently Tested Efficacy on Variant

At a media briefing on Monday, Professor Shabir Madhi, principal investigator on the South African arm of a Phase 2 trial on the two-dose AstraZeneca vaccine, the progress of the trial and its findings, which included 1750 largely young and healthy participants. 

Initially, the vaccine showed 75% efficacy at 14 days, but as the trial progressed – and the majority of participants who became infected by the variant – this protective plummeted until it was “not statistically significant”, said Madhi.

“Inadvertently, because of the timing of when we enrolled participants into the study, 95% of all of the individuals infected after two doses, were infected as a result of the variant, so this study was able to show the vaccine’s efficacy on the variant” said Madhi.

Of the 42 people who contracted the virus, 23 were in the placebo arm and 19 in the vaccine arm. 

“What data doesn’t tell us is whether or not this vaccine might still protect against severe COVID-19, as two thirds of those infected had mild symptoms and a third had moderate symptoms,”, said Madhi. 

It remains possible that the AstraZeneca vaccine may offer protection against severe illness, insofar as it uses the same viral vector technology as the Johnson & Johnson vaccine, which was found to be 85% effective at reducing severe illness and death in a recent Phase 3 trial.

The J&J study involved over 44,000 people, a third of whom were over the age of 60. Overall, it showed 72% efficacy against the virus in the US but only 57% efficacy rate in South Africa because of the B.1.351 variant, reported Dr Glenda Gray, head of the SA Medical Research Council who ran the South African arm of the study.

Gray said that, given J&J’s proven efficacy in protecting against severe illness and death, she would be expanding her study to health workers within the next few days while waiting for it to be approved in the country.

Meanwhile, AstraZeneca and Oxford University are already developing a booster shot based on the locally-identified variant. 

“Efforts are underway to develop a new generation of vaccines that will allow protection to be redirected to emerging variants as booster jabs, if it turns out that it is necessary to do so,” said Sarah Gilbert, Professor of Vaccinology at the University of Oxford in a press release.

“We are working with AstraZeneca to optimise the pipeline required for a strain change should one become necessary. This is the same issue that is faced by all of the vaccine developers, and we will continue to monitor the emergence of new variants that arise in readiness for a future strain change.”

Professor Barry Schoub, co-chair of the South African Ministerial Advisory Committee on COVID-19 vaccines, described the AstraZeneca results as “rather disappointing”, but said there may be a way to salvage the vaccine.

“For example, we need to look at the cell mediated immune responses; we may need to look at a combination of AZ vaccine with other vaccines which may in fact give a synergistically good response. So I just think we need to maybe suspend use of AstraZeneca, but investigate more fully [if we] can utilise it more effectively,” Schoub told the Sunday media briefing.

South Africa’s Professor Salim Abdool Karim summarised what the country knows about the variant for a recent press breiefing.

 

Meanwhile, Mkhize said that the country needed to figure out its next step in regard to the vaccine, which it paid more than twice the price that the European Union did, with the guidance of scientists.

Novavax and Moderna have also shown decreased efficacy against the 501Y-V2 variant. 

Australia’s Minister for Health, Greg Hunt, said on Monday that “there is currently no evidence to indicate a reduction in the effectiveness of either the AstraZeneca or Pfizer vaccines in preventing severe disease and death.”

Australia is on the brink of approving the AstraZeneca vaccine and has ordered 53 million doses, largely relying on the Oxford/AstraZeneca vaccine to inoculate the whole population. But the 501Y-V2 variant has already spread to at least 32 countries, including Australia. 

WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) was meeting on Monday to review AstraZeneca’s clinical trial results and propose recommendations to WHO on the provision of Emergency Use Listing to the vaccine. 

This setback for AstraZeneca is on top of the decision by several European countries last week to implement an age restriction for the vaccine due to a lack of efficacy data in people over the age of 65 and Switzerland’s rejection of AstraZeneca’s application for regulatory approval until more data is received. 

WHO Director General Dr Tedros Adhanom Ghebreyesus at the body’s biweekly press briefing. on Monday: “Yesterday, South Africa announced that it was putting a temporary hold on the rollout of the Oxford AstraZeneca vaccine. After a study showed it was minimally effective at preventing mild to moderate disease caused by a variant first identified in South Africa.

“This is clearly concerning news. However, there are some important caveats, given the limited sample size of the trial, and the younger healthier profile of the participants. It’s important to determine whether or not the vaccine remains effective in preventing more severe illness.”

 

Dr Mariângela Simão, WHO Assistant-Director of Access to Medicines and Health Products.

The World Health Organization (WHO) expects to make a decision next week on whether to issue emergency use licenses for the AstraZeneca/Oxford COVID-19 vaccine being produced by the Serum Institute of India (SII) and South Korea’s SK Bioscience on 15 February, according to Dr Mariangela Simão, the organisation’s assistant director general of Drug Access, Vaccines and Pharmaceuticals.

The WHO had only received the full dossier from SII on 15 January, and the SK Bioscience dossier last week, Simao told the biweekly WHO COVID-19 press conference on Friday.

Meanwhile, the two Chinese vaccine manufacturers, Sinopharm and Sinovac, both have COVID-19 vaccines in very advanced stages of WHO’s Emergency Use Listing process, with a decision expected in early March. 

“We have a team of inspectors in China since the second week of January. They are waiting for their quarantine to finish and then they will start inspections next week,” said Dr Simão.

Sinopharm’s full dossier has been accepted for review, while WHO is expecting additional data from Sinovac today and again at the end of February. 

Of the two vaccines, Sinopharm yielded efficacy results between 79.3% and 86% in Phase 3 multi-country trials and has been approved in China for general public use. But Sinovac, on the other hand, yielded wildly varied efficacy scores ranging from 50.3% – 91.3%.

Sinovac applied for conditional approval in China on Wednesday and said that the preliminary results showed an “efficacy rate [that] meets the standards of the WHO and the guiding principles for Clinical Evaluation on Preventive COVID-19 Vaccine (tentative) issued by the NMPA [National Medical Products Administration, China’s medicines regulatory agency].” 

Companies Can Issue Voluntary Licenses to Speed Up Manufacture, Says Tedros

However, the WHO is concerned that vaccine supply is still lagging way below demand and Director General Dr Tedros Adhanom Ghebreyesus urged companies and countries to use the options available to increase manufacturing capacity, particularly as 130 countries have not yet started vaccinations.

“Countries are ready to go. But the vaccines aren’t there,” said Dr Tedros. “We need countries to share those once they have finished vaccinating health workers and older people. But we also need a massive scale up in production.”

He praised last week’s announcement by Sanofi that it would make its manufacturing infrastructure available to support production of the Pfizer/ BioNtech vaccine. 

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

“We call on other companies to follow this example. Companies can also issue non-exclusive licences to allow other producers to manufacture their vaccine, a mechanism that has been used before to expand access to treatments for HIV and hepatitis C. The COVID-19 technology access pool or C-TAP enables the voluntary licencing of technologies in a non exclusive, and transparent way by providing a platform for developers to share knowledge, intellectual property and data,” said Tedros, stressing that this would help to build additional manufacturing capacity in Africa, Asia and Latin America.

Meanwhile, WHO Chief Scientist Dr Soumya Swaminathan said that one of the top research priorities was whether different vaccines could be combined – for example, the Pfizer and Moderna vaccines that are both mRNA two-dose vaccines, or  “even more interesting would be to combine two different platforms so inactivated vaccine followed by an mRNA spike protein”.

“Information about vaccines both from the rollouts that are happening now in countries and observational studies, but also more randomised clinical trials are going to be needed to look at questions like the duration, and the gap between doses, as well as the combining different vaccines,” said Swaminathan, indicating that the Coalition for Epidemic Preparedness (CEPI) had already issued a call for applications from researchers to examine these questions.

Dr Soumya Swaminathan, WHO Chief Scientist.

The WHO officials welcomed the fact that the new infections were reducing in many parts of the world, but Dr Maria Van Kerkhove, COVID-19 technical lead, said this could not be ascribed to vaccine rollouts alone.

The decline was “due to a combination of factors, most notably the public health and social measures” such as active case finding, using rapid antigen-based tests, isolation of cases, and good clinical care.

“What is really critical is that countries that are reducing transmission continue to take all measures they can to drive down transmission,” stressed Van Kerkhove. “Individuals have a role to play in this, with physical distancing that must continue, the wearing of masks, making sure that you open windows, you avoid crowded spaces. All of these actions are driving down transmission.”

In regard to the push for the anti-parasitic drug ivermectin to be repurposed for treating COVID-19, Van Kerkhove said that the WHO “haven’t made a recommendation on the use of ivermectin, but we’re closely following the research that is ongoing related to this drug, which has shown some promising results in some trials for the treatment of COVID-19.”

However, Swainathan said that ivermectin had not been prioritised for inclusion in the solidarity trial, which fastracks potential treatments and warned that small studies were open to misinterpretation. 

China Joins COVAX, Commits To Supply Vaccines to LMIC Countries

In another move to “make vaccines a global public good,” China has officially joined the COVAX Facility, a WHO co-led mechanism to ensure the equitable distribution of COVID-19 vaccines, and has committed 10 million doses of vaccines to low- and middle-income countries, China’s Foreign Ministry Spokesperson, Wang Wenbin, announced on Wednesday. 

“We attach great importance to Director-General Tedros’ call to vaccinate priority populations in all nations within the first 100 days of this year,” said Wang Wenbin. “We also attach great importance to the difficulties facing the practical implementation of COVAX, in particular the huge vaccine supply gap in February and March.”

It has not yet been revealed exactly which Chinese-developed vaccines are committed to COVAX and the prices of the vaccines are currently unclear, but China pledges to “offer its vaccines at fair and reasonable prices,” said the Foreign Ministry Spokesperson. 

Over 24 countries have signed vaccine deals with Sinopharm and Sinovac so far, most of them low- and middle-income countries. Most recently, China decided to donate 100,000 doses of a Chinese-developed vaccine to the Republic of the Congo and to forgive US$13 million in public debt.

Sinopharm and Sinovac vaccines have already been exported to countries that have authorized the vaccines for emergency use, including the United Arab Emirates, Indonesia, Turkey, and Brazil. 

China is currently providing vaccine aid to 13 developing countries, including Pakistan, Palestine, Sierra Leone, Zimbabwe, Myanmar, and Brunei, according to Wang Wenbin. And the country plans to assist another 38 developing countries with vaccines.

China is also encouraging domestic vaccine companies to conduct joint vaccine R&D and production with foreign partners, an effort which is encouraged by WHO.

Decision on Olympics Will Be Made With Correct Data

Responding to Japan’s declaration that the Olympic Games would go ahead later this year, Dr Michael Ryan, executive director of Health Emergencies, said that  “there is a collective desire around the world to move ahead with the Olympics” as it is  “a massive, important symbol of unity and solidarity around the world”. 

Dr Mike Ryan, WHO Executive Director of Health Emergencies Programme.

“What I do know is that the government of Japan, the organising city of Tokyo, and the International Olympic Committee have been working diligently together,” said Ryan. “And I’m absolutely sure that they’re taking every ounce of data into consideration as they move towards the Olympics. We work with them. We input to their taskforce on risk management. We will continue to do so. 

“The desire to have the games is a laudable desire, and the will to move forward is laudable as well. But I am sure, the government of Japan will take all of their data into account as they move towards the games and they will make the correct decision on behalf of the people of Japan, the athletes and potential spectators.”

Image Credits: Sinopharm, WHO.

Vials of the Oxford/AstraZeneca COVID-19 vaccine.

The COVID-19 vaccine developed by AstraZeneca and Oxford University offers similar levels of protection against the new, more contagious variant first discovered in the UK when compared to previous variants, Oxford researchers said in a paper released on Friday. 

The new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 infection in the UK from November 2020 with its high transmissibility when compared to previous strains of the virus. The variant has since been reported in more than 70 other countries.  

Preliminary findings from the paper show that vaccine efficacy against infection from B.1.1.7 was 74.6%, and its efficacy against other strains was 84%, though small sample sizes created a broad range of estimates. 

Andrew Pollard, Chief Investigator on the Oxford vaccine trial, said in a statement released on Friday, “The vaccine not only protects against the original pandemic virus, but also protects against the novel variant B.1.1.7, which caused the surge in disease from the end of 2020 across the UK.”

From 1 October 2020 to 14 January 2021, Oxford researchers used swabs taken from volunteers with both symptomatic and asymptomatic infection enrolled in their phase II/III vaccine efficacy study to determine which strain of the virus they had been infected with after receiving either the vaccine or the control. 

These are the first findings regarding the efficacy of the AstraZeneca/Oxford vaccine against new variants, adding to preliminary data from the vaccines of Pfizer and Moderna that also suggest good protection against the B.1.1.7 variant. 

These findings come after Switzerland rejected AstraZeneca’s application for regulatory approval, the first European country to do so. Other European countries also have declared the data on the AstraZeneca vaccine insufficient to permit its use in people over the age of 65. 

However, in a statement released on Wednesday, AstraZeneca had published a primary analysis of its Phase III clinical trials, stating that its vaccine was safe and effective at preventing COVID-19, with no severe cases and no hospitalizations, more than 22 days after the first dose. 

Despite some hesitation over the vaccine, Sarah Gilbert, Chief Investigator on the Oxford vaccine trial, maintains the importance of modifying existing vaccines quickly to protect against the new variants. GlaxoSmithKline and CureVac have also announced an agreement to jointly develop a COVID-19 mRNA vaccine that targets new variants. 

Said Gilbert: “Coronaviruses are less prone to mutation than influenza viruses, but we have always expected that as the pandemic continues, new variants will begin to become dominant amongst the viruses that are circulating and that eventually a new version of the vaccine, with an updated spike protein, would be required to maintain vaccine efficacy at the highest level possible.”

“We are working with AstraZeneca to optimise the pipeline required for a strain change should one become necessary. This is the same issue that is faced by all of the vaccine developers, and we will continue to monitor the emergence of new variants that arise in readiness for a future strain change.”

Image Credits: University of Oxford, AstraZeneca.

The WHO team arriving at the Wuhan Institute of Virology on Wednesday.

The World Health Organization’s (WHO) investigative team in Wuhan, China, visited the biosafety laboratory that has been at the centre of numerous conspiracy theories about the COVID-19 pandemic on Wednesday, making it the most controversial site for the team’s fieldwork so far. 

The team of 13 experts spent three-and-a-half hours at the Wuhan Institute of Virology (WIV), one of China’s top virus research labs and the only one in mainland China with a Biosafety Level 4, the highest level of biocontainment. 

Visiting the lab that has an archive of genetic data on coronaviruses and bats, which are presumed reservoirs of coronaviruses, is an important part of the investigation into the origins of SARS-CoV2, the virus behind the COVID-19 pandemic. 

“Very interesting. Many questions,” said Thea Fischer, a Danish team member, as the group was leaving the site, responding to a question about whether the team had found anything. 

“Extremely important meeting today with staff at WIV, including Dr Shi Zhengli. Frank, open discussion. Key questions asked & answered,” said Peter Daszak, the British team member, zoologist, and president of EcoHealth Alliance, on Twitter. 

Dr Shi Zhengli is the director of the Center for Emerging Infectious Diseases at the Institute, and a well known virologist who specialises in bat-borne coronaviruses. The lab’s investigation into zoonotic viruses prompted speculations that deadly pathogens either escaped from, or were created in, the lab. 

Former US President Donald Trump was among those pushing these unfounded theories, claiming that he had seen evidence that gave him a “high degree of confidence that the Wuhan Institute of Virology was the origin of this virus”.

“We’ve said from the beginning that this was a virus that originated in Wuhan, China,” said former US Secretary of State Mike Pompeo in an interview with ABC News in early May. “China has a history of infecting the world and they have a history of running sub-standard laboratories… I can tell you that there is a significant amount of evidence that this came from that laboratory in Wuhan.”

Several leading infectious disease experts, including WHO officials and Shi – who found that none of the viruses sampled in the lab matched the viral genome sequences of the SARS-CoV2 samples – refuted these conspiracy theories. 

Experts from the US, United Kingdom and Australia concluded that “SARS-CoV2 is not a laboratory construct or a purposefully manipulated virus” in a study published in the Nature Medicine journal in March 2020. 

Dr Peter Daszak, member of WHO’s investigative team in Wuhan and zoologist.

“I know that lab really well,” said Daszak, speaking from his experience working with Shi to investigate the origins of the SARS 2003 outbreak. “It is a good virology lab that was doing good work that got close to finding what the next SARS-related coronavirus would be. But it didn’t find it as far as I know. But you know, unfortunately, it maybe got so close that people now ironically start to blame it.”

In response to suspicions that WIV was the source of the virus, the Chinese Foreign Ministry spokesperson, Wang Wenbin, stressed that “the pandemic shall not be exploited to stigmatize others… We hope that like China, all parties will adopt a positive and science-based attitude towards close cooperation with WHO.” 

Despite China’s claims of avoiding the politicization of origin research, Chinese officials have continued to suggest that the virus originated elsewhere. 

“More and more clues, reports and studies have indicated that the infections broke out in multiple places in the world in the latter half of the year 2019,” said Wang Wenbin at a press briefing on Tuesday. 

Wang Wenbin, Chinese Foreign Ministry spokesperson, at a press briefing on Tuesday.

“According to a US CDC report, COVID-19 antibodies were detected in blood donations collected in December 2019, which means that the virus may have already been spreading in the United States by then, earlier than January 21 when the first official confirmed COVID-19 case was reported in the country.”

The WHO team has not ruled out any possibilities and is reportedly looking into “all the key aspects of the Wuhan Institute of Virology,” as well as the possibility that the virus could have been circulating before it was identified in Wuhan. 

“If there are data that point towards any hypothesis, we’ll follow the data, we’ll follow the evidence where it leads us,” said Daszak in an interview on Tuesday with Sky News. “Everything’s on the table and we’re keeping an open mind.”

The WHO Mission is Collecting a “Wealth of Data”

With the world watching and governments politicizing WHO’s origin mission, the team has reported that it is getting valuable data from its consultations with its Chinese counterparts and from its week of fieldwork in Wuhan. 

“[Chinese scientists] are sharing data with us that we have not seen before, that no one has seen before. They are talking with us openly about every possible pathway,” Daszak told Sky News. “We are really getting somewhere.” 

The site visits, particularly to the Huanan market, are “beginning to help us look at the right directions for this virus,” according to Daszak.  

The market, where a cluster of COVID-19 cases were first detected in late 2019, has been heavily disinfected and shut down for nearly a year. Despite the time that has passed, team members expressed the value of visiting the site that has long been considered the potential origin of the outbreak. 

Wuhan’s Huanan seafood market that has been closed since early 2020. The WHO team visited the market on Sunday.

“Even if the place had been to some extent disinfected, all the shops are there – and the equipment is there. It gives you a good idea of the state of the market in terms of maintenance, infrastructure, hygiene and flows of goods and people,” Peter Ben Embarek, leader of the WHO team and a food safety specialist, told CNN. 

“It’s clear that something happened in that market. But it could also be that other places had the same role, and that one was just picked because some doctors were clever enough to link a few sporadic cases together,” he added. 

Team Needs to Explore Bat Caves To Trace Virus Origins

The next crucial step in the investigation is finding the “true wildlife origin” of SARS-CoV2, which will consist of tracing the genetic sequences of the virus in bat caves. Coronaviruses, including the 2003 outbreak of the SARS virus, have previously been linked to bats in caves in the southwest province of Yunnan. 

“The real work we are doing here is to trace back from the first cases back to an animal reservoir, and that’s a much more convoluted path, and may have happened over a number of months or even years,” Daszak told Reuters. 

Once the sources of the virus can be found, contact with the animal can be reduced. 

The team members are starting to see a “picture coming through of some of the scenarios looking more plausible than before,” said Daszak, although they continue to caution that the investigation will likely take a considerable amount of time.

The mission will result in a report, produced by the international team members and the Chinese team members, that will be based on the activities of the investigation, an analysis of the data gathered, and the findings of the early studies conducted.

“[The report] needs to be done by the scientists who are in the field…There are a number of studies that will be done and we will have some results but that’s just the start,” said Maria Van Kerkhove, WHO COVID-19 Technical Lead, at a WHO press briefing on Friday. “The report itself will not provide all of the answers, it was never intended to because that’s just not possible, but it will provide a summary.”

Even if the origin is eventually discovered after several studies and missions, COVID-19 has become endemic and “will be with us forever,” warned Daszak. 

“But we’ll come to terms with it. We’ll have a vaccine that works and [if] we get an escape variant, we’ll modify the vaccine,” he added. 

Image Credits: CNN, Ministry of Foreign Affairs of the People's Republic of China, Deutsche Welle.

The US decision to join COVAX “is likely to mean resources” to be able to get vaccines for people, Dr Tony Fauci, US President Joe Biden’s Chief Medical Advisor, told the International AIDS Society’s COVID-19 conference this week.

Fauci also told the conference that scientists were taking the SARS-COV2 variant identified in South Africa so seriously “that we’re actually going to make a version of that in an mRNA and do Phase One and Two clinical trial”. 

Anthony Fauci, The Director of the National Institute of Allergy and Infectious Diseases

He added that if vaccines already approved by the US Food and Drug Administration (FDA) needed to be modified to address the new variant, he hoped that the FDA would consider this as “a strain change” so that the vaccine did not have to go through a new approval process.

But Fauci expressed concern that, while modifying vaccines to address variants “immediately attacks the problem at hand.. the downside is that you don’t want to be chasing mutations over the next couple of months and making an upgrade, upgrade. 

“So the long game of what we want to do is to get a universal coronavirus [vaccine] that is specific for SARS-COV2 so that we don’t have to keep chasing every time there’s a relevant mutation.”

He said that it was “very scary” to see situations where some people who seemed to be adhering very closely to non-pharmacological interventions – like wearing masks and physically distancing – were still getting infections. 

“We have a lot of discussion in our country right now about the proper use of masks.”

An executive order signed by President Biden on 21 January, made it mandatory for everyone on public transport to wear a mask.

A Most Extraordinary, Cunning Enemy

Fauci also described the SARS-COV2 as “a most extraordinary, cunning enemy that has so many characteristics that have foiled us along the way”.

“It has the spectacular capability of spreading from person to person, and more than half of the people who get infected get infected from someone who has no symptoms, while about 40% of the people who are infected have no symptoms. 

“It then seeks out vulnerables, the elderly, and those with underlying conditions. It seeks out people who are in so many respects throughout their lives in compromised positions in the United States.

“So we’re in an unprecedented challenge. But there is light at the end of the tunnel if we can implement a global programme to get the world vaccinated, not just the rich countries, but the entire world.”

Seth Berkley, CEO of Gavi, the Vaccine Alliance

Earlier on Tuesday, Dr Seth Berkley, CEO of the vaccine alliance GAVI, said that while he agreed with activists on the urgent need to get everyone vaccinated, he was not sure that the tactic trying to get intellectual property rights waived on COVID-19 related products at the World Trade Organisation would work for vaccines.

“For drugs and diagnostics, getting rid of the TRIPS arrangements and having patents freely available may be the solution. But the critical issue for vaccines is know how.”

“AstraZeneca had enabled the Serum Institute of India to make its vaccine via a tech transfer and actually we want to pay for those tech transfers to other companies.”

Waiving intellectual property rights may prevent cooperation, whereas with tech transfers meant that,  “as problems in manufacturing have occurred, these have been discussed on a daily basis across the different manufacturers moving forward”.

“And that’s allowed this scale up, which has occurred in absolutely record time.”

Image Credits: R Santos/HP Watch.

Police seize bags of ivermectin illegally smuggled into South Africa

CAPE TOWN – The South African police have arrested six people in the past two weeks for trying to smuggle large quantities of the anti-parasitic medicine, ivermectin, into the country from India as demand for the drug as a treatment for COVID-19 surges internationally.

Ivermectin is only registered to treat parasitic infections in animals in the country, although it is used throughout Africa to treat people with river blindness and scabies. However, under pressure from doctors and patients, the South African Health Products Regulatory Authority (SAHPRA) announced late last week that it would allow doctors to apply to use it for COVID-19 patients on “compassionate grounds” via a complicated process. 

On Tuesday, following a court challenge by an organisation, Afriforum, a doctor and two patients, SAHPRA also agreed to allow doctors to use the medicine without waiting to be given permission. 

So far, over 500 doctors and health professionals have petitioned SAHPRA and President Cyril Ramaphosa to fast-track clinical trials and consideration of Ivermectin’s use on humans.

There is already widespread use of ivermectin as a COVID-19 treatment – not only in South Africa, but throughout Latin America. Both Peru and Bolivia have already granted doctors permission to use it as a COVID-19 treatment.

But the head of the South African health minister’s advisory committee on COVID-19, Professor Salim Abdool Karim, said in a weekend media interview that  there was “no compelling case” to use ivermectin to treat COVID-19, available studies were “of really poor quality” and that “the amount of drug needed to kill the virus is toxic to humans”.

Last month, the US National Institutes for Health (NIH) held a special meeting to review data on the role of ivermectin in the prevention and treatment of COVID-19, and is considering the available data. 

Dr Andrew Hill from the University of Liverpool, who has been researching ivermectin for UNITAID and the World Health Organization (WHO), and representatives from the Front Line COVID-19 Critical Care Alliance (FLCCC) presented the NIH with data from 18 randomized controlled trials involving over 2,100 patients, ranging from a 400-person, 5-day Egyptian study to 24-person one day study in Spain.

Small Studies Show Faster Viral Clearance, But Still Insufficient Evidence

Combined, these “demonstrated that ivermectin produces faster viral clearance, faster time to hospital discharge, faster time to clinical recovery, and a 75% reduction in mortality rates”, according to a press release from the FLCCC.

But Hill was cautious: “Many studies included were not peer-reviewed and meta-analyses are prone to confounding issues. Ivermectin should be validated in larger, appropriately controlled randomised trials before the results are sufficient for review by regulatory authorities.”

After the meeting, the NIH released a statement saying that there was “insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19”. 

“Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19,” said the NIH.

Piero Olliaro, Professor of Infectious Diseases of Poverty at Oxford University’s Centre for Tropical Medicine and Global Health, said: “There is experimental evidence from in-vitro studies that ivermectin has antiviral action against the SARS-CoV-2, but this requires giving humans doses which are much higher than those normally used for the current indications for ivermectin. So, the question is: will it be safe?”.

“A dose-escalating study of healthy adults given increasingly higher doses of ivermectin assessed for adverse events and the levels reached in blood with the different doses, concluded that it would be safe to give 10 times the highest FDA-approved dose of 200 micrograms per kilogram,” said Olliaro. “We need well-conducted, sufficiently-powered trials treating patients with increasing doses of ivermectin to see if a satisfactory compromise between efficacy and safety can be found”

So far, there are very few therapeutic options to treat COVID-19. Two drugs that were touted to be re-purposed as COVID-19 treatments – hydroxychloroquine and remdesivir – turned out not to be effective, despite hype from various health professionals.

There are currently over 50 trials on ivermectin at present involving over 7000 people, but it is hard to know whether any of these will provide the evidence needed to license ivermectin as a treatment for COVID-19.

Image Credits: SA Police Service.

COVAX will begin shipping its COVID vaccinations to Africa this month.
COVAX will begin shipping its COVID-19 vaccine doses to Africa this month.

COVAX aims to start shipping nearly 90 million COVID-19 vaccine doses to the continent this month – in what will be Africa’s largest ever mass vaccination campaign, said WHO Regional Director for Africa Matshidiso Moeti at a press briefing Thursday.

COVAX has notified countries in Africa of the estimated dose allocation for the first phase of COVID-19 vaccine delivery, Moeti said. The global initiative is led by the World Health Organization (WHO), Gavi the Vaccine Alliance, and the Oslo-based Coalition for Epidemic Preparedness Innovations (CEPI).

“Africa has watched other regions start COVID-19 vaccination campaigns from the side-lines for too long. This planned roll-out is a critical first step to ensuring the continent gets equitable access to vaccines,” said Moeti at the briefing. “We know no one will be safe until everyone is safe.”

AstraZeneca To Be Main COVAX Product Delivered For Now
AstraZeneca's COVID vaccine will be the bulk of the COVAX products shipped to Africa
AstraZeneca’s COVID vaccine will be the bulk of the COVAX products shipped to Africa

The AstraZeneca/Oxford AZD1222 vaccine will comprise the bulk of the products to be shipped by COVAX. And that still remains subject to the vaccine being listed for emergency use by WHO. The organization is currently reviewing the vaccine and the outcome of the review is expected soon, WHO has said.

The AstraZeneca vaccine faced a setback yesterday when Swissmedic, the Swiss regulatory authority, gave it a thumbs down for the moment, saying that more evidence about efficacy was still needed.  At the same time the European Medicines Agency approved the vaccine last Friday – although half a dozen European Union countries have restricted the use of the vaccine in older people because data on people over the age of 55 was lacking in the vaccine’s Phase 3 clinical trials. At the same time, the United Kingdom, which was the first to give the vaccine regulatory approval, is rolling it out in older people.

COVAX notified countries through letters last week of their expected vaccine allocation.

Amid surging demand for COVID-19 vaccines, the initial allocations were based on a  “fair allocation strategy” developed by WHO, based around countries’ population, infrastructure readiness, mortality rates and trends, as well as and risks faced by health workers.

Initial Pfizer Vaccine Distribution To Countries That Can Handle Ultra-Cold Chain Requirement

In addition, around 320 000 doses of the Pfizer-BioNTech vaccine have been allocated to four African countries -Cabo Verde, Rwanda, South Africa and Tunisia – which have more capacity to handle the vaccines ultra cold-chain requirement of storage at -70 C.

The Pfizer vaccine has received WHO Emergency Use Listing – and Pfizer’s CEO Albert Bourla recently offered 40 million vaccine doses to the Facility at-cost. Thirteen African countries submitted proposals for the vaccine, and were evaluated by a multi-agency committee based on the fair allocation criteria – as well as the vaccine’s ultra-cold chain needs.

“This announcement allows countries to fine-tune their planning for COVID-19 immunization campaigns. We urge African nations to ramp up readiness and finalize their national vaccine deployment plans. Regulatory processes, cold chain systems and distribution plans need to be in place to ensure vaccines are safely expedited from ports of entry to delivery. We can’t afford to waste a single dose,” said Dr Moeti.

The initial phase of 90 million doses to be delivered over the first half of 2021 will support countries to immunize 3% of the African population most in need of protection, including health workers and other vulnerable groups. As production capacity increases and more vaccines become available the aim is to vaccinate at least 20% of Africans by providing up to 600 million doses by the end of 2021.

To complement COVAX efforts, the African Union has secured 670 million vaccine doses for the continent which will be distributed in 2021 and 2022 as countries secure adequate financing. The African Export-Import Bank will facilitate payments by providing advance procurement commitment guarantees of up to US$2 billion to the manufacturers on behalf of countries.

Image Credits: GovernmentZA/Flickr, Tim Reckman/Flickr.

Doctors reviewing a patient’s medication in a rural TB clinic in South Sudan.

IBADAN, NIGERIA — A new fixed-dose combination (FDC) tuberculosis (TB) treatment could improve the ease of treatment regimes, increase the availability of treatments, and get the world back on track to achieve the goal of ending TB. 

The short-course preventative treatment, consisting of two drugs – rifapentine and isoniazid – will reduce the pill burden from nine to three pills a week for adults and will be first rolled out in five TB high burden countries: Ethiopia, Ghana, Kenya, Mozambique, and Zimbabwe, beginning in February and March. 

According to the World Health Organisation (WHO), about 1.4 million people died from TB-related illnesses in 2019. Of the estimated 10 million people who fall ill with TB every year, some 3 million are underdiagnosed or underreported, preventing them from receiving adequate care and treatment.

World map of the countries that had at least 100 000 incident cases of TB in 2019.

Dr Tedros Adhanom Ghebreyesus, WHO Director General, described equitable access to quality and timely diagnosis, prevention, treatment and care as major current challenges.

“Accelerated action is urgently needed worldwide if we are to meet our targets by 2022,” Tedros said.

New TB Treatment to Reduce Pill Burden

The large number of pills that a patient is required to take in the current treatment regimen has been a major bottleneck, making it difficult for many individuals living with tuberculosis to stick to the treatment plan as recommended by health authorities.

Under the new TB therapy, rolled out through a partnership between Unitaid, the Clinton Health Access Initiative (CHAI), and Macleods, a pharma company, the number of pills required for treatment reduces from nine to three. 

The fixed-dose combination tablets, which include rifapentine and isoniazid.

Dr. Pereira Zindoga, a clinician with the Mozambique Ministry of Health’s National TB Program noted that adherence has always been a challenge for patients with TB, especially when people have to take many pills for long periods of time. 

“This is changing. The FDC allows patients to take just three pills once a week for 12 weeks. This will be so much better,” Zindoga said.

Efforts to treat latent TB, a specific form of TB where individuals have no symptoms, are not contagious and often don’t know they are infected, will be strengthened by this partnership. Global data shows that without treatment, up to 1 in 10 of these people will develop active TB, the form which makes people sick and can be transmitted to others. 

By creating a more affordable, accessible, shorter and more easily tolerated regimen, patients with latent TB could have fewer difficulties with accessing and adhering to the treatment program. 

“Getting people to adhere to a treatment when they are not sick has always been a challenge. The lower number of pills — three pills versus nine pills for an adult — means the treatment is now easier to take, stick to and complete,” said Ahmed Bedru, KNCV Tuberculosis Foundation country representative for Ethiopia.

In addition, with fewer drugs required, treatments could be provided to more people. In 2021 alone, enough treatments for up to 3 million patients are expected to be made available for countries that are eligible for the new fixed-dose combination.

Partnership Helps Make Progress on Global TB Targets

This treatment and partnership, combined with the effort to introduce generic TB medications in low- and middle-income countries, could contribute to moving towards the UN High-level Meeting target to provide TB preventative treatments to at least 30 million people by 2022.

Progress towards global TB targets as of late 2019.

WHO has thrown its weight behind the new treatment plans. Dr Tereza Kasaeva, Director of the WHO Global TB Programme, said the global health body welcomes the new fixed-dose combination TB preventive treatment, noting that it will result in reducing the pill burden for people with TB infection, enabling better adherence and outcomes.

“This collaboration between Unitaid, the Clinton Health Access Initiative and manufacturers has been vital to support the uptake of TB preventive treatment as recommended in WHO guidelines. We now look forward to a surge in action from national programmes supported by donors and partners to scale-up access to TB preventive treatment and reach the UN High-Level Meeting targets,” Kasaeva said.

The manufacturer of the FDC, Macleods, agreed to offer a ceiling price of US$15 for a three-month patient course of weekly rifapentine and isoniazid, making this an affordable treatment for low- and middle-income countries. 

The agreement joins one announced in 2019 between Unitaid, the Global Fund to Fight AIDS, Tuberculosis and Malaria and Sanofi, a biopharmaceutical company, to lower the price of rifapentine by nearly 70% for the governments of 100 countries burdened by TB and TB/HIV coinfection.

“Effective TB prevention will be a game-changer in the global fight to eliminate one of the major killer diseases,” said Unitaid’s Executive Director Lelio Marmora. “This life saving drug has, until now, been completely unaffordable in developing countries. This agreement will help transform political commitment to tangible action.”

A total of 12 countries are expected to start receiving the treatment before the end of the year, while the five pilot countries will begin in February and March through IMPAACT4TB, a four-year project introducing a new way to tackle latent TB infection, that is funded by Unitaid and is led by the Aurum Institute. 

Other countries are expected to receive supplies with the support of PEPFAR and the Global Fund to Fight HIV, Tuberculosis and Malaria.

TB, HIV and COVID-19

Although TB on its own is a disease of major public and global health concern, it is also often seen in the light of the HIV pandemic, since the risk of co-infection with HIV and TB is high, particularly in high burden regions. 

Dr. Angeli Achrekar, Acting U.S. Global AIDS Coordinator, noted that this agreement also has important implications for HIV/AIDS programmes. 

“The availability of a shorter, more easily tolerated, and safer regimen for TB prevention that is also affordable is critical for accelerating the fight against TB. This also has important implications for the HIV response, as TB remains the leading cause of death for people with HIV around the world,” Achrekar said.

The COVID-19 pandemic has disrupted numerous TB programmes and services worldwide, threatening the progress made and potentially worsening outcomes in patients and creating new challenges. 

But Professor Gavin Churchyard, founder and CEO of the Aurum Institute, argued that the emergence of preventive and short-course therapy could quickly get the world back on track to meet the goals of TB prevention and control.

“2020 was a hard year for TB prevention and treatment, as many services were disrupted by lockdowns,” said Churchyard. “But with the roll-out of this new FDC, alongside the existing formulation provided by Sanofi, I’m feeling a renewed sense of optimism that we can get back on track to meet our ambitious global TB prevention goals. Saving lives is the priority. We lose in the end if COVID-19 mortality goes down, but TB rates go up.”

Instead of having patients visiting a health center to replenish their TB drug supply, a complete course of treatment for eligible adults is now included in one box, which also ensures that prevention therapy can be provided conveniently for individuals at risk for TB.

Even as advancements in closing TB treatment gaps continue to be made, Dr Osman Eltayeb, Country Representative of Damien Foundation, a key partner for TB case detection and management in Nigeria, told Health Policy Watch that a major challenge that still exists in the global fight against TB is case finding in TB high burden countries like Nigeria.

“It appears that we are going to meet the set targets for treatment outcomes but we may never close the gap of case finding,” he told Health Policy Watch.

Trends in monthly notifications of TB cases during the COVID-19 pandemic. WHO modelling suggests that a 50% drop in TB case detection over 3 months could result in 400 000 additional TB deaths in 2020 alone.

Image Credits: WHO/John Rae Photography, WHO, IMPAACT4TB.