Some countries in the European Union have temporarily suspended use of the AstraZeneca COVID-19 vaccine as a precautionary measure based on reports of rare blood coagulation disorders in persons who had received the vaccine. Other countries in the EU – having considered the same information – have decided to continue using the vaccine in their immunization programmes.
Vaccination against COVID-19 will not reduce illness or deaths from other causes. Thromboembolic events are known to occur frequently. Venous thromboembolism is the third most common cardiovascular disease globally.
In extensive vaccination campaigns, it is routine for countries to signal potential adverse events following immunization. This does not necessarily mean that the events are linked to vaccination itself, but it is good practice to investigate them. It also shows that the surveillance system works and that effective controls are in place.
WHO is in regular contact with the European Medicines Agency and regulators around the world for the latest information on COVID-19 vaccine safety. The WHO COVID-19 Subcommittee of the Global Advisory Committee on Vaccine Safety is carefully assessing the latest available safety data for the AstraZeneca vaccine. Once that review is completed, WHO will immediately communicate the findings to the public.
At this time, WHO considers that the benefits of the AstraZeneca vaccine outweigh its risks and recommends that vaccinations continue.
COVAX has notified countries in Africa of the estimated dose allocation for the first phase of COVID-19 vaccine delivery. The global initiative led by the World Health Organization (WHO), Gavi the Vaccine Alliance and The Coalition for Epidemic Preparedness Innovations (CEPI) aims to start shipping nearly 90 million COVID-19 vaccine doses to the continent in February, in what will be Africa’s largest ever mass vaccination campaign.
The roll-out of the AstraZeneca/Oxford AZD1222 vaccine is 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.
“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 Dr Matshidiso Moeti, WHO Regional Director for Africa. “We know no one will be safe until everyone is safe.”
COVAX notified countries through letters which were sent on 30 January 2021. Amid surging demand for COVID-19 vaccines, the final shipments will be based on production capacities of vaccine manufacturers and the readiness of countries. Recipient countries are required to submit finalized national deployment and vaccination plans to receive vaccines from the COVAX facility.
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. This vaccine has received WHO Emergency Use Listing but requires countries to be able to store and distribute doses at minus 70 degrees Celsius. To access an initial limited volume of Pfizer vaccine, countries were invited to submit proposals. Thirteen African countries submitted proposals and were evaluated by a multi-agency committee based on current mortality rates, new cases and trends, and the capacity to handle the ultra-cold chain needs of the vaccine.
“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 will support countries to immunize 3% of the African population most in need of protection, including health workers and other vulnerable groups in the first half of 2021. 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.
WHO chief Tedros Adhanom Gheybreyesus emphasized how testing has been common among countries which have worked to control the virus.
“As vaccines are rolled out, testing will continue to play a vital role”, he said.
“Initially, health workers, older people and other at-risk groups will be prioritised for vaccination. That will still leave the virus with a lot of room to move, and testing will remain a vital tool for controlling the pandemic.”
However, Tedros stressed that though vital, testing is only part of the strategy against COVID-19.
“Testing is the spotlight that shows where the virus is. Investments in testing must be matched by investments in isolation facilities, clinical care, protecting health workers, contact tracing, cluster investigation and supported quarantine”, he stated.
More evaluation needed
Meanwhile, WHO said more information is needed concerning the vaccine developed by the pharmaceutical company AstraZeneca and Oxford University.
The partners announced this week that clinical trials showed a regimen consisting of one half-dose of the vaccine, followed by a full dose a month later, was more effective than two full doses.
Dr. Katherine O’Brien, Director of Immunization, Vaccines and Biologicals at WHO, underlined the need for further evaluation as the data were reported in a press release.
“I think what we can emphasize, though, is that from what we understand about the press release, there is certainly something interesting that has been observed. But there are many reasons that could underlie the differences that were observed,” she said.
WHO’s Chief Scientist, Dr. Soumya Swaminatha, pointed out that less than 3,000 people were given the lower-dose regimen, according to the press release, all of whom were 55 years old or younger.
She added that the other group consisted of more than 8,000 people of varying ages, thus making it very hard to compare the two, while overall, their numbers were too small to come to any definitive conclusions.
“It would be speculation at this point,” Dr. Swaminathan told reporters.
She said AstraZeneca has informed WHO that it intends to run a full trial of the lower-dose regimen.
Lessons from Ebola
Global experience with storage and distribution of the Ebola vaccine could inform delivery of any potential inoculation against COVID-19 once developed, according to WHO.
“There is demonstrated experience of delivering ultra-cold chain vaccines, even in some of the most difficult and remote areas,” said Dr. O’Brien. “But that has also taken enormous resources to do that.”
The WHO official was responding to a journalist’s question concerning the experimental vaccine developed by pharmaceutical companies Pfizer and BioNTech, which was recently submitted to authorities in the United States for emergency approval.
The vaccine, which has shown a more than 90 per cent efficacy rate, requires very cold storage of -70 degrees Celsius or below, prompting concerns about potential distribution in African countries.
“We do have experience in a number of countries, specifically in Africa, being able to deploy a vaccine with that ultra-cold chain requirement”, said Dr. O’Brien, referring to the Merck Ebola vaccine used in outbreaks in the Democratic Republic of the Congo.
“So, as we anticipate the use of the Pfizer vaccine, the intention is certainly to be able to use it along with other vaccines because no one vaccine is going to have adequate supply, nor will any one vaccine necessarily have suitable operational characteristics to meet all of the needs.”
Dr. O’Brien added that Pfizer has developed a special “shipper” which can maintain the vaccine’s temperature for up to 10 to 15 days.
Furthermore, the vaccine can be stored at refrigerated temperatures for five days, she continued, while portable freezers that do not run on electricity, and even dry ice, also can be used.
Small NIH clinical trial conducted in partnership with AstraZeneca.
A drug approved to treat a severe form of asthma dramatically improved the health of people with rare chronic immune disorders called hypereosinophilic syndromes (HES) in whom other treatments were ineffective or intolerable.
This finding comes from a small clinical trial led by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and conducted through a partnership with the global biopharmaceutical company AstraZeneca. The results were published online today in the New England Journal of Medicine.
“People living with a rare disease often have few, if any, effective treatment options,” said NIAID Director Anthony S. Fauci, M.D. “This promising treatment advance for people with hypereosinophilic syndromes is just one example of how NIH research responds to the unique medical needs of individuals with rare diseases.”
HES is caused by higher-than-normal numbers of white blood cells called eosinophils(link is external) in the blood, tissues or both. While most people have 0 to 500 eosinophils per microliter (µL) of blood, people with HES typically have more than 1,500 eosinophils/µL. The symptoms of HES vary widely from one patient to the next and can affect the heart, lungs, skin, gastrointestinal tract, central nervous system and other organ systems.
Nearly all existing therapies for HES involve drugs that are not specifically approved for treating the syndromes, have significant side effects and sometimes become less effective over time. The study reported today was only the second randomized, placebo-controlled trial — the gold standard of medical research — to test the effectiveness of a drug specifically for treating HES. The trial was led by Amy Klion, M.D., chief of the Human Eosinophil Section in the NIAID Laboratory of Parasitic Diseases.
The medication tested in this Phase 2 clinical trial is benralizumab, also known by the brand name Fasenra. It consists of an antibody that binds to a protein, called IL-5 receptor a, found on the surface of eosinophils. Scientists hypothesize that once this binding takes place, immune cells called natural killer cells approach and destroy the eosinophils.
In an earlier clinical trial, benralizumab safely improved the symptoms of people who have a form of asthma associated with an excess of eosinophils in the lungs. Subsequently, the U.S. Food and Drug Administration approved the drug for treating this condition, called severe eosinophilic asthma. AstraZeneca developed and manufactures benralizumab and provided it for the HES trial through a cooperative research and development agreement with NIAID.
The NIAID trial involved 20 people with severe forms of HES who had at least 1,000 eosinophils/µL of blood when they enrolled in the study and whose condition had been stable on other HES therapies for at least a month before enrolling. These study participants all lacked a genetic marker associated with a type of HES that responds to treatment with a different drug. All study visits took place at the NIH Clinical Center in Bethesda, Maryland.
The trial had three phases over a period of 48 weeks. At the start of the first phase, which lasted 12 weeks, study participants were assigned at random to receive either 30 mg of benralizumab or a placebo solution through an injection under the skin once every 4 weeks while continuing to take their current HES therapy. Neither the participants nor the investigators knew who was receiving the study drug or what the participants’ eosinophil counts were during this first phase.
In the second phase, which lasted from week 12 to week 24, all study participants were given 30 mg of benralizumab through an injection under the skin once every 4 weeks. Eosinophil counts were revealed beginning at week 13, and participants could taper their original HES therapy if doing so was tolerable.
During the third phase, those participants whose symptoms or eosinophil counts had improved by week 24 could continue receiving benralizumab until week 48.
At the end of the first phase, blood eosinophil levels were undetectable in nine of the 10 participants who received benralizumab and had declined by 50 percent or more in three of the 10 participants who received the placebo. While the use of an immunosuppressive drug explained why eosinophil counts declined in one of the placebo recipients, the reason for the decline in the other two placebo recipients is unknown.
After at least 12 weeks of benralizumab therapy during the first phase, second phase or both, 17 of 19 participants had undetectable levels of eosinophils in the blood and a reduction in HES-related symptoms, with few or no side effects. (One person withdrew from the study at week 6 for logistical reasons.) These beneficial responses lasted through the end of the third phase in 14 of 19 participants, (74 percent). Nine of those 14 participants (64 percent) were able to taper off other HES therapies during the third phase. The 14 participants continued taking benralizumab for another year after completing the third phase.
In addition, eosinophils were undetectable in the bone marrow of nine of the 10 participants in the treatment group in the first phase, and in the tissue of all eight participants whose tissue was tested at the end of the second phase.
A larger placebo-controlled trial of benralizumab for treating HES is needed to confirm these results, according to the study investigators.
“We are grateful for the dedication of our study participants, who gave so generously of their time and were willing to undergo numerous invasive tests to help improve treatment options for the HES community,” said Fei Li Kuang, M.D., Ph.D., lead associate investigator on the study and a clinical fellow in the Human Eosinophil Section of the NIAID Laboratory of Parasitic Diseases.