RIO DE JANEIRO, BRAZIL – British actor Sir Ian McKellen, 81, who portrayed the mythical wizard Gandalf in the Lord of the Rings films, was one of the first people last week to be administered an authorized vaccine against Covid-19.
“I am very happy to have been vaccinated. I wouldn’t hesitate to recommend it to everyone,” McKellen said on Thursday. The actor was administered 30 millionths of a gram of Tozinameran, a molecule containing genetic information of the novel coronavirus, in the left deltoid muscle.
This tiny injected formula contains instructions for the human cells to produce the genuine vaccine: harmless fragments of the virus that prepare the body’s defenses.
On December 2nd, the United Kingdom became the first country in the world to authorize a vaccine against Covid-19, the aforementioned Tozinameran, developed by German BioNTech and North American Pfizer. The European Union may approve it this week.
Gandalf’s interpreter did not hesitate to be vaccinated, and over 70% of citizens will also be required to do likewise to contain the pandemic, but many people still have doubts and only 39% of Spaniards would be willing to be immunized tomorrow. These are the answers to their most common questions.
Are these vaccines developed in record time safe?
Something is safe when it is risk-free, according to the dictionary, but in medicine the meaning is different.
“Safety is the favorable balance between benefit and damage,” sums up British statistician Stephen Evans. The benefit for men over 80, like Gandalf’s interpreter, is tremendous: the coronavirus killed approximately 15% of infected octogenarians during the first wave in Spain, according to data from the National Center for Epidemiology. The risks related to the vaccine, on the other hand, are low. Some 22,000 people have been administered the Pfizer vaccine during trials, while another 22,000 were injected with saline solution for comparison.
The incidence of severe adverse reactions was very low and similar in both groups: 0.6% and 0.5%, respectively. Fatigue and a mild headache were common symptoms in approximately half of those vaccinated.
“We do not yet know the very rare reactions, often less than one case per 1,000 people vaccinated; or those that occur in groups excluded from clinical trials, such as people with a history of anaphylaxis [severe reaction to food or medication]; or those that may emerge in the long term, over four months,” explains Evans, ex-president of the International Society of Pharmacoepidemiology.
After 137,000 people were immunized in the UK in the first week, only two cases of severe allergic reactions were detected, followed by a third case in Alaska (USA). The patients, already recovered, had a similar medical history.
Argentinean doctor Fernando Polack directed Pfizer’s vaccine trial with 44,000 subjects. The safety data, with an average follow-up of two months, are similar to other vaccines already authorized against viruses, such as the multinational GSK against herpes zoster.
American Moderna, the second vaccine developer to cross the finish line, also submitted the detailed results of its vaccine -similar to that of Pfizer- this week after a trial with 30,000 subjects. “Both have been very safe until now, as safe as vaccines in the schedule, ranging from measles to flu,” says Polack.
The Argentinean doctor minimizes the fact that there are still no data about its long-term safety. “A somewhat fanciful notion of candidate vaccine assessments in the past has been created. No vaccine that successfully completes a phase 3 clinical trial [with tens of thousands of people, like Pfizer and Moderna’s] will remain under observation and unapproved for years,” he says.
As Polack emphasizes, this is the standard procedure: to continue monitoring a vaccine after it has been approved to examine its efficacy in the real world and its potential adverse reactions. “What’s different now is that vaccines have never been tested under the watchful eye of six billion people,” says Polack.
Could there be surprises in the long run?
Virologist Agustín Portela, from the Spanish Agency of Medicines and Sanitary Products, does not expect major surprises.
“There are vaccines against some 20 pathogens. If we start searching in how many of them an adverse reaction occurred one month after vaccination we will have to look through a magnifying glass”, he emphasizes.
Portela recalls some exceptions. In 2017 it was found that Sanofi’s new vaccine against dengue aggravated the disease in a small percentage of people vaccinated, a phenomenon also observed in animals immunized against another coronavirus detected in China, causing severe acute respiratory syndrome (SARS). The authorities monitored any evidence of this phenomenon in experimental vaccines against Covid-19.
“We have data on almost 60,000 people who have been vaccinated with three different vaccines – Pfizer, Moderna and AstraZeneca – with a follow-up lasting several months, and in none of them is there any evidence of the disease escalating. I believe the evidence is solid enough to assume that this phenomenon is not going to happen,” reassures Portela, also a member of the European Medicines Agency’s Vaccine Committee.
The virologist recalls a second exceptional case: the Pandemrix vaccine, from multinational GSK, authorized in Europe in 2009 against the H1N1 flu pandemic, the famous swine flu.
Sweden and Finland detected a negligible risk of narcolepsy months after its approval, deep sleep attacks during the day, with about four cases per 100,000 people vaccinated. Other flu vaccines have since been associated with minimal cases of narcolepsy.
“If such a phenomenon occurs, no one knows when it will occur, but we have a whole past experience of vaccination against many pathogens and it never happened. Waiting six months [to authorize Covid-19 vaccines] wouldn’t provide us with an additional guarantee,” Portela says.
Will the vaccines prevent contagion?
Pfizer and Moderna’s vaccines – and AstraZeneca’s to a lesser extent – have proven to be effective in preventing people vaccinated from contracting Covid-19, but there is still no solid data on whether they also prevent a person from being infected with no symptoms and continuing to spread the virus.
“The vaccine could reduce the number of diseases and deaths caused by the coronavirus, but the virus will continue to circulate,” alerts virologist Isabel Sola, co-director of another experimental vaccine against Covid-19 at the National Center of Biotechnology in Madrid.
In a film shooting session, Gandalf’s interpreter, despite being vaccinated, could cause an outbreak among actors who play the elves, for instance. In a hospital, vaccinated healthcare professionals must continue to take extreme precautions. “The percentage of the population that would need to be vaccinated for herd immunity would have to be higher. And until then, measures such as the wearing of masks and social distancing would have to continue to be adopted,” says Sola.
There are vaccines, such as for measles, that prevent the disease and also interrupt asymptomatic infections, thereby easing the control of epidemics. Other vaccines, such as GSK’s Bexsero, to prevent meningitis B, do not prevent a vaccinated person from turning into an epidemic outbreak, while not suffering from the disease.
“No one yet knows if the vaccine prevents transmission, although the coronavirus is not exactly swift. This germ is much more harmful for being new rather than being agile,” says Fernando Polack, the main author of Pfizer’s study.
“Traditionally, respiratory vaccines, such as the respiratory syncytial virus, fail in the upper tract -in the nose and throat- and have a 40% efficacy in the prevention of lung diseases. This is cause for celebration. Here -and this was somewhat surprising to me- the vaccine prevented 95% of all Covid-19,” he praises.
The scientific community hopes that this high efficacy in the prevention of the disease will translate at least into the reduction of contagion.
Preliminary data from Moderna and AstraZeneca already point to some prevention of asymptomatic infections. Moreover, data from Singapore published on Friday by The Lancet medical journal suggest that the infectivity of asymptomatic contagions accounts for only a quarter of the infectivity of symptomatic cases.
“We have no solid evidence that these vaccines will interrupt transmission and produce herd immunity. We will collect this information once we start vaccinating a large population, for instance, 50% in all age groups, and find that the rate of the disease drops by 80%. This gap of 30 percentage points would show that the vaccine is interrupting transmission,” explains Portela.
“In the beginning, while there are not many people vaccinated, the only way to protect everyone is to wear a mask,” he warns.
How long will the vaccine protection last?
The published data on Pfizer’s vaccine include a two-month follow-up of people vaccinated, with a subgroup reaching three and a half months. The company itself recognizes that it is not yet known how long protection against Covid-19 produced by the vaccine will last.
“The immunity length is another question to be answered, although data from initial phase trials suggest that antibodies will be present for a long time,” says Polack, Infant Foundation director.
The most recent data from Moderna are encouraging: four months after being given the first dose, all those vaccinated, including people over 71 years of age, presented higher levels of antibodies than those who overcame Covid-19. The more advanced vaccines seem to generate robust and durable defenses.
“The worst-case scenario, reasonable but unlikely, is to need to revaccinate annually. It doesn’t seem dramatic, as today we do that with the flu, once vaccine production is resolved,” opines the Argentine doctor.
Virologist Agustín Portela, from the Spanish regulatory agency, is also optimistic. “We never know how long a vaccine immunity will last when we approve it”, he explains.
Portela recalls the case of another virus, that for chickenpox. The U.S.A. introduced a single dose vaccine made by MSD pharmaceutical company in 1995 and the incidence of the disease quickly fell by 90%.
However, years later, outbreaks of chickenpox began to be detected in schools where children had been vaccinated. The U.S. health authorities in 2006 recommended the administration of a booster dose. “And the problem disappeared,” says Portela.
“What we achieved with Covid-19 vaccines is to teach the immune system to fight SARS-CoV-2 and defeat it. That’s what Pfizer and Moderna’s data tell us. If the immune system forgets or loses power within four years, what we do is to give it another vaccine dose to remind it how to be prepared to fight the virus. Typically, the more doses you administer, the more encouraged the immune system becomes. If there is a drop in immunity after four years, the next one may occur within 20 years,” considers Portela.
Are there other countries that prefer to wait before vaccinating?
“Vaccination in haste is not the answer for Switzerland,” said the Central European drug regulatory agency Swissmedic in a statement dated December 11th.
“The safety of Swiss citizens is the top priority,” the agency said. Switzerland has emerged in recent weeks as the prudent alternative given the urgency to start vaccinating the UK and U.S., but the agency’s spokesperson, Lukas Jaggi, denied this this week.
“Swissmedic is not embracing a slower or overly-cautious strategy. We are in line with other agencies, with which we cooperate,” Jaggi said on Tuesday.
In Switzerland, home to 8.5 million people, there have been fewer than 6,000 deaths from Covid-19 since the pandemic began, which is why the authorities did not seem to have the same urgency as other countries.
However, on Saturday Switzerland became the first country to authorize a vaccine against Covid-19 – Pfizer’s – under the normal procedure, rather than the emergency one. “The Swiss health authorities have already announced their vaccination strategy, which is scheduled to begin in early January,” explains Paul-Henri Lambert, a vaccinologist at the University of Geneva.
Lambert is one of the experts in the Brighton Collaboration, an international organization to guarantee vaccine safety. The researcher alerts that by vaccinating millions of people, many diseases that seem to be related to the shots will emerge, but are not. “It won’t be easy to rule out a cause and effect relationship. We’ll need major epidemiological studies,” he alerts.
Virologist Isabel Sola encourages the undecided to be vaccinated as soon as possible: “We need to have trust. Not blind trust, but trust in what we know, in the scientific evidence. The results we have are convincing: these vaccines are effective and safe. If we are not vaccinated, what alternative do we have?”
Source El País