For those who asked me at the beginning of the Covid-19 pandemic when we would have an approved vaccine being applied to the population, I said: not before July 2021. I was wrong! In this article I commented on why vaccines against Covid-19 were being developed so quickly. But no one can deny that 2020 was a year sui generis.
On 08/12/2020, considered “Day V” (of vaccination and victory), the United Kingdom began vaccinating its population, with a new vaccine based on messenger RNA (mRNA), BNT162b2, the first vaccine approved for emergency use with this fantastic technology.
Historic moment!
A friendly 90-year-old woman, about to turn 91, Margaret Keenan, was the first person to receive the dose. The second was an 81-year-old man named William Shakespeare. Both return in 21 days for the second dose. The plan foresees the application of 800 thousand doses in the first week and the preferential vaccination of elderly people over 80 years of age, health professionals, nursing home residents and employees.
The ministers of the United Kingdom's National Health System (NHS) hope that both Queen Elizabeth II, who is 94 years old, and Prince Philip (Duke of Edinburgh), who is 99 years old, will offer their arms to take the vaccine and influence the subjects, which would be considered an important gesture against the criminal anti-vaccination movement that is strong there.
And other European countries, as well as the United States and Canada will also start vaccination soon. Science, how I love you! Am I upset that I got the prediction wrong? No, I'm very happy. But vaccination begins with an interim, preliminary analysis of a phase 3 scheduled to be completed only in...July 2021. Yes, the initial forecast was for phase 3 to be completed in July 2021 and I was still being very optimistic, as the vaccine needed to show efficacy after a longer period of time.
Anyone who is immunized in the United Kingdom will receive a card proving that they have taken the doses, containing the name of the vaccine, the batch number and the date of each dose, with the suggestion to keep the card in your pocket or wallet. It will serve as a passport, you can be sure.
Other countries, such as the United States, France and Canada, plan to start vaccination in 2020, while China and Russia have already been vaccinating some priority groups with their own vaccines. Are Brazilians following and wondering when the desired vaccine will reach our arms?
Meanwhile in Brazil ...
In Brazil, which occupies the less than honorable second place in the number of deaths from Covid-19, behind only the United States, the Brazilian population, appalled, is witnessing a political fight between President Bolsonaro and the governor of São Paulo, João Dória.
Minister Eduardo Pazuello (Health) stated on 8/12/2020, in a meeting with governors, that it is the responsibility of the Ministry of Health to plan the vaccination campaign for the population "across Brazil", in a criticism of Governor Dória's decision to start vaccination on 25/01/2020. Another comment from the Minister, one that I'm still trying to understand, was: “If there is demand and price, the federal government will buy the “Butantan vaccine”. Demand? Do we need more deaths and more infected people and an even longer quarantine?
The Minister of Health also informed that the plan is to start applying the Oxford/AstraZeneca vaccine at the end of February 2021, around 30 days after the date of January 25th announced by the government of the state of São Paulo. Curious, as it is not known when the Oxford/AstraZeneca vaccine will have its phase 3 efficacy data released. The Ministry of Health's plan has been harshly criticized by scientists from the Covid Observatory-19 BR, who state that there is still no reasonable national plan to combat Covid-19.
As the Minister announced that Anvisa needs at least 60 days to approve the use of any vaccine against Covid-19, I imagine that it will also need the same 60 days to analyze both CoronaVac and ChAdOx1 data, the Oxford/AstraZeneca.
So, making a bakery case, if the CoronaVac phase 3 results are sent to Anvisa on 15/12/2020, as Butantan promises and considering that the interim analysis shows good effectiveness, the government of the state of São Paulo vaccination could only start after 15/02/2020 and not on 25/01/2020, as announced. And if ChAdOx3 phase 1 results are not released by the end of December, the Federal Government will not be able to start vaccination at the end of February.
The fact is that these deadlines for starting vaccination cannot be taken seriously, as the Minister of Health and the governor of the state of São Paulo are setting dates for starting vaccination, without having approved and authorized vaccines.
But look what is happening in my holy and beautiful Santa Catarina, crowded beaches, parties, clubs, and the number of cases and deaths skyrocketing. And Brazil recorded the largest percentage increase among the five countries most affected by the new coronavirus this week. So, I'm sorry, but we are in a pandemic folks, the number of cases increasing significantly in Brazil, the vaccine was developed so quickly, science and scientists did the hardest part, in less than 12 months we have promising vaccine candidates, and the Does Anvisa need 60 days to analyze?
Covid-19 is a priority issue. In 60 days, many people could die and thousands could become disabled. The evaluation of the vaccine registration request by Anvisa can take up to 60 days after submission, but I believe it will be done in a much shorter time. Look at what happened in the United Kingdom, where the Pfizer/BioNTech vaccine began to be used on an emergency basis on 08/12/2020, less than 30 days after the results of the studies were sent to the local surveillance agency for analysis. .
I trust Anvisa's technical staff, who I think will not bow down to political issues, but I worry about the direction of the agency, which is equipped with the federal government.
In this huge confusion that became Pindorama, 11 states and the Federal District intend to follow what the Ministry of Health defines and will adhere to vaccines incorporated into the PNI. The 11 states are Acre, Alagoas, Amapá, Amazonas, Goiás, Pernambuco, Paraná, Rio de Janeiro, Rio Grande do Sul, Santa Catarina and Tocantins.
The states of Ceará, Pará, Paraíba, Rio Grande do Norte, in principle, intend to adopt CoronaVac, together with the state of São Paulo. The states of Bahia and Minas Gerais will, in principle, try to negotiate directly with vaccine developers. Other states did not respond.
what to expect in 2021
The year 2021 will be one of major mass vaccination campaigns, as we will at some point have an overlap between the Covid-19 and flu vaccination campaigns (which should start in April). The National Immunization Plan (PNI) has to prepare for parallel campaigns, which can overload service rooms, fill the refrigerators at vaccination stations, and cause logistical problems in the distribution and transportation of the different vaccines.
And we cannot forget that we have observed measles outbreaks in the country due to the drop in vaccination coverage of our main vaccines on the calendar. We have yellow fever, polio, mumps and other infectious diseases that require care.
Will we have syringes, needles, cotton, gauze, refrigerators, disposable gloves, thermal boxes, plastic bags and packaging in sufficient quantities? Is there space in the refrigeration chambers? What about the logistics of delivering hundreds of millions of doses? Everything indicates that 2021 will be a real trial by fire for our experienced National Immunization Plan and for our weakened, but super valuable, Unified Health System (SUS).
After all, will we have the Pfizer/BioNTech vaccine in Brazil?
Pfizer sold 59,4 million doses of the Covid-19 vaccine to Mexico, Chile, Peru, Costa Rica and Ecuador. The European Union purchased 300 million doses, the United Kingdom another 40 million, Japan purchased 120 million, totaling almost 520 million units sold. The United States purchased 100 million doses and is expected to purchase another 500 million doses. Incredible!
Minister Pazuello changed his mind regarding the Pfizer/BioNTech vaccine and reported on 08/12/2020 that the Ministry of Health (MS) signed a letter of intent to purchase 70 million doses of the vaccine produced by Pfizer/BioNTech , which would be delivered in 2021. The Ministry of Health must invest in the purchase of refrigeration chambers to adapt the cold chain for storage in the case of purchasing the Pfizer/BioNTech vaccine. I'm a fan of the vaccine's messenger RNA platform, despite the logistical issue related to the -70 degrees Celsius temperature for storage.
But as we die from Covid-19 in Brazil, but not from boredom, the Minister informed on 09/12/2020, that emergency vaccination in the country could even start in December or January, as long as Pfizer manages to deliver the doses ordered in the agreement of intentions. There you have it. Previously, the Pfizer vaccine was not useful, for reasons related to the cold chain and price, but now it is useful, if only to start vaccinating the population before the governor of São Paulo.
And in the midst of this mess, the Brazilian population is lost and whoever writes this column is incredulous... and lost too... But then I remember that in this country we have a Constitution, which in Articles 6, 196, 197 and 198, says that health is the right of Brazilians and the duty of the State. Therefore, all Brazilians have the right to health and the federal government has the duty and obligation to guarantee it.
And speaking of vaccination in São Paulo...
The governor of the State of São Paulo announced on 07/12/2020, the State Immunization Plan (PEI) against Covid-19, with the first dose of CoronaVac, produced by the Chinese laboratory Sinovac in partnership with the Butantan Institute, being administered starting on 25/01/2021 and the second dose from 15/02/2021. The start of vaccination was scheduled even without Butantan having the vaccine approved in phase 3, with a guarantee of safety and efficacy.
The plan envisages first vaccinating healthcare professionals over the age of 60 and vulnerable groups such as indigenous people and quilombolas, if CoronaVac is approved and authorized by Anvisa. The plan, quite bold, foresees the vaccination of 9 million people in the first phase and that the vaccines will be free for the population, not just in the State of São Paulo.
The preliminary results of Coronavac's phase 3 clinical study (first interim analysis) should be released in the next few days and if it shows the effectiveness that we all hope and hope for, the government of São Paulo will request its registration and a request for emergency approval to Anvisa (National Health Surveillance Agency).
There is no mass vaccination without approval from Anvisa, which we hope will be autonomous, independent, republican, exempt and act in the interests of the Brazilian population, not of politicians from the federal or state government. The government of São Paulo announced this plan to vaccinate the state's population, but also hopes that CoronaVac will be incorporated into the National Immunization Program (PNI), which has existed for 47 years (it was created in 1973) and enter the national vaccination calendar. .
The plan also foresees the following vaccination phases:
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people aged 75 or over from 08/02/2020, with the second dose from 01/03/2020.
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people aged 70 to 74 years, from 15/02/2020, with the second dose from 08/03/2020.
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people aged 65 to 69 years, from 22/02/2020, with the second dose from 15/03/2020.
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people aged 60 to 64 years, from 01/03/2020, with the second dose from 22/03/2020.
The São Paulo government reported that it will significantly expand vaccination sites, from the current 5.200 to 10.000, with the inclusion of pharmacies, Military Police barracks, schools during weekends, bus terminals, train stations and a drive system thru. Although municipalities in São Paulo can define their strategies, vaccination times on weekdays will be from 7am to 22pm and from 7am to 17pm on weekends and holidays.
The governor of the State of São Paulo also announced that the state has a stock of necessary needles, syringes and personal protective equipment and that 4 million doses of CoronaVac will be destined for the immunization of health professionals from other states, among the 46 million doses that the state plans to have available in January. According to the São Paulo government, CoronaVac will not be available in private clinics, but they can participate as vaccination sites, free of charge and on a voluntary basis.
The 60-year-old age group was defined as the initial age group, as around 77% of the 42,5 deaths from Covid-19 in the state of São Paulo were in this age group. As people over 60 were included in the initial vaccination plan, but there is still no indication that CoronaVac protects this group, the plan may undergo changes. Having a plan is great, but having a calendar without having a vaccine can cause harm, mainly leading to relaxation on the part of the population in non-pharmacological measures to combat Covid-19.
The ideal would be to wait for the results of the interim analysis of phase 3, which involves 13.000 volunteers, to define the best plan. It is not possible to question the plan, but rather the date set on the 467th anniversary of the city of São Paulo, 25/01/2021, a municipal holiday in the capital of São Paulo.
It would be better to have set another day as the scheduled date, as it depends on authorization from Anvisa, although the agency can grant temporary and emergency authorizations for application in some groups of the population, even if these vaccines are not registered. This is the “Guide on Minimum Requirements for submitting Temporary Authorization for Emergency Use, on an experimental basis, for Covid-19 vaccines” (Read here).
The problem is the expectations it creates among the population. Anvisa reported that it did not receive data from phase 3 studies, which confirm safety and efficacy and are essential for evaluating the request for authorization for emergency use, but the Government of São Paulo says that the complete report will be sent in the next day 15.
All vaccines approved in phase 3 and authorized by Anvisa should be incorporated into the National Immunization Program (PNI) for wide distribution to the entire Brazilian population. If CoronaVac is not incorporated into the PNI by the Ministry of Health, it will be an unprecedented event in the history of mass vaccinations in Brazil. We will witness parallel campaign events in some Brazilian states, which will certainly affect the mass vaccination campaign, potentially leading to lower vaccination coverage.
It would be regrettable in every way if this happens, both for the PNI, for the SUS and for the Brazilian population, which is being the victim of two petty and selfish power projects. Let's hope that the SUS is not weakened. In addition to the state of São Paulo and other Brazilian states, four countries plan to use CoronaVac against Covid-19: China, Chile, Indonesia and Turkey. And at the moment, we can only hope that CoronaVac actually becomes a vaccine, because it isn't yet.
Pfizer/BioNTech Vaccine Restrictions
Pfizer had already released a protocol with restrictions for pregnant and breastfeeding women, who should not use the vaccine. On 09/12/2020, the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom, issued a note warning that people with a history of a significant allergic reaction to vaccines, medicines or foods, with a history of an anaphylactoid reaction [similar to anaphylaxis] or people who need to carry an adrenaline auto-injector should not take the Pfizer/BioNTech vaccine.
Another indication is that vaccination should only be carried out in facilities where resuscitation measures are in place. There were two cases of allergic reactions to the vaccine, with two NHS employees (UK health system), but the patients are doing well. This could have been detected in phase 3 studies, but apparently no volunteers in the vaccine group had this history of severe allergies. Vaccinating the real world is always different and challenging.
Degrees of protection from a vaccine
We have a serious public health problem with Covid-19, we have no effective treatment alternative available, nothing that prevents the spread of the virus and the progression of the pandemic, so we need vaccines that protect at least part of the population, without causing unwanted side effects that negate the gains from vaccination. A good vaccine or a good immunizer, the one we dream about and desire every day, can basically present one of these three degrees of protection:
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Totally preventing infection by SARS-CoV-2, preventing the virus from entering our body, leading to the so-called “sterilizing immunity”;
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Not prevent infection or not prevent the ability to transmit the virus to others, but prevent infected people from getting sick. In this case, the virus even manages to enter the body, but the vaccine would protect against the manifestation of symptoms;
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It does not prevent infection with the virus or Covid-19, but prevents the development of a more serious illness, avoiding hospitalizations and deaths.
So at this point, we really don't know whether “phase 3 efficacy” means complete protection and immunity, whether the “immunized” person can still transmit the disease, or protect themselves against the most serious effects of Covid-19. And we don't know the immunological memory that the vaccine will leave and how long the immune system's reaction will last.
To date, none of the vaccine development laboratories have disclosed the degree of protection of their vaccine candidates. Only when the preliminary phase 3 results are published in international journals will the data be available for evaluation by the global scientific community. But we will certainly need time post-immunization to have this answer. Only with mass vaccination, with high adherence by the world population, could the so-called non-pharmacological measures, such as social distancing, personal hygiene habits and the use of masks, be reduced in intensity. But even with vaccines we will have to wear masks for a long time, as only in the first case, of “sterilizing immunity” for everyone, could non-pharmacological measures be eliminated.
If a sterilizing vaccine is available and is effective for the elderly and vulnerable populations at greater risk of contracting Covid-19, these groups should be prioritized. If we are limited in terms of doses, it is more important that a sterilizing vaccine is preferably applied to the elderly and at-risk groups (as long as it protects these groups). In a pandemic situation, having a great vaccine, with more than 90% efficacy, even if it is more expensive and has logistical problems to be resolved and needs to be stored at low temperatures, it is worth purchasing.
We cannot deny that the future of vaccination lies in vaccines that involve adenovirus or messenger RNA platforms. There are logistical factors that must be considered, such as storage temperature, ease of handling and difficulty in logistics for more remote locations, to avoid loss of effectiveness, but we need to readapt the cold chain and logistical issues. The future is right there and we will learn a lot from the first vaccines developed and applied to the population.
CHECK TESTING PROGRESS UPDATE
Efficacy of BNT162b2
Pfizer announced more details about the 95% efficacy observed with its vaccine candidate in the first preliminary analysis carried out. According to the company, this 95% efficacy was achieved, as of the total of 8.000 volunteers in the clinical trial, 162 infected volunteers were observed in the group of 4.025 people who received the placebo (4,02%) and 8 infected volunteers in the group of 3.975 who received the vaccine (0,20%). Efficacy is reached by making the count: [1 – (0,20/4,02)] x 100. This means that when taking the vaccine, 95% or 3.776 people from the group of 3.975 volunteers who received the vaccine would be protected.
Oxford / AstraZeneca
The Oxford/AstraZeneca vaccine candidate had the preliminary results phase 3 published in the medical journal The Lancet. The study was randomized and used the MeningoACWY vaccine as a placebo. The publication confirms the safety and average effectiveness of the immunizer of approximately 70%, which can reach around 90%, depending on the dose, as announced in November 2020 through a press conference. Phase 3 trials involved 23.848 volunteers (around 80% of the total) aged between 18 and 55 in the United Kingdom, Brazil and South Africa.
In volunteers who received two full doses, the effectiveness of the vaccine was 62,1% (27 infected volunteers [~0,6%] of the total of 4440 volunteers in the group that took ChAdOx1 nCoV-19 versus 71 infected volunteers [~1,6 .4455%] of the total of 62,1 volunteers in the placebo group. This leads to an efficacy of 1% calculated using the formula [0,6 – (1,6/100)] x XNUMX, without considering rounding.
In volunteers who received a half dose followed by a full dose, the efficacy was 90,0% (3 infected volunteers [~0,2%] of the total of 1367 volunteers in the group that took ChAdOx1 nCoV-19 versus 30 infected volunteers [~2,2%] of the total of 1374 volunteers in the placebo group. This leads to an approximate efficacy of 90% calculated using the formula [1 – (0,2/2,2)] x 100, without considering rounding.
The overall efficacy of the vaccine in both groups (two full doses and half dose + full dose) was 70% (30 infected volunteers [~0,5%] of the total of 5807 volunteers in the group that took ChAdOx1 nCoV-19 versus 101 infected volunteers [~1,7%] of the total of 5829 volunteers in the placebo group. This leads to an efficacy close to 70% calculated using the formula [1 – (0,5/1,7)] x 100, without considering the rounding. In the 21-day period, between the two doses, there were 10 cases hospitalized for COVID-19, all in the placebo control group; 2 classified as severe COVID-19, including one death.
SPUTNIK V, the vaccine from Russia
Russia, the first country to register a vaccine against the new coronavirus, began free and voluntary vaccination against the coronavirus in the last week of November 2020, with the vaccine candidate Sputnik V, an immunizer developed by the Gamaleya Research Center. The initial stage involves immunizing citizens of Domodedovo (near Moscow) exposed to the virus, such as social workers, healthcare workers and teachers. Russia reported having already vaccinated 100 people and intends to immunize 2 million by the end of December. Of the 100 vaccinated, 20 belong to the group that is participating in the phase 3 clinical trial and around 80 are not part of the clinical study. Sputnik V is still in phase 3 clinical trials with 40.000 volunteers and an interim analysis with just 40 volunteers showed 92% efficacy, according to preliminary results.
Modern
The American biotechnology company MODERNA reported through press release on 03/12/2020, which intends to make available between 100 and 125 million doses of its messenger RNA (mRNA) vaccine candidate against covid-19 in the first quarter of 2021, with 20 million doses already being available in the end of 2020 for the United States. The company intends to manufacture around 1 billion doses in 2021.
MODERNA's vaccine candidate showed 94,1% efficacy in a preliminary phase 3 study and the company states that the data also shows 100% efficacy in preventing serious diseases caused by the new coronavirus. Let's wait for the publication of the phase 3 results to check it out, hoping that's it. MODERNA has never put a vaccine on the market, but the mRNA technology is fantastic.
Vaccination in private clinics in Brazil
According to ABCVAC (Brazilian Association of Vaccine Clinics), private vaccination clinics should only receive the first doses of vaccines against Covid-19 in the second half of 2021 or later, due to the fact that companies developing vaccines are only negotiating with the public sector of the various countries and which risk groups should receive the vaccines first. Only with the approval of more vaccines will private clinics be able to receive their doses. In fact, the Senate Plenary approved the bill on 03/12/2020 (PL 4.023 / 2020), which prioritizes the SUS in the purchase and distribution of approved vaccines against Covid-19 until reaching the goal of national vaccination coverage. The PL will still be evaluated in the Chamber of Deputies. The PL does not make vaccination mandatory in the national territory, but it guarantees that the vaccine is free for Brazilians who wish to be vaccinated.
Note: This text does not necessarily reflect the opinion of Unicamp.
