The Butantan Institute postponed the date for announcing the phase 3 efficacy of CoronaVac, developed in collaboration with the Chinese pharmaceutical company Sinovac. Anvisa granted, according to publication in the Official Gazette dated 21/12/2020, the certificate of good manufacturing practices for the CoronaVac vaccine factory, in China, valid for 2 years. This certificate is an important part of both the registration process and the request for authorization for emergency use of this vaccine.
The Federal Government finally gave in to pressure and should even acquire CoronaVac, from Butantan, incorporating it into the National Immunization Plan (PNI). Although the purchase initially planned by the Federal Government is around 45 million doses, Butantan announced that it can offer another 55 million doses, reaching 100 million doses of the immunizer for the PNI in the first half of 2021. In addition to Brazil, Indonesia, Turkey, Chile and China are awaiting phase 3 efficacy and safety results and must vaccinate their populations with the vaccine.
The government of the state of São Paulo announced that it will receive a batch of raw materials to prepare another 5,5 million doses on December 24th and will have 10,8 million doses of CoronaVac available by 31/12/2020.
A VACCINATION AROUND THE WORLD
SWITZERLAND COMES FORWARD AND AUTHORIZES NON-EMERGENCY USE OF PFIZER/BIONTECH
A Switzerland is o first country to register and authorize non-emergency use of Pfizer/BioNTech vaccine in its population, based on safety, efficacy and quality criteria. Switzerland has 8,6 million inhabitants and purchased 15,8 million doses of vaccines, 3 million from Pfizer/BioNTech, 7,5 million from Moderna and 5,3 million from AstraZeneca.
The vaccine has already been approved for emergency use in several countries, including the United Kingdom, United States, Canada, Bahrain, Saudi Arabia, Mexico, Chile, Ecuador and Singapore, with the United Kingdom, United States and Canada having already started application campaigns. of the immunizer in their populations.
THE ADVERSE EFFECTS OF PFIZER/BIONTECH
AIn addition to the two people with a history of anaphylaxis who had allergic reactions to the Pfizer/BioNTech vaccine in the United Kingdom, another six people in the United States, out of 272 who took the vaccine, also had allergic reactions. Everyone is doing well, but one of the Americans had no history of serious allergies. Treatments for allergic reactions and anaphylactic shock typically involve the use of corticosteroids, antihistamines, epinephrine or adrenaline injections.
A possibility that is still only suspected and very speculative is that lipid nanoparticles (LNPs) based on polyethylene glycol (PEG) may be responsible for allergic reactions. PEG has never been used before in vaccines, but it is found in several medicines that cause adverse events such as anaphylaxis, but also in toothpastes, cosmetics, shampoos and fabric softeners. Therefore, it is possible that people who have already used medications containing PEG have acquired an immunological response of antibodies such as IgM, IgG and especially IgE, which can cause allergic reactions as a protective mechanism against PEG, which could trigger the anaphylaxis response.
Both Pfizer and Moderna excluded people with a history of allergies to vaccine components from phase 3. Pfizer did not include people with severe allergies to other vaccines. Certainly, more studies are needed and the United States National Institute of Allergy and Infectious Diseases (NIAID) is investigating the case. This does not prevent vaccination campaigns, but people with severe allergies should be on alert.
MODERN VACCINE: THE FANTASTIC RNA PLATFORM
The American FDA (Food and Drug Administration) approved the Moderna vaccine, based on the fantastic messenger RNA (mRNA) platform for emergency use in people over 18 years of age. The FDA confirmed that the treatment is 94,1% effective and that the vaccine shows no safety issues that would prevent it from issuing emergency use authorization. The CDC (Center for Disease Control and Prevention) has already approved and the United States will have the second vaccine approved for emergency use in its population (the first was that of Pfizer-BioNTech, also using mRNA, approved for emergency use in people over 16 years of age).
Moderna, which does not have any approved vaccine in its portfolio, plans to make around 125 million doses of its vaccine available in the first quarter of 2021, with up to 100 million for the United States and up to 25 million for other interested countries. The vaccine must be stored at a temperature of minus 20 degrees Celsius.
CHADOX1 + SPUTNIK V TOGETHER IN THE FIGHT AGAINST COVID-19?
The pharmaceutical company AstraZeneca announced on 21/12/2020 that it will carry out clinical studies combining its vaccine candidate ChAdOx1 (AZD1222) with Sputnik V, a vaccine from Russia. ChAdOx1 uses as its platform an adenovirus-based viral vector that causes colds in chimpanzees, while Sputnik V is based on two different human adenoviruses, Ad5 and Ad26, that cause colds in humans.
The goal is to increase the efficacy of ChAdOx1, which was only 62% after the interim analysis with two full doses, although the greater efficacy of 90% with a half dose followed by a full dose is still being investigated. According to the Russians, Sputnik V was 92% effective in the first interim analysis.
The bet is that the use of two different vectors can lead to greater efficacy than using a single viral vector in both doses. The partnership aims to evaluate immunogenicity and safety, combining one of the components of Sputnik V with the vaccine adenovirus AZD1222.
On 10/12/2020, AstraZeneca removed from its website the forecast for testing ChAdOx1 in older children.and 5 years among volunteers. The company is talking to Anvisa and hopes to obtain approval for the use of its vaccine in Brazil soon. Around 2 million doses of ChAdOx1 will be delivered to the Ministry of Health from 08/02/2021, with the forecast being to receive 100,4 million doses of the AstraZeneca vaccine even in the first semester, according to Fiocruz.
EUROPEAN UNION UNIFIED VACCINATION CAMPAIGN WILL BE STARTED
After the start of vaccination against Covid-19 in the United Kingdom, a historic milestone in the fight against Covid-19 and to show unity in facing the pandemic, the 27 countries of the European Union (EU) will begin unified vaccination campaigns on the 27th /12/2020, as the European Medicines Agency (EMA), the EU regulatory body, approved the Pfizer/BioNTech vaccine. The United Kingdom left the European Union on 31/01/2020. We are rooting for it to actually happen, as it would be great to have good prospects to start forgetting 2020 and the virus. We will only be safe when everyone is safe. Without a doubt, one of the most gratifying news to bring to this space.
NEW VARIANTS OF SARS-COV-2 IN THE UNITED KINGDOM
A new strain of SARS-CoV-2, named VUI–202012/01, was recently detected in more than 60 locations in the United Kingdom, after 1.108 cases of Covid-19 were identified. To date, just over 40 countries have temporarily suspended flights from the UK. But we still don't have concrete data to prove that these mutations mean the virus is evolving to be transmitted more easily between people, to become more virulent or to cause a more serious disease.
This increase in the number of cases may also be related to the relaxation of the population, especially younger people, not respecting non-pharmacological measures to combat Covid-19. Human behavior during this pandemic is worrying. Scientists have already observed thousands of mutations in SARS-CoV-2, but some variations in the protein Spike (spike), which is used by the virus to enter our cells, attract attention. In this case, scientists observed 17 mutations in the virus genome, 3 of which were in the Spike protein. One of the mutations, known as N501Y, occurs in the receptor-binding domain, which the virus uses to bind to and enter the ACE-2 protein in our cells. The other mutation (H69/V70) has previously been observed in humans and in the more than 10 million minks infected and euthanized in Denmark.
The British government is reevaluating the strategy to combat the pandemic due to the recent disclosure of this new strain of the SARS-CoV-2 virus, which could be more transmissible and be responsible for boosting the spread of the virus there. But the fact is that there is no robust scientific evidence that the new variant is transmitted more easily, causes a more serious disease or even renders vaccines useless.
The SARS-CoV-2 variant known as D614G, which is dominant in Brazil, is more easily transmitted than the previous lineage without this mutation. If H69/V70 behaves like D614G, the impact will be greater on the proliferation of the disease than on mortality, but the fact that it is more transmission would be enough to wreak havoc on health systems, as with more people infected, the demand for hospital treatment will be greater in less time.
One of the Another variant of SARS-CoV-2 known as N501.V2 was detected in South Africa and may be responsible for the majority of cases in the second wave in the country, infecting young people and people without comorbidities, who developed more severe cases of the disease. This new strain was also observed in the United Kingdom, may have undergone further mutations and may have a high transmission rate, according to British authorities.
For the virus to become resistant to the vaccines being developed, it would be necessary a very large change in its genetic code in the Spike protein region. The fact is that after the start of mass vaccination campaigns, to infect people who have been immunized, the virus will have to adapt and undergo major transformations in its Spike protein. If this happens as a natural process of virus evolution, we will most likely have to update vaccines, as is done for seasonal flu, but so far there is no evidence that these mutations can harm the effectiveness of vaccines under development.
RNA viruses like SARS-CoV-2 mutate all the time, this is normal, so it is very important to carry out Epidemiological monitoring, monitor the behavior of the virus, increasing sequencing capacity, to quickly detect mutant forms that may cause concern. The fact is thatThe more the virus spreads and circulates among people, the more people will be infected, an increasing number of random mutations will occur, some of which will be advantageous for the virus, but others will not. In this process, the virus can evolve.
The vaccines under development produce neutralizing antibodies that will bind to different points on the virus' Spike protein, neutralizing it. Therefore, mutations that are not in the Spike protein should not hinder vaccines in development and even mutations that occur in the Spike protein would have to occur to a large extent in order to prevent recognition of the protein by neutralizing antibodies. And if this happens in the future, simply adapt platforms that use fragments of the Spike protein, such as those from adenovirus and messenger RNA, to prepare a more robust vaccine. Or use the new, inactivated strain of the virus, but I think that adenovirus and especially messenger RNA platforms have come to occupy this space. Science is paying attention and with science we will get out of this pandemic.
VACCINE, ONE PASSAGATE TO THE FUTURE
Soon, countries will require proof of vaccination against Covid-19. It will be like a passport to the future, if we want to achieve a world without Covid-19. If you don't have it, don't enter the country, or get a vaccine when you enter, sitting there at the airport. The federal government published on 17/12/2020, an ordinance requiring a negative RT-PCR test for Brazilians or foreigners who want to enter the country by plane. The measure will come into effect from 30/12/2020 and the test, which must be carried out up to 72 hours before the flight, will be required upon boarding.
OVERVIEW OF COVID-19 IN BRAZIL
THE FIRST CASES OF REINFECTION IN BRAZIL
The Ministry of Health confirmed both first cases of reinfection by Covid-19 and reported that it is monitoring other suspected cases that were reported by state health departments and are being evaluated in 9 states. Some suspected cases have already been discarded, as they do not meet the minimum period of 90 days between the first and second infection, or did not present positive RT-PCR results, or did not yet show different lineages after the complete sequencing of the coronavirus genome in both cases. infections.
The term lineage corresponds to a group of viruses that contain several mutations in common. The first confirmed case was a 37-year-old doctor from Rio Grande do Norte, infected by two different strains of SARS-CoV-2, collected in João Pessoa on 23/06/2020 (lineage B.1.1.33) and the second on 13/10/2020 (lineage B.1.1.28), which confirms that these are new cases. The short time between the first and second infection, less than 4 months, shows that the doctor did not acquire protection in terms of immunity to avoid reinfection. Another case of reinfection was confirmed by the Adolfo Lutz Institute, in São Paulo, after genetic sequencing of two clinical samples from a 41-year-old woman.
The analysis showed that they are two different lineages, with the first lineage, diagnosed in June, circulating only in Brazil, while the lineage responsible for the second infection, 145 days later after the first, involves a variant that has already been identified circulating in the United Kingdom. , Australia, Chile and the United States. Apparently, the reinfection process is not frequent, but genetic surveillance of the virus needs to continue.
FAKE NEWS OF THE FUTURE ABOUT VACCINES
The SARS-CoV-2 virus is one of the worst enemies humanity has ever faced. But today we face other dangerous enemies, such as the viruses of misinformation, scientific denialism, ignorance and false narratives created around ineffective medicines in the fight against Covid-19 and around vaccines. I already commented here about misinformation o anti-vaccine movement e fakenews, and that we would be hit by the biggest wave of disinformation in history. Clearly, the benefits of vaccines outweigh any harm they may cause. However, we need to prepare to combat the biggest wave of lies and fake news in history, which will emerge around adverse effects related to vaccines. The anti-vaccine movement will use this moment to create false narratives about deaths being caused by vaccines.
In the coming months, post-vaccination, people will die of natural causes, some by accidents, but false, fanciful and lying evidence will be released linking deaths with the fact that people have taken this or that vaccine. Narratives will be constructed appealing to coincidences in deaths or health problems that appeared post-vaccination, even if they were already going to appear, with certain vaccines. If a person who was vaccinated dies from some natural cause, or accident, suicide, cancer, no matter the reason, this criminal movement will spread the word that the person died because they had a chip in the vaccine, that they had the virus that causes HIV in the vaccine, because the vaccine caused cancer, which was to control population, the vaccine altered the DNA and the person became sick.
When choosing where to stay, We will need to be alert and anticipate combating the lies of these groups that use their creativity to promote disinformation because they reject science, motivated by political or religious interests, or other nefarious interests. And to combat this criminal movement, we will need a lot of organization in the pharmacovigilance phase, post-vaccination and society enlightenment campaigns.
A JUDICIALIZATION OF VACCINES
the endWe have been in the midst of a pandemic for a year that has already claimed the lives of almost 190 Brazilians and, as incredible as it may seem, we are dealing with a process of judicialization of vaccines. The Federal Superior Court (STF) ruled that parents must vaccinate their children under 18 years of age and denied authorization for parents not to vaccinate their children based on “philosophical, religious, moral and existential convictions”.
Another important decision was the authorization for state and municipal governments to pass laws with sanctions for people who do not take vaccines against Covid-19. These decisions cannot be prevented by the Federal Government. The Federal Council of the Brazilian Bar Association (OAB) filed a lawsuit with the STF requesting "full validity and applicability" of law no. 13.979/2020, in case of omission by Anvisa. Then, an injunction from the STF minister, Ricardo Lewandowski, on 17/12/2020, authorizes states and municipalities to import and distribute vaccines that have been registered by foreign health authorities from the United States, China, Japan and the European Union, if The Anvisa fails to meet the deadline to evaluate emergency requests. This applies to the federal government with the national vaccination plan against Covid-19.
Anvisa informed on 14/12/2020 that the process of analyzing the emergency use of vaccines with clinical trials being carried out in Brazil will be completed within a maximum period of 10 days and that it will work between Christmas and New Year. According to the Agency, only Vaccine candidates with phase 3 clinical trials being conducted in Brazil may receive emergency approval. Among the vaccine candidates in phase 3, four are being tested in Brazil: Pfizer/BioNtech; that of Oxford/AstraZeneca; that of Sinovac/Butantan; and the Johnson&Johnson vaccine.
RESTRICTIVE MEASURES FOR THOSE WHO DON’T GET VACCINATED
In the country of obscurantism and denial of the pandemic and science, the STF authorized, on 17/12/2020, states and municipalities, to adopt restrictive measures for those who do not get vaccinated against Covid-19, when vaccines are approved and included in the National Immunization Program. The STF (as well as people with a minimum of common sense) argues that collective health cannot be harmed by individual decisions. These are not coercive measures, no one will be forced to get vaccinated, but there will be sanctions for those who do not do so. The issue is that the STF only authorized, or gave its approval, so that the President of the Republic, governors and mayors can adopt restrictive measures. The president stated that he will not take the vaccine against Covid-19 and called anyone who sees him as a bad example for not getting immunized an “idiot”.
It's absolutely unbelievable, science gave such a quick, efficient response and we have vaccines being approved for emergency use in less than a year from the start of the pandemic, but in this country some leaders promote misinformation against vaccination. This is the time for all authorities to embrace and demonstrate unconditional support for mass vaccination campaigns against Covid-19, so that we can have the high vaccination coverage that will begin to lead us out of the pandemic.
The Brazilian Constitution, in articles 6 and 196, clearly states that health is a right of the population, a right for everyone and a duty of the State. It is up to the Brazilian State to guarantee the use of social and economic policies with the aim of reducing risks and combating diseases that afflict the population, kill or disable them, providing universal and equal access to actions aimed at protecting the population's health. If the vaccine shows safety in all phases of clinical studies and efficacy in phase 3, being approved, it is because it was considered safe for use, although restrictions regarding groups that cannot take the vaccine must appear in the leaflet.
Society will not organize itself, we need leaders, for the Federal Government to lead the Nation, but not into the hole. This unfortunate scenario is happening, it's not fiction, but it looks like one of those movies with bizarre scripts that would make Ed Wood a little jealous.
VACCINE DEFENSE RESPONSE
Vaccines can stimulate the immune system to produce a more efficient defense response than the response obtained by natural infection with the wild virus. The viral load or amount of virus, as well as the routes of entry into the body are different. SARS-CoV-2, which causes Covid-19, enters our body through the respiratory system and activates the immune system, but the response in terms of mucosal immunity is less powerful. Once inside the organism, the immune system can produce a humoral adaptive response with the production of neutralizing antibodies and a cellular response, with the production of T lymphocytes, the so-called CD4 T cells and the cytotoxic CD8 T cells, but whose duration of protection is not yet well known. .
According to available data, this protective response does not appear to be very long-lasting. Vaccines work by introducing a foreign body into our body to trick the immune system into believing that there is an intruder that needs to be fought. Vaccines can stimulate the immune system to produce a more robust response of neutralizing antibodies and T lymphocytes, but not necessarily both responses (humoral and cellular). Vaccines based on inactivated viruses, adenoviruses, as well as those based on attenuated or weakened viruses, require the use of adjuvants, which are chemical compounds, some based on aluminum salts, to reinforce and help the immune system's response. Messenger RNA (mRNA) vaccines contain protective lipid nanoparticles based on polyethylene glycol (PEG) that can function as adjuvants.
Another important point is that in the case of natural infection with the wild virus, as in the case of SARS-CoV-2, our immune system is activated only when the virus has already entered the body, it was not prepared, having to respond of protection and combat a virus that may already be causing some damage by infecting our cells. With vaccines, by inoculating a foreign body that has some characteristics of the virus into our body, our immune system is being trained to fight that intruder, so, when the real, wild virus enters our respiratory tract, our immune system remember that you have seen something similar to that strange body before and go and fight. It's ingenious.
FIOCRUZ BOOKLET FOR THE END OF THE YEAR
Preserving lives is the best gift at the end of 2020. This is not the time to take risks. Fiocruz released a material very didactic and informative, containing a coexistence plan with guidelines for the end of the year. More information here.
I would add that if you think about taking the RT-PCR test to reunite with family this year-end, be careful. You can be infected, be asymptomatic, then the risk of a false sense of security with a false negative result is enormous, due to the lower sensitivity of the test in this situation, which even depends on when and how the material is collected.
A negative result does not mean that you are not infected and will not transmit the virus to your family and friends. No one can relax non-pharmacological protective measures. This business of using the RT-PCR test as a security passport does not exist. In case of a positive RT-PCR test, this is social isolation.
A FINAL MESSAGE
To date, just over two million people have been vaccinated against Covid-19, in eight countries. I already said this, but I repeat, vaccines, along with basic sanitation, drinking water and treated sewage, are our best public health strategy, they are the best alternative that humanity and science have to combat diseases that kill or disable people .
We still don't know which vaccines will protect different populations, so we need all vaccines that prove to be safe and effective, approved for emergency use or duly registered by Anvisa. We need to get out of this pandemic as a Nation. Enough of political disputes that put the health of the Brazilian population at risk, the time is for dialogue, conversation, balance and common sense. Or the virus will continue among us, the year 2020 will not end in 2021 and perhaps not even in 2022.
The development of vaccines against Covid-19 was recognized as the “Scientific Advancement of the Year” by the scientific magazine Science. It is undoubtedly the greatest legacy of this pandemic. We need to embrace the cause of vaccination against Covid-19 and combat the anti-vaccine movement, scientific denialism and obscurantism, with SCIENCE. If the symptoms of anti-scientism persist, good scientists must be consulted.
Eu 
I close the 2020 columns in this space in Jornal da Unicamp, expressing solidarity with the families of the almost 190 people who died in Brazil from Covid-19 in this year of challenges for all of us.
I wish everyone who survived this fateful year a Christmas of peace, light, balance, wisdom, reflection, serenity and may 2020 end, may it not continue in 2021. And may 2021 be a year of encouragement, solidarity, affection, empathy, common sense, hope, respect for the community and safe and effective vaccines against Covid-19.
And may 2021 be the International Year of Celebration of Life! Stay safe and well, everyone.
