The SARS-CoV-2 virus is not becoming more lethal or pathogenic. It is a very personal opinion, reflecting and studying a lot about the pandemic, since 31/12/2019, when the SARS-CoV-2 virus was presented to the world. The virus, in this process of natural evolution, is trying to escape the immune system response of its natural hosts, humans. Then, it undergoes random, unplanned mutations so that it can continue replicating and producing millions of copies of itself.
The virus wants to adapt to the organism of its host, us, the little humans. For the virus, it is not interesting to destroy its natural host, to kill human beings, because in doing so, it does not replicate. For the virus to continue replicating, it is also not interesting to make everyone very sick, otherwise people will be isolated and there will be community transmission. Ah, but then they'll say, the virus is not a living organism, it doesn't have that intelligence. Then I appeal to Darwinism, natural selection.
We have been in the pandemic for just over a year and a half, a little less than that in Brazil. Almost 200 million people have been infected by SARS-CoV-2 and its variants and around 4,1 million people died from Covid-19 in the world, with just over 542 thousand deaths in Brazil alone (numbers most likely underreported).
Some variants of concern have emerged, but despite being more transmissible, they are not becoming more lethal, fortunately. These new variants of attention, such as Delta, which recently arrived in Brazil, are not causing more serious illnesses, are not more lethal, butis virulent or more pathogenic, when compared to the original virus. Apparently none of these variants of concern, Alpha, Beta, Gamma, Delta (the most dangerous) or the variants of interest Epsilon, Zeta, Eta, Theta, Iota and Lambda are more lethal. They are becoming more transmissible, infecting more people, as that is what the virus wants, to spread more and more.
In a slow vaccination process, the virus may try to adapt again, now to escape the vaccine response, leading to possible vaccine escape, but as we accelerate vaccination, this process will occur more slowly, making it difficult for new variants to emerge. of attention, as stated in the following point, with studies showing that mass vaccination reduces the speed at which the virus evolves. Bingo, that's great.
This is the future, mass vaccination, although we will possibly have to live for a few years with a virus that can cause a milder illness, perhaps something like the flu. This is how I see the future of this pandemic.
Variants fight for space
The Delta variant is fighting for space in Brazil with the Gamma variant and could become dominant, and in this scenario of slow vaccination, it could still lead to an increase in the number of infections, but the vaccines will continue to be useful and effective and will prevent hospitalizations and deaths.
The important thing will be to be able to vaccinate more quickly so that, even in a scenario where cases increase in some places, as people think the pandemic is coming under control and tend to relax non-pharmacological measures, these will be milder cases due to the protection afforded by all vaccines in use in Brazil, without exceptions.
When vaccinated, with any an of the vaccines in use, people can still be infected if they come into contact with the virus, but the disease will be milder, milder. I see a way out right there, but rapid mass vaccination, with the maintenance of non-pharmacological measures until we reach around 75-85% of the vaccinated population, is essential. And we will reach this percentage of vaccinated people, because we are overcoming denialism and the lies of supporters of the anti-vaccine movement.
These are vaccines that slow the virus’s evolution
Um study published on 05/07/2021 still in the form of preprint on the portal medrxiv, but which can be considered very good for humanity, was led by the British biotechnology company difference and showed that vaccines reduce the speed at which SARS-CoV-2 evolves. Scientists have observed that the diversity of the virus is decreasing as the rate of mass vaccination increases.
Scientists mapped the SARS-CoV-2 genomes available in the GISAID database, which contains genetic information about the virus, and showed that attention variants, such as Delta, have relevant mutations in the Spike (S) protein. The good news is that vaccines are reducing genetic diversity in the virus gene responsible for synthesizing this protein.
By comparing the virus genomes of 23 patients infected after vaccination with those of 30 unvaccinated patients who were infected, the scientists observed that despite not preventing infection, vaccines reduce the speed at which the virus evolves, which implies reducing possibilities for evolutionary escape. That is great. The virus takes advantage of the opportunity to spread more quickly in places with slow vaccination, but the advancement of vaccination reduces the appearance of new variants of the virus.
INTERCHANGEMENT STUDIES
Nroe strains
Initially, let's make it clear that there is no scientifically proven beneficial effect of revaccination against Covid-19 at this time. People doing this will not have any benefit and it is an act of selfishness, lack of empathy and social responsibility, as they are taking vaccines from those who have not yet taken the first dose or have not completed the vaccination schedule. e damaging the action of the National Immunization Program (PNI).
On 14/07/2021, Anvisa approved a new study of the AstraZeneca vaccine in humans. The clinical trial will involve a specific assessment of protection against the Beta attention variant (the B.1.351 variant, which emerged in South Africa), in addition to an interchangeability study, or combination of different vaccine platforms, with the messenger RNA vaccine from Pfizer. The change in the vaccine platform involves replacing the genetic material of the Spike (S) or spike protein of SARS-CoV-2, now extracted from the new Beta attention variant, inserting this new material into the chimpanzee adenovirus.
This phase 2/3 clinical trial will involve the participation of 2.475 volunteers over 18 years of age in Brazil, the United Kingdom, South Africa and Poland and foresees three groups with vaccines already registered with Anvisa:
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The first group takes a single dose of the AstraZeneca vaccine adapted for the Beta variant, with the participation of volunteers who have already taken two doses of the AstraZeneca vaccine or two doses of the Pfizer vaccine;
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The second group involves volunteers who have not yet been vaccinated, who take two doses of the AstraZeneca vaccine adapted for the Beta variant;
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The third group will involve volunteers who have already taken the first dose of the current AstraZeneca vaccine and will take a second dose of the AstraZeneca vaccine adapted for the Beta variant.
Combination of Oxford/Astrazeneca and Pfizer/Biontech vaccines
The Spanish CombivacS study, led by the Carlos III Health Institute in Madrid, showed that heterologous vaccination of people with a first dose of the Oxford/AstraZeneca vaccine and a second dose of the Pfizer/BioNTech vaccine produces a potent immune response against the SARS virus. -CoV-2. The preliminary results of this heterologous booster study, which show the benefits of combining different vaccines against Covid-19, involved the participation of 663 volunteers and were initially announced on May 18 by the Carlos III Health Institute and magazine Nature, but published on 10/07/2021 in magazine The Lancet.
Based on these results, Pfizer's vaccine increased antibody responses in people vaccinated with one dose of Astr's vaccine.aZeneca. It would be great if vaccination regimens using different vaccine platforms could trigger stronger and more robust immune responses than administering two doses of a single vaccine.
The Oxford/AstraZeneca vaccine uses a chimpanzee adenovirus as its vaccine platform, incapable of replicating in the human body, but capable of providing instructions for our cells to produce parts of the S spike protein (S).ARS-CoV-2. All volunteers involved in this randomized, double-blind clinical study received the Oxford/AstraZeneca vaccine as a first dose and approximately two-thirds of the volunteers received the Pfizer/BioNTech mRNA-based vaccine as a second dose, approximately eight weeks after vaccination. first dose. A control group of 232 people received no booster.
After this second dose of the Pfizer/BioNTech vaccine, the volunteers produced higher levels of antibodies, which inactivated the SARS-CoV-2 virus in tests vitro laboratory. Volunteers in the control group who did not receive the Pfizer/BioNTech vaccine as a booster had no change in antibody levels.
When compared to previously obtained data, the researchers involved in the study emphasize that the antibody response to using the Pfizer vaccine as a second dose appears to be even stronger than the response that most people generate after receiving two doses of the Oxford vaccine. /AstraZeneca. At this time, it is not yet clear how the antibody responses in this study compare to those seen in people who receive two doses of the Pfizer/BioNTech mRNA vaccine, which as we know triggers a potent antibody response after a second dose.
We can speculate that if a third dose is necessary as a vaccine booster, in the case of regimens involving repeated doses of adenovirus-based vaccines, such as that from Oxford/AstraZeneca, the immune system may produce a protective response against the adenovirus itself, the which may lead to a less robust response.
A third dose of an mRNA vaccine like those from Moderna and Pfizer/BioNTech could trigger a robust protective response, but also stronger side effects. Without a doubt, it will be very exciting to wait for the next chapters of vaccine combination and interchangeability studies, including a possible third dose as a booster. In the CombivacS study, only mild side effects similar to those seen in regimens using the Oxford/AstraZeneca and Pfizer/BioNTech vaccines were observed..
About a possible third dose
AstraZeneca and Sinovac are updating their vaccines to combat the new variants of concern. AstraZeneca is adapting its vaccine for the Beta variant, which emerged in South Africa, and Sinovac is updating CoronaVac for the Gamma variant, which emerged in Brazil. If in the future we need a third dose or booster dose, these will most likely happen with vaccine platforms already adapted to the new variants of care.
All new vaccines must undergo phases 1 and 2 testing to assess safety and immunogenicity, but phase 3 will most likely involve non-inferiority studies comparing them to current vaccines in use. The adaptation of vaccine platforms to new variants should be faster, as both the safety of the method and the production of antibodies will have already been validated. Pfizer has been conducting studies of a possible third dose, but using the same original formula, not yet adapted to the new variants. Pfizer and AstraZeneca are already carrying out tests in Brazil, while Butantan is expected to carry out the clinical trial in Brazil during the second half of 2021, as soon as it receives the updated batches from Sinovac, scheduled for August.
Anvisa releases tests with ButanVac
On 07/07/2021, Anvisa authorized the start of phase 1 and 2 trials of the ButanVac vaccine candidate in volunteers, after Butantan presented data on the inactivation of the virus. A ButanVac uses technology based on the virus that causes Newcastle Disease, using a genetically modified. This virus only attacks birds and is used as a viral vector for the coronavirus Spike protein to induce a protective response.
A ButanVac will be produced using chicken eggs, the same technology used to prepare vaccines against the flu. As Butantan masters this technology, the country will have autonomy and the entire process will be carried out in Brazil, as we will not need to import the raw material. The study will involve six thousand volunteers over the age of 18 who have not been vaccinated against the new coronavirus and will be divided into three stages: A, B and C.
Anvisa authorized the beginning of phase A, with 418 participants recruited by the Hospital das Clínicas of USP in Ribeirão Preto, when Butantan must define the dosage, the quantity of milliliters of each of the two planned doses, with an interval of 28 days between them , in addition to evaluating safety. The initial studies were carried out by scientists from Icahn School of Medicine at Mount Sinai, in New York. Butantan reported that it has already there are 10 millions of stored doses of ButanVac.
The antivirals that never were
According to a study conducted by researchers at the University of California, San Francisco, published on 22/06/2021 in the respected magazine Science, some of the medicines in the so-called early kit, are not active against the virus that causes Cvid-19. Scientists tested 23 drugs, including chloroquine, amiodarone and sertraline, and found that what appeared to be antiviral activity in cells was actually the result of a mechanism called phospholipidosis, which disorganizes cells by disrupting fundamental cellular processes. The conclusion of the work is that these medicines have no future in the fight against Covid-19.
Typically, antiviral compounds use different strategies to stop viruses from replicating.who in a cell and one of the possibilities is to prevent the production of essential enzymes. Phospholipidosis consists of the accumulation of lipid (fat) molecules outside the cell membrane. This process occurs when organelles called lysosomes can no longer break down or distribute proteins to the rest of the body.
Phospholipidosis harms cells infected by the virus, but is not a therapeutic alternative, as it can cause serious damage, including lung and liver damage. In the case of the molecules studied, the antiviral activities observed are correlated with phospholipidosis, an effect responsible for damage to infected cells. The molecules with the best antiviral activity were cationic and fatty medicines, which are inactivating the virus in a way that is not useful for humans.
More evidence against the use of invermectin in the treatment of Covid-19
One of the meta-analysis published in the magazine Clinical Infectious Diseases on 28/06/2021, one of the most important in the area of infectology, shows the total ineffectiveness of ivermectin to combat Covid-19. This systematic review of gold standard randomized clinical trials was published in a high-impact magazine, bringing together publications with the highest level of scientific evidence to date. The authors surveyed randomized clinical trials (RCTs) evaluating the effects of ivermectin in adult patients infected with Covid-19, published or accepted as preprints until 22/03/2021. The primary outcomes were: Mmortality, length of stay and adverse events. Secondary outcomes included viral clearance and serious adverse events.
The Cochrane RoB 2 tool was used to analyze the risk of biased results. Ten randomized clinical trials (with n = 1173) were included, comparing with 5 trials with a control group with standard of care treatment and 5 trials with a placebo group. The severity of Covid-19 was mild in 8 randomized controlled trials, moderate in one trial, and mild to moderate in one of the trials. The review showed that, unfortunately, ivermectin was not able to reduce mortality, did not reduce hospitalization time or viral clearance when compared to the control group in patients with mild disease.
The conclusion of the studies is that ivermectin is not a viable option to treat patients with Covid-19, because does not bring any benefit and does not change the natural history of the disease. The University of Oxford will test ivermectin in a large-scale study such as Principle, who, in January, ruled out the use of azithromycin and doxycycline in early stages of Covid-19. The University awaits generate robust evidence to determine whether there are benefits or harms associated with the use of ivermectin to combat Covid-19.
Communication with society and combating denialism
We scientists need to continue transmitting correct and transparent information to society. Unfortunately, we have some pseudoscientists in Brazil, some pseudojournalists and many doctors who do not understand science and the scientific method, spreading misinformation and Fake News. The leftovers cabinet (the shadow cabinet) and hate, it actually exists. For a recent article about the disinformation and lies machine, with the dissemination of false scientific data about Covid-19, shared by parliamentarians, see publication by The Globe and Folha de S. Paul.
Brazilian society needs to understand that the opinions of qualified scientists cannot have the same weight as the opinions of politicians or pseudo-journalists who have no scientific training or doctors who do not follow the evolution of science. The population needs to understand that science saves lives and saves people from denialism and obscurantism.
We are realizing that in times of pandemic, the population's trust in science increases and Covid-19 is showing that there is no safe world without science. We will win the battle against the virus and against those who spread Fake News and misinformation and we will win with science. Only science saves.
Article retracted by the magazine Vaccines
A publication in the magazine Vaccines (open access journal from the Swiss publisher MDPI) on 24/06/2021 led to the resignation of several virologists and vaccinologists from the position of editors of the journal. The movement was a protest against the publication of an article that improperly used data to conclude that for every three deaths prevented by vaccination against Covid-19, two deaths were caused by vaccination. Yes, revolting and irresponsible. O article was retracted by the journal after notifying the authors, who did not agree. The authors suggested, without proving a causal relationship, that all deaths occurring after vaccination were caused by vaccination, suggesting that the vaccines used against Covid-19 are not safe. The data was distorted and once published, the article was disseminated by activists of the anti-vaccination movement, an irresponsible and criminal group that defends the virus.
Observation: This text is the responsibility of the author and does not necessarily reflect the opinion of Unicamp.
