TRANSMISSION, SYMPTOMS AND SUPERBACTERIA
Ttransmission by children
A study published in JAMA on August 28 by researchers at Children's National Hospital in Washington shows that asymptomatic children can carry and transmit Sars-CoV-2 for weeks. The study involved data from 91 children in 22 hospitals in South Korea, where those infected with Sars-CoV-2 remain hospitalized until complete recovery. Another study carried out with 192 children by Massachusetts General Hospital (MGH) and Mass General Hospital for Children (MGHfC), published on 19/08/2020 in The Journal of Pediatrics supports these conclusions by showing that very high viral loads were observed among younger patients. The researchers took samples of secretion from the nose and throat and found a large amount of the virus in the children. These results are worrying at this time of back to school, as it is certain that children and young people can infect other people, even if they do not show signs of being sick. And yes, children and young people can die or suffer from the consequences of a Covid-19 infection. We cannot renounce non-pharmacological measures, such as the use of masks, physical distancing and hygiene rules. A model that involves alternating between in-person and online classes may be an alternative. A challenge will be testing our children to detect and isolate those who are asymptomatic and their families, or testing only students with symptoms.
Asthma and Covid-19
Good news for asthmatics, although I won't risk it, is that it seems that Asthma does not appear to be such a big risk factor. Studies carried out with 436 patients admitted to the University of Colorado Hospital with more severe cases of Covid-19, show a low number of asthmatics who needed to be intubated when compared to non-asthmatics. This was the conclusion of a work published on 31/08/2020 in the magazine Annals of the American Thoracic Society. The group of researchers believes that the use of inhalers with corticosteroids makes it difficult for Sars-CoV-2 to enter the airways. O low number of asthmatics among hospitalized patients in other published international studies support these conclusions, but I I prefer to wait for even more comprehensive studies and the vaccine, even to go to the beach in peace.
Persistence of Covid-19 symptoms
In addition to the sequels already described in organs such as the lungs, heart, kidneys and brain in patients who were affected by more serious cases of Covid-19, many of the patients recovered, even those with milder or moderate cases of the disease, keep feeling for many weeks some symptoms such as pain in the head, legs and chest, tiredness, shortness of breath, fatigue, drowsiness, memory changes, difficulty concentrating, accelerated heartbeat, changes in the central nervous system, numbness in the hands and loss of smell and taste. A German study published on 27/07/2020 in Jama cardiology with 100 patients between 45 and 53 years old showed that 78% developed cardiac abnormalities due to inflammation in the heart. Another very interesting study involving researchers from the Unicamp Task Force to combat Covid-19 was published in the journal Cell metabolism. The researchers showed that the higher the glucose content, the more the Sars-CoV-2 virus accumulates within defense blood cells called monocytes and the more exacerbated the inflammatory response of these cells, which would help explain the severity of Covid-19. in people with diabetes. Professor Clarissa Lin Yasuda, a neurologist at Unicamp, leads a research which has been showing that Sars-CoV-2, which we already know leaves serious consequences in various parts of the body in people suffering from more serious cases of the disease, also triggers neurological complications. One study about is being carried out by the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN). Another study by Professor Daniel Martins-de-Souza's group points out that human neurons and astrocytes (other cells of the nervous system) derived from stem cells in culture, when exposed to Sars-CoV-2, can also be infected by the virus. These cells express the ACE-2 protein, used by the virus to enter human cells, and the researchers observed, in addition to infection and increased viral load in nerve cells, significant changes in their functions. All these studies add to several others already published and raise a very worrying alert for a post-Covid19 syndrome, with possible consequences even for people who had a milder case of Covid-19.
Beware of superbugs
The misuse of antibiotics has led to a reduction in their effectiveness due to acquired resistance by bacteria and it is imperative to create innovative medicines. The new coronavirus pandemic may contribute to the worsening of this situation, leading to multi-resistant bacteria, as many patients with Covid-19 are receiving antibiotics, but probably only a percentage of these have a bacterial infection during hospitalization. And we have also seen the uncontrolled distribution of azithromycin in several pseudo-miracle drug kits distributed by various mayors in this country.
THE VACCINE RACE
Sputnik V, the Russian vaccine candidate
And the long-awaited phase 1 and 2 study of the Russian vaccine candidate (Sputink V) came out, published on 04/09/2020 in the magazine The Lancet. Sputinik V is based on a platform that uses two vectors with more weakened forms of human adenovirus type 26 (rAd26-S) and type 5 (rAd5-S), which are incapable of replicating in the human body. The open study involved only 76 adult volunteers (18-60 years old), with 38 volunteers in each phase, was not randomized and did not have a placebo group. In each phase, nine volunteers received the vector (rAd26-S), nine received the vector (rAd5-S), and 20 volunteers received both vectors (rAd26-S on the first day and rAd5-S after 21 days). The results are interesting, showing that Sputinik V, developed by the Gamaleya Institute, was safe, not causing considerable adverse effects and inducing a good immune response with antibody production (21 days after application) and T cell cellular response.CD4+ and TCD8+ (28 days after application) in all volunteers. The most common adverse effects were pain at the application site, headache and moderate muscle pain and fever. These results are similar to those observed with other vaccine candidates and help bring transparency to the process, although preclinical trials have not yet been published. A clinical trial with 40 volunteers, in phase 3, which will show whether it really protects people, is underway and the results should be released in the coming months. Interestingly, they designed two formulations of Sputinik V, a frozen one, which needs to be stored at –18°C and can be produced on a large scale, and a freeze-dried formulation, which is stored at slightly higher temperatures (between 2–8°C ), which was developed for application in more remote regions of Russia. Producing a freeze-dried form takes more time and is more expensive. They justify the rapid development of Sputinik V based on their own experience in previous studies of attempts to develop vaccines against the viruses that cause Ebola and MERS.
The other candidates
In times of ideologization in the race to develop a vaccine, in a movement to revive nationalist pride, Russia, which had announced the registration of the first “vaccine” without phase 3 testing, is already running after the second. At the end of August, China approved Sinovac's candidate (CoronaVac), which is in phase 3 of clinical trials also here in Brazil, for emergency use by healthcare professionals and people at greater risk of infection by Sars-CoV-2. Also Chinese Sinopharm announced that it has obtained emergency use authorization for one of its two phase 3 candidates. The Chinese government's intention is to prevent new outbreaks during the autumn and winter there. In the USA, with presidential elections scheduled for November 03rd, the FDA stated that it also intends to approve a vaccine for emergency use against Covid-19, before phase 3 clinical trials are completed. The CDC, United States Center for Disease Control and Prevention, even notified the 50 states about the possibility of distributing the vaccine to health professionals and risk groups at the end of October. This will probably happen in other countries and in Brazil. In São Paulo, the optimistic State Secretary of Health, Jean Gorinchteyn, estimates that by June 2021, the State will have immunized the approximately 45 million inhabitants, starting in December 2020 with priority groups (health professionals, the elderly, and people with comorbidities and chronic illnesses).
However, only phase 3, after rigorous testing, will prove the efficacy and safety of the vaccine candidates and bring confidence to the population. No vaccine will be 100% effective, but approving any candidate in a hurry may not help and may even be very disruptive. The ideal would be a single-dose vaccine, with at least 70% efficacy, considering that we will have around 100% of the population vaccinated. If the percentage of people being vaccinated is lower, we will need greater vaccine effectiveness. In Brazil, we are 212 million people, if the vaccine is 100% effective and half of the population is vaccinated, we will have 106 million people immunized, but the other 106 million people will continue to be at the mercy of the virus. If the vaccine is only 50% effective and half of the Brazilian population is vaccinated (106 million people), we will have 53 million people protected and 159 million not immunized and even if 100% of Brazilians take the vaccine, we will still have 106 million not protected. See the importance of encouraging a mass vaccination campaign with a high adherence rate. We need to show the population that this vaccination campaign is fundamental and everyone must be vaccinated, for the common good, based on ethical and citizenship principles. The population needs and cantrust in a vaccine approved in phase 3, following the rigors and ethical principles of science. The research titled “Global Attitudes on a Covid-19 Vaccine” carried out in 27 countries by Ipsos for the World Economic Forum showed that 88% of Brazilians intend to be vaccinated against Covid-19, while the global average is 74%.
Even if there is some kind of political pressure to announce a vaccine, science will provide the final answer and only phase 3, with extremely reliable safety and efficacy results, should guarantee the approval or not of any vaccine candidate. This is a scientific decision, not a political one, where the benefits generated from the use of the vaccine must far outweigh any possible risks to human health, even in the context of a public health emergency such as the Covid-19 pandemic. In the end, the human organism and the virus will give the final verdict. “Operation maximum speed”, launched by the USA to accelerate the development of vaccines, cannot exceed or trample the rigor of science and caution is needed.
And it is essential that we combat the anti-vaccine movement, which seems to emerge with strength at this time of political polarization and the spread of fake news. recent data from WHO show that campaigns mass vaccination for diseases such as diphtheria, measles, whooping cough, polio, rotavirus, pneumonia, diarrhea, rubella and tetanus today avoid around four deaths per minute in the world.
Free vaccine?
Vaccines are very public. Bill 4424/20 (https://www.camara.leg.br/noticias/689477-projeto-preve-vacina-de-graca-contra-covid-19-e-prioridade-para-beneficiarios-do- Bolsa-familia/), under analysis in the Chamber of Deputies, foresees a free national vaccination campaign against Covid-19. The project also proposes equal and equitable coverage for the Brazilian population, starting with health, security and public order maintenance professionals, people over 60 years old, people with comorbidities, pregnant and postpartum women, beneficiaries of the Bolsa Família Program, teachers and support professionals from public and private schools and public service professionals. This Bill joins other proposals being processed in the Chamber, related to rules for vaccination against Covid-19, such as PL 4174 / 20 and PL 3982/20. Other 4433 / 20 Bill under analysis in the Chamber of Deputies inserts the measure of including potential future vaccines against Covid-19 in the coverage of private health care plans and insurance in Health Plans Law.
Read more:
Project defines criteria for vaccination against Covid-19
Proposal anticipates and establishes rules for vaccination against Covid-19
MEDICATIONS AND TESTING: UPDATE
Dexamethasone, reparixin and azithromycin
Confirming previously described results by other researchers, an article published on 2/9/2020 by the Covid-19 Brazil Coalition showed that the corticosteroid dexamethasone reduced the length of hospital stay in adult patients with severe cases of Covid-19. The study involved 299 patients aged around 61 years, with severe acute respiratory syndrome, admitted to ICU conditions and undergoing mechanical ventilation. A group of 151 patients was treated with dexamethasone, while the control group had 148 people, followed with standard clinical support. Dexamethasone was administered intravenously and allowed a faster exit from the artificial respirator. This is medicine based on scientific evidence. Reparixin, from the Italian company Dompe, being developed for organ transplants, is entering a Phase 2 clinical trial in Brazil with 48 volunteers to evaluate efficacy and safety. Reparixin will be tested on adult patients hospitalized with more serious cases of Covid-19 in the States of São Paulo, Bahia, Minas Gerais, Santa Catarina and the Federal District. Phase 3 will be conducted in the United States. The proposed mode of action for reparixin involves inhibition of interleukins 8 (IL-8), proteins associated with pneumonia observed in patients with more severe Covid-19 conditions. One open study and randomized trial of the Covid-19 Brazil Coalition published on 04/09/2020 in the magazine The Lancet, involved 397 volunteers in 57 centers in Brazil and revealed that the antibiotic azithromycin is not effective in treating seriously ill Covid-19 patients, confirming results obtained in previous studies. A group of 214 volunteers received azithromycin + hydroxychloroquine and the control group received only hydroxychloroquine, as this it was part of standard treatment in Brazil for patients with severe Covid-19. According to the authors, the rates of adverse effects such as ventricular arrhythmias, cardiac arrest, acute renal failure and prolongation of the corrected QT interval were not different between the groups and in conclusion, the researchers do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe Covid-19.
Antibodies and Covid-19
Even considering that serological tests are not 100% reliable, recent serological research carried out in several Brazilian cities shows that people who have recovered from Covid-19 have a drop in the level of neutralizing antibodies (IgG), those that defend us from reinfection. This has been observed frequently, but it is not surprising and the cases of reinfection being confirmed lead us to believe that the immune response in the case of Covid-19 is not only based on neutralizing antibodies (humoral response), but also involves a memory response cellular (cytotoxic CD4 T cells+ and T CD8+). The drop in antibody percentages shows that some recovered people may be susceptible to a new infection, but this does not mean that they are not immune.
Note: This text does not necessarily reflect the opinion of Unicamp.
