An attentive and academic look at the COVID-19 pandemic
During April, 4 FMUL TALKS were carried out dedicated to the disease COVID-19, given by several FMUL professors and specialists and whose main objective was to inform the community about several aspects about the Sars-Cov-2 virus.
Below you will find a summary of the main ideas and reflections of the second talk.
FMUL Talks – 7 April - Update on Diagnosis and Therapy
Lectured by Professor Emília Valadas and by Professor Thomas Hanscheid
This webinar brought us two familiar speakers, Professor Emília Valadas and Professor Thomas Hanscheid, to offer us a different perspective on the pandemic. The two infection specialists shared with us their reflections about a time when we do not speak of a peak, but of a plateau in the epidemiological curve, a curve that is so familiar to us today.
Professor Thomas started by clarifying the “Covid test”. Surprisingly, he said that there is no test to screen for COVID-19, saying that what exists are tests for the detection of the virus genome. According to the specialist, serological tests, blood tests to detect the presence of antibodies and tests for antigens can be done. Both are distinct. The first is more complex, due to the requirement of means and qualified resources to carry it out. In total, there are already more than 440 tests on the market, including 100 unreliable rapid tests.
Precisely because of this growing number of tests, it is necessary to choose those of the highest quality. Thomas Hanscheid stated that even the “top of the range” test only detects, in the first swab, between 30% to 70% of infected cases. Performing a CT scan may be one of the most accurate forms of diagnosis.
There is currently a study, carried out by Chinese researchers, which aims to understand the changes in the test set of each patient, with the aim of ascertaining, with the maximum possible certainty, which patients are infected with the coronavirus. This study can be accessed and powered through this link by any health unit.
In this initial phase of Talk, dedicated to the relevance of the diagnosis, Professor Thomas warned of the need to use the swab correctly in the fluid collection procedure, as the incorrect use of this tool it may also compromise the result of the diagnosis. The ideal would be to test each person with 3 swabs at three different times.
Immunity certificates, achieved through antibody tests, were also mentioned. The Professor said that it is necessary to be cautious: "We still don't know if the person is effectively immune and for how long".
Then, the floor was passed to Professor Emília Valadas, who spoke about the need for effective, available and affordable treatment, since this pandemic affects both rich countries and countries with very fragile health systems.
In the second phase of the Talk, dedicated to therapy, Emília Valadas warned of the danger of using hydroxychloroquine, a substance used to treat malaria, and medications such as lopinavir or ritonavir, used in HIV. These options may be far from the most correct, with no strong scientific evidence that they work in the treatment of COVID-19. She underlined the potential of some drugs, such as remdesivir, azithromycin and ivermectin, whose therapeutic effects are being evaluated in some studies. However, her opinion is that there should be special caution not only in the combination and administration of these substances, but also in communicating the potential of these therapies to the general public.
Recently, a new strategic possibility to fight COVID-19 has emerged, which consists in the use of plasma from cured patients, but here too, it is necessary to be prudent. In her own words: “we have to ensure that it is from a convalescent person and that there are no viruses in circulation”.
In parallel, a large randomized study is being carried out sponsored by the WHO, which aims to compare four substances: remdesivir, lopinavir, interferon and hydroxychloroquine. “I believe that we will have results at the end of next month”, she said.
Another strategy on the table, and aimed at very serious situations, consists of a cascade of cytokines (extensive group of molecules), where the objective is to try to block receptors.
In conclusion, and after analysing some hypotheses, at the moment it seems that hydroxychloroquine + azithromycin, when combined, have an effect on decreasing the time and severity of the disease. However, with regard to the cure, we still know little.
We are grateful for the availability of Professor Emília Valadas as well as Professor Thomas Hanscheid!
FMUL Talks – 14 April - Immunity and Vaccination
Lectured by Professor Luís Graça
Professor Luis Graça started by expressing his regret at the death of Professor Maria de Sousa, a great Portuguese epidemiologist, which represents a major loss to the world of research.
Then he moved on to the topic of his lecture. He talked about viruses and how they develop in our body from the moment they enter the host's body until they disappear. We have two responses, one first, innate to viruses and the second that will lead to their elimination, through the so-called acquired immunity cells (CTLs). The same applies to Sars-Cov-2.
He explained that in cases where the disease progresses severely, in some patients there is an inadequate production of cytosines. Some immune cells release these cytosines and will cause widespread inflammation that can lead to serious problems in these patients. That is why some patients benefit from medication that neutralizes these cytosines.
He also mentioned that there is more lethality in older people, but perhaps this is not the most important factor, but the presence of comorbidities (cancer, heart disease, hypertension, obesity, and stroke, among others). At least 75% of deaths occurred in people with two of these diseases. As comorbidities are more present in the elderly than in young people, more deaths occur among the elderly.
Professor Luís Graça referred to the importance of the IGG antibodies. IGM antibodies are produced 1 to 2 weeks after infection, but it is the IGG antibodies that are produced later that will protect us from reinfection. In a new infection, the production of IGG is enhanced. As we move from a population without antibodies to a population with antibodies, we become immune and are not infected. Susceptible people will be a low percentage of the population and therefore there is a low probability of being infected. This immunity can occur through infection or vaccination. And the data suggest that in a large percentage of cases these people's antibodies are protective. They also suggest that the convalescent's plasma may neutralize the virus for some time.
The Professor then explained that, in relation to vaccines, there is a primary and a secondary response. The goal is to produce quantities of neutralizing antibodies that will prevent the virus from spreading if we contact it again. He gave examples of the flu vaccines and the human papilloma virus. He said that there is a huge effort to develop vaccines. One hundred and fifteen vaccine candidates have already been listed, at various stages of development and with a huge multiplicity of strategies. There are already 5 in clinical trials.
He then said that it is necessary to be cautious with the use of tests that measure antibodies. When there are few cases in the population, using these tests will lead to a greater likelihood of false positives. So it makes sense to use in diagnostic situations, but in screening situations, it will only be effective when the frequency of the disease is greater than a certain probability. Or it is a possibility to use two different tests, using the second one in everyone who tests positive in the first, to increase the percentage of certainty that that person is immune.
The explanations given by Professor Luís Graça were followed by questions asked using chat by the over 80 people who were viewing the webinar about vaccination possibilities, among other questions.
This FMULTalk was very enlightening and allows us to understand how our immune system works against viruses and the possible responses to fight Sars-Cov-2.
FMUL Talks – 21 April - Ongoing Clinical Trials
Lectured by Professor João Parracho da Costa
For this talk, Professor João Costa and his team conducted a survey to find the clinical trials that are taking place and made their comparative analysis to be able to show us some characteristics of these trials.
The Professor started by saying that to date there are no therapeutic options for treatment or prophylaxis that are particularly effective. This pandemic has sparked much interest and many clinical studies have been started. Thus, the questions that arise are: from the set of clinical research which tests will give clear answers? Will they have significant results from the patients’ point of view? And will it occur in a short period of time?
With their research on clinical trial platforms and other sites, they found about 389 records of protocols. The overwhelming majority, 359, are clinical trials to fight COVID-19, 92% treatment, 8% prophylaxis, and the other 30 trials are directly related.
One of the first characteristics that they noticed in all clinical trials is that there is poor registration quality, with omissions to include severe or critical patients, no perceived maximum age, and without registration and/or knowledge of all risk factors.
Of the 92% of clinical treatment trials, 49% are on drugs, 27% on traditional Chinese medicine, and the remaining 24% are on various treatment alternatives such as convalescent plasma.
Regarding the characteristics of the global sample in these clinical trials, 40% have patients over the age of 80, 60% have patients with severe symptoms of covid-19, 35% have critically ill patients and 4% have patients with associated risk factors (cardiovascular diseases , diabetes, etc.).
In terms of design and characteristics of the clinical trials, the vast majority are being carried out in China (76%), 50% have a random design, 41% are multicentre (carried out in several research centres, not just one), and only 17% are financed by industry. Regarding measuring the beneficial results for the patients, only 16% assess mortality, and few assess the % of cure and length of hospitalization.
Two aspects also identified were that, on average, clinical trials last 171 days and the sample is 100 people.
Professor João Parracho da Costa also spoke of the results in each type of clinical trial. In pharmacological treatment clinical trials, he concluded that: severe patients, when included, are very different from each other, the industry mainly finances antiviral trials and the trials evaluate very little the variables with clinical relevance.
In the 8% of trials dedicated to prophylaxis (e.g. vaccines), it was concluded that none of the trials aimed to assess mortality and only 57% evaluated the incidence of COVID-19.
The Professor then went on, noting that more than 2.5 million cases have been reported since January and that the scientific community was quick to start research to fight this virus. However, in his opinion, and taking into account the data analysed, the ongoing research seems insufficient to find clear answers in a short period of time.
He believes that for greater efficiency, research would have to be faster, more flexible and integrated.
Analyzing the data more deeply, clinical trials are not prioritizing patients at higher risk, which will be a missed opportunity. He points out that only 15% of trials have control groups. Also, the fact that 59% of the trials are not multicentric is a warning factor, as they will have a greater risk of bias and inflated estimates.
In addition, most trials are not looking at relevant and critical variables for patients, the duration of trials is relatively short, and the samples in each trial may not be sufficient.
In terms of treatment trials, most are antiviral, with few patients at risk in the sample and most trials exclude patients with comorbidities.
A question that the Professor also asks pertains to the benefit of 27% of the trials involving traditional Chinese medicine. What results that are relevant to patients can we expect from these trials? He also mentioned the limitations in data collection: this type of work becomes out of date very quickly because new trials are always starting. In many of the trials there are omissions in the fields and poor quality of records.
The last considerations were that it is necessary and urgent to have a global and high quality registration in relation to COVID-19 and that it is vital that the research carried out is coordinated and in relation to each other, to the detriment of isolated and independent research. So, with a word of hope, Professor João P. Costa ended his presentation by saying that he believes in the value of the scientific community and that we still have time to create more robust clinical trials.
Then, those viewing the webinar asked questions, focusing mostly on the issue of excluding patients with comorbidities from the trials, the methodological quality of the studies and the fact that the majority of the studies are independent and not agreed among various partners.
This webinar was very clarifying to understand the characteristics of the clinical trials that are being conducted and the possible developments and improvements that can be made for a more robust, quality research with benefits for those who present this disease.
Sónia Teixeira
Editorial Team
