Prof. Sabino's Research Group Sequences SARS-CoV-2 in Less Than 48 Hours

Interview conducted on 4/14/20

1. What made you decide to become a researcher?

Since I entered medical school at the University of São Paulo (USP), I had the desire to work in research. I've always enjoyed doing research more than working in clinical practice. Early in my career, I started to work at the Adolfo Lutz Institute. I really like public health research.

2. What made you interested in tropical medicine?

I have changed a lot during my career. I started working with HIV at the Adolfo Lutz Institute. After that, I worked for a long time with bloodborne diseases at the Pro Blood Foundation/Blood Center of São Paulo. Tropical medicine was something I got involved in more recently, in 2011, when I started working at USP. When I was still working at the foundation, I was working with Chagas disease, which is also a bloodborne disease. That is when I started to get involved in tropical disease research. But I have worked with bloodborne diseases for most of my life.

3. How did you start working with SARS-CoV-2?

After I joined the Institute of Tropical Medicine, the Zika epidemic started. So, I started to work again with epidemics. While working with Zika, I had contact with several groups, mainly from England, because of a grant funded by the UK for arbovirus sequencing. We have worked for a year with the Adolf Lutz Institute team on arbovirus epidemics, including dengue, chikungunya, Zika, and yellow fever epidemics. While we were doing this, the COVID-19 pandemic started. We already had everything set up to sequence the dengue virus, and thus, the whole structure to sequence SARS-CoV-2 was already there. In fact, before that, none of us had been working with coronaviruses, but everyone ended up working with SARS-CoV-2. That is kind of what happened to me, too; I was sequencing another virus, and then SARS-CoV-2 came along. [laughs]

4. So, was it your research on dengue that allowed you to sequence SARS-CoV-2 in less than 48 hours?

In fact, what happened was this: we deposited our sequences in a database system where most sequences were being deposited an average of 15 to 30 days after notification of the first case. In our case, as soon as the first notification was made in Brazil, we were able to sequence the virus in 48 hours. The sequence technique itself is fast and takes 24 to 48 hours. We did not do anything different with the technique. What we did was to organize the data ahead of time so that we could sequence the virus when the first case was detected...it was a matter of organization, of being prepared to do that.

5. In layman's terms, could you explain why SARS-CoV-2 genetic sequencing is so important?

Genetic sequencing allows you to understand how the virus is moving in all the places it has been. The sequence information can be deposited in a database and made available to scientists around the world. Today, there are numerous SARS-CoV-2 sequences deposited in databases, and scientists from several countries are depositing sequences. So, you can access the map and understand how the strains are going from place to place. Sequencing helps give an overview of how a virus is evolving and what mutations are being accumulated. With this information, you can see, for example, that although the borders have been closed to travel from China, the virus strain that ended up entering a certain country came from Europe. That is, sequencing helps you understand the flow of a virus through different geographic areas; it's important to see how much a virus is changing in order to make vaccines.

6. Are there any differences between the SARS-CoV-2 strain found in Brazil and those found in other countries?

No. The strains around the world are very similar to that in China. That sample we sequenced already has three different mutations compared to the original strain from China. That is very few; there are 30,000 base pairs, so three mutations is one mutation per ten thousand. So, all the strains are very similar. There are few mutations that cause the strains to differ from each other.

7. Some milder coronaviruses that cause the common cold tend to weaken in warmer months. Is there any research showing that this will be the case for SARS-CoV-2 in Brazil?

Apparently, the virus is behaving the same way that it is behaving in China and Europe. Now it is summer, and the virus's behavior is apparently unchanged.

8. Do you think the low number of cases in Brazil is due to the lack of tests, the behavior of SARS-CoV-2 in warmer climates, or some other factor?

In my opinion, the virus has not spread as fast in Brazil because we reduced people's mobility much earlier than the U.S., even though the reduction was not complete. The U.S. reduced people's mobility only after the epidemic had already started. In Brazil, mobility reduction was introduced before the epidemic was fully established. So, we managed to slow down the rate of transmission of the virus a little bit because actions were taken at the right time, especially here in the state of São Paulo. We may pass our threshold, but our curve isn't growing as fast as that of New York State.

We may be wrong and not realizing what is really going on because of the lack of tests, but the reality is that our hospitals are not overcrowded yet. They were expected to be overcrowded by the end of April or early May. Apparently, the growth curve keeps increasing, but not at the pace it would have been if we had not reduced people's mobility. After all, you can see that mobility has decreased a lot in São Paulo; air pollution has improved, the numbers of cars on the streets have decreased, and shopping malls are closed. The restrictions occurred well earlier than in the U.S., which took a long time to act. The numbers of cases in the U.S. then increased, just like those in Italy.

9. Although Brazilian culture is much more socially oriented than some other cultures, it seems to me that Brazil has taken social isolation more seriously than other countries.

In my opinion, we had to be aware. The images on television from Italy were very impactful, and the press played an important role in that. The press of Brazil has released several things that have made people aware, even if not completely aware – even though people's movement in São Paulo has decreased a lot, we still see many people in the city. But I do not know how long things are going to stay like this. Isolation for a long period of time is very difficult.

In turn, China had no way of being aware. By the time the Chinese realized what was going on, COVID-19 was everywhere. There was no way to know; no one knew about this disease beforehand. They started seeing people die from pneumonia from late November to early December. Soon after, they discovered the virus and developed tests. It's not easy for you to see pneumonia in the hospital and think it's something unlike anything you've ever seen.

Several pneumonia cases arose before they considered that this could be a new disease, because in winter, hospitals are always full of people with viral pneumonia. Finding out that the pneumonia cases one sees in the hospital are actually cases of a new disease caused by a different agent takes time, usually from 20 days to a month. By the time the Chinese realized the disease was caused by another agent, there were already a lot of people infected. However, in Brazil, things were different. In addition to China's experience, we saw the experiences of Europe and the United States.

This awareness is not so simple. People really are moved when they see that their acquaintances are sick, but it is very difficult to get people to stay at home without them having had this experience before or to have them stop doing things just because they are told to stop. Besides, when people stop working, they don't get paid. And this has a huge impact on people's lives, especially when they don't have anything saved. This is the reality in Brazil, where people live paycheck to paycheck and don't have savings. It is really very difficult.

10. Considering your entire career, which discoveries of yours have had the greatest impact on society?

Regarding HIV, I worked a lot here in Brazil with the Ministry of Health on viral sequencing and primary resistance in the AIDS program. During that period, my greatest contribution was to the AIDS program. In the field of transfusion safety, I have participated in several projects related to the risk of HIV transmission. I published an important article about the risk of dengue transmission. Regarding Chagas disease, my greatest contribution was in relation to test evaluations, the natural history of Chagas disease, and markers of disease evolution. I also participated in a Zika project with the Oxford University group. In that project, we analyzed a large number of samples and determined when the virus entered the country – which was a year before the first cases were detected.

We have worked with many different things. Here in Brazil, we must work on things for which we have financial resources. In the United States, it is easier for one to focus on only one line of research. We cannot do that here. Therefore, I have had to change my research focus according to the possibility of receiving resources. Because of this, I have ended up researching many different things.

11. What kinds of obstacles, if any, prevent you from doing your job in the best way?

We don't have many resources for research in Brazil. Also, we often don't receive full funding, and the funding is not continuous. It depends a lot on the economy.

12. Is there any legislation you would change to improve the way science is done in your field?

Here in Brazil, there are tax incentives for sport and culture, but there are none for science. That needs to change. Science needs that incentive.

13. To finish, what do you like to do when you're not doing research?

I love exercising, playing the piano, and going to the movie theater.

Posted on 05/18/2020

Prof. Sabino's photo credit: Leo Ramos Chaves

Thanks to Flavia Jaszczak for conducting the interview, Sheila Vieira for the interview preparation, transcription, and translation, and Molly Amador for English editing.

About Dr. Sabino

Dr. Ester Sabino earned both a degree in medicine and a PhD in immunology at the University of São Paulo (USP). After completing her PhD, she worked as a postdoctoral fellow at the Irwin Memorial Blood Center (IMBC, USA). From 2015 to 2019, she served as the director of the Institute of Tropical Medicine at USP, and she is currently an Associate Professor at the Department of Infectious Diseases of the USP School of Medicine; the Principal Investigator of the NIH "Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric" and "Sao Paulo- Minas Gerais Neglected Tropical Disease Research Center for Biomarker Discovery" projects; the Coordinator (Principal Investigator) of the São Paulo Research Foundation (FAPESP) Research Partnership for Technology Innovation Program (PITE) project "A translational study for the identification, characterization and validation of severity biomarkers in arboviral infections"; and the FAPESP/Medical Research Council (MRC) Brazil-UK Centre for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE) project funded by the MRC (UK) and the FAPESP. Her main research areas include transfusion safety, HIV, Chagas disease, arboviruses, and sickle-cell anemia.

Some of Dr. Sabino's publications regarding the subject discussed:

1. Candido, Darlan D. S., Watts, Alexander, Abade, Leandro, Kraemer, Moritz U. G., Pybus, Oliver G.; Croda, Julio, Oliveira, Wanderson, Khan, Kamran, Sabino, Ester C., and Faria, Nuno R. Routes for COVID-19 importation in Brazil. Journal of Travel Medicine, taaa042, https://doi.org/10.1093/jtm/taaa042.

2. Oliveira, Léa C., Pereira, Natalia B., Moreira, Carlos Henrique V., Bierrenbach, Ana Luiza, Salles, Flavia C., Souza-Basqueira, Marcela, Manuli, Erika R., Ferreira, Ariela M., Oliveira, Cláudia, Cardoso, Clareci S., Ribeiro, Antonio L., and Sabino, Ester C. ELISA Saliva for Trypanosoma cruzi Antibody Detection: An Alternative for Serological Surveys in Endemic Regions. The American Journal of Tropical Medicine and Hygiene, Vo. 102, Issue 4, 1 Apr 2020, p. 800 - 803, DOI:https://doi.org/10.4269/ajtmh.18-0330.

3. Rezende, Helder R., Romano, Camila M., Claro, Ingra M., Caleiro, Giovana S., Sabino, Ester C., Felix, Alvina C., Bissoli, Jefferson, Hill, Sarah; Faria, Nuno R., Silva, Theresa C. C.; Santos, Ana Paula B., Cerutti Junior, Crispim, and Vicente, Creuza R. First report of Aedes albopictus infected by Dengue and Zika virus in a rural outbreak in Brazil. PLoS One, vol. 15, 2020. https://doi.org/10.1371/journal.pone.0229847.

4. Oliveira, Claudia D. L., Nunes, Maria Carmo P., Colosimo, Enrico A., Lima, Emily M., Cardoso, Clareci S., Ferreira, Ariela M., Oliveira, Lea C., Moreira, Carlos Henrique V.; Bierrenbach, Ana Luiza, Haikal, Desireé S., Peixoto, Sérgio V., Lima-Costa, Maria F., Sabino, Ester C., and Ribeiro, Antonio L. P. Risk Score for Predicting 2-Year Mortality in Patients With Chagas Cardiomyopathy From Endemic Areas: SaMi-Trop Cohort Study. Journal of the American Heart Association, vol. 9, No. 6 p. 1-13, 2020. https://doi.org/10.1161/JAHA.119.014176.

5. Blatyta, Paula F., Kelly, Shannon, Sabino, Ester, Preiss, Liliana, Mendes, Franciane, Carneiro-Proietti, Ana B., Rodrigues, Daniela O. W., Mota, Rosimere, Loureiro, Paula, Maximo, Claudia, Park, Miriam, Mendrone-Jr, Alfredo, Gonçalez , Thelma T., Neto, Cesar A., and Custer, Brian. Prevalence of serologic markers of transfusion and sexually transmitted infections and their correlation with clinical features in a large cohort of Brazilian patients with sickle cell disease. Transfusion, vol. 60, Issue 2, p. 343-350, 2020. https://doi.org/10.1111/trf.15619.