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TP

Covid-19: O que é que sabemos baseado em dados científicos

 

O que é o Covid-19?

Covid-19 também conhecido por SARS-CoV-2 (Síndrome Respiratória Aguda Grave – Coronavírus 2) é um vírus de RNA [1]. A comparação bioquímica e estrutural do Covid-19 com outros coronavírus permitiu concluir que este optimizou a sua ligação ao receptor ACE2 (receptor da enzima de conversão da angiotensina 2) que, por sua vez, leva à internalização do vírus para o interior das células humanas [1, 2]. Fisiologicamente, o receptor ACE2 (expresso na membrana das células do pulmão, coração, rins e intestino) é responsável pela maturação da angiotensina, uma hormona responsável pelo controlo da vasoconstrição e da pressão sanguínea [3, 4].

Quanto tempo é capaz o vírus de se manter estável?

No “New England Journal of Medicine” foi publicado recentemente um estudo científico sobre a estabilidade do Covid-19 no qual o vírus foi aplicado através de aerossóis (com uma carga viral controlada) em cobre, papelão, aço inoxidável e plástico, mantidos entre 21 e 23 °C e 40 % de humidade relativa ao longo de 7 dias.

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Figura 1 – Estabilidade do vírus Covid-19 (vermelho) e estabilidade do vírus SARS-CoV-1 (azul, vírus que causou a pandemia de SARS em 2003) em diferentes materiais. Copper: Cobre; Cardboard: Papelão; Stainless Steel: Aço inoxidável; Plastic: plástico. Adaptado de [5].

 

O estudo indica que:

O Covid-19 é mais estável em plástico e aço inoxidável do que em cobre e papelão: vírus viáveis ​​foram detectados até 72 horas após a aplicação nessas superfícies (Figura 1) embora a “quantidade” do vírus tenha sido bastante reduzida.

Mais precisamente:

  • No cobre, nenhum Covid-19 viável foi detectado após 4 horas
  • No papelão, nenhum Covid-19 viável foi detectado após 24 horas (1 dia)
  • No aço inoxidável, nenhum Covid-19 viável foi detectado após 48 horas (2 dias)
  • No plástico, nenhum Covid-19 viável foi detectado após 72 horas (3 dias).

Importa salientar que estas conclusões implicam que, nos períodos de tempo anteriores aos limites descritos, para cada material, amostras de Covid-19 foram ainda detectadas apesar da respectiva carga viral ser mais reduzida quando comparada com o valor inicial.

O estudo apresenta igualmente a comparação entre o Covid-19, (em vermelho) e o retrovírus mais semelhante, capaz de infectar humanos, SARS-CoV-1 (em azul). Os autores descrevem que a diferença de estabilidade entre os vírus não é significativa sugerindo que o problema epidemiológico que se está a verificar com o Covid-19está relacionado não só com a sua estabilidade (que, ainda assim, permanece como um dos grandes focos de preocupação), mas também com outros factores levando a duas hipóteses:

  • altas cargas virais de Covid-19 no tracto respiratório superior (em relação ao anterior SARS-CoV-1)
  • alto potencial de transmissão de Covid-19 por pacientes assintomáticos ou com sintomas muito ligeiros (não considerados como estando doentes)

 

Quais os sintomas despoletados pelo Covid-19?

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Figura 2. Sintomas e temperatura máxima corporal, de acordo com o dia de doença e o dia de hospitalização, do primeiro caso de Covid-19 reportado nos Estados Unidos da América. Fever: Febre; Cough: Tosse; Rhinorrhea: Corrimento de nariz; Fatigue: Fadiga; Nausea: Náuseas; Votiming: Vomitar; Diarrhea: diarreia; Abdominal Discomfort: Desconforto abdominal. Adaptado de [6].

 

A Figura 2 representa o primeiro caso de coronavírus descrito nos EUA. Neste estudo, os autores descrevem a identificação, diagnóstico, curso clínico e tratamento do caso incluindo os sintomas leves iniciais do paciente na apresentação com progressão para pneumonia no dia 9 da doença [6].

De notar que este é só um exemplo e que a progressão da doença pode ser diferente de indivíduo para indivíduo.

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Figura 3. Sintomas de indivíduos positivos para Covid-19 em Portugal recolhido pelas identidades portuguesas. Fonte: https://covid19.min-saude.pt/ponto-de-situacao-atual-em-portugal/ [consultado  a 19 de Março 2020]

 

Em Portugal, as autoridades locais têm vindo a recolher os sintomas descritos pelos indivíduos positivos para Covid-19 (Figura 3) [7]. Como podemos ver na Figura 3, a maioria dos pacientes descreve como primeiro sintoma a tosse seca imediatamente seguida da febre. Como descrito pela OMS (Organização Mundial de Saúde), cerca de 80% das pessoas infectadas é capaz de recuperar sem a necessidade de tratamento hospitalar [8]. Contudo, a OMS aponta pessoas idosas e pessoas com tensão alta, problemas cardíacos, diabéticos e imunossuprimidos como indivíduos de alto risco tendo maior probabilidade de desenvolver sintomas graves [8].

 

Podem pessoas assintomáticas transmitir a doença, ou seja, transmitir o vírus Covid-19?

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Figure 4. Tempo de exposição de diferentes pessoas a pessoas infectadas, o tempo que demoraram a ter sintomas e que testaram positivo para Covid-19 (descrito no gráfico como “Positive PCR”). Adaptado de [9].

 

Na Figura 4, está descrito o estudo de uma linha de transmissão na Alemanha. Um indivíduo que fez uma deslocação entre a China e a Alemanha, onde participou em reuniões de trabalho, e que só desenvolveu sintomas quando regressou à China. Contudo, contaminou as pessoas com quem contactou na reunião na Alemanha (ainda em período assintomático). Note-se que os sintomas foram apenas reportados pelos diferentes indivíduos alguns dias após o primeiro contacto. Além disso, o paciente 1 foi o elo de transmissão para os pacientes 3 e 4. Em outro estudo, foi também descrito que um paciente assintomático testou positivo para Covid-19 (Figura 5). Estes estudos demonstram, pois, que indivíduos sem sintomas podem transmitir Covid-19 para outros indivíduos servindo de argumento para as recomendações das autoridades de Saúde Pública de todos os países sobre a restrição do contacto social de modo a diminuir a propagação deste vírus.

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Figura 5.  Acompanhamento de pessoas que embarcaram em um voo de evacuação de Wuhan, China, para Singapura. Adaptado de [10].

 

O que quer dizer achatar a curva?

Como vários especialistas têm vindo a público explicar, achatar a curva quer dizer reduzir o número de casos positivos ao mesmo tempo permitindo aos hospitais ser capazes de responder a casos urgentes sem sobrecarga (Figura 6). Porque é que isto é importante? Se o número de casos não escalar (curva azul em comparação com a curva vermelha), o número de doentes em estado crítico em simultâneo será menor, o que quer dizer que vamos ter profissionais de saúde e equipamento disponíveis para estes casos críticos (algo que não acontecerá se toda a gente adoecer em simultâneo).

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Figura 6 – Gráfico ilustrativo “achatar a curva”. Without protective measurements: Sem medidas preventivas; With protective measurements: Com medidas preventivas;  Healthcare system capacity: Capacidade do Sistema Nacional de Saúde; Number of cases: Número de casos; Time since first case: Tempo após o primeiro caso. Adaptado de CDC/The Economist.

 

É o Covid-19 um vírus produzido em laboratório?

Um artigo científico publicado recentemente fez a comparação do genoma do Covid-19 (ou seja, do seu “cartão de cidadão”) com outros coronavírus demonstrando que o Covid-19  NÃO é um vírus manipulado em laboratório [11]. O Covid-19 tem aproximadamente 80% de semelhanças com o SARS-CoV-1 e 96% de semelhanças com o coronavírus de morcego BatCoVRaTG13 [1].

 

Quais os websites onde posso encontrar informação fidedigna sobre o Covid-19?

Em Português:

Em inglês:

 

 

 REFERÊNCIAS:

[1] https://www.nature.com/articles/s41586-020-2012-7

[2] https://science.sciencemag.org/content/early/2020/03/03/science.abb2762.full

[3] https://www.ahajournals.org/doi/10.1161/01.RES.87.5.e1

[4] https://www.biorxiv.org/content/10.1101/2020.01.26.919985v1.full

[5] https://www.nejm.org/doi/10.1056/NEJMc2004973

[6] https://www.nejm.org/doi/full/10.1056/NEJMoa2001191

[7] https://covid19.min-saude.pt/ponto-de-situacao-atual-em-portugal/

[8] https://www.who.int/news-room/q-a-detail/q-a-coronaviruses

[9] https://www.nejm.org/doi/full/10.1056/NEJMc2001468?query=featured_home

[10] https://www.nejm.org/doi/full/10.1056/NEJMc2003100

[11]https://www.nature.com/articles/s41591-020-0820-9?utm_source=facebook&utm_medium=social&utm_content=organic&utm_campaign=NGMT_USG_JC01_GL_NRJournals

TP

Covid-19: what do you know based on scientific data?

 

What is the SARS-CoV-2?

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), is a positive-strand RNA virus [1], that causes the disease COVID-19. The structural and biochemical comparisons of SARS-CoV-2 led to the scientists to conclude that this virus appears to be optimized to bind to the ACE2 receptor (angiotensin converting enzyme 2 receptor), and this binding is responsible for the virus internalization into the cells [1, 2]. ACE2 is responsible physiologically for maturation of angiotensin, a peptide hormone that controls vasoconstriction and blood pressure [3], and it is expressed in the cell membrane of lung, heart, kidney and intestine tissues [3,4].

 

How long is the virus able to maintain its stability?

It was recently published in the New England Journal of Medicine a scientific paper where the authors show that SARS-CoV-2 is more stable in plastic and stainless steel than in copper and cardboard [5]. In this study they applied SARS-CoV-2 using aerosols (with a controlled viral load) into the different materials, and left those materials between 21 – 23 ºC and 40% humidity for 7 days.

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Figure 1. Stability of SARS-CoV-2 and SARS-CoV-1 in different materials. Adapted from [5]

 

More precisely, what they observe is that:

  • copper: no viable SARS-CoV-2 was detected after 4 hours
  • cardboard: no viable SARS-CoV-2 was detected after 24 hours (1 day)
  • stainless steel: no viable SARS-CoV-2 was detected after 48 hours (2 days)
  • plastic: no viable SARS-CoV-2 was detected after 72 hours (3 days)

Importantly, this means that before the timings described for each material, although the loads of virus were decreased in comparison to the initial virus loads, they were still detected.

On this study, they also compared the stability between SARS-CoV-2 (red curve in Figure 1) and the previous closest coronavirus known, SARS-CoV-1 (blue curve in Figure 1). The results show that stability between the two virus is actually similar, suggesting that the epidemiologic problem that we are facing with SARS-CoV-2 is not only related with its stability (although is one of the important factors), but can be also due to other factors, raising two hypotheses:

  • high viral loads of virus in the superior respiratory tract
  • the high potential of infected people with SARS-CoV-2 to transmit the virus while they are asymptomatic or with mild symptoms (which are not taken at that time as illness)

 

Which symptoms does SARS-CoV-2 trigger?

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Figure 2. Symptoms and Maximum Body Temperatures According to Day of Illness and Day of Hospitalization of the first case of   Covid-19 reported in United States patient. Adapted from [6]

 

In the same journal, it was recently published the case study of the first SARS-CoV-2 reported in United States patient (Figure 2). In this report they describe the identification, diagnosis, clinic course, and treatment, including the mild symptoms described initially by the patient and the progression of symptoms to pneumonia at day 9 of the disease [6].

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Figure 3. Symptoms of positive SARS-CoV-2 patients in Portugal gathered by local Portuguese authorities. Source: https://covid19.min-saude.pt/ponto-de-situacao-atual-em-portugal/ [consulted on March 19th, 2020]

 

In Portugal, local authorities have been gathering the symptoms that each positive SARS-CoV-2 patient has experienced (Figure 3) [7]. As we can see in Figure 3, majority of positive patients describe dry cough as a symptom, while fever is only the second symptom described.  As described by WHO (Word health Organization) around 80% of people recover from the disease without the need of a special treatment [8]. Nevertheless, WHO describe as high-risk groups older people and people with other health issues such as high blood pressure, heart problems or diabetes, are more likely to develop serious illness [8].

 

Can asymptomatic people transmit SARS-CoV-2?

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Figure 4. Timeline of exposure of different people until they show symptoms and test positive to SARS-CoV-2 (described in the graph as Positive PCR). Adapted from [9].

 

In Figure 4 it is described a case report of a transmission line in Germany. An individual that went from China to Germany, where he attended business meetings and only after returning to China start feeling the first symptoms. Important to notice that patient 1 only describes symptoms days later after the meeting with Patient 0. In addition, patient 1 was a transmission individual to patient 3 and 4, that only contacted with patient 1, and again only show symptoms days after those contacts. Interestingly, another case report shows that asymptomatic patient can already test positive for SARS-CoV-2  (Figure 5). These studies show that although no symptom was described by these individuals, they were able to transmit SARS-CoV-2  to other individuals. This is why the decrease of social contact is so crucial to decrease the spreading.

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Figure 5. Follow up of people who boarded an evacuation flight from Wuhan, China, to Singapore. Adapted from [10].

 

What is this “let’s flatten the curve” and why #staythefuckhome is so important?

As many specialists have come to public to explain, flattening the curve means reduce the number of cases at a time – allowing our hospitals to be able to take care of the urgent cases without overloading them (Figure 6). Why is this important? If we get the same number of cases but during a longer period, we will reduce the number of patients in critical condition at the same time – which means, we will have not only professionals but also equipment available for these critical cases.

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Figure 6. Flatten the curve graph

 

Is SARS-CoV-2 a laboratory made virus?

Comparative genomic data of SARS-CoV-2 with other coronavirus show that Covid-19 is NOT laboratory manipulated virus [11]. SARS-CoV-2 is approximately 80% similar with SARS-CoV-1 and 96 % similar to bat coronavirus (BatCoVRaTG13) [1].

 

Which trustworthy websites should I read to know more about SARS-CoV-2?

 

REFERENCES:

[1] https://www.nature.com/articles/s41586-020-2012-7

[2] https://science.sciencemag.org/content/early/2020/03/03/science.abb2762.full

[3] https://www.ahajournals.org/doi/10.1161/01.RES.87.5.e1

[4] https://www.biorxiv.org/content/10.1101/2020.01.26.919985v1.full

[5] https://www.nejm.org/doi/10.1056/NEJMc2004973

[6] https://www.nejm.org/doi/full/10.1056/NEJMoa2001191

[7] https://covid19.min-saude.pt/ponto-de-situacao-atual-em-portugal/

[8] https://www.who.int/news-room/q-a-detail/q-a-coronaviruses

[9] https://www.nejm.org/doi/full/10.1056/NEJMc2001468?query=featured_home

[10] https://www.nejm.org/doi/full/10.1056/NEJMc2003100

[11]https://www.nature.com/articles/s41591-020-0820-9?utm_source=facebook&utm_medium=social&utm_content=organic&utm_campaign=NGMT_USG_JC01_GL_NRJournals

TP

Around and around until falling in love again with academia

I have decided not too long ago that I was going to pursue my career in academia. After a tough PhD, I have to say that this sounded the craziest idea that I could have… So, how did I get into this decision? After working a while as a microbiologist analyst, I realized that routine is not my thing. I finally understood that is the ability to use my critical thinking, asking questions and improving every day, which drives me and makes me happy. Thus, my decision was easier than it seems and as someone told me recently, I already did my PhD grief.
Importantly, I do not regret the decision to try a “kind” of industry in Portugal as I learned a lot about myself! (I say a “kind of” because I know from many friends that working in industry can also be challenging, which was not my reality). I can much easier deal with the pain of no results than the pain of having the same routine every week. Thus, I don´t feel as these 7 months were a waste of time! On the contrary, I realized that industry job is not what I idealized and I have now a different perspective of what I want to do career wise!
Therefore, I have recently joined a new lab! If I may give an advice, go ahead and endorse projects that you think suits you! Even if they don’t, you will always learn something from them!

TP

Paying ode to Drosophila

As soon as I joined the new lab, I was invited to attend the Portuguese Drosophila Meeting. The meeting was hold in Tomar, center of Portugal, and combined people from different institutes. The major goal of this meeting every year is gathering together the Portuguese scientific community that uses Drosophila melanogaster as a model system, and share expertise: from new tools to new methodologies.

The Portuguese Drosophila Meeting was casual with a good amount of time to socialize. The talks were as broad as you can imagine, from immunology, to developmental biology, population genetics, host-pathogen interaction, neuroscience and oncobiology.

As usual, in this kind of meetings, we have international speakers giving amazing talks. However, what catch up my attention was one of the speaker’s main message: keep spreading the word and show how powerful Drosophila model is. It’s incredible but true, Drosophila is getting forgotten. How many of the new raising scientists know that, for example, the Hippo signaling pathway was first discovered and characterized in flies? Drosophila is the most well understood model organism, studied for more than a century. Its genome is smaller, known since March 2000 and there are libraries of RNAi for all your favorite genes. Moreover, you can manipulate their growth rate by maintaining them in different temperatures (ranging between 18 ºC and 29 ºC). Did you ever try to mutate/insert a gene? In Drosophila is so much easier than mice (imagine an entire year reduced to one month, with amazing genetic tools to know if your gene was inserted or deleted!). And for the sceptics, the fruit fly and humans are not as distant as you can think! Many physiological, neurological and biological properties are maintained between mammals and fruit flies, with about 75 % of the genes that cause diseases in humans have functional homologs in Drosophila!

Finally, you can find more reasons why use the fly as a research model in:

https://www.yourgenome.org/facts/why-use-the-fly-in-research

http://modencode.sciencemag.org/drosophila/introduction

 

TP

What should you know before choosing a lab

My PhD wasn’t easy and neither was my master. So, you may ask, if my master was “painful” why did I go for a PhD? First of all, I’m crazy, I admit. But I thought that the PhD couldn’t be worse than my master. Wrong! I think it was different but it wasn’t “great”… Do not misinterpret me, I end up having results to publish but they only showed up really late… Nevertheless, after a PhD mourning period (as my PhD supervisor calls it) I realized that I still love science and I actually think I can do science for the rest of my life.

I presume that at least 50 % of PhDs recognize themselves in this story. During my master and PhD (especially when I was struggling with the pain of no results) I would have several talks with my colleagues about how to choose the best project/lab. I now realize that at the time that we have to choose the lab/project most people don’t know exactly what they should pinpoint as key aspects to consider.  Thus, looking to what was my friends experience and mine, I believe that there are some key points that you should take into consideration when choosing a lab and project to work on!

Starting with the field of study (neuroscience, stem cells, immunology…), when students are choosing a lab/project they tend to think that the field of study that they pick is what will define their future path. Well, I believe that is not true! What will define you is your skills! Of course, the field where you will be working on is important, but it will be the combination of what you know theoretically and experimentally that will make you unique. So, don’t forget to ask yourself, if I choose this lab/project what will I learn? Don’t focus your choice only in the field of study.

What about the supervisor? To choose a “good” supervisor you should know yourself! A good supervisor for me doesn’t mean is a good supervisor for you. Why? Because people give importance to different supervisor personalities and methodologies. For example, if you are an open mind you don’t want to choose a supervisor that is closed mind. You should try to know with the lab members how is the supervisor for example in terms of methodologies – do you have to do exactly how he/she says or do you have freedom to design an experiment to accomplish a specific goal previously discussed? Does he/she tries to understand your results when they do not fulfill the work hypothesis? Is he/she able to change the working hypothesis? These are some of the examples that you should consider. Someone told me once “you should choose a supervisor that you admire as a scientist”.

And what about coworkers? I think is obvious that you will take advantage of a lab where people discuss ideas, results and problems! Believe me, you will find so many problems along the way, if you are surrounded with open minds that are problem solvers you will be in good hands! Of course, you don’t know that for sure but you can always have an idea about it when talking with them. Oh, and make sure that there is a “friendly” environment!

Finally, the project per se! As mentioned above, make sure that your project will make you have a hand full of skills. Nevertheless, if you are starting your PhD and you would like to design your own project, make sure that you are engaged in a lab colleague’s work. That will make you learn the lab procedures, you will help on his/her experiments which means you probably win co-authorship on his/her paper and importantly these will give you solid bases of a good PhD hypothesis because you will have then increased your know-how on the subject of study.

At the end, balance the pros and cons of the labs that you are considering and good luck on your choice!