The Impact of the COVID19 Pandemic in Scientific Research

May 25th, 2021
Image Source: Nature Magazine

In this blog post I will discuss how the development of the COVID19 vaccine impacted scientific research. We are now sure that one specific event dominated the year of 2020: a deadly and previously unknown virus wreaked havoc across the globe, killing more than 3.5+ million people to date, infecting many more and causing economic devastation around the globe. The speed of the coronavirus’s spread in the world has been matched only by the pace of scientific research for drug discovery and vaccine development. Almost as soon as SARS-CoV-2 was discovered, research groups worldwide started sequencing the virus genomes, comparing different strains, epidemiological studies started, data collection from patients and molecular discoveries on how this new virus infect cells and cause the signs and symptoms were identified, while other groups developed diagnostic tests and investigated public-health measures to control it (for more information check “COVID and 2020: An extraordinary year for science”).

Collaboration is key

Scientists also raced to find treatments and create vaccines that could bring the pandemic under control amongst several political problems, especially in the United States. Fortunately, now the United States has more than 50% of the population vaccinated with at least one dose of different types of vaccines and life in some places are coming back to a new “normal”. Of course, another discussion that I also wrote about was how people around the world would be part of the biggest experiment of history since, even though, several studies were done, the long-term effects of these different types of vaccines were not completely understood. Well, we are still learning in the process of vaccination that is ongoing globally (faster in some places and slower in others). The main accomplishment that I think came to stay is what last year meant to scientific research both in the academic and private sectors. The first change was that we saw much more collaborations between scientists. In addition, the COVID19 experience almost certainly changed the future of vaccine science. The COVID19 pandemic should see some permanent changes in vaccine development. For a start, it might establish the use of mRNA vaccines – which hadn’t previously been approved for general use in people – as a speedy approach for other complex and rare diseases. Still, other vaccines can probably only be developed at a comparable speed when infection levels are high, making it possible to run massive clinical trials relatively quickly with data acquisition in real-time and with huge amounts of funding (for more information check “The lightning-fast quest for COVID vaccines – and what it means for other diseases”). Another important change that we see now is that people in general are more “curious” about scientific research and biology in general. Science, like scientists, has been changed by COVID19. New collaborations, funding routes and systems for sharing data will shape research from now on. The technologies developed for rapid tests will be adapted for other infectious diseases. In future pandemics, genetic surveillance will be the norm with scientists sequencing pathogens for every positive test as a matter of routine (for more check the article “The great project: how COVID changed science forever”)

Science communication: what does a scientist do?

Thus, I believe that science communication (even with a lot of “fake news” in social media) has been positively impacted. I can tell by my own experience after doing podcasts (you can listen to one of these here) and being interviewed on this subject that there were changes. People, taxpayers, did not have a clue why innovation in science are important and that this needs lots of money to be accomplished. Scientists and the profession of being a scientist either in academia or in the private sector was not very well understood. Even my family members, when I was in my academic career path (derailed by becoming a serial entrepreneur, but always keeping track of academic discoveries and doing collaborations with academia) did not have a clue what I was doing. I always got the questions: What scientists do? Stay in the laboratory mixing stuff to see what happens? What is their importance? My take on this: science was and it is still not a very “sexy” subject for the general public. The scientific system is to blame for this since scientists work a lot, are always in the laboratory and have no time to do science awareness. Even graduate students and Post-Docs are treated badly, with low salaries and crazy working hours. I’ve wrote and said it in several interviews that the scientific system (especially in academia) is broken and needs a change.

What is next? Are we safe now?

Scientists are the ones responsible for this new accomplishment: developing vaccines to COVID19 in less than a year – something that would take a decade. So, people reading this post, being a scientist is a profession and needs to be recognized as such. If you are still confused on what scientists do, I think it is clear now: jump in in situations such as a pandemic to develop drugs and vaccines to save people. They are in the laboratory testing lots of things and doing “crazy” experiments. To summarize, I really hope that the media and people in general start paying more attention to science and the scientific system. Lots of changes are still needed for sure, but last year meant a lot to scientific research. I hope the lessons were learned and this will be applied in a next pandemic to help in other situations like this.

Coronavirus Vaccination Globally – An Update

March 8th, 2021
Image Source: STAT News

In my last blog post last year, I’ve wrote about the obstacles, especially the logistics involved in the vaccination of the world population for the Covid-19 disease. After some months and the vaccination ongoing in different countries we can have an idea on how unprepared for this the world was and still is. Countries such as the United States surpassed ~20% of the population vaccinated with at least the first dose (for more information check the “Our World Data” website for all the numbers and metrics for all countries). In the meantime, different variants and mutations started to scare the researchers and doctors. Strains that infect and spread faster and some more deadly. Moreover, several questions still remain for everyone: What is the best vaccine to take? Which one should I take? Are all of them 100% safe? When I will get vaccinated? The vaccines being distributed and used right now will be able to protect me and my family from the new variants and mutant viruses? Unfortunately, we don’t have answers yet to these questions. In addition, one terrible thing that I criticize a lot is the disparity on how each country is dealing with the vaccination of their population. For example, in Brazil there is a chaotic fight between the state governors and the president. Each state has a policy, some cities are partially locked down right now and others are not. Brazil’s strategy and logistics shows how my home country is disorganized and polarized. Putting politics in front of saving lives is the worst attitude ever, but that is what is going on there. It is unbelievable that people there (and in other places of the world) still believe that the virus is “fake” and that this pandemic is a fabrication of the mainstream media. Fake news is still dominating and helping disseminate miraculous treatments that are not scientifically and clinically proven to work. There is no standardized treatment protocol for infected patients, meaning that each case will be treated differentially. On the other hand, countries such as the United States already have vaccinated (at least the first dose) more than 60+ million people – in a very chaotic and confusing way. It is so sad to see people that could be saved by any of these vaccines approved and available, but they are not able to get it on time because of the political disputes everywhere. What is happening to us? We sometimes treat animals such as dogs and cats (our pets) better than our neighbors. Nobody cares about the unity of humankind as a species; the world is polarized and individualized. Sir Anthony Hopkins, the famous actor of 83 years old, just gave an interview to the magazine “The New Yorker” and he said something that has caught my attention: “The great liberation for me is to know that we are insignificant, that finally it’s all a dream within a dream. Look at this moment. The pandemic has got us worried, because we thought we knew everything. We don’t. We’re in the grips of an invisible little microbe.” Indeed, complex human beings already went through deadly pandemics in the past caused by microbes (either bacteria or viruses) and these invisible beings and particles can indeed expose us to a mass extinction. In Hopkins’ words, we don’t know everything and will never do. We live in a world that humans are a minority compared to the amount of other animals and microbes that live on earth. Thus, we will be always exposed to sometimes deadly microbes (especially viruses). So, my update for the vaccination against the Covid-19 disease is that it is still confusing, each country having a different policy (Israel is an example with almost all its population vaccinated) and now new strains of the virus making things even more complex and challenging. Like I’ve wrote in my last blog post (“Humankind’s Biggest Biomedical Experiment”), we are indeed in the middle of the biggest experiment of humankind. Interestingly, we are the guinea pigs right now. My take home message is for everyone to get vaccinated independent on the type of vaccine. I believe this will be better than get exposed to an infection with the virus and eventually die. That is a fact!

Humankind’s Biggest Biomedical Experiment

December 15th, 2020
Image Source: BBC News

This year is finally coming to an end and it will make history. In one century, we have never seen something like this: a pandemia that affected every single person in the planet. Scary right? Imagine in a decade from now or even when we are old (hopefully surviving to all this craziness) telling how the world stopped because of a nanoparticle, a virus, in the year 2020. Well, this is my last blog post for the year of 2020, a year that changed the world in all countries without exception. I’ve been writing about the pandemia (or pandemic if you are british) since it started. What a year! Lockdowns, masks, social isolation, deaths, healthcare systems burning out. If we could go back in the early 2000s and would be able to tell this history to someone it would look like a Hollywood movie, however in this case no hero came to save us all. Except the scientists and healthcare workers who were the real heroes this year (even TIME magazine devoted a special issue to these heroes in their last issue). A year to be forgotten; to be remembered as an example on how unprepared all countries (no exception) are for something like this. In a recent podcast I’ve did (as soon as it is released, I will post the link) I discussed how this year was interesting in the sense that all of us had to stop our “auto-pilot” and accelerated lives to rethink everything: from family to our professional lives to who we really are as human beings. It was a “pit stop” or sabbatical for several people to re-evaluate their lives (especially for me). On the other hand, for the kids and the new generations being born this year and the teenagers, this year was confusing and will leave marks forever. The world was already virtual and mobile-driven before and now it got worse. Anyway, let’s go to the point of the post: the biggest scientific and biomedical experiment for humankind; to vaccinate 7 Billion+ people in the globe.

Vaccination Logistics

We now have around 7 options of vaccines that started to roll out to the public with the hope that it will stop the coronavirus. Now I can give some perspectives and leave some questions for the reader. Vaccines in general take 5 to 10 years to be evaluated for all their effects in long clinical trials with hundreds to thousands of people. The thing is that even after a successful vaccination we need time to see the mid to long-term side-effects. The clinical trials for all of the vaccines available now took less than a year and were done with a number of people below the regular number, even with the efficacy ranging from ~60-95%. In addition, now we have a new type of vaccine, using genetic material to make living human cells in our body produce a protein from the virus creating an immunological “memory” for the virus in a second encounter. I believe that in a year, scientists have learnt a lot and that was a kind of preparation for other pandemia(s) that could happen in the future. It is unquestionable that this is the greatest achievement in science and biomedicine this year. However, some questions still remain unanswered.

Unanswered Questions

My questions and concerns are: 1) How the logistics of the vaccination will work from country to country?; 2) which vaccine each country will choose since we know there is a lot of money involved in licensing, production and in the distribution; 3) Some protocols already have information that elderly and healthcare workers will take it first – what about the rest of us?; 4) each country will use different measures and we don’t really know if this will negatively affect developing and low-income countries; 5) with these new technologies we can expect lots of side-effects; remember we are all genetically different and scientific studies have already shown that each person responds differentially to the viral infection – what about the response to the vaccine?; 6) people that already got COVID19 and is cured can take the vaccine? – we really do not know how their bodies will respond yet; 7) International flights will go back to normal – I just read that besides the passport people will need a vaccine “passport” to start flying around the globe. How will be the logistics for this since each country will use a different vaccine and/or protocol for vaccination?; and the last one 8) How governments will “sync” the vaccination and evaluate the concerns I just pointed out above? We will be “guinea pigs” or “lab rats” in the biggest scientific experiment humankind ever had. The year of 2020 was a year of lots of learnings in the personal, professional, societal and global levels. Let’s hope the vaccines (all of the approved ones) work with few side-effects and the virus fades away so we can go back to our lives, but now with a different perspective.

Bye Bye 2020!

One thing is for sure, 2020 is gone, but 2021 will still be a year of lots of learning. And most importantly, masks and procedures to avoid viruses and bacteria that can cause another pandemia came to stay. Thus, be used to that! The world changed forever. I wish the worst is ending and good times are ahead of us. Let’s cross our fingers and continue taking care of ourselves and our loved ones. Finally I can scream: Bye Bye 2020! I wish a better 2021 to all the readers.

Updates & Lessons for a Post-pandemic World

November 16th, 2020

As I write this blog post there has been a lot of updates related to the coronavirus pandemic in the world. We are approaching the end of 2020 and there is currently a second and third waves of coronavirus infections in Europe and the United States, respectively. In the United States the number of daily confirmed cases are reaching the 200,000 mark and in Europe several countries are locking down and imposing restrictions again. The testing of the virus is still messy with misinformation and lots of false positives and false negatives. Doctors and healthcare practitioners are struggling to understand (or don’t have time) which is the best applicable test for each phase of the viral infection. For example, if the person is in the peak of the viral infection and did not develop antibodies against the virus yet, a serological rapid test will not detect the virus (false negative). If the PCR (“gold standard” test) is done after the infection phase and the body has cleared the virus, we will also see a false negative. Very confusing indeed. Regarding treatments for the infected people, I believe the healthcare systems are evolving but there is no “global protocol” to be followed by healthcare practitioners in all the countries. Thus, what we see is a trial and error, use of drugs that are not approved for viral infections, use of antibiotics in the wrong phase of the infection. Bottom line: It is still a big mess. Regarding the vaccines, in the last week we had several good news of vaccines from big pharma companies such as Pfizer, CoronaVac and the Russian Sputnik V having good efficacy (above 90%), Today I just read that Moderna Therapeutics released a statement in the media reaching almost 95% efficacy (check the NYTimes Vaccine Tracker and some other news here). I hope until the first quarter of 2021 we will have more good news for the vaccine research. However, the problems after the approvals will be the logistics to deliver it to people in poor countries (we already know that vaccines based in RNA are unstable and need very low temperatures to transport). Prices, country policies to distribute, who will get it first are also open to discussion. Well, there are several lessons we have been learning “on the go” with this pandemic. When I think in a post-pandemic world, I see a lot of people affected mentally mainly because of the restrictions, a generation of kids that will be living with fear, confused and probably still using masks (this is not going away soon). I think governments in the world need to join forces to overcome another pandemic if it comes; the response to this one was a disaster in my perspective (and from a lot of other people). With all the technological innovations and scientific accomplishments we have in the year 2020, we will probably see  around 2 million people dying (or even more) of the coronavirus globally with at least 100 million+ infected (unfortunately I have been reading a lot of reports of recovered people with long-term problems in the brain, heart, chronic fatigue, weird syndromes that will take a while to understand). Societies and political leaders will need to join forces in a world that is so divided right now. I am not talking about rich and poor, I am talking about us, humans, the human race as a whole. The world will never be the same after 2020. A “brave” new world will surface with more compassion, empathy and hope – I am trying to be an optimist. This pandemic affected everyone (of course differently) from Hollywood stars to people living in slums, from billionaires to middle class people. The world of sports such as NBA, MLB, soccer, car racing (I am a fan of Formula 1 and Indy Car Racing) were all affected in some way. Live TV shows were affected. All businesses were somehow negatively affected (exceptions are technologies such as videocalls, and retail with delivery such as the tech company Amazon, etc). The world economy is broken, a lot of people unemployed, kids having virtual classes and other changes that will need some years to go back to “normal”. And what this “normal” will be? I do not have the answer yet, but I hope next year will be better than 2020.

Why Information and Speed Matters in Industry

October 1st, 2020

We all know how competitive markets can be, especially when there are billions of dollars in stake. Both pharmaceutical and biotechnological sectors are indeed very competitive. Companies spend millions (sometimes billions) of dollars to get drug approvals and place a new medicine, drug or treatments in the market and it can take a decade to get the proper approvals. Regulation and approval are always a hurdle, but these are very important steps to evaluate a drug’s safety, toxicity, and the effects in the population in general, thus several clinical trials in different populations have to be done before any approval. We can see this going on with treatments and vaccine development for the coronavirus disease (for more information please check my previous blog posts). However, today in my blog post I will shift gears a bit to discuss about an area that has become very important for pharma companies: Immuno-Oncology (IO) and the drugs associated with cancer treatment. In fact, these drugs in a simple explanation, use the person’s immune system to attack cancer cells and shrink the tumor (sometimes even cure the patients). Thus, several tests and “facts” need to be checked before these types of treatment could be applied. I will discuss today about Business Intelligence (BI) and competitive advantage in life sciences. The example here will be two specific treatments that have been approved by the American Food and Drug Administration (FDA) to treat various cancer type. Immunotherapy combo drugs such as Opdivo or Nivolumab (developed by Bristol-Myers Squibb – BMS – NASDAQ: BMY) and Keytruda or Pembolizumab (developed by Merck – NASDAQ: MRK) have changed the cancer treatment landscape, but it’s becoming increasingly clear from clinical trial results that these potent therapies need to be targeted to the right patient populations to have the best clinical results; something named precision medicine. Both treatments use specific genetic profiles and background of the patient’s immune system to be successful, which is the expression of two proteins by patients’ immune cells: the so-called “check point” proteins PD-1 and PD-L1. These treatments actually block PD-1 with monoclonal antibodies (mAb) helping the patient’s immune system to kill cancer cells. That is the basic concept (for more information on the molecular biology of these treatments check “A molecular and preclinical comparison of the PD-1 targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab”). In that regard, the brand names Keytruda from Merck and Opdivo from BMS mainly function by blocking the PD-1 ligand protein and have several structural similarities. In fact, both were approved in the same timeframe by the FDA in the end of 2014. However, Keytruda (Pembrolizumab) is projected to generate at least U$22.5 billion in revenue by 2025, according to an analysis by Global Data, a data and analytics company. In 2019, Keytruda generated more than U$7 billion in revenue and, based on more than U$5 billion it earned in the first half of 2019 it could hit U$10 billion or more by the end of 2020. Keshalini Sabaratnam, a pharma analyst at Global Data, said Keytruda has developed into Merck’s biggest product since it was first approved by the FDA in 2015. On the other hand, BMS’ Opdivo (Nivolumab), a rival checkpoint inhibitor to Keytruda, is expected to be in fourth place for global revenue and AbbVie and Janssen’s Imbruvica will take the fifth position, according to Global Data’s prediction. In 2018, Opdivo earned U$5.7 billion (for more information check “Keytruda Set to Become World’s Top-Selling Drug, Forecast Shows”). Why is that? Well, trying to understand why this market share change occurred in such a small timeframe (3 years or so) since both treatments were approved by the FDA in about the same timeline, I started digging in the approvals for both treatments since then. The main points I want to discuss in order to answer why Merck’s treatment is “winning” the competition now are: 1) Merck started combining biomarker identification to stratify groups of patients that would respond better to their drug, even in the clinical trials before approval, especially patients with high expression of both PD-1 and PD-L1; 2) big data analytics probably helped Merck to gain more information and faster approvals, so maybe people working for Merck were paying more “attention” to the advancement and developments of “targeted therapies” in immuno-oncology, which means that speed in getting information and data makes a big difference in business intelligence for big pharma and 3) it seems that Merck’s treatment can now be applied to several types of cancer and the one from BMS is a little more “restricted” to specific cancer types in terms of FDA approval. Thus, the take home message here is that we are in need of better tools, especially for life sciences’ companies, to get trustful information faster and use it smarter. There are already some solutions that can help big pharma in the market such as the Elsevier database (NYSE: RELX), Thomson Reuters Corp. database (NYSE: TRI), etc which are bringing revolutionary tools to speed this process. Indeed, sometimes being the first is not enough; keeping track of the information and the evolution happening in the scientific and biomedical fields are the differentiation factor to “win” in such a competitive market.

Understanding SARS-CoV-2 and COVID19

September 14th, 2020
Image Source: Ann Kiernan for “The Washington Post”, June 18, 2020

Here we go: another blog post on the coronavirus pandemia that is ongoing globally. The race to a vaccine continues (will discuss a little about that below), however this post will be focused on the virus that caused the disease COVID19 (Coronavirus Disease 2019), named SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), its biology, complexity, how changes in its genetic material could make harder to develop vaccines against it, the latest reports on tropism to specific human cells and organs and how the outlook for the near future looks like. In addition, I will discuss cases being reported of secondary infections in the same person and people that was “cured” from a first infection developing complex syndromes (especially children) and long-term neurological problems in older people. This pandemia is ongoing for more than 6 months, and I am very happy with how the scientific community is collaborating worldwide (collaboration in science is key, totally opposite to the system we were used to before) accelerating our understanding on the invisible enemy we are dealing with. Unfortunately, it is still not enough to eliminate it yet, but we are on the right track.

Biology of the Virus

What is the best way to understand a virus and its biology? First, we need to isolate the virus from patients and sequence its genetic material. With this information, we can use the databases available to scientists to compare its sequence and even identify how it is evolving comparing different strains in different places of the globe. The second thing to do is to study how the virus “attacks” the host (yes, us, humans). The good news are that both information is getting out fast with several scientists studying both topics very deeply. There is already a catalogue of SARS-CoV-2 mutations available and comparisons to see which genetic changes facilitate the infection and how it will affect the disease course (for more information check the article describing it here). To date, more than 100,000 isolates have been sequenced and made public (www.gisaid.org). Two SARS-CoV-2 viruses collected from anywhere in the world differ by an average of just 10 genetic letters out of 30,000 (the virus genome has 30 Kilobases or 30,000 bases) that could confer evolutionary advantages. Based on these studies, it is a possibility that the virus will acquire mutations that could change its susceptibility to antibodies and immunity affecting treatment and vaccination. The second way to understand the disease is to analyze the the tropism of the virus when it enters the human body. Tropism is which cells it binds to and in which organs it affects when inside the body. A recent report just released from a group that evaluated thousands of cell types (a type of “coronavirus cell atlas”) and organs from patients infected identified that the virus enters our respiratory system, however it has tropism to several other cell types and organs – see the Figure below. The idea here is that all these cell types in different organs in the human body have a protein (lock) that binds to the virus “spike” protein (key). When the key unlocks that lock the virus enters the cell and multiply, killing it and causing all the signs and symptoms that we see in the disease. Based on this study, we can tell how complex is the spread of the virus in the human body and why each person has a different reaction to the disease.

Source: Figure from article entitled “A single-cell RNA expression map of human coronavirus entry factors” published in the journal “Cell Reports”

Re-infection Cases

Another problem that worries the research community, especially for a successful vaccine to work, is the recent reports of cases of re-infection with the virus. Most of these are probably re-infection with other strains, very similar to the common cold or flu virus that we can get it more than once in a year, for example. The first report was in Hong Kong (see article here) and now we see a lot of reports with cases of re-infection. Most people who are infected with the coronavirus produce detectable antibodies that would be expected to protect against a second infection by the virus. Even people who had only mild symptoms may also have immune “memory” that prevent symptoms on a second exposure. It is clear now that is not the case. Even though it is early to make conclusions, this could impact vaccination when a vaccine is ready.

Post-COVID19 Syndrome

The last important issue that have been reported since April of this year when the spread of the virus started and now it is much clearer is that people considered cured developed neurological problems and other signs and symptoms that persist until today. Remember (check the Figure above) that the virus infects cells from the brain and the nervous system, so neurological problems would be expected. For the sickest patients, infection with the new coronavirus is proving to be a full-body assault, causing damage well beyond the lungs. And even after patients who become severely ill have recovered and cleared the virus, physicians have begun seeing evidence of the infection’s lingering effects (check the article for more information here). Another worrying post-coronavirus effect that has been reported is a mysterious, new disease called multisystem inflammatory syndrome in children (MIS-C, and also known as pediatric multisystem inflammatory syndrome or PIMS). It has affected hundreds of children around the world since it was first discovered earlier this year. Other syndromes have been reported everywhere now and that is concerning. What is causing these post-COVID19 syndromes? Why in children? We still do not have the answers to these questions. Let’s hope the scientists can uncover this mystery.

Updates on the Vaccine Race

Finally, let me discuss a bit about the “pause” that the AstraZeneca/Oxford University vaccine had last week because of a severe side-effect in one patient that had inflammation in the central nervous system. First, that is common to happen, especially when you are dealing with a fast-track vaccine trials and with people with different genetic backgrounds. Second, the “pause” was important to show to the world that this vaccine is trustworthy since the researchers from both places coordinating it are using the best scientific guidelines with very strict rules (trust is important!). Third, side-effects will happen, the severity of them that will be key for a successful vaccine. Finally, the vaccine race continues and I just read that AstraZeneca and the University of Oxford is going forward with their trial after the “pause”.

Final remarks

All the information I just discussed here is just the tip of the iceberg on the complexity of this virus and how it infects humans. We are starting to understand several processes on how the virus infects human cells, which cells and organs have the tropism for it and how people with different genetic backgrounds from different places react to it. Post-COVID19 effects are getting clear (it happens) but we still have lots of WHYs to focus on right now. I always finalize my posts with some advices: the best thing to do now is still social isolation, take the measures to avoid getting infected and stay mentally sane. I confess that I am already having mental issues (don’t leave the house for almost 4 months!). Stay strong. We will overcome this crazy pandemia. And let’s thank the scientists and healthcare professionals everywhere that are making it possible to gather all the information we have to date on this disease. A brighter future is closer… I hope!

Coronavirus Pandemia and the Vaccine Race

September 1st, 2020

This blog post will be focused on the race for a coronavirus vaccine that is happening globally. My main objectives here will be to explain in a general way how a vaccine works, to give some examples of successful ones, and the difficulty to develop specific vaccines for viruses. In addition, I will discuss some of the vaccines in the last clinical phases for the coronavirus and last, but not least, how it will get to you, me and to all global citizens when it is ready; this is the most complicated part. Just as a reminder today, September 1st, we have at least 850,000+ deaths and 25.5+ Million people infected by the coronavirus globally (data from the “Johns Hopkins University COVID19 Global Tracker”). We really need a vaccine to decrease the spread of this virus otherwise things will definitely get worse. Vaccines typically require years of research and testing before reaching the clinic, but scientists are racing to produce a safe and effective coronavirus vaccine by probably the beginning of next year (best estimate). To date, the number of vaccines under development worldwide are in the hundreds, however I will focus here on the ones that are in later stages in clinical trials with more possibilities of being successful. Researchers are testing 36 vaccines in clinical trials on humans, and at least 89 pre-clinical vaccines are under active investigation in animals (to see more information check “The NY Times COVID19 Vaccine Tracker” updated daily).

Types of Vaccines

Vaccines consist of five specific types: live attenuated microbial particles, inactivated microbes (by heat or any other methods), toxoid vaccines (part of the virus or bacteria that cause an immune response and immunological “memory”), conjugated or hybrid (most of it will be a non-pathogenic virus/bacteria with parts of it as targets) and new technologies such as nucleic acids (DNA & RNA) vaccines (for more information on vaccine types check this article). One example of a vaccine that used the attenuated virus is the polio vaccine that was able to almost eradicate the disease from the world (eradication just happened in Africa this week thanks to a lot of efforts from the WHO and its partners, but we still have isolated cases – check the article here).

Viruses and The Challenges Ahead

There are two types of viruses: DNA and RNA ones. They differ in the way they use our cells to produce more viral particles. The trickier ones are the RNA viruses since they use the cell machinery in a more successful way to “reproduce” and kill cells. For instance, the HIV virus is an RNA virus and until today researchers were not able to develop a vaccine mainly because HIV infects directly our immune cells, the ones that should “remember” and kill them in a second infection. For viruses causing infection in the respiratory tract such as the common flu, the H1N1 and now the SARS-CoV-2 it is not easy to develop vaccines. These viruses mutate a lot and the way our immune system “attacks” viruses can be different from other pathogens such a bacteria, for example. Additionally, each person has a different genetic background, thus different immune responses. This is why we are in this situation right now.

Vaccines Under Development

Let’s discuss some of the vaccines that probably will come first in the race and how they work: the AstraZeneca in collaboration with the University of Oxford in the United Kingdom (UK) and the Moderna Therapeutics in the United States of America. These are among the handful in Phase 3 clinical trials. Others include vaccines by Merck, the University of Queensland, GSK, Pfizer, Sinovac, Casino Biologics – the Chinese vaccine that was just reported, amongst others. Well, the AstraZeneca/Oxford and the Chinese Vaccine (their clinical study was just published on the well-respected journal The Lancet) use an adeno-associated virus genetically engineered as a “Trojan Horse” with an immunogenic protein (or an immunogenic part) of the Coronavirus (COVID19). It is difficult to explain right, but genetically engineered viruses have been used in research and clinical laboratories for research for decades. The idea here is that our immune system will fight “lightly” this foreigner hybrid virus and “create” a memory against it. The “secret sauce” for a vaccine efficacy and efficiency that we still do not know for the coronavirus is how long this immunological memory will last. For the polio virus one shot can last almost our whole lives, for the common flu and H1N1 we need to take it every year and probably from what I am reading about the coronavirus, we will need several shots during a single year based on the reports showing that the immunological “memory” doesn’t last too long. The Moderna vaccine uses a different approach based in nucleic acids. An RNA vaccine uses viral genetic material (in this case the coronavirus RNA) to produce antigens that would allow the body to learn to respond in a second infection by it. This is the first of this kind, that is why there is a lot of skepticism and concern. The last one that I wanted to write about is the “russian” vaccine that the media is discussing a lot recently. For me, as a scientist, if there is no data, no publication, no clinical trials and no information available I do not trust. The russians did not disclose anything: how the vaccine was developed, how it works, the tests that were done, if it is safe enough or not, etc.* To finalize, the most problematic part after all clinical and toxicological tests are cleared and the vaccine is ready is to produce it in large scale and distribute it globally.

What The Future Holds?

Several questions are still open to discussion based on the clinical scientific facts we have until now: Which country will get it first? How much a dose will cost per person? How many immunizations we will need to be safe and start walking around going back to normality? How the governments will deal with the bureaucracy to buy and distribute it to its citizens? We never had in my lifetime something involving so much money and interests in healthcare in a global scale like this. A lot of people can get filthy rich with the outcome of a successful vaccine, that is for sure. Thus, what the future holds in this race? Who will win? And, most importantly, when the first vaccine is approved what will be its immunological efficacy? 50%? 60%? Meaning that some people will not get the expected immune “memory”. Other factors that should be taken seriously are side effects of the vaccine (for example, in the Chinese vaccine study more than 90% of the group that received it had at least one side effect). Well, we are just watching this race and rooting for a good winner. I hope we will have something until the end of this year, and that it could reach every single person in the globe. A little utopic to think like this but we need to be positive. To close this post we still have an open question: Who will be the winner? What do you think?

*Footnote: An article describing a non-randomized phase I/II clinical study from Russia was published today, September 4th, with 76 people after my post was published. The strategy used was based on an engineered adeno-associated virus with an immunogenic protein from SARS-CoV-2. Even with a very low number of participants, the study is encouraging; however as stated in the Conclusions, the authors make it clear that further clinical investigation will be needed to test effectiveness. To check the full article in the journal “The Lancet” click here.

Please send your comments, questions, ideas or some information that you think is important to my email at fcosta@genomicenterprise.com or contact me at genomicenterprise.com/contact_us.

Coronavirus Tests: what you need to know

August 21st, 2020

This blog post will focus on the tests that have been offered for the coronavirus pandemia in order to evaluate individually and in geolocations how the virus is spreading. I am writing this post since most people do not really understand how these tests work, their differences, specificity, efficacy and also what means to have a positive and/or negative test depending on the technology used. I would say that 99% of people is “blind” when it comes to information on the tests and how to proceed after receiving a result. Well, since I am a researcher and have been reading a lot about the types of test, I will try to describe the ones in the market in an easy way to understand with no technical jargons. The main problem, like everything related to this coronavirus pandemia is misinformation or lack of it; this is expected since people in general know nothing about virology and the technologies used in research and clinical laboratories. In addition, most governments are not helping at all with confusing guidelines. There are two main ways to detect viral infections: immunoassays and by the PCR technique. Immunoassays are the widespread ones since they are cheaper and need just a droplet of blood or body fluids. PCR which means “Polymerase Chain Reaction” is a classic technique used in molecular biology since the 1990s. It was invented in 1989 and I have been using it since my undergraduate academic studies; this is not new at all. However, the way it is used and the type of it can impact the results. I will start with the immunoassay tests and then discuss PCR. Lastly, I will give my take home message with some guidelines and remarks on how people should proceed.

Immunoassays

Immunoassays have been used in laboratories for a while. I will not discuss the types of tests but how it works. These assays will detect an immune reaction caused by a pathogen, such as the virus, since our immune system generates what we call antibodies against the pathogen and a cellular “memory” against it in some cases.  One of the problems with this coronavirus is that we still do not know how long the immune cells will “remember” the virus and generate a better response in a second infection (the base to develop an efficient vaccine). This is still open to discussion. There are several ways to do immunoassays, but the best way is to detect indirectly the presence of these antibodies. Most antibodies are created against proteins in the outside part of the viruses. Thus, this type of test is indirect and will detect a response against the virus. Here that the problem happens. Most tests are binary: yes or no for the presence of antibodies against that specific virus (in this case the coronavirus). Just to make sure people understand: these tests are not measuring the virus, but a body response to it which will vary individually. The main problems that can happen are what we call false positives and false negatives. False positives happen when even without coronavirus infection you have a positive test. The main explanation for this is a cross-reaction with other viruses that the person was infected in the past that are very similar to the current virus. Another important point is that immunoassays will only detect the reaction of the body to the virus after the infection when the body was able to create antibodies after getting in contact with the virus. So, if you do these tests early in the timeline of the infection you can get what we call false negative. Finally, the pros to these tests is that they are fast, cheap and need just a few people and reagents. These are the ones that most people are doing now globally.

PCR and qPCR

The basic steps of the PCR test start with sticking a long swab far into a person’s nose (body fluid) or getting the person’s blood. To clean up the starting material, most test protocols then call for performing an assay that extracts out just the genetic material, clearing away all the debris and inconsequential bits. This requires time and specific reagents, which can be in short supply. PCR, like I wrote before, is not a new technology. However, in this case PCR will measure directly the presence of the viral particles (the nucleic acids or genetic material of the coronavirus) in the blood and/or body fluids. Thus, this test is mainly indicated during the infection period timeline since it will measure directly if the viral particles are circulating in the body. If you do the PCR test before the infection or after it, most likely it will be a negative test. The “upgrade” so to speak of the PCR is the qPCR or quantitative PCR, which can measure the number of viral particles per volume of blood and body fluid. For example, this is the test used to detect and to administer HIV viral infections in AIDS patients. That is the “state of the art” method indicated to detect the virus, even in small amounts. In this case a false negative will be very unlikely since it is designed for that specific virus. False positives could happen if the PCR test was badly designed and gets the genetic material of other viral particles infecting the person. These types of test have lots of pros since they are very specific; false positives and false negatives will be almost impossible. The cons are mainly the time it takes to get a result (generally days to a week), it is laborious, involves more people, reagents and it is expensive to be used for big populations. Moreover, most health insurance companies probably will not cover it, especially in the US. Recently, new technologies based in PCR were improved to decrease the costs, increase the specificity and efficacy making it more accessible (see this article for more information).

Take home message

The main message for the readers of this post is that there is no test that is 100% efficient and reliable, however as shown above in a very clear way qPCR is the best test if you are looking for a reliable result. However, be careful, the PCR tests should be used during the timeline of the viral infection since it will measure the viral particles directly. On the other hand, the immunoassays (there are several fast tests based in immunoassays) will measure indirectly the response of the body to the infection. Thus, these tests would be indicated maybe in the end of the timeline of the infection and after some time to see how long we can detect antibodies against the virus. All this information is very complex to understand but I believe these simple tips I am giving here are important to the general population and even governments to make decisions. Last, but not least, independent on the test you did or will do please do it at least 3 times, especially the immunoassays. For the PCR if you got a positive test it means you have an infection by the coronavirus at that moment. Then protect yourself and others and stay alert to symptoms. The tips I am giving here could be helpful so you won’t be confused by all this deluge of information (most times “fake news”) about tests and their results. Be aware and good luck – to all of us. We are in this together.

Coronavirus Pandemia: Why Science Matters Now?

August 3rd, 2020
Image Source: Chemical & Engineering Society

This is my fourth blog post on the coronavirus pandemia and I will focus on science and how general people are getting more interested in biomedical research. I’ve written in several occasions that the scientific system is broken, and I’ve criticized how the scientific funding system works, the peer-revision process, the low salaries and long hours of work, etc. In fact, let me just remind the readers how the scientific cycle works (I’ve already discussed this in an old post – check it here): First, when you want to get into academic research you need to do a Ph.D. in a very “famous” laboratory; this is the “business card” to get a Post-Doctoral Training in an even better laboratory (either in the US or in Europe); second you will need to publish your research after long hours of work (working like a “slave”, Pardon my French…) with a very low salary – not very exciting right?; third, with good publications in high-level journals you will need to bring in research money from well-respected funding agencies since this will enable you to start your own laboratory in a different Institution. If that does not happen you are already “out of the game”; fourth, if you are successful in all the first 3 steps, which are tremendously difficult, you can start your own laboratory and get funding  (the statistics are terrible: less than 5% of Post-Doctorates get to this stage, so what happens to the other ~95%? Do another Post-Doc, become jobless, change profession or go into the private sector). Thus, it is very competitive and the “big labs” always get the funding and grants. It is a very old-fashioned system. Another interesting fact is this: when you do experiments, draw an hypothesis out of them, write an article with your own intellectual skills, most times you will need to pay to publish (and a lot; we are talking depending on the publisher and journal at least 1,500 US Dollars) and give all copyrights to the publisher (well, there are some “open source” options, however it is not working well mainly because the big publishers are not happy, they want to keep getting their profits). Then, after giving the publisher all the rights for your work, paying a lot to publish, getting nothing in exchange financially – just “scientific prestige” (check my old blog post on this subject here), the publisher charges people to download the article (a range of 30-50 US dollars per article!). This is outrageous. Another fact: the private sector has full access to all these scientific articles (paying for downloads) and use them to develop “products” that they will come back and sell to Academic Centers and Laboratories for a very high price. It is a terrible cycle. Even Nobel Prize scientists are not happy at all with how science works (see my blog post about it here). It is a win, loose, loose, loose game. The only one winning here is the Publisher and eventually biotech and pharma companies. The most important aspect that will be the focus of my post: general people that pay taxes (part of it go to the funding agencies to finance research) have no clue how science and the scientific system works. Now, with the coronavirus pandemia, I believe everyone in the world is trying to understand how this system works. I always get questions like: Why there is not a medicine for the virus? Why there is no treatment? Why it took so long for governments all over the world to catch up and we are still in this mess? Simple answer: Scientific Systems are unprepared for any global pandemia. The system definitely has to change. Science communication has to come out strong after that (please stop the “fake news”!). Why is it so difficult to deal with the spread of the disease and lack of trustful information from the media and the governments? I don’t know. Lots of politics involved here. However, I think the positive point is that general citizens all over the world are trying to understand the scientific system, how we respond to pandemic situations such as this one and are demanding answers (true answers!). Now we see strong collaborations between Academic Centers and pharmaceutical companies (i.e.: University of Oxford and AstraZeneca) for a vaccine (this already happened before, but it not the rule). I will discuss the race to a vaccine for the coronavirus in my next blog posts (coming soon…). Let me give, as I always do, a personal example on how the scientific system is slow and old-fashioned: I just had an article accepted in a journal recently and we got the Cover of the Journal. I will not cite names here to avoid problems, but we (mainly my ex-Ph.D. student) took our creativity, time, resources and designed a “masterpiece cover” for the journal. We sent it to the Editorial Office and got the reply saying that the Cover was very nice and we would need to pay a fee of 1,700 US Dollars to have it published with our article. I said what? I wrote back questioning that we took our time, resources and creativity to design a cover and would have to pay to give them our copyrights – no thank you! The Editor wrote back apologizing and waiving 100% of the fee. This is a “toxic” business that is really affecting careers of young scientists. Another important fact: several if not most scientific articles published are already “old-news” since it takes an average of six months to a year if you are lucky to get your study published anywhere. Thus, now that this pandemia has impacted the globe, I see a “fast and furious” race both in academia and in the private sector to develop vaccines and treatments. I hope after we get an efficient treatment and/or vaccine the whole scientific system changes for the better. In addition, I defend that all the scientific community find better ways to communicate with the general public, mostly non-scientists, with trustful information in a way they can understand – no technical stuff, please. Science communication is key and it has to change for the better. People say that there is always a good side for every history and I hope this pandemia changes the whole scientific system for the better. We will see. I have my fingers crossed: to overcome this global pandemia and for changes in the way science is done everywhere!

Coronavirus Pandemia New “Normal”: Now and Then

July 20th, 2020

Image Source: World Economic Forum, 2020

On my last blog post I wrote about the misinformation that we are having to deal with in a daily basis with the coronavirus pandemia (see my blog post here). I also discussed how this misinformation is negatively affecting our society and the individuals, especially people that are not very careful in selecting trustful media and/or social media sources to gather information. This blog post will be more “positive” since I will discuss something that I see people asking everywhere: what will be the new “normal” after the pandemia? I mean, when things get in a stage that we can be more comfortable in going out and there is a vaccine that is efficient enough in the future (hopefully!). Well, there are five specific things happening right now that we could use as examples on how things will be after the pandemia. Actually, these factors have been accelerated by the pandemia since all of them were already happening “organically” in a slower fashion. I will try to discuss and show examples on how these areas have been affected and will be completely changed forever. First, let’s talk about remote work or working from home; something that most people in countries with “lockdown” have been currently doing. I am one of these people. Actually, I have been working remotely for more than a decade now. Remote work came to stay. Some companies before the pandemia were already using the option of “working from home” for one day a week or more, however from now on I believe that this will became more of a rule than an exception. I have examples of working remotely with Teams of people in South America, Europe, Asia and other places. The technology and faster broadband internet are already here. This came to stay, however how people that needs to go to an office or a laboratory or even a production line of a factory to work will do in the near future is still a question mark. Second, in the same way remote work came to stay, telehealth and digital healthcare solutions are expanding. I see people having videocalls with their doctors, psychiatrists, family doctors, etc. Solutions and technologies that are facilitating this connection between the patients and their healthcare professional also came to stay. Of course, that a lot of things need to evolve, and the patient privacy is still an issue, but this will be the new “normal” in medicine. Third, the impact of this pandemia on education (high school and college/university levels): EdTech (or virtual education) and education online is becoming more widespread now. Before, it was just a small percentage of the schools and colleges/universities that offered online courses. Now, all students from the globe are facing a different way of getting classes via internet. This trend was already in place by companies such as edX, Coursera, Udemy, the Khan Academy, etc. During and after this pandemia, online education has become more widespread as the technology evolves and the students get more used to it. I do courses online since 2015 and I really like it; I do not see any problem here. I think that the old-fashioned “medieval” education “on-site” is gone forever. Fourth, is the e-commerce sector and how big players such as Amazon are monopolizing it and will dominate (check this article entitled: “How the coronavirus and retail closures are accelerating the rise of Amazon”). Well, commerce in general has been affected by the pandemia and now we see all the companies (small, midsize and big ones) improving their websites, apps and other ways for online sales. Since nobody is able to go to the stores, the products have to come to us. Well, this trend started more than 20 years ago and now I believe it will become something “normal”. Unfortunately, owners of stores and commerce that are or were not prepared to move their sales online will be disappearing. That is a fact. Fifth and last, I think the bigger impact now and after the pandemia will be on the way we relate to each other. The consequences of social distancing will not disappear soon. One interesting personal example is that I went to a store the other day to buy groceries (of course with a mask and hand sanitizer in my pocket) and what I felt and saw was every single person getting far away from me and the other people around. When asking questions to people that worked in that specific place, I saw fear in their eyes and trembling hands when getting “closer” to others. Social distancing came to stay for a while, and it will affect even more the way we lived before – connected all the time with our mobile devices in our hands and not socializing at all. In my opinion, this will really affect social interactions between people for some time, I would say years if not forever. These are some of my perspectives on the new “normal” that we are facing and will face from now on. The world will never be the same, that is for sure. A “brave” new world and ways to deal with people came to stay. Let’s just hope that people will become more distant socially but closer in a general perspective, aware of the human species fragility, the nature around us and our planet. We need to take really good care of our “home”; and by “home” I am referring to the globe. The virus will be controlled at some point. However, how we as humans will live after that will change completely.