Saturday, June 27, 2020

Why vaccines are important? And especially for COVID-19!

I would prefer to be writing about the fantastic ways to improve and boost your immune system backed up by scientific evidence, but I can’t because I feel the duty to explain the importance of “vaccines education”. 

First, let me clarify that there are a lot of different types of vaccines and you CAN NOT put them all in the same bag! I will explain 5 of the most promising SARS-COVID-2 vaccines further below. 

Second, a bit of a history lesson: we should be grateful for the existence of vaccines that have helped prevent the spread of terrible diseases, such as tuberculosis and polio. Both brought huge suffering in multiple countries around the world and were controlled thanks to the implementation of vaccines! 

Third, look at the current situation when people refuse to vaccinate: we have an outbreak that puts others in danger. “Why?”, you ask. Because viruses need a host or reservoir to continue existing and non-vaccinated people can be that reservoir. Therefore, don’t do to others what you don’t want done to you: to infect you with a disease!

Currently, more than 125 vaccines for COVID-19 are in pre-clinical development, which means that they are being tested in non-human subjects (cells, mice, rats, ferrets, rhesus macaques, etc). 10 vaccines are being tested in humans for safety and dosages (this means in healthy subjects), 8 vaccines are in phase II, which involves testing the safety in expanded studies. Only 3 vaccines are starting phase III, meaning large scale efficacy tests. In this phase, the vaccine is tested in thousands of people separating the volunteers in 2 groups: one will receive the actual vaccine and the other - the placebo one to determine if the vaccine protects against the coronavirus. The last step can be a phase IV trial with an even bigger and diverse group of volunteers and a review of the results by the local regulatory entity which will evaluate if the vaccine is approved or not for use in that region. Notice that each country has its own regulatory organization and some medicines are approved for use in the USA but not in Europe.

Types of vaccines:

Attenuated or inactivated virus vaccine

These vaccines use a weakened or inactivated version of the coronavirus to trigger an immune response. The Chinese companies “Sinopharm” and “Sinovac” are starting to test their attenuated and inactivated vaccines for phase III internationally.  “CoronaVac”, the Sinovac’ vaccine, has shown promising results in Phase I/II of the trials: 743 volunteers reported no severe adverse effects and produced an immune response. Sinovac is building a facility to manufacture up to 100 million doses annually.

Attenuated bacteria vaccine

This vaccine contains live bacteria that have been weakened or attenuated. One such vaccine is the Bacillus Calmette-Guerin (BCG) vaccine which was developed in the early 1900s as a protection against tuberculosis.

After a study reported a relationship between Covid-19 outcomes and the BCG vaccination status, a Research Institute in Australia started conducting a Phase III trial, and several other trials are underway to understand if this vaccine partly protects against the coronavirus.

Viral Vector Vaccines

These vaccines use a different type of virus that wouldn’t affect humans in a negative way (called a vector) to deliver coronavirus genes into cells and trigger an immune response.

The British-Swedish company “AstraZeneca” and the University of Oxford are working on a viral vector vaccine using a chimpanzee adenovirus that will expose the coronavirus’ S protein on its surface in order to trigger an immune system response in the people that will be vaccinated. The vaccine is in Phase II/III trial in the UK and Phase III trials in Brazil and South Africa, and it might be ready by 2021. “AstraZeneca” claimed their total manufacturing capacity stands at two billion doses.

Vaccines with viral genomic material

These vaccines use one or more of the coronavirus’ own genes to trigger an immune response. USA based company “Moderna” uses the viral messenger RNA to produce only the viral proteins in the cells that will trigger an immune response. The company tested this vaccine in 8 volunteers with positive results, and they are moving to phase III in July. The trial was dosing volunteers in Phase I with 3 different amounts of mRNA species, and after testing the immunogenicity (whether or not these doses produce antibodies) they reported that by day 15 after the first injection, the volunteers generated antibodies.

The German company “BioNTech” is collaborating with “Pfizer” and “Fosun Pharma” to develop their mRNA vaccine. They started the Phase I trial in May, “Pfizer” hopes to have a few million doses for emergency use in 2021 if all goes well in the trials.

Another interesting one, the Imperial College London is collaborating with “Morningside Ventures” to develop a “self-amplifying” RNA vaccine, which boosts the production of a viral protein that stimulates the immune system, and they began Phase I/II trials in June.

 

Protein-Based Vaccines

These vaccines use a coronavirus protein or a protein fragment to trigger an immune response.

One such vaccine is worked on by the USA company “Novavax” which started a Phase I/II trial on a vaccine made up of particles carrying fragments of coronavirus proteins.

 

The list goes on and I encourage you to check on the links below and learn more about the different vaccines and the research behind them. Be aware of your own cognitive bias, for example, stop citing the inexistent connection between autism and vaccines, that research has now been thoroughly debunked, the Lancet journal issued a retraction on Wakefield’s paper, and he lost his medical licence.

Let me leave you with this great advice from the WHO about how to respond to vaccine deniers:

“Vaccine-preventable diseases can be very severe, and still cause millions of deaths per year around the world. Even with the best available care in the world, vaccine-preventable diseases can cause permanent disability and even death. Prevention is by far the best intervention.”

 “There are no equally safe and effective alternatives to vaccinations.”

 “The scientific evidence is clear: vaccination is the most effective health intervention for prevention of many serious diseases.”

 “We as an institution/agency are aiming to sustain the health of every individual member of the public. We are sorry that you have lost trust in our effort, but we hope to regain it.”

 “The scientific evidence is clear; vaccination is a safe way to prevent many serious diseases. Any theoretical risk to the individual and society is far outweighed by the risks to one and all of not doing so.“

 

References:

https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines

https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html

https://www.statnews.com/2020/03/11/researchers-rush-to-start-moderna-coronavirus-vaccine-trial-without-usual-animal-testing/

https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker

https://www.youtube.com/watch?v=-dYWZMx-Lfs

https://www.who.int/immunization/sage/meetings/2016/october/8_Best-practice-guidance-respond-vocal-vaccine-deniers-public.pdf



Tuesday, April 28, 2020

Ways to boost your immune system

Boosting your immune system is a great strategy in general, but especially during a pandemic. I have been researching a lot about real options to properly activate the immune system, in a way that does not over-activate it, hint to all my allergic pals suffering the spring haze fever!
In this quest for healthy protocols, I found forest bathing. Back in 2007, a group of American and Japanese scientists studied the effect of forest bathing on the human immune system. Particularly they measured some cells involved in the protection of the body, such as natural killers (NK); measuring the number of NK cells, and perforin, granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields. The study involved 12 healthy male adults who experienced a three-day/two-night trip and walks in three different forest fields. As a control, they took the same measurements on a working day without visiting any forest. Almost all the subjects (11/12) showed higher NK activity after the trip (about 50% increased) compared with before. The forest bathing significantly increased the numbers of NK, perforin, granulysin, and granzymes AlB-expressing cells. They concluded that their findings indicate that a forest bathing trip can increase NK activity and that this effect is at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins.
Moreover, they followed up with an investigation of how long the increased NK activity lasts and compared the effect of a forest bathing trip on NK activity with a trip to places in a city without forests. Blood and urine were sampled from the 12 subjects that participate in the study and also phytoncide concentrations in forest and city air were measured. They reported that: “the forest bathing trip significantly increased NK activity and the numbers of NK, perforin, granulysin, and granzyme AlB-expressing cells and significantly decreased the concentration of adrenaline in the urine. The increased NK activity lasted for more than 7 days after the trip. In contrast, a city tourist visit did not increase NK activity, numbers of NK cells, nor the expression of selected intracellular anti-cancer proteins, and did not decrease the concentration of adrenaline in the urine. Phytoncides, such as alpha-pinene and beta-pinene were detected in the forest air, but almost not in the city air. These findings indicate that a forest bathing trip increased NK activity, the number of NK cells, and levels of intracellular anti-cancer proteins, and that this effect lasted at least 7~ays after the trip. Phytoncides released from trees and decreased stress hormone may partially contribute to the increased NK activity.”
In 2009 they investigated the effect of essential oils from trees on human immune function in twelve healthy male subjects, who stayed at an urban hotel for 3 nights. Aromatic volatile substances (phytoncides) were produced by vaporizing Chamaecyparis obtusa (hinoki cypress) stem oil with a humidifier in the hotel room during the night stay. Blood samples were taken on the last day and urine samples were analysed every day during the stay. NK activity, the percentages of NK and T cells, and granulysin, perforin, granzyme AlB-expressing lymphocytes in blood, and the concentrations of adrenaline and noradrenaline in urine were measured. Similar control measurements were made before the stay on a normal working day. The concentrations of phytoncides in the hotel room air were measured. Phytoncide exposure significantly increased NK activity and the percentages of NK, perforin, granulysin, and granzyme AlB-expressing cells, and significantly decreased the percentage of T cells, and the concentrations of adrenaline and noradrenaline in urine. Phytoncides, such as a-pinene and ~-pinene, were detected in the hotel room air. These findings indicated that phytoncide exposure and decreased stress hormone levels may partially contribute to increased NK activity.
These results are very encouraging, but the reduced number of participants puts a question mark on the results. Fortunately, there are no known adverse events (besides the allergies that I mentioned before) for a nice stroll in a park or forest, so why not just go for a walk and take a deep breath hoping that will boost our immune system, or at least that the placebo effect will do the job!

References:



Bluebells in London

Friday, April 17, 2020

14 Facts That Will Make You More Aware About COVID-19

by Jesica Levingston Mac Leod, PhD.

After reading and listening to a lot of COVID-19' hoaxes that friends have shared with me over the last few weeks, which broke my little virologist heart, I realized that it is not their fault believing fake information, but ours, as scientists for not correctly educating the public on this topics. Therefore, I hope this post helps to clarify and to educate the public about COVID-19.
First, let me tell you what a virus is, and what it is not... They are not bacteria, they are obligate intracellular parasites, as they need to infect a cell to reproduce. A virus requires the cellular machinery in order to reproduce, therefore, if you leave a viral particle isolated it won't multiply, and at some point depending on the type of membrane that covers/protects the genetic material, it will "die". Viruses are made of genetic material (in this case RNA ribonucleic acid), lipids (a type of fats that helps to keep the membrane structure) and proteins, some binding the RNA, protecting it, some for replication and regulation of the hosts' immune system and some in the viral membrane. The viral particles are quite sensitive to the environment, soap can destabilize/destroy the external membrane of the virus and therefore "kill it". I use quotation marks because there is a huge philosophical dilemma about calling viruses "living entities" or not and if you can kill them but destroying their structure. Contrary, bacteria can reproduce by themselves as they have the whole machinery to function independently of eucaryotic cells (human cells are eukaryotic cells) and have a way more sophisticated metabolism than the viruses

1-Can kids catch COVID-19?
Yes, people of all ages can be infected by COVID-19. A Chinese retrospective study showed that COVID-19 occurred in children, causing moderate-to-severe respiratory illness.

2-What do we know about the COVID-19 structure?
The whole virus has been sequenced, given that scientists have worked 24/7 to get this done, so we have the Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1 complete genome is now available to compare with other viruses and follow up on anti-viral research. Similar viruses, members of the coronavirus family have been studied by virologists since approx 1970s.

3-What can you do to avoid being infected by COVID-19?
- Limit interaction with other people, avoid crowded places and gatherings.
- wash your hands, at least 20 seconds of old school soap and water washing are enough, hand sanitizer is good too, just be aware that it contains alcohol that can dry the skin
- Avoid touching your face, yes the virus can enter through holes other than your mouth and/or nose
- Use a mask if you are sick or taking care of a sick person (mostly for the placebo effect)
- If you have a deficit of vitamins, a multivitamin pill might help (again mostly for the placebo effect)
- Clean and disinfect regularly touched objects and surfaces using your regular cleaning products to reduce the risk of passing the infection on to other people.
- Be kind and have compassion: treat others as you would like to be treated, and take care of yourself as you would for a person you love.

4-What are the symptoms?

This is a tricky one because of the wide spectrum of symptoms recorded so far... most of the patients start with cold-like symptoms (fever, dry cough and difficulty breathing) and then it goes to a more intense phase of joint and muscle pain, sore throat, sneezing, congestion, and even pneumonia. The virus infects the lower respiratory tract and causes severe pneumonia (approx 10% of cases) and mortality in 3-5% of cases, mainly among the elderly and/or people affected by other diseases. One article that analyzed thousands of patients' records, reported that the main clinical symptoms of COVID-19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), dyspnea (21.9%). Minor symptoms include headache or dizziness: (12.1%) diarrhea (4.8%), nausea, and vomiting (3.9%).

5-What does testing mean?
The main test consists of detecting the viral genetic material using a very sensitive technique called reverse transcription-polymerase chain reaction (RT-PCR). They will take a nasal and/or mouth swap to collect some fluid that is then sent to the laboratory and it takes approx. 4 h to get a result. An Argentinian group developed a faster test based on CRISPR, it takes only 60 min to get a result, but it still under development.

6-How long does COVID survive on surfaces?
According to the latest research, still under review. it depends on the surface: the viable virus was detected up to three hours in the air, up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel.

7-How long is the incubation period?
Guess what? it depends on your immune system and viral charge you got... generally around 4-6 days. A review of the Chinese clinical data reported an average incubation period of COVID‐19 is around 6.4 days, ranges from 0‐24 days. So travel restrictions to and from high-risk areas and/or 14 days quarantine of travelers coming from high-risk areas are recommended to prevent possible importation of COVID-19. This is why it is so important to stay home even if you don't have symptoms, at least for 14 days after you were in contact with a COVID-19 patient.

8-Is there a vaccine?
Not yet, and other vaccines don't work because the COVID-19 proteins won't be recognised by the antibodies that your body generated based on previous vaccines. The development of a safe and approved vaccine will take at least 2 more years.

9-Is there a treatment?
There are no specific treatments to date, but again, it depends on the severity of the symptoms and if by the "treatment" you mean just keeping the patient hydrated... Overall, no, there are no antivirals available yet and no, a big NO to antibiotic usage as they do not work, they only work for bacteria, and as we stated before viruses are not bacteria. Some vitamins, like Vitamin A have been shown to be important to maintain a healthy immune system in animal models, BTW, the Asian population has a general deficit of Vitamin A due to their diet. Importantly, you can get these vitamins from fruits and vegetables, and it seems they only work if you have a constant intake before you get infected.
Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of COVID-19 in China.

10-Can you take ibuprofen?
The consensus is yes, you can. Some false claims were published in social media about ibuprofen. However, until we have more information about the effects of non-steroidal anti-inflammatory (NSAIDs), like ibuprofen, some authorities recommend taking paracetamol to deal with fever and pain. Paracetamol must be taken strictly according to the recommended dose because too much of it can damage the liver. If you are already taking ibuprofen or another  (NSAID) on the advice of a doctor, do not stop taking it without checking first.
https://sciencetechreviews.blogspot.com/2020/03/should-you-take-ibuprofen-if-you-have_18.html

11-How to boost your immune system for real?
A healthy lifestyle!
- Sleep at least 7 h every night
- Eat healthy (a plant-based low-calorie diet is ideal... but you know, life is too short eat dessert first)
- Exercise (from a walk to HIIT or dancing, get your heart rate up)
- Drink plenty of water (the 2 liters per day is under debate, but aim for 1.5 liters at least)
- Avoid stress, I know easy to say difficult to do. Breathing exercises and meditation can help.
- Be aware that viruses and bacteria are everywhere, including inside of you, and not all are bad.

12-Can you be re-infected?
We don't know. Probably not, based on previous knowledge on coronaviruses behavior, if the virus doesn't increase its mutation rate. There is one report of a potential re-infection in China and another one in Japan.

13- What wouldn't work?

- Probiotics intake during the infection, they showed very low activity.
- Vitamin C intake during the infection, it is not a shield!
- The 10 secs breathing test, is not a real thing!
- Ensuring your mouth and throat are moist and humidity myth... eh, nope. Although drinking water is always recommended, this claim is false. While staying hydrated by drinking water is important for overall health, it does not prevent coronavirus infection.
- Gargling with salt and won't work, because the highest viral load was found in nasal swabs.
- Cold weather and snow CANNOT kill COVID.
- Taking a hot bath does not prevent the COVID infection.
- There is no evidence from the current outbreak that eating garlic has protected people from the new coronavirus. Though, it is a healthy food that may have some antimicrobial properties

- Antibiotics are for bacteria, not viruses!
-So far, it can't be transmitted by cooked food

14-Is COVID-19 airborne?

Initially, COVID-19 was considered not airborne, because it can't be transmitted just by air but it needs large respiratory droplets. However, preliminary research (as it hasn't been peer-reviewed yet) reported the detection of COVID-19 up to 3 hours after aerosolization and can infect cells throughout that time period.

Please be kind and show compassion to others at all times! Big kudos to the scientist, doctors, nurses, and volunteers working 24/7 to treat patients, produce vaccines, tests, and treatments ASAP. Please help the ones in need and in risk groups during the lockdown. To paraphrase Brandon Sanderson: "the original plan for this article was to be short. It ends up being quite long. Ah well. That just happens sometimes. (Particularly when you are me)"

If you have any questions please post them in the comments and I will try to answer them ASAP.
Some ideas about what do to at home: read (you can get free books from the library, amazon, google and other websites), take an online course, learn a new language, cook, play board games and/or video games, workout, call your friends and family, meditate, try an online tour...




An electron microscope image of a coronavirus. Photograph: AP

Thanks Dr. Ilse Daehn for the edits.

Recommended links:
https://youtu.be/E3URhJx0NSw
https://sciencetechreviews.blogspot.com/2018/04/chasing-one-drug-to-rule-them-all.html
https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6
Avril, Tom. “Coronavirus has shut down schools and events. Here’s why that helps, short- and long-term.” Philadelphia Inquirer. 8 Mar 2020.

“Coronavirus COVID-19 Global Cases.” Center for Systems Science and Engineering, Johns Hopkins University. Accessed 27 Jan 2020.

“Coronavirus disease 2019 (COVID-19) | Situation Report – 51.” World Health Organization. 11 Mar 2020.

Johnson, Krys. Assistant professor of epidemiology and biostatistics, Temple University. Email to FactCheck.org. 12 Mar 2020.

“Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19).” World Health Organization. 20 Feb 2020.

“Steps to Prevent Illness.” U.S. Centers for Disease Control and Prevention. Accessed 12 Mar 2020.

Weinberg, Abigail. “There’s a Facebook Coronavirus Post Going Viral Claiming to be From Stanford. Don’t Believe It.” Mother Jones. 11 Mar 2020.

“WHO Director-General’s opening remarks at the media briefing on COVID-19 – 11 March 2020.” World Health Organization. 11 Mar 2020.
“WHO Director-General’s opening remarks at the Mission briefing on COVID-19 – 12 March 2020.” World Health Organization. 12 Mar 2020.
World Health Organization Western Pacific (@WHOWPRO). “Q: Does drinking water alleviates a sore throat, does this also protect against 2019-nCoV infection? A: While staying hydrated by drinking water is important for overall health, it does not prevent coronavirus infection.” http://bit.ly/COVID19Mythbusters… #COVID19 #KnowtheFacts.” Twitter. 26 Feb 2020.

Monday, April 13, 2020

COVID-19 projections assuming full social distancing through May 2020

Information is the pillar tool that we can use to make an educated decision, both individually and collectively. Therefore, here are 3 fantastic links to see how scientists are tracking and modeling the pandemic:

COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University
https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6

COVID-19 projections assuming full social distancing through May 2020
You can check your country projection in this link:

http://covid19.healthdata.org/united-kingdom


Confirmed Cases and Deaths by Country, Territory, or Conveyance:
https://www.worldometers.info/coronavirus/


Wednesday, April 1, 2020

COVID-19 Effects Might be Related to Your Blood Type and Your Vaccination History:


Besides the comorbidity and age-related differential symptomatology seen in COVID-19 infected patients, another intriguing contrast has been the different outcomes seen in patients based on blood type. A new study from China indicates that people with blood type A may be more vulnerable to Covid-19. According to this study, patients with blood type A had higher rates of infection and developed more severe symptoms compared to non-A blood types. The blood type O was associated with a lower risk for the infection compared with non-O blood types.
This study, however, had multiple limitations, one being the limited sample size analyzed (2,200 COVID-19 patients in China and tens of thousands of healthy people). Also, the blood type-related differences in COVID-19 risk may, in fact, be due to certain antibodies in the blood. Further studies are needed and the original research article needs to be peer-reviewed (this means being scrutinised by other scientists to verify their validity and accuracy).

Blood types are determined by the presence or absence of antigens -- proteins that can trigger an immune response if they are foreign to the body. There are four major blood groups which are determined by the presence or absence of two antigens (A and B) on the surface of red blood cells. If you have the antigen A your blood type is A, if you lack the antigens A or B, your blood type is O. The USA National Center for Biotechnology Information (NCBI) research shows that about 41 % of the US population is type A and 44 % is type O. Type B and type AB are the rarest blood types.

A dichotomy recently found to potentially impact COVID-19 recovery outcomes is the vaccination profile of patients. A new epidemiological study proposes that the BCG (Bacillus Calmette-Guerin) vaccine appears to impact recovery by reducing morbidity and mortality for COVID-19. Preliminary evidence proposes that national differences in COVID-19 impact could be partially explained by the different national policies around BCG vaccination.

Originally designed to protect against the tuberculosis bacteria (TB), the BCG vaccination offers broad protection to some respiratory infections and reduced the number of reported COVID-19 cases in a country with BCG vaccination policy. The study reported that countries without universal policies of BCG vaccination (such as Italy, the Netherlands and the USA) have been more severely impacted versus countries with universal and long-standing BCG vaccine policies. Interestingly, countries that were late in implementing universal BCG vaccine policies (such as Iran in 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population.
Some countries, like the USA, are not vaccinating based on the low number of TB cases, the cross-reactivity of the vaccines with the TB test that they use and the “effectivity based on the early vaccination”. My opinion is that they should vaccinate their population, as TB is a highly contagious and dangerous disease that can be easily controlled through universal vaccination!
Fortunately, other countries, like Australia and the UK, are fast-tracking large-scale human testing to see if the BCG vaccine can protect health care professionals from contracting COVID-19. One of the trials will be conducted with 4,000 health care professionals in hospitals around Australia to determine if it can reduce COVID-19 symptoms.

Being born and growing up in Argentina, I was vaccinated as a child and 27 years later, when I was tested as a new employee at New York City’s Mt. Sinai Hospital… I tested positive for TB. An X-ray was required to prove that my lungs were healthy, and that I didn’t have TB, merely the antibodies that the BCG vaccine helped me produce to keep me safe from TB. Again, this is an anecdotal situation, I had contact with a person with COVID symptoms and I self-isolated myself, although I haven’t presented any symptoms… was it because my blood type is O? or was it because of the BCG vaccine? I don’t know but I am hoping we will get answers to this soon from research that would be correctly conducted, controlled and peer-reviewed.




BCG scar/ COVID-19 cartoon.

Thanks Tom Keeter and Ilse Daehn for the edits.

Monday, March 30, 2020

What is the Relevance of the Different Strains of COVID-19?



In early March, a group of Chinese scientists analysed the genome sequence of the new coronavirus extracted from 103 patients. They found that the virus was not mutating into a more dangerous version, instead, they hypothesized that newer mutations are making the virus less deadly. Interestingly, they also identified two strains, one which they initially classified as very aggressive and the other as a less aggressive version. Nevertheless, with more information about patients’ outcomes and other available viral genomes, they changed this classification, to clearly identify which strain of infection will produce more severe symptoms.
Their disclaimer: “We now recognize that within the context of our study the term “aggressive” is misleading and should be replaced by a more precise term “a higher frequency”. These two virus types or lineages were named L and S. The L type is the more prevalent and S type is the “original” version found in Wuhan, China. The prevalence of the L type might be due to the selective pressure human interaction placed on the original S type.

It is clear now that COVID-19 impacts people differently, with some asymptomatic and others needing hospitalization (around 20-15%). Moreover, the strains are quite similar to each other as COVID-19 appears to mutate slowly, and key opinion leaders suggest that it appears unlikely the outcome differences are related to people being infected with different strains/types of the virus.
With more viral genome sequences to analyse from all over the world, now scientists have identified 8 strains. You can watch COVID-19 evolutionary development here:
https://nextstrain.org/ncov?animate=2019-12-09,2020-03-25,0,0,30000

Positive news coming from this global collaboration of research is confirmation that the mutation rate (the speed at which the virus changes) is 8 to 10 times slower than the one for the influenza virus. Therefore, when vaccines are ready ( hopefully in 12-18 months) they will be effective for a longer period of time, because they will be targeting the same type of slow-to-mutate viral particles.

One of the silver linings of this COVID-19 crisis is the revalidation and appreciation of scientific research and the subsequent boost in both funding and support for the scientific community and pharmaceutical companies.



COVID-19 Transmissions

Thanks Tom Keeter and Ilse Daehn for the edits

Thursday, March 26, 2020

COVID-19: Hopeful News, Treatments are Under Development

COVID-19: Hopeful News, Treatments are Under Development

All over the world researchers are looking for treatments for COVID-19, and some drugs are showing promising results. These results, however, are preliminary and proper clinical trials (normally conducted in 4 phases), with randomization and controls need to be carried out. The World Health Organization (WHO) has started a large global clinical trial (named SOLIDARITY) testing the four leading drugs (all previously passing clinical trials and approved for the treatment of other illnesses). To participate in the SOLIDARITY clinical trials, COVID-19 patients need to fulfill the inclusion criteria, assessed by the physician ( such as being COVID-19 positive and presenting respiratory symptoms), and sign the informed consent form.

1- Remdesivir. This compound inhibits the activity of the viral RNA polymeranse, a protein that the virus needs in order to replicate. The pharma company Gilead Sciences, initially developed the drug to inhibit the Ebola virus, but it failed to show any significant improvement in Ebola patients. In 2017, early drug development studies showed that remdesivir inhibited the RNA-polymerase of MERS and SARS viruses (2 coronaviruses) both in-vitro (tested on proteins and/or cells grown in the lab ) and in animal studies. Recently it was tested in two American patients with severe COVID-19 symptoms, and both patients recovered rapidly.

2- Chloroquine and hydroxychloroquine
These compounds work by decreasing the acidity in separated compartments inside cells that are used by some viruses as a point of entry into the cells. Clinical trials using these drugs on other viruses, however, have shown negative results. Interestingly though, these compounds efficiently inhibited SARS-CoV-2 infection in vitro. One letter published by Chinese researchers claimed that patients treated with these compounds showed improvement in their recovery outcome. Unfortunately, the study results have not yet been published. In another study, hydroxychloroquine, a more tolerable form of chloroquine, didn't perform better than placebo at clearing the coronavirus among Chinese patients with mild cases, or at helping them reach lower temperature sooner. Other researchers from China and France tested these drugs in COVID-19 patients and reported a significantly reduced viral load in nasal swabs. The USA Society of Critical Care Medicine, however, has declared that “there is insufficient evidence to issue a recommendation on the use of chloroquine or hydroxychloroquine in critically ill adults with COVID-19.”
Researchers are also raising flags about the dose and general use of Hydroxychloroquine as it has shown to cause adverse effects.

3- Ritonavir and lopinavir. Initially, this combo drug treatment was developed by Abbott Laboratories to treat HIV infections. These compounds inhibit a viral protein that is vital for the correct processing of other viral proteins. The first study using these drugs in “very ill” COVID-19 patients in China did not show positive results.

4- Ritonavir/lopinavir and interferon-beta combined. In this study, each antiviral (Ritonavir or lopinavir) is used in combination with interferon. Interferon is an antiviral used to treat patients suffering flu and other viral infections. Interferon is a regulatory protein that modulates inflammation in humans. It is well established that some interferons activate an antiviral gene program in epithelial cells with minimal perturbation to the specific immune response. Furthermore, it has been tested for the prevention of Winter colds and flu alone and in combination with other anti-virals. Interferon has also been used to treat poultry against flu.

Other potential therapies include:
Regeneron and Sanofi-marketed antibody, Kevzara, a drug used to treat arthritis, is now being tested in patients with severe COVID-19 infection. Fujifilm-marketed Avigan (favipiravir), a drug used to treat flu-infected patients, is being studied for the treatment of COVID-19. Studies in China and Japan have shown moderately positive results, depending on the severity of the patients’ condition. Patients who were given the medicine in Shenzhen turned negative for the virus after approximately four days following having become positive, compared with a median of 11 days for those who were not treated with the drug. They also showed improvements in lung condition in about 91% of the patients who were treated with favipiravir, compared to 62% on those without the drug.

Researchers, for example at Mount Sinai Hospital in New York and at the Pasteur Institute in Paris, are testing in vitro (on human cells grown in the lab that are infected with COVID-19) hundreds of compounds and drug combinations trying to identify potential therapies.
Another promising therapy, coming from Mount Sinai Hospital in NYC, is the use (or re-use) or antibodies from patients who recovered from COVID-19. The body-rich plasma from COVID-19 patients to help critically ill patients was already used successfully in China, as they reported that some patients improved within 24 hours, with reduced inflammation and viral loads, and better oxygen levels in the blood.

Some interesting ideas are also to be tested, for example Dr. Dan Batlle has a paper in Clin Sci. discussing the potential therapeutic utility of overwhelming the body with more soluble ACE2 protein (the receptor in the membrane of human cells that interacts with COVID-19 surface proteins) in an attempt to diminish viral infection into membrane-bound ACE2. COVID-19 surface proteins need to interact (bind) to the ACE2 proteins (located in the surface of human cells) in order to enter the cells. This hypothesis is based on the idea that the free ACE2 protein (not in the surface of human cells) will bind and therefore block the membrane/surface proteins on the COVID-19 that are necessary for the viral infection. In this case the viral proteins won’t be able to bind to the ACE2 protein on the surface of human cells, and therefore they won’t infect the cells.

Importantly: you should NOT take any of these treatments without a prescription from your doctor, as they can cause adverse effects and even death.
For now, the best way to take care of your health and avoid contracting COVID-19 is to wash your hands thoroughly and regularly, keep your hands away from your face, stay in self-isolation or and maintain social distancing, have good hygiene (aka wash your hands).