The COVID-19 outbreak undoubtedly has been unprecedented and has brought the whole world to a grinding halt currently. It is something, that we, virologists as a community have always feared and have always thought about as a distinct possibility. Virologists have mentioned such possibilities in many scientific publications and we have always imagined what would such a scenario look like outside the Hollywood movies that have been made on such outbreaks. And we had imagined it to be quite different from such hyped, commercial disaster movies. But the reality is now merging with the surreal and people’s reactions have been from nonchalant to hysterical. The whole outbreak has highlighted faults in the systems and how much we take everyday things for granted. It’s incredible how much the social, political, psychological, financial and maybe even environmental landscape would have changed by the time we are done with this.

With such uncertainty, I felt that I could create a simplified set of FAQs on the biology of coronaviruses that would be understandable by anyone. I have had a number of people including friends and family ask me questions about COVID-19, its biology, its spread and its properties. This would be an attempt to bring together all of those queries, concerns and comments and attempt to answer them on this post. I feel it is really important for virologists to help everyone understand the 'enemy' here and ways to combat it and at the same time put to rest a ton of misconceptions, fake news and false ideas that are floating around in this massive beast that is the internet.

Even though I have worked with the genetic material of coronaviruses during my tenure at Harvard, and designed potential vaccine candidates for SARS and MERS, and I am also currently involved in related projects, I do not claim to understand all of the biology of COVID-19. So my friends who are virologists - feel free to chime in and add to this list of FAQs. This is designed to be a mutual exchange of scientific accurate information and answering questions to the best of our knowledge.

So here are the salient points:

1. Ask me any question about COVID-19 or other viruses and I'll try on answer to the best of my capabilities and seek help form other experts too.

2.I've started with a few questions I got asked and I'll keep adding more questions and their answers to the list as you ask them.

3. Feel free to ask about any doubts, any concerns, any biological aspect you want to understand in greater detail, any questions you might have about conspiracy theories, remedies, ideas that you might have heard about on the internet or elsewhere. No judgement.

4. This is designed to make one more at ease and be confident about how to handle oneself in this current scenario. I must admit that knowing in depth about this virus and keeping up on top of the research that has come out has kept me completely calm throughout this entire world crisis - just because I can see exactly what is happening (I wouldn't be able to say the same thing if a financial crash happened around the globe due to cryptocurrency upheaval or something). For me that would be the fear of the unknown. I just want to be able to share at least some of the biology of the virus so that it does not appear so unknown and so scary and maybe help reduce some anxiety and concern.

5. Please share this if you feel this might benefit other people and encourage them to ask questions if the FAQ does not cover their concerns.

6. Let me know if any of the answers is hard to understand due to scientific jargon. The attempt is to make it understandable by all. I’ll try to simplify it further without losing details.

For further details the CDC or WHO sites are always good resources..

Here are the official CDC guidelines on what to do if you have symptoms;

https://www.cdc.gov/…/20…/downloads/COVID-19_CAREKit_ENG.pdf

Here are some of the basic questions I had from people before this:

What is the virus 2019-NCoV or COVID-19?

Let me start with the most basic question first. COVID-19 is a virus that belongs to a large family of viruses known as Coronaviruses. Other viruses in this family that many people would recognize by name are SARS and MERS that had appeared and caused outbreaks of infection in 2003 and 2012, after which they have not resurfaced much as of yet.
Another member of this family is a virus called OC43 – which causes – a form of common cold! So coronaviruses though similar in their shape, form and properties may have wide ranging effects on our daily lives and not all coronaviruses cause deadly disease.

What does this virus look like?

Based on studies by electron microscopy and other methods – the virus has its genetic material in a central core together with a few proteins surrounded by a layer of fatty membrane – similar to what surrounds our own cells. But in addition, there is a type of protein embedded into this membrane which sticks out like toothpicks from the viral particle (the image of the virus which everyone must be very familiar with so far as it is been splashed across all forms of news sources, currently). This pincushion appearance seen flat under a microscope gave the appearance of a ‘crown’ or ‘corona’ and hence the name. Lets call the protein that resembles pins sticking out from the virus as ‘Spike proteins’

How does it infect humans?

The abovementioned Spike proteins are the most critical players here. As these are the proteins that forms the outermost coating of the virus, they get to come in contact with anything first. The virus, as we know by now gets taken up through the nose or mouth and ends up in the respiratory tract eventually. Here in the respiratory tract, we have an abundance of an enzyme known as ACE2, which in turn sticks out from the lung cell membrane. The coronavirus Spike protein can bind this ACE2 protein and get taken up inside the lung cells. Here the virus will make many many copies of itself using its genetic material, some of the proteins it has brought along and hijack some of our own proteins for its purpose. This creates many many such viruses which are released and the process keeps repeating itself inside the infected person’s body until billions of viruses are produced and released. As a result the lung cells are completely taken over and are destroyed by the virus literally turning them into factories producing more of its kind.

How does it spread from person to person:

As it is the lung cells that the virus grows in – it causes severe respiratory distress by damaging the cells in our lungs that exchange oxygen with the air that enters the lungs. As more and more of these critical cells in our airways are destroyed by the virus, the exchange of oxygen in the lungs gets more and more difficult and hence people in severe cases might require hospitalization with respirators to help with breathing. The virus can be released from these damaged lung cells and into the airway and back out in the open encased in small droplets of our mucus. As the person has difficulty breathing, the body coughs trying to eject any occluding item in the lungs and with this cough, the droplets containing virus can be ejected out into the air and infect a person within close range. Each such droplets may carry tens of thousands of particles – enough for an initial infectious dose for the nest person.

Where did COVID-19 come from?

COVID-19 has shown characteristics of what we call a zoonotic virus. Which means it used to reside in some animal, likely bats or other animals (the exact source hasn’t been identified yet). At some point due to some manner of close contact with humans, the genome of the virus mutated thus changing the Spike protein and maybe other proteins in the virus, in such a way that the Spike protein of COVID-19 was able to strongly attach to ACE2 proteins in human cells and hence could grow in human cells.

If it’s an animal virus how can it infect humans?

This kind of ‘species jump’ is very characteristic of zoonotic viruses and there are many examples of these including Ebola virus, Bird Flu, Swine Flu, Lassa virus, etc. So the sudden emergence of this virus is nothing unique and these species jumps are happening with viruses all the time between all kinds of species – we just get to see the ones that jump to humans and cause disease. In this particular case, as we know the virus most likely had mutated in some animal species being sold in the Wuhan live animal market in China and this mutation just happened to be one that helps the virus infect humans. Studies with SARS has shown that a set of mutations in the Spike protein (all coronaviruses have spike proteins) of a closely related bat coronavirus resulted in the current version of the spike protein that SARS carries on its surface. In similar studies closely related sequences have been found in bats for COVID-19 but the closest viral predecessor from which the jump happened is yet to be identified.

What happens when a human gets COVID-19:

The initial incubation period until the virus has multiplied enough, damaged enough lung cells in order for respiratory distress/cough to show appears to be up to 14 days and sometimes in some cases it was even longer. Which means from the point someone gets the virus to the point where they realize they have got the virus and gets tested, one might not even feel any distress at all. But as I mentioned above only when sufficient cells of the lung are damaged so that oxygen uptake is hampered, does the body go into damage control mode and start showing symptoms. However, in the meanwhile the virus has already started producing more virus particles in the lungs cells and are releasing them in droplets – this is why one is infectious even when one does not show symptoms – and this is one of the most dangerous aspects of this virus as the infected individuals can’t be identified right away. This is why the average length of isolation is prescribed as 14 days.

Why are some individuals getting very sick and even dying but others have no symptoms.

The exact reason behind this has not been identified for COVID-19, but based on our experiences with lung biology there could be various factors which might be relevant. Our lungs usually have a lot of reserve capacity of cells that exchange oxygen between the air and the blood – this comes in use when the lung has to work overtime – during exercise or coping with low oxygen at high altitudes. So for many healthy individuals the damage caused by COVID-19 to lung cells might not even reach the level which causes respiratory distress due to lack of these cells in normal breathing conditions, before the body’s immune system clears out the virus. For others, the damage may extend so far as to reduce it to a fraction of the normal capacity before the body’s immune system can beat the virus. For other unlucky persons – the elderly, people with underlying conditions – there could be additional complications including the lack of proper response or even over response by the immune system that could lead to very severe disease or death.

How can I prevent myself getting infected by COVID-19?

As being reiterated many times over now – washing hands very well in the proper way for 20 seconds with soap, not touching your face, maintaining distance, social separation, etc are currently the only ways you can do something to prevent yourself from getting infected. Using soap breaks down the fatty membrane of the virus thus destroying virus particles, not touching your face prevents viruses on your hand from touching the ‘mucus membranes’ of your body – the inside of the mouth starting with the lips, near your nostrils where it can be sucked in by your breath and even the eyes – which also has a mucus membrane covering it. Maintaining distance and social separation helps you get out of the range of droplet infection from another person and not touch any surfaces that an infected individual may have touched. This is important as the virus can last up to 72 hrs on some surfaces and is certainly not purified after 12 hrs or by exposure to the sun.

What are the potential cures?

As COVID-19 emerged rapidly and due to its ability to spread very rapidly, it has caught us a bit on the backfoot. But thankfully we have learnt a lot about SARS after the outbreak of 2003, and this helped really well as I have never seen findings come out so rapidly on a newly discovered virus as it has for COVID-19. So even though there is no cure as of yet, given the massive worldwide effort – sooner or later we shall see some positive news emerging on that front. Testing those for efficacy, toxicity, etc and putting them through clinical trials however will take months. The most rapid way a drug could be successful is if some already licensed and tested drug is there on the market that is found to be effective against COVID-19. Some candidates have been proposed and the testing is on its way.

What about a vaccine?

Vaccines would be the most effective way to limit the spread of COVID-19 by protecting uninfected individual and breaking the chain of spread of the virus. Vaccines are built by using a small part of the virus itself (or sometimes whole inactivated virus) that are delivered to the body. The body’s immune system in turn, believing that the actual virus infection is occurring, generates a set of proteins known as antibodies which match the virus proteins like a two Lego blocks fitting each other. The body essentially plays the Vegas slot machine probability matching game with parts of these antibody proteins creating all sorts of permutations and combinations of bits and pieces of the antibody proteins to finally create one which very strongly the invading protein from the virus. Once such an antibody is created and a match is found, the body makes more and more of that particular antibody and overwhelms the virus by binding to all the available virus proteins, in the end making the virus ineffective. But this whole matching process takes a few weeks for the body to accomplish. As of now at least 16-18 different approaches to create vaccines against COVID-19 has been started. One has even gone to clinical trials – so it looks like at least a vaccine would be very much in the works. But again, the whole testing, validating, clinical trials and production phases will take months.

Is there any evidence of this virus being airborne ? I am not getting the aerosol concept.

There are two ways a virus can be spread - one is through droplets which may contain thousands of virus particles encased in mucus propelled by sneezing and coughing - these won't go far ~ 6ft as they are heavy. The second way in which the virus particle itself could travel through the air if its stable enough, sometimes sticking to other particulate matter - these could travel longer distances. There is some evidence about the latter which the WHO also shared - so its possible it could travel much further than six feet. But in the latter case, it is aided by dry air and colder temperatures - like the flu. So there is a chance it may become less potent as temperatures rise if the above is found to be true.

Is the malaria medication working on this virus?

The malaria medication (chloroquine) study has a lot of caveats - especially with group size and the control group. The study was obviously done in a hurry without good controls. But since its something positive - many other labs are parallels trying to repeat it including the CDC I think - so that if these trials work it can get quickly approved.

Why are some patients having gastric issues?

There are some members of the coronavirus family which are known for causing gastric disorders. If you remember 3-4 years back there was a gastric coronavirus outbreak making kids very sick. The lung mucus lining has similar properties and proteins like the GI tract - so it’s not surprising that in some cases the GI tract could get infected by COVID19 causing diarrhea. Other symptoms like loss of appetite could be the body’s general reaction in coping with an infection.

Is the COVID19 virus engineered in a lab?

Thank you! This is a question that I have answered the most so far. Firstly, other than random WhatsApp posts and FB shares, the only 'evidence' presented on this theory so far was a paper from a bacterial lab that did no lab experiments but only analyzed sequences online. The whole theory seemed to have originated from that single source. Firstly, the paper was not peer reviewed and was published on an online platform and not a scientific journal. A few days later it got retracted as well. Secondly, I have personally read this manuscript in depth and tried out some of the online sequence comparisons myself. Other virologists I know have done this and come to the same conclusion as myself.

The paper claims that there are 4 small segments of genetic material in this virus that resemble portions of HIV virus proteins and which are unique to COVID19 and are not found in any other members of the family. Proteins are large polymers of small units called amino acids, of which there are 20. The probability of the exact set of 7 or so amino acids highlighted by the paper occurring in a particular sequence could happen entirely by random chance. In fact I could find a number of other proteins in nature which have this sequence. Why did the paper choose the HIV sequences then? Secondly, the claim that these are unique for COVID19 is false as 2 of these sequences are also found in other members of the family. So the claims of this paper has been debunked.

In this conspiracy theory on of the biggest things we have chosen to ignore is the fact that this kind of emergence of a novel virus from an animal host has happened many many times before for many viruses and in many parts of the world - true for Ebola, Lassa, Bird Flu, MERS, etc. Without us knowing nature is carrying out billions and billions of experiments in animals worldwide with all viruses which are randomly;y mutating. The most fit viruses get to propagate while the others die out. In case of COVID19 and these other 'zoonotic' viruses they have by chance attained the ability to bind to a human version of a protein vs the animal one they were originally binding. Just by chance through billions of permutations and combinations. As viruses make millions of progeny each, you can guess that the chance of an animal to human jump though small comes up quite frequently by sheer chance.

Human science hasn't reached a point where we can just predict exactly what will make a novel virus highly transmissible and highly pathogenic at the same time let alone making it such that only a certain segment of the population is at a risk. We can't match nature's mega scale Russian roulette and come up with a 'perfect' engineered virus. So all of this makes it extremely unlikely that COVID19 was 'engineered' in any way. Also HIV and coronaviruses viruses have very different life cycles - so even if someone put in a piece from HIV into this virus there is a greater possibility of messing up the COVID19 rather than making it more pathogenic - coz by itself that piece of HIV is completely useless.

Can heat kill the virus?

We have to be very careful in determining what we mean by the word 'heat' and these different meanings of 'heat' should not be confused with each other. Firstly, there is direct applied heat which obviously will start cooking the virus proteins above temperatures of 47-48 degrees C. But obviously neither our body temperatures nor the ambient temperature will go up that high. If it does, we have more serious problems than a virus. Secondly, there is human body temperature which is ambient at 37 deg C (98.6 F). The human body harbors the perfect conditions for human viruses to multiply. The body raises its temperature during fever which slows down replication of the virus to an extent and activates a lot of innate immune systems of the body. But the body can't go beyond 40-41 deg C without causing serious damage to the brain and the organs of the body as the entire machinery of all the organs in the body operate at 37 degrees - any deviation from that the body tried to bring it back to 37 deg C using a series of sensors in a process called 'homeostasis'. So finally, the only aspect in which 'heat' could affect the virus is the ambient temperature and climate. Certain viruses like the flu are seasonal as they are transmitted by air and the virus is more stable in colder and drier climates. There is one current report that suggests that this might be the case for the COVID19 virus, but in no way the ambient temperature that can reach that point at which the virus will be destroyed right away. As there is another report suggesting some aspects of spread of the virus might be airborne other than droplet and surface transmission, if this report is true then this will be the aspect that will be affected if the summer tempertaures hit. The virus might be slowed down in its spread as it loses that aspect of transmission (but remember the other modes will still be active). This though along with stringent isolation measures, personal hygeine, lockdowns and a chance of the virus mutating into a very benign form could 'flatten the curve' as the warm weather hits.