Around the world, COVID-19--the disease caused by the novel coronavirus (SARS-CoV-2)--is affecting patients’ respiratory systems. Several reports have highlighted how, in patients who need intensive care, lungs are severely affected.

Viruses such as the Middle East respiratory syndrome (MERS) are extremely lethal, and hence do not have the chance to be more infectious, Sanjay Mukhopadhyay, directory of pulmonary pathology at the Cleveland Clinic in the US, tells us in this interview. On the other hand, viruses that cause the common cold are very infectious, but not as lethal. SARS-CoV-2 is in the middle of these extremes, Mukhopadhyay says, explaining why it is behaving differently.

Early trends in the US suggested that places that have followed social distancing measures well were seeing fewer cases, he said, adding that while no one is immune to the virus, a person’s health before they are affected determines how they will fare.

Mukhopadhyay was earlier a surgical pathologist, and is also a leader in global pathology education in social media.

Edited excerpts from the video interview:

Why are the lungs the target of the COVID-19 virus? And how does that play out as the infection attacks an individual and then progresses?

The SARS Corona Virus-2 (SARS-CoV-2), which is causing the global pandemic right now, is a part of the family of coronaviruses. And the coronaviruses--both this one and the earlier SARS-CoV-1, the one that caused the original SARS [severe acute respiratory syndrome] epidemic before this--sort of attach to cells by what you could think of as a lock-and-key mechanism. So, the virus is trying to use its key to open the lock in a variety of different cells. It just happens to be that both SARS-CoV-1 and SARS-CoV-2 have found a lock that they have the key to. That lock is called a “receptor” in medical terminology. There are receptors that do normal things in normal cells in the body, they have normal functions, but the virus exploits those receptors to enter the body.

For SARS-CoV-2, the receptors happen to be on the cells that are on the back of your throat and your nose--called the nasopharynx. So, the virus goes and attaches there. And viruses, as you know, cannot replicate on their own. They cannot divide. They cannot make babies. So, they need to go inside a cell, and then they use the cell’s machinery to replicate. The SARS-CoV-2 virus goes inside the cell--we call them epithelial cells in medical jargon--they go inside the cells of the back of your nasopharynx and then they travel down, infecting cells in their way all the way to the lung.

A short answer to your question is, because the receptors the SARS-CoV-2 uses are in [respiratory tract] cells, it attaches to those cells. The receptors are called ACE 2.

Since you described the path of the virus, how is it that it then spreads from one person to the other?

When the virus is attacking the body, it is actually getting into a cell. But when you sneeze or cough, the virus is being expelled out of the body, in what is known as a droplet. It is out there in the air; it hangs out in the air and then drops down to a surface. And people have done experiments on this in the very early days of the pandemic. They have seen that if the virus lands on hard surfaces, like a metallic surface, then it lingers on there for as long as a couple of days. And then if you touch that surface, and that surface touches your mouth or eyes, then you can transmit that droplet to yourself.

This is a little different than a virus that lingers in the air for a long time and then you inhale it from the air. That seems to be not as important for this one, as actually falling to the surface and then you get it from the surface.

How does it then survive on the surface for so long?

I am not sure what the mechanisms are, but viruses can stay outside a cell (extracellularly) for a little while before they die off on their own. Experiments have shown that the time period is about two or three days. But why exactly, I am not sure, I do not know what the mechanism is.

You mentioned an early study by Chinese researchers, which looked at patients from Wuhan. And one of its conclusions was that 50 of those 54 patients died because they had Acute Respiratory Distress Syndrome (ARDS). And that is how the disease progresses to become lethal. Tell us about that.

People in that study were all hospitalised--so these are the severe end of the infection; they are not those who are at home with mild symptoms. So, they looked at the people who are in the hospital and of [those, the ones] who developed ARDS were much more likely to die.

As the virus goes down into the lungs, it causes the little blood vessels (you can think of them as the smallest branch of the artery) to be leaky and damages the alveoli (the little air sacs that are in the lung). And that kind of damage, if you look at it on a chest X-ray or chest CT, it makes a normal X-ray or CT--which is black because it has air inside it--turn completely white on both sides. And that is happening, at least in some patients in the pandemic. And the patients who develop ARDS are the ones who are on the ventilator, and those tend to have a very bad outcome. And they tend to be the ones who do not survive.

Is ARDS also the reason why hospitals are admitting COVID patients, because they are likely to have ARDS?

Well, the hospitals are admitting people who have symptoms to the point that they cannot survive out in the community. Yes, they are admitting people who have severe symptoms and some of them, the ones who develop ARDS, who get very, very short of breath, those are the people that need to be on a ventilator.

The point of being on a ventilator is not that it is curing a patient. It is just that without the ventilator, they will not be able to breathe. That wall of the alveolus is so damaged by ARDS that without a ventilator, those patients will die. They need ventilatory support. You are literally pushing oxygen into their lungs, which otherwise would not go.

On the flip side, if you are feeling breathless or have low oxygen, that means you could very well be having an advanced condition of COVID-19.

That is a very good point. People who were previously well and then have fever and cough, it is OK to perhaps self-quarantine. But if you get severely short of breath, one must seek medical attention. That might be the sign that you are developing the later stages of the disease.

Since the lungs are really what is collapsing here, leading to the need for ventilator support, can we then strengthen the lungs in some way?

No, I am not aware of any magic way to do it. That is why social distancing is so important--because there is no way to protect yourself from this. You want to prevent the infection in the first place, because once you are infected, there is really nothing you could do to decide whether you go into the mild path or the severe path. We just do not know how to predict.

We do know [that the elderly are more likely to be severely ill], though, from studies that have happened in multiple places. There was a study in the state of Washington in the US, in nursing homes or long-term care facilities. The residents were all sick elderly people, the median age was 83 and all of them had underlying conditions such as hypertension, heart disease, etc. Long-term care residents, almost all of them who were tested, had the disease and a large proportion of them died. Almost 33% of them died of the disease. But when they looked at the staff who were taking care of them, some of them also got infected. But they did not die, as they were younger and healthier to begin with.

So that is well known now, that if you are young and healthy to begin with, the chances of dying are lower than those who are elderly and are immuno-compromised or have an underlying condition. So, you want to keep the infection away, especially from those people because they are most at risk.

So it is not like, for instance, if I am a sportsperson, obviously I have stronger lungs, better breathing capacity. Or I am a diver, I can hold my breath—all that does not mean that I am more immune to an attack on my lungs the way COVID-19 does?

Yes, there is a distinction to be made here. You are not at all immune from getting infected. You can get infected and people are getting infected at all ages. But it does seem to be that once you do get infected, how your health was to begin with, determines how you will do later. That is really the main difference.

Let us come to ventilators. You did say that because your lungs are unable to perform, you must provide ventilator support. At what stage are the lungs and the body, in general, really do ventilators help? Are you already at the last mile, so to speak, because of which the chances are bleak?

That is a very good question. And the answer is yes. By the time you need a ventilator, you are already at a pretty advanced stage in the disease, which is why once you get on a ventilator, the earlier you recover--the ventilator is not curing, it is just giving you time when the body is fighting back the infection--and get off the ventilator, the more the chances that you will recover from the disease.

So, there is a percentage of patients who will recover and go back to the regular hospital ward or be discharged to go home. They are recovering. That is relatively a small fraction. Now, the more you stay on the ventilator, the further out you get, the lesser the chances of recovery. Time is a critical factor here.

Is that also because there are other organs in the body that are failing, particularly for older people?

Yes, correct, and the lungs are getting more and more damaged. The walls of the lung--which should be thin [so that] oxygen can go back and forth--are getting gradually thicker and thicker, and are creating a barrier for the oxygen to go into the bloodstream.

Are the data so far giving you any better understanding of this disease or of the way it is affecting humans or the way it is causing a certain degree of casualty?

Yes. Initially, it quite did not make sense why this virus was any different than influenza or any of the others. But the way I would like to explain it is, as a virus, you have two things that are critical: How easy is it to take it from one person to the other (i.e., infectiousness)? And, how lethal is it when it does infect somebody?

So the viruses that were the most lethal… let us take the example of MERS [Middle Eastern Respiratory Syndrome]. The moment it infected somebody, those people were killed in a high proportion of cases. So, they never really had a chance to be infectious to other people. So [at] that level of lethalness, it never spreads and the infection sort of dies out on its own because it kills the people that it infects. So that is at one end. At the other end are your coronaviruses that cause the common cold, so it is very infectious; it goes from person to person, but it does not kill too many people, so it is not that much of a problem in the community.

SARS-CoV-2 is in the middle of those two extremes. So, the people who are infected are asymptomatic for a while and are moving around and infecting other people. And then, as opposed to the common cold, and seven days later or so, people start getting symptoms and the virus becomes lethal. So, it now becomes very well established that because SARS-CoV-2 behaves in this way, it is both infectious and lethal. And that is why it is causing this… we are beginning to understand why it occupies this unique position among viruses.

While we look for a vaccine--and maybe we will find it in the coming months or year--lives and lifestyles will change. Is there anything you would specifically recommend, as advice, to those who are reading/watching this?

My recommendation is, keep an open mind. It is okay to be skeptical; it is ok to read everything that you read but in terms of reacting, you can take two paths: You can say well, I do not care, and I will do whatever I want. The other is to be over-cautious, stay at home and follow all the recommendations. My recommendation would be: be over-cautious. If it turns out [that] some of the things are wrong, you lose nothing. You protect yourself, the family and the people who are vulnerable. My recommendation would be, be overcautious, follow social distancing guidelines, do not gather in large crowds and your family, your elders and parents will thank you in the long run for that.

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