'SARS-CoV-1 and SARS-CoV-2 exploit the receptors of the cells to enter the body,' says Dr. Sanjay Mukhopadhyay, Director, Pulmonary Pathology, Cleveland Clinic to BOOM's Govindraj Ethiraj.
He explained in detail as to how the virus enters the body. Here are a few points he made in the interview -
* The virus uses the cells' machinery to spread.
* The patients who develop Acute Respiratory Distress Syndrome (ARDS) are the ones who need the support of the ventilators and those are the ones who tend to have a very bad outcome. They are the ones who do not survive.
* Patients with ARDS need ventilators which push oxygen into the lungs which otherwise is not possible.
* If someone is severely short of breath, they should seek medical attention. As that might be a sign that the individual is developing the disease.
* SARS-CoV-2 is very infectious and hence is very lethal.
Here is an edited transcript of the interview:
The number of cases of COVID-19 in India has now almost crossed 6000 and the number of deaths is rising as well. As we follow those numbers and hope that the curve flattens sooner than later, the other thing we are trying to understand is what causes this damage. The lung is pretty much, to use a pun, at the heart of the problem. And to understand that better, I am joined by a renowned expert in the field, Dr Sanjay Mukhopadhyay, Director of Pulmonary Pathology at Cleveland Clinic. He was earlier a surgical pathologist, and is also a leader in global pathology education in social media.
Govindraj Ethiraj: Let me start off with a straight question. Why is the lung the target of the COVID-19 virus? And how does that really play out as the infection attacks an individual and then progresses?
Dr. Sanjay Mukhopadhyay: The SARS Corona Virus-2, which is causing the global pandemic right now is a part of the family of Corona viruses, as you know. And the Corona viruses, both this one and the earlier SARS COV-1, the one that caused the original SARS epidemic before this, both of them 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. So 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-C0V-2, the receptors happen to be on the cells that are on the back of your throat, on the back of 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. So what the SARS-C0V-2 virus does is: it goes inside the cell, we call them epithelial cells in medical jargon, they go inside the cells of your 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 those receptors, the SARS-C0V-2 uses are in those cells, it attaches to those cells. The receptors are called ACE 2.
Govindraj Ethiraj: I am going to come back to the lung in a moment. So, tell me, since you described the path of the virus, how is it that it then spreads from one person to the other?
Dr. Sanjay Mukhopadhyay: What happens is, 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 land 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 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.
Govindraj Ethiraj: How does it then survive on the surface for so long?
Dr. Sanjay Mukhopadhyay: I am not sure what the mechanisms are, but viruses can stay (extra-cellularly) outside a cell for a little while before they die off on their own. Experiments showed that the time period is about 2 or 3 days. But why exactly, I am not sure, I do not know what the mechanism is.
Govindraj Ethiraj: You did this very interesting and early studies, where you looked at patients from Wuhan. And one of your 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 and why we, wherever we are, should be worried about that?
Dr. Sanjay Mukhopadhyay: Just to clarify Govind, that was not my study. It was study done by Chinese researchers in Wuhan and I was just analyzing it for the purpose of the audience, trying to explain what was happening. But you are completely right, people in that study were all hospitalized—so these are the severe end of the infection. They are not those who are at home with mild symptoms. They were severely affected. So, they looked at the people who are in the hospital and of the patients who were in the hospital, who developed ARDS were much more likely to die. ARDS stands for Acute Respiratory Distress Syndrome. What happens is 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, it makes it turn completely white on both sides. And that is happening, at least in some patients in the pandemic, it is happening 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.
Govindraj Ethiraj: Is ARDS also the reason why hospitals are admitting COVID patients because they are likely to have ARDS?
Dr. Sanjay Mukhopadhyay: 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 the ventilator is curing a patient, it is just that without the ventilator they will not be able to breathe. So, 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.
Govindraj Ethiraj: On the flip side, if you are feeling breathless or have low oxygen, which I am sure you cannot self-diagnose, but the breathlessness you can, that means you could very well be having an advanced condition of COVID-19.
Dr. Sanjay Mukhopadhyay: That is a very good point. I think one thing you should put out there is, 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.
Govindraj Ethiraj: Since the lung is really what is collapsing here, and leads to the need for ventilator support, I will come to it in a moment, can we then strengthen the lung in some way? Normally you would say I take Vitamin C and become more immune (and you are welcome to counter that). Can the lung also be strengthened?
Dr. Sanjay Mukhopadhyay: No Govind. I am not aware of any magic way to do it. Because there is no way to protect yourself from this that is why social distancing is so important. 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, though, from studies that have happened in multiple places...I was just reading one from the State of Washington in the United States. They did a well-done study on nursing home—long-term care facility people— who got the infection. So, of the people who were tested there—they 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.
Govindraj Ethiraj: So, age of course and all the data seems to be showing that. So it is not like for instance, if I am a sportsperson, obviously I have stronger lungs, better breathing capacity or I am 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 does?
Dr. Sanjay Mukhopadhyay: Yes, there is a distinction to be made here. You are not at all immune from getting infected, right. So, no question about that. 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 be to begin with, determines how you will do later. That is really the main difference.
Govindraj Ethiraj: Let us come to ventilators. You did say that because your lungs are unable to perform, you must provide ventilator support. Now, at what stage are the lungs and the body in general...really do ventilators help? I know they do but are you already at the last mile, so to speak, because of which the chances are bleak?
Dr. Sanjay Mukhopadhyay: 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. There are recovering. That is relatively a small fraction. Now, the more the and more you stay on the ventilator, the further out you get, the lesser the chances of recovery. Time is a critical factor here.
Govindraj Ethiraj: Is that also because there are other organs in the body that are failing, particularly for older people?
Dr. Sanjay Mukhopadhyay: Yes, correct and the lungs are getting more and more damaged. The walls of the lung, which should be thin because oxygen can go back and forth, those walls are getting gradually thicker and thicker and are creating a barrier for the oxygen to go into bloodstream.
Govindraj Ethiraj: There are many treatment paths that are being followed right now. There is a lot of debate and discussion as well. I have been talking to a lot of doctors in India, some of them are using anti-retroviral plus hydroxychloroquine and other things. One thing is, they do not have any option and that seems to be doing the job for now. How are you seeing the different treatment paths from your vantage point?
Dr. Sanjay Mukhopadhyay: Let me give a full disclaimer here Govind. I am a pathologist and a lung pathologist. I do have expertise at looking at the lung tissue, but I am not seeing any patients directly in the ICU. So, I would like to stay out of the treatment controversies, because that is not something, I have direct expertise with. So, I would prefer not to comment.
