All of the decades that i have been involved in chasing Infectious Diseases, i have never seen anything that is so protean to theres no other Infectious Disease that goes from 40 of the people having no symptoms, to some having mild symptoms, to some having severe, some requiring staying at home for weeks, someone going to the hospital, some getting intensive care, some getting intubated, some getting ventilated, and some dying. So depending on where you are in that spectrum, you have a different attitude for this particular thing. But anyone who gets infected or is at risk of getting affected, to a greater degree, is part of the dynamic of the dynamic process of the outbreak. Susan that is dr. Anthony fauci discussing the various outcomes so far of covid19. Dr. Siddhartha mukherjee, you won the Pulitzer Prize for a book on cancer. It proclaimed the number of maladies. How is covid19 shaping up as a biological foe . Prof mukherjee as dr. Fauci described it, it is a protean we are in the long span of Human History we have just basically encountered this novel coronavirus. And we are still learning things about it which are really fascinating, somewhat counterintuitive, things we have not thought about before. Im an oncologist but really my training is an viral immunology. So the features of virology are very familiar to me. I would echo dr. Faucis opinion on this. In my lifetime i have seen influenza pandemics in mumabi. I saw from a distance, sars. I worked on influenza is a as a graduate student. I have never seen anything like this. The strain features of this virus are truly something that are out of the ordinary. Susan how does it strange features affect our ability to conquer it . Prof mukherjee lets talk about these strange features. The first strange feature is the degree of asymptomatic and presymptomatic carriers. You might be walking in the community, and there might be someone in a closed space or closed environment who is not really symptomatic but is carrying the virus. You may get some somatic days you may get symptomatic days after. Some of them do not even have. They have extraordinarily mild symptoms. That makes it extremely challenging because you cannot , simply isolate and Contact Trace these people based on symptoms if they do not even have symptoms or they are presymptomatic. That means the only thing that will work if you are in close proximity with them in a closed space, the only thing that will really work is masking and social distancing. So that is one feature. The second feature is we dont know what the relationship is between why some people seem to get infected and some people dont seem to get infected. There has been a series of extraordinary reports. The one that struck me the most was a report in prestrain, that i read from a crew that went to the antarctic. On that crew, one person was infected to start with. They were isolated to the best of their ability, but unfortunately the virus is extremely contagious and it spread. And if im remembering the numbers correctly, 50 of the people on the cruise got infected. Heres what is interesting about it. There were couples sharing the same room in which one couple, one of the couples infected, one of the couple is infected, while the other was not infected. In a closed travel space, for reasons that we still do not understand, we have now accumulating evidence that some of this may have to do with previously existing, crossreactive immunity against other coronaviruses. That may be one explanation. That is probably not the only explanation. Three is, how much virus is required to have an infection. The newe a piece in yorker, which i would encourage people to read, called how coronavirus acts in the patient. We dont know whether there is a relationship for many viruses, including influenza and for expiratory viruses theres a , relationship between the dose of the virus you receive and the chance that you will get infected, and also potentially the severity of the disease you have. Its a dynamic battle between your immune system and the amount of viral exposure youre getting. Which is again to emphasize why it is important to reduce that viral load, and to reduce the viral load, as i said, masking, social distancing, and the three cs. Avoid close spaces, avoid close contact, avoid crowds. That is yet another conundrum. Now lets get to the facts. When the virus is actually in your body, it of course affects the lungs. We knew that. It is an expiratory virus. It seems that the virus, the infection really has two phases. Phase one of the infection is when the infection is being driven primarily by the viral infection itself. This is when your lung cells are being destroyed, and you may have a fever, you may have chills, and the famous loss of smell, loss of taste, loss of appetite, etc. But then that moves to, in some patients but not all, we dont know why, but in particularly men, it moves to the second phase of the infection where it is being driven by the immune response to the virus, and to dead cells that are accumulating. That phase is very dangerous , because your air sacs fill up with immunological debris, debris from dead cells, and fluid, inflammatory consequences of the virus. So, why this virus behaves in these two phases is a mystery. There are two or three other mysteries i would like to highlight. Then comes the question of what else the virus infects. It turns out that the receptor that the virus uses on human cells has now been established. The major receptor has been identified. The virus, for reasons that we do not understand, causes a diffused set of symptoms. I will name some of the symptoms. In children, in a small number of children, it causes an autoimmune disease of the blood vessels and the arteries. Very similar to a disease called kawasakis arthritis. Why this virus is causing those symptoms, we do not know. As of yesterday, there was a big case report of all these children. It has also become clear it causes a state in which your blood tends to clot more. This blood clotting can lead to strokes, it can lead to cardiac attacks, it can lead to blood clots being spread to various parts of the body, including the lungs, where it can be lifethreatening. And just to make one last point, we still do not know what the longterm sequelae of the infections are in people who survive. So, lets say you do recover hopefully from the coronavirus infection, and lets say you have a severe infection. We dont know what the longterm effects are. Longterm sequelae are. People are finding kidney problems, arthritis problems. Some of these may or may not be related. Some may be related to the fact if they went to the icu. So, right from exposure right up to the end of the disease, a series of truly interesting, and i would say, devastating things that we just did not understand. We are beginning to understand some of it. As i said, i gave you some clues as to what we are understanding and what we are not understanding. As we understand each of these phases, its important to recall that different interventions will work in different phases. So obviously once you are in the icu, the Health Care Workers need to be protected from you in terms of viral exposure. But depending on what phase of the infection you are in, the socalled virological phase in which you have exuberant viruses whether you are in the inflammatory and immunological phase, the medicines that work for one do not work for the other. Antivirals like remdesivir and new antibody cocktails from several companies, they are likely to work and we know they work based on good trial data in that first phase of the infection when you want to kill the virus. But these have no effect whatsoever in the second phase when you had the inflammatory response. There, its antiinflammatories such as steroids and a bunch of other medicines that seem to work, where is the antivirals do not seem to be doing much in that phase. I would say that we are involved in two or three projects to address both phases of this infection. Susan so, as complicated as this is, it sounds like really only time, lots of its peer lots of experimentation and information sharing is key to understanding and attacking this disease. Prof mukherjee and i should say that this i have not seen a level of collaborative spirit within the Scientific Community of this ilk or stature in my life. That is very encouraging to me. Encouraging news. Things have moved as fast as it can possibly move. We will have, hopefully by the end of this month, two to three, to maybe four potential drugs including antibodies that will attack the virus. They are still in advanced phase ondies, so i cannot comment whether they work or not, or what settings they work on. And we will also have four or five or six new modalities to treat the inflammatory phase of the virus, including, as i said, steroids, but also proteinbased drugs and, in my case, we are experimenting with a certain kind of t cell called regulatory t cells. So, this is moving as fast as we can. Of course, we will have to wait for the vaccine, and optimistically, i think most people think that will take about 15 to 18 months. Susan focusing on the United States, we are talking at the very end of june here, and at this moment there are 2. 6 million cases known in the u. S. , 120,000 deaths, and deaths are on excuse me, cases are on the rise in as much as 29 state. States. Overall how would you assess the states response to this virus . Prof mukherjee again, i would encourage people to read a very long piece dissecting some of this that i wrote for the new yorker called what coronavirus has exposed about american medicine. Where i go through piece by piece by piece every step of the response. I think it is, despite best efforts, i must say that the initial response in the United States was abjectly problematic. I cannot describe to you the what might have happened if we had taken faster and more Decisive Action against the virus when we knew that there was a pandemic brewing in china, and when we knew that cases were already spreading into parts of europe, including spain and italy. Crucial mistakes were made during that time. I will give you two examples. One example was the lack of testing in the early phases. Now it is extremely late, but in the early phases, testing and isolation, strategy that worked in wuhan and more recently in beijing, could have worked and wouldve worked if the number of cases had been low. There was a 42day delay. That was from the day the first coronavirus patient appeared in a hospital near seattle and in washington state, to the day that commercial testing for the virus became available. 42 days in the lifespan of a highly contagious virus may as well be a century, because by that time, people have taken flights, people have moved all around the United States, and parts of the original virus were spread all over. That is one example. The second example is that the cdc and other authorities made what i think was a crucial error in not asking people to isolate, mask, and maintain social distancing as soon as, even while the tests were being made. And secondly, in particular, a particular tragedy is that we were desperately unprepared not just for testing, isolation, quarantine, but to give healthcare workers, particularly frontline workers, the ppe masks sorry, not the ppe, but the n95 masks, which truly do protect against small aerosol particles. Healthcare workers were in particular need of them. We saw many healthcare workers die in this pandemic, and i feel extraordinarily sorry for them. But at the same time, encouraging the public to avoid the three cs crowds, close, and close contact. Wearing the masks would have been a successful solution. We have now, i would say, strong to sufficient data to suggest that that strategy works. Of course it does not work 100 . No one expects it to work 100 . But in virology and epidemiology, the reduction of spread of a virus from one person infecting five people, to one person infecting less than one person, in other words, driving the infectious spread, is of great consequence. So you do not need a strategy to work 100 . All you need to do is to decrease that famous number of the r 0, or the rnaut. I want to make one last point which is very important. There are two pieces of good news is the number of deaths in the number of deaths in that the United States has actually tapered off and is plateauing and is showing signs of decreasing. I do not know why. Again, it is a mystery. It because we are seeing this is the absolute number. I do not know why. Maybe we are taking better care of patients, there is more loadness, less viral spreading because of masks, etc. But the number of deaths is decreasing. But as you know in places like houston, dallas, florida, arizona, the number of cases is increasing. And this is most data it would suggest it is because we are doing more testing. Of course if you test more, you will find more. But the majority of data shows it is also because the infection is increasing in its spread. So i would not rest on laurels, although there is good news. I would not rest on laurels. I would continue to watch, because the wave of deaths usually is about two to three weeks after a wave of infection. Susan you mentioned masks several times. I want to show you a clip from very recently in a congressional hearing of a debate between the chairman and a member about the wearing of masks. Lets watch. [video clip] we have to be consistent. And if you say i want you to wear a mask, i will wear a mask. You are the chairman of the committee. But i want us to make decisions based on sound data and information. Yes sir, i will. Are you arguing that we should not meet in person . No sir. Not at all. Sounds like it to me. Because there is no certainty. The masks may not work. We know how the disease is transmitted. So the mask has a low probability of working. Maybe we ought not to be meeting in person. If you are asking me my clinical opinion, my opinion is that patients who are at high who are in highrisk categories, those anyone 65 years or older, with comorbidities, should wear a mask. If you dont, i am telling people in tennessee, it not required. Susan the unmasked member is also a doctor. The chairman is wearing a mask. My question to you is the debate over Wearing Masks is happening in the halls of congress. Are we surprised that people nationally are at odds about wearing a mask or not . Prof. Mukherjee well, i am disappointed in the sense that i do not understand i really, really have a hard time understanding why this is such a major issue. The questions asked in both sides in that debate were absurd questions. The first question is you suggest we stop meeting. No one is suggesting that. People are suggesting if you meet and if you can, then wear a isk while the meeting happening. You can communicate with perfect fidelity. It is not the most comfortable thing, but being infected by a deadly virus and ending up in the icu is not the most comfortable thing either. So the line of questioning is absurd. The second thing that is absurd about the line of questioning is we cannot run a randomized trial of masks versus not masks. Although some have been run. But right now we cannot run easily randomized trial of asking, sequestering half of the population, asking them to where masks and asking the other half not to where masks for lots of , reasons. Some ethical, and some logistic. The overwhelming evidence in the scientific literature suggests that mask work. Masks work. They do not work 100 , but like i said, in order to reduce the virus, you need to decrease the socalled rnaut of the virus, which is the amount of the virus spread from one person to another. If you make absurd strawmen then it is very easy to throw them down. If you are saying masks do not work 100 so i am not going to wear one, that is an absurd strawmen of a mask. Again, the idea is to decrease the load of infection by a person who is symptomatic or presymptomatic, and it is amplified by the fact that the wearer who may not be infected was also protected. So if you ask absurd questions and say masks do not work 100 , should we stop meeting, this is not the mechanism all of which are factually incorrect then you will get absurd answers. We should have a consistent, simple, mandated policy, and i have encouraged over and over again for the president to lead on this. We should have a simple policy that applies across, and governors should apply that policy. Because we still have a long way to go before this epidemic abates, and the last thing that we want to do is to have inconsistencies from people about this. And again, to me especially, the troubles that you have to go through to mask yourself in a closed, crowded space where you are having contact, is minimally tricky. Sometimes we have to make decisions based on evidence where the encumbrance to the patient or to the user is minimal, and the potential gain is there, and may be quite large. We err on the side of caution. And this is one example of erring on side of caution. There are many things where we can say, gosh, a seatbelt is an affront to my liberty, i am not going to wear a seatbelt. But we have mandated the wearing of seatbelts. So similarly, i do not think it is a far stretch to mandate the wearing of masks. And of course if you have a medical condition that is not about you to wear a mask for whatever reason, then you may in exception to that. Susan so in states where the incidence rates are rising are generally the states that have opened up their societies. I know you are serving on governor cuomos commission on reopening the economy in new york state. Can you talk to us about new york city, and as it opens up, and how you prevent it from becoming like houston, or worse, like beijing has experienced . Prof. Mukherjee again, i think what is going to happen is the best Case Scenario that i think will happen in new york city is that we will open in phases and watch every phase. The good news right now is that i think to the extent possible, phase one is going well. I was just outside. Virtually every person who is entering a store is wearing a mask. There is legal immunity for a store worker to deny a person not wearing a mask entry to that store if that store owner can so decide. There is, i would say that after a very long period in time we are seeing a dramatic decrease deaths in our icus. Work is slowly resuming. I think the way to move forward is to ask the question, at what phase are we safe reopening . The particular concern is schools, restaurants, and bars. I would say we have a very crucial threemonth window when Public Schools will be naturally closed. It is during this window of time when i think we have to act very decisively, and to bring that rnaut down to as low as possible. What will happen at the end of that period is i think what will happen in places like beijing and south korea. There will be local outbreaks. There will