RCB Presents The Godrej Science Award To Dr. Zarir F. Udwadia, MD, DNB, FCCP (USA) & FRCP (London)
I am thankful to the Rotary Club of Bombay and the Godrej family for this award. I remember being in the audience when my father got it some years ago, so there is a considerable familial pride as well. Sohrab Godrej was not only the founder of the Godrej Empire but he was a philanthropist, environmentalist and a man of science. He was seized by social justice and social causes. So, I would like to think that he would have been interested in what I am about to say today. I have titled my talk as follows: Has another corona virus hijacked the world?
It wouldn’t be an exaggeration to say that over the last two years, this pandemic has etched a scar over the face of humanity that will take decades to disappear, and which will endure for many years. It would also not be an exaggeration to claim that this has been the global emergency of our life time, no matter how old we are and it is strange how a virus could have locked down a world, shot down our cities, bankrupt our economies and, in the process, kill almost six million and sicken about 400 million.
Let me begin with this introductory slide from the famous book of French author Albert Camus. He gives an account of a fictional plague which affected the city of Oran, the second largest city in Algeria. And this was written a few years ago before he went on to die and what he said holds remarkably prescient even today. He said, ‘There have been as many plagues as wars in history yet, always, plagues and wars take equally by surprise.’ And clearly, in today’s climate, he is right about the plague and the war. But should we have been surprised? Unprepared, yes, but should we have been surprised?
Well, not really, because if you put this corona virus in context, we have been hijacked by many other viruses in the last century. So, Covid-19 took 6 million lives; MERS and SARS, from 2012 and 2002, mercifully killed only in the 100s. I say mercifully because MERS had the mortality of 40% and, in a sense, we were lucky. Imagine what could have happened if the SARS Covid had that kind of mortality. Of course, the granddaddy of all pandemics remains the 1918 Spanish Flu which killed at least 50 million.
This is another famous science writer, Laura Spinney, and I urge you to read this book, Pale Rider: The Spanish Flu of 1918 and How It Changed the World. She said, ‘A war has a victor, but a pandemic has only the vanquished.’ And how many vanquished were there in the last few years? All of us remember friends, family who have died with this virus. In terms of actual numbers, 6 million. In fact, we are considerably underestimating our mortality rates. A lovely article in The Economist, that scientifically looked at the actual number killed, estimated that we are undercounting by at least a figure of 5. So 13 million, getting us closer to the 50 million Spanish flu mortality I talked about. We owe it to our living to be accurate in counting our dead. It would be so easy for the Indian Government to be doing this accurately.
The actual estimated deaths in India, and this is a wonderful paper in science by Prabhat Jha and colleagues from Duke University is between 3.1 million and 3.4 million while the official figures place it at 400,000. Now, whether this is on purpose, forged or whether this is just because the death certificates are not well-kept, we can’t be sure. But we are undercounting by at least 7 times. So, our mortality is actually 3 million. So, this is how a pandemic starts.
We don’t know who patient zero was, but we know ground zero, for sure, was Wuhan. Wuhan is the 9th largest city in China, it has a population of 12 million, this is from Google maps, and it is the capital of Hubei province which is somewhere in the centre of China. This was probably the epicentre of the pandemic and there are two very important players you need to know about: the Wuhan Institute of Virology and the Huanan Seafood market. Seafood is a misnomer; it is a wet market selling all kinds of animal products. So, let’s time travel back to the last week of December 2019. Because that is when the people in Wuhan were sickening in large numbers and the doctors there were confused. This was a mysterious pneumonia illness which was spreading all over the chat groups in China and soon the wards and the corridors of the Wuhan Central Hospital was filled with patients, and then with dead bodies. The morgues were full as well. It was that bad according to the people who were there.
It took an ophthalmologist, Li Wenliang, attached to the hospital to point out that this viral pneumonia was very similar to the SARS Covi-1, the original SARS outbreak 17 years ago. On WeChat, the Chinese equivalent of WhatsApp, he wrote to 100 or 200 people on his group, mostly doctors, and said, ‘Protect yourself, your friends and family, mask up.’ The Chinese authorities were in denial at that time. They came down on him hard, they censored him, removed all his posts and sadly, and tragically, he died of the very disease he was warning his colleagues about at the age of 34. Pictures of him sprung up all over the world, of Wuhan and China with barbed wire replacing the mask and he was the hero and he was the first of 200 doctors and healthcare workers, the WHO estimates, to have died of this disease.
This is how a virus spreads, it has an “R naught” of 3 and that is frightening. It means that patient will go on to infect 3 others. Chinese Lunar New Year happened to be very bad for humanity and very good for the virus. Those who are familiar would know that this is the time when millions of people migrate from cities to smaller villages across China. That can be tracked, and everything can be tracked these days. If you track cell phone data, records reveal that 175,000 people left Wuhan on just this one day, January 1st, 2020. Some to escape the illness and some to meet family and friends. It is a well-connected city as well. So, there were 49 flights locally every single day and this is the distribution of 800,000 plus passengers from Wuhan airport to different provinces and cities across China. And this is well-connected internationally as well. You can see 28 international flights leave Wuhan every day. This will expose why shutting down borders is a wasted exercise in my opinion because there were flights and let’s look at them: Los Angeles, London, New York, and across South-East Asia, Japan, Dubai and, of course, India and Mumbai.
Our patient zero was a medical student from Kerala desperately trying to escape Wuhan. She was a second-year medical student who was tested and confirmed to be positive, and she was the patient zero of this pandemic.
The Chinese authorities closed the air space and locked down the city pretty ruthlessly on January 30th, 2020, but there was no stopping the virus now. So, the entire world was slowly getting Covidised, if I may use the word, and you will understand what pandemic means when you know that pan is all, and demos is people. Literally all people everywhere were affected. Finally, the last untouched continent Antarctica, where a global polar research station had about 10 Covid cases, just two months ago; then, you can really understand that yes, pan-demos is all people.
This is the face of the enemy which is more recognisable than the face of the moon I would say. It is a single stranded RNA virus, point one micron which means it is one-hundredth the diameter of the human hair. It is the 7th corona virus known to infect man. The others are very trivial, there are circulating viruses like OC43 which is a common cold, you and me must have got it 100 times as children. Of course, the most serious like the MERS outbreak which I talked about. And, it has zoonotic origin because it bears close genetic resemblance to the bat corona virus. It shared 96% of the genome with bat corona virus. And this is the last, unclear mystery of our times as far as this pandemic goes: is it nature or is it lab?
Initially, I thought all lab related theories were conspiracy theories because Donald Trump loved them, for example. But I think they need a more patient hearing; let’s look at both sides. What really happened in Wuhan? On the natural origin side, what we do know is that every single virus known to cause a pandemic has arisen due to an animal whether it is SARS, MERS, AIDS, Ebola – they have all started in animals, and bats seem like a natural host. Bats house thousands of corona viruses. There are caves full of bats across China but strangely enough not in the Hubei province and so, it is very conceivable, and it is the prevailing and likely theory that it maybe jumped to humans perhaps via intermediary host in this seafood market or wet market.
Let me tell you about this wet market: two-and-a-half-years before the pandemic, 48000 animals, dead and alive, often exotic species which you and I wouldn’t have heard of, were sold at this market. So, the market was just being a melting-pot maybe with an intermediate host, maybe just amplified in the market. That is why it is a prevailing theory. But is it coincident or is it ominous that this famous institute, in fact the world’s premier corona virus institute, just happens to be 20 minutes away from the hospital which bore the brunt of the pandemic? It is not totally inconceivable. For example, we know that at this very institute, there were at least 2000 corona viruses being genotyped. We know that gain-of-function research was going on there. It is a kind of research where you tweak the virus and see if it can become more transmissible. So, you are tinkering with the DNA of the virus.
And by the way guess who refunded that gain-of-function research? It was funded all through for 10 years by NIH in America when Anthony Fauci was the head of the NIH. So, it is hard to say what happened. We know that a couple of workers in the lab were very sick about two weeks before and who knows that these were not patient zero? All traces of them have been wiped from Chinese records. The Chinese will come down on anyone who they think is dissenting.
This is the last unexplained issue: there were two papers just this week claiming that everything is clustered around the market but that doesn’t mean that it could have been a virus that originated here, of course, though it is hard to say. For a physician it was a new disease, we were really flying blind, it was like a pilot reading the manual and trying to land at the same time. There were some unusual symptoms, like loss of smell, and I used to take a big sniff of my coffee every morning before setting foot to go to work just to convince myself that I was okay. It was a very diverse spectrum. Do you have any other disease where 30% of people may have no symptoms at all and, on the other side of the spectrum, you had people who died in large numbers due to lung failure?
What added to the fear and stigma was that it was highly unpredictable. You could not know which way the disease would turn. Husband and wife, when infected, you didn’t know who would die and who would live. We did know that certain populations were very vulnerable. For example, elderly – 90-year-olds had a 10000% times higher mortality from this virus than a 9-year-old. Obese, diabetic, hypertension, so, there was a population that was at high risk, but it was an unpredictable disease. And, it was almost like being shot from a double-barrelled gun; you had two responses, the initial was the viral response and then as it was petering out, the blue triangle, the orange triangle took over when your host went into an overdrive and, around days 7 and 8, when most people settled, some people went into a Cytokine storm and, in fact, that decided the treatment they should get. We know that in early stages anti-viral worked; later, it was steroids in second weeks and later stages just supportive care.
For some patients, the problems don’t end with the acute illness because you end up with long Covid and it is estimated that the symptoms linger on for months after the acute phase is over. Studies show that 54% are still symptomatic after 6 months and 40% till one year after Covid. A host of symptoms: most common is brain fog, it is not just depression, it is more that that. Then second is very fast pulse, third is unexplained breathlessness despite all your tests being normal. So, it is a constellation of symptoms.
The mechanisms put forward, maybe the autonomous nervous system has been tweaked by the virus, the autoimmune and the antibodies level is found suspicious, the autoimmune system is activated. The EB virus might be activated, or it can just be the problem due to micro-circulations which we can’t even image with our best scanners. The treatment is rest. It is non-negotiable; holistic rehab helps, vaccination helps even to these groups of people and drugs have been investigated at many trials.
But, in addition to the millions of dead, there is also a great collateral damage that the pandemic caused. It was a pandemic of economic loss. It cost the globe about US$82 trillion, and the world discovered that it is far more expensive to treat a pandemic than prevent one. I hope these lessons will be retained for the future. It was a pandemic of poverty because at least 100 million Indians were pushed into poverty; those who had just pulled themselves out of poverty were thrown down again. It was a pandemic of learning; 1.5 billion children did not attend school. Don’t tell me online is the same because a study from five large Indian states showed that 60% of these children could not even connect online. It is not the same. The kids have not only forgotten where their schools and classes are but also how to read, write and do their basic math. It will cause a generation of future problems along the way.
It was a pandemic of inequality: covid exposed the inequalities that existed in our society. The world’s richest billionaires got much richer, in fact their excess wealth in these two years could have paid to vaccinate the globe two times over. The poorest got much poorer; the market equity of Louis Vuitton went up by US$ 183 million in these two years and it became the 18th most valuable company in the world. So, the rich got richer, and poor got poorer.
It was also pandemic of misinformation – what WHO labelled as infodemic: so, Bill Gates caused Covid, 5G spreads Covid, vaccination is highly dangerous and so on; it was a pandemic of misinformation. Then, think about what happens with other diseases like strokes, heart-attacks, cancers, and chemotherapy, they didn’t go away, they were there. They were below the radar; people were just dying at home, I guess. For TB, WHO has shown that there will be 7 million additional cases in the next two years and one-and-a-half million cases will die of TB. It was a tsunami of mental health diseases that came as well: 30-40% increase in anxiety and depression across the globe according to a survey and, of course, there were no psychiatrists to help them.
This is from the most devastating pandemics of all in the 13-1400s: the black death or great plague which killed an estimated 300 million people in Asia and Europe. It was estimated to have killed 1/4th population of London and 1/3rd of Italy at the time it peaked. This reminds me of where we were at the start of the pandemic. We knew nothing about it, no treatments and so we advised people to be distant, signalled the staff and we had quarantine signs, N95.
No other disease has been this studied or will ever be. A huge number of medical articles in a short frame. Medical information was shared with great speed, all articles would be out, you don’t need to be reviewed. You just need to write that your article is not plagiarised, and the article is out there for the world. The problem is that wheat and chaff were mixed together, and you just didn’t know. You had to be updated and the one thing that this disease has taught us is how little we know about it.
What works at the end of 2022? Three anti-virals, three immune-modulators, monotone antibody at great cost. Blood thinners in hospitals, most people just need this and a little assurance plus simple treatment. The basic science response was indeed remarkable. In the seven days, the genome was made public; in 10-days the NIH optimised the sequence of vaccinations. Moderna started the manufacturing process, and in 30 days the first PCR test was available. In 60 days, phase I vaccine trials had begun and in 111 days results of Pfizer came out in five countries and about 10,000 people were already out and published. In less than a year the first patients received their vaccine dose outside trial and that happened to be Margarette Kinnen, 19 years of age in NHS. They should be clapping for the vaccine because I would say covid vaccine is the safest and most effective therapy. Where would we be if not for this?
And unvaccinated adult is an astonishing 68 times more likely to die of Covid than one who is double vaccinated and boosted. The speed at which the vaccines were rolled out is incredible, 21 million vaccinated every day. This is the time between the discovery of the disease and the vaccine becoming available. For typhoid fever it was 105 years, polio was 50 years, measles was 10 years. So, this was remarkable. There is an abundance of vaccine right now, we are throwing them away because we don’t know what to do with them and they are expiring. There are at least 33 approved vaccines right now. The pandemic is not shaped by the virus alone but our collective response to the virus. So, we need to ask why some countries did so well and why some did so bad? South Korea and UK have the same population, yet in these 2 years the mortality in South Korea was 6000 people and in the UK it was 160,000. That is remarkable. I think there are complex reasons for it.
The USA, superpower of the world, had 1 million people die which is more than all those who died in America in the Spanish flu when there were no drugs, no anti-biotics, nothing at all. So, these are the errors that come to mind. Failure to appreciate its exponential growth, failure to appreciate air-borne transmission and recognise the importance of masks, lockdowns, slow to realise that mutants would come. We allowed vacci-nationalism and of course unchecked misinformation on social media. So, this is what I mean by exponential spread which is completely different than linear spread. It starts slowly but suddenly amplifies.
The best analogy I could give a lay audience of an exponential spread is the famous analogy of a poor man in India who asked a king for a single grain of wheat on the first chess square and to double it on every consequent one till he reaches 64. The king thought it is nothing and agreed rapidly till he realised, half way through, that this would have mean at 64 squares, 32 million cubic meters of wheat, 2000 times the current world’s production of wheat and 12,000 Giza pyramids full of wheat. The legend has it that when the king realised this at about square 10, he executed the poor man.
The WHO has done a great job all said and done but the initial response was characterised by a mix of delay and hesitation, denial, with the net result that they allowed in a sense an outbreak to rapidly become an epidemic and an epidemic to assume pandemic proportions. For example, they denied initially that aerosols are the dominant mode of spread, a minute on this as well because this is frightening. Droplets are produced when I cough or sneeze, those sink down. Aerosols are what are produced as I breathe or speak just now, and these can go for 6 feet and that is why we have our 6-feet distance rule. So, it took us time to realise that aerosols are the dominant mode of spread. With that realisation comes the fact that the mask is the most important public health intervention.
Lockdowns: I wish we had known more about lockdowns then than we do right now. It began on March 24th, 2020. It was a complete lockdown, less than a four-hour notice, ruthlessly imposed. It affected millions of migrants, didn’t affect the people like you and me as much as these people in cities – reservoirs of Covid by then – where they were unwelcome, without a pay at all being daily wage workers and then the pressure mounted. We asked them to quickly leave and go back. The lucky ones got the last trains, and the rest had long migration-like scenes from Partition, trekking for hundreds of kilometres in the March heat.
Jayati Ghosh, an economist in Delhi, said that the most stringent lockdown in the world destroyed our economy, forced millions into poverty and hunger and did nothing to control the viral transmission. I wish we had access to this article which was out just a month ago by Johns Hopkins; it is a scholarly tome which looks at the effect of lockdown on every single country that had a lockdown. The main points of the article:
- Lockdowns have little or no public health effects – we didn’t know about that.
- They impose enormous social and economic costs where they are adopted.
- They are ill-founded and should be rejected as a pandemic policy instrument.
We were slow to recognise the mutants. They were rising from the trunk of the tree in different directions: delta, omicron, but we can consider ourselves lucky that although it was more infectious, it was a milder strain. Perhaps because it was let out on a vaccinated population. So, we don’t know if it was originally intrinsically more benign which I don’t think it was or was not a novel strain anymore.
We allowed vacci-nationalism. The world has been unequally vaccinated; guess how many are in fortunate positions? Only 52% and vacci-nationalism can be defined as an economic strategy to hoard vaccines, government policies, to increase the supply in one’s own country. Canada has stocked enough vaccines for 400% of their population. In the US, kids received 3rd doses and now 4th dose while only 5% of the African countries are vaccinated. Parts of Africa, central Africa, there are at least 20 countries where the single vaccine rates have reached to 1-2%. Even today, they just can’t afford it. So I think vaccination is not only a moral obligation but it also serves our own self-interest because each unvaccinated person anywhere is another opportunity for another mutant to occur. It is a very short-sighted policy. Hoarding vaccines in Canada and US instead giving them freely across Africa.
And then, unchecked misinformation on social media. I think WhatsApp and Facebook have a check; the conscience is questioned. I found this out the hard way when a distinguished gentleman, claiming to be me, said that ginger cures Covid. And today I had a patient who said, ‘Doctor I am following all of your talks; I have been buying ginger since then.’ I said, ‘Does he look anything like me?’ She said, ‘Some resemblance but not much.’ Initially I was furious, then I was amused and this is how fake news can spread. You should take responsibility for forwards.
So, last three questions.
- Will it end?
Yes, it has to. All pandemics eventually end. They end when enough people have gained immunity from vaccination or infection and we are in that category and the virus just runs out of people to burn through. The corona virus then transforms to what we call an endemic phase. Endemic means start of a new phase which we will have to negotiate. The virus becomes part of the landscape of diseases that populate our land. It doesn’t kill people in staggering numbers, doesn’t cripple hospitals and resources, but it is still something that we have to deal with. - How will it end?
That is a spectrum as well. You have an endemic disease like the flu which doesn’t bother us at all and the other end you have tuberculosis and malaria which are also endemic and kill. My guess is that this will be something like seasonal influenza and remember that influenza kills 500,000 people every single year across the world. We have a vaccine but that needs to be tweaked because it develops mutations and I think that is the course. - When will it end?
Don’t hold your breath. Omicron is not the last mutant, there will be more, for sure. Remember in Venice in 1350 when plague first struck for 170 years there were 22 outbreaks of plague before it finally ended. So, it is hard to know.
Rotarians Ask
So, it is inevitable that there is going to be a variant?
I guess; viruses rise from the tree, they don’t come from the branches. So, the next variant can come anywhere on the SARS Covid, it won’t necessarily come from Omicron, and may not be necessarily milder than Omicron. We just need to hope that the vaccines keep holding out, science continues to keep pace with the virus and that variants should never be as deadly as the Delta variant because we lost too many people during Delta.
The fourth wave is evident?
At present we don’t see that evident, it is in a trough, but you can’t say anything about the virus, it is so unpredictable.
Why don’t the RTPCR tests show whether it is Delta or Omicron; if you get Omicron or a new variant, is the chance of re-infection very high?
The PCR can give at the most indirect evidence of Omicron if you have the S-gene drop out. It is fine print; at the same time, it can be BA2 which is the subvariant of omicron. It is a bit confusing. To know more and accurately you need to take Geno technique test which take much longer. The simple PCR is not designed to do this. Secondly, we will not know that till the time elapses. There is no guarantee of being protected completely.
