Saturday, May 15, 2021

Battles lost and Battles won

My daughter tells me to think about the times I've won and of what I've left behind. Of course, I can't take anything with me -- not even memories -- yet talking about better times seems like something to do other than looking at my foot, which leaks and looks like a battle wound. I've left discussing memories until it was too late. Now every word is hard to say.

I liked fights and arguments because I always used to win. I was smart, handsome, and had an almost uncanny ability to work hard and see through things and people. I also had an amazing memory, and was good at telling jokes, which helped lighten the mood. Since I liked being in charge, I chose the military. However, I never wanted to kill people. I wanted to fight death and win. So, I combined the two ms: military and medicine and became a military doctor. These two interests are combined during the COVID period at national and world level in a way I did not belive I would live to see happen. Now I am too ill to fight anything other than my own body and with every battle lost more and more of my resources are gone. I struggle to breathe, I struggle to swallow and choke on every other mouth of drink or food. There is almost nothing left. Still life drags on.

I married the most smartest, kindest and most beautiful woman in medical school, and treated dating her as a form of battle. I did not give up no matter what she said until she accepted to marry me. The first time we went out together, I introduced her as my future wife. Some might think it was creepy. I'd like to think it meant I was determined, and knew what I wanted from life. I wanted a family with her. So with determination I pursued that goal, and when she turned 28 and worried that if she did not accept me she won't have a family, we married.

We soon found out that our family dream won't be easy to achieve. My wife suffered from a combination of severe hyperemesis gravidarum and a hormonal imbalance, which resulted in very difficult pregnancies that ended prematurely. The babies she miscarried moved, but could not breathe because they were too young. After a number of failed pregnancies, and progesterone treatment with pills that did not work for her, my wife wanted to adopt. Working as a gynecologist gave her the opportunity to see many abandoned children. She would have taken all of them home if she could. I did not agree because I did not want to accept defeat. I told her we will succeed in having our own children. Eventually, we found out that if she took intra-muscular progesterone injections instead of pills, it stopped the miscarrigies. I'd do the injections. They were painful and after some months the oily substance would come back out though what looked like mild infections, and so we could not reuse the same skin space, and ended up having to do them in many different muscles. However, unlike the pills, they worked. She gave birth to Mihai at 34 weeks. Neither of us had ever seen an uglier baby, but he could breathe. He was old enough. After almost four years of bed rest combined with vomitting almost everything she ate, we had won. My wife was so weak she could not walk over a threshold, but we had a son. The hospital put him in an incubator. We took turns watching him. The first night was my turn. At some point I saw cockroaches coming out of the incubator. The child was red and he was crying. I put my hand it. It was too hot. Another few minutes, and his lungs would have been affected. A few weeks later another child who had been born on term and had a cold, used the same incubator and died from the same malfunction. Several such accidents happend all over the country in the years to come.

Mihai did not have the strength to nurse, and at first my wife did not have any milk. So, I'd go to the maternity ward, and ask the nurse for milk. The lady who provided us with milk in those first days was a gypsy. Later we joked that it was the gypsy's milk that is causing his current nomad lifestyle (Of course, today, the assumptions that gypsies are nomad is a stereotype. Plenty of gypsies are settled and most take good care their families.) Once my wife was able to milk herself, we went home. It took two months for Mihai to start nursing on his own. The first month he lost a kg. In the second he started to gain weight. Once he started nursing, he seemed to almost never stop. At 4 months he weighted 8 kg. We were convinced he was the smartest and most beautiful baby in the world by then.

In Mihai's first winter my wife developed pneumonia, but eventually made it through. She wanted to live to raise her son. I remember I made tea for her by put half a tea pot of leaves, and added loads of sugar. She could not drink it because it was too sweet. I tried again without the sugar, and the same number of leaves. Then it was very bitter, but I made her drink it through tears. I told this story proudly until my stroke. I've been sick for almost four years since. For the past year, I have been able to eat only banans, unsalted cheese, and an egg from time to time. I can't even swallow water properly. I've learned, of course, that not everything is a battle. One should be kind and considerate especially when people are ill.

Once Mihai was a bit older, we fought to have a second child. My wife had an exam that year (primariat) and after that exam came the misscarriage. He was pasted 22 weeks, and might have lived had he been born today. He lived for more than half an hour even then. It was spring, and we buried him under a tree that was full of flowers. It seemed the price she paid for eventually becoming a full doctor (doctor primar) was too high. But life move on. Mihai was a year and a half. He was talking, walking, and we were so very proud of him, and so very lucky to have help from my in-laws and to be able to work. Our last son would have had my father-in-law's nose, had he lived.

Three years after Mihai our daughter was born. The director of the hospital was on duty. My wife had not felt comfortable having him there during the birth process. He also happened to be away at the time. So, she did not call him and since her colleague who had monitored the pregnancy was on vacation, my wife led her own delivery with a nurse. She was already the best gynecologist in the hospital and I supported her decision. At 37 weeks, the baby was almost on time. My daughter was beautiful. I remember saying she'll look like me and be stronger than her husband one day. An hour or so after the delivery we came home. Our departure correlated with the temerity to leave before being checked by a doctor caused an uproar. When the discussion arose, I told them the hospital was dirty, and that after my first child was almost burnt alive, he was ill with conjunctivitis for months. I only exerted my right as a father to protect my daughter and my wife from their dirty hands. They were furious.

I told the truth at a time when a mis-spoken word could lead to arrest, torture and death. The directors were not chosen on merit, but on political connections, and they were sometimes known for betraying their own colleagues and for sending them to prison for mis-spoken words. This would have been a fate worse than death. So, my wife and I left that night for Bucharest to try to mitigate the damage, while my mother and father in law cared for the baby. When they started the investigation, my wife wrote only positive things about her boss. He continued to make her life difficult for some of the 7 years that followed until we moved to Timisoara. Retrospectively, I wish I was more of a diplomat. Saying exactly what you think has a price, which I never quite paid. My wife always tried to predict when problems would arise, and did everything in her power to solve them peacefully and to protect me, and our family.

I loved fishing, walking and I loved spending time outside. It's funny how I have not been able to walk well for more than 10 years, and not at all for more than three years. It had seemed impossible that it would be my fate. I used to walk so fast that a few miles seemed nothing to me. I would cross both Bucharest and Timisoara by foot. For the first fifty years of my life I seemed invincible. I battled for my life with illness only once. We had gone fishing at Balta lui Ion near Alexandria -- it was a bigger pond with water weeds, mud, and some fish. When I stepped in the mud I cut my food on a broken can. My wife offered to clean my wound. I ignored her, and kept fishing. A few days later I developed very high fever. My skin and eyes were yellow. Death felt near. My wife suggested we go to the hospital. We thought it was a pseudo-viral hepatitis. They would have never diagnosed me properly or treated me correctly. I chose to stay home and signed that I was responsible for my own fate. I was in my mid thirties and did not want to die. My wife thought of the cut on foot, which had healed since. She took my urine to the hospital. The vial broke in her purse, but she gathered what was left and tested it. It came out that both the liver and kidneys were severly affected. My wife immediately thought of the healed cut. It must be leptospirosis, she said. I took antibiotics, and went into shock. The disease is weakly contagious, but the children were with their grandparents in Lugoj, and my wife did not catch it. Eventually, things got better and I recovered.

My main fault was that I did not compromise unless I was forced to. I did what I enjoyed until I lost my helath and stopped being able to do much. I overate and drank, and gained weight slowly -- a bit every year. I also spent too much time on various screens. I combined overeating with exercise, which kept things going to some degree. I built a huge house with my own hands and with help that my wife struggled to send along. I had a garden inside and outside, and I had pets. I never accepted moderation, and never thought of the consequences even though as a doctor my job was to help people make good choices.

As I struggle to breathe, the only thing I feel is pain mingled with a certain detachment from it as if it is not my pain any more. I've been bedrid for more than 3 years. I had a major stroke on the 11th of January 2017. I did not think I'll live, and I was not quite ready to die. I thought I'll either recover or die, but I did neither. I've been living in a form purgatorium since with a few more strokes which happened whenever things looked like they were improving. All my life I was so very sure I knew right from wrong. Now I am no longer sure what victory entails. I find it difficult to let things go even when there is nothing left to fight for.

Sunday, May 9, 2021

Going Against Nature: Reproducing the Math?

In this post, I try to reproduce the mathematics that led the COVID Nature paper to conclude the COVID patients who die lose an average of 16 years of life.

First, let us place an upper bound for YLL (years of life lost) for people dying from a specific cause.

For a first estimate, we can assume that people live up to 100 years and all people who die have been born and their age is above zero. Thus, an upper bound for YLL would be 100*lives lost.

On second iteration we could look at how old people are at the moment of death. Thus, people dying aged 20 will lose 80 years per death.

We can then adjust the upper age to some realistic number. Lowering the life expectancy to 95, I was able to obtain a YLL of 14 years for Italy and 12.7 for Belgium. Still, the real life expectancy of Belgium is 81.6 and for Italy is 83.35. Thus, assuming the COVID patients would have lived to 95 seems unreasonable.

So, what went wrong in the article? I think the authors made an error of judgement as follows:

An 85 years old just died of COVID, in a country where the average life expectancy is 80, but, people aged 85 and alive will continue to live on average another 2 years.

The authors assume these 2 years to be the YLL. This is however wrong and not how YLL is generally calculated in the literature .

To make matters clear, I will propose a thought experiment:

Let us consider a disease X that does not exist. This disease will consist of marker people receive without any effect of their knowledge. The marker is assigned randomly by a computer based on their social security number or information from the telephone book.

Naturally, there should be no years of life lost to disease X. Thus, YLL_X=0.

People marked with the non-existent disease X will die in the same way as unmarked people. Some will die young, some will die old. Their average age at death will be the same as that of the general population and their life expectancy again identical to the unmarked population.

However, every individual who dies belongs to an age group that still has some years to live. If the average life expectancy at birth is 85, a child marked with X dying at birth will be accounted as a YLL of 85.

If 85 years olds in this population are expected to live to 90, a man dying at 85 will be accounted as having a YLL of 5 years.

Thus, if we apply this algorithm for calculating YLL to the disease X that doesn't exist, we get 15-19 years for various European populations. If we apply it to corona, we get 16 years.

A correct way to estimate YLL should yield zero for a disease that doesn't exist, like X.

The way I estimated the YLL in March 2020 was to look at the difference between the average age of the Corona deaths and the life expectancy of the general population. The result was 2 years.

I argued that this is an overestimate. Corona kills members of the general population who are more likely to be sick. Thus, unlike disease X, these people wouldn't, on average, reach the average life expectancy of the general population.

Thus, the YLL for Corona won't be the full 2 years I estimated in March last year, but the difference between their average age of death and their potential life expectancy as adjusted for their pre-existing conditions.

Thus, a 20 years old with terminal cancer who dies of Corona loses, perhaps, a few weeks of life and not 80 years.

It is however difficult to estimate the potential life expectancy of this heterogenous population as too many variables have to be taken into account. I guessed the 2 years YLL to be half Corona and half the other conditions. I think this guess is reasonable, but if someone would argue for a YLL 2 years, I wouldn't argue back.

The Nature paper, however argues for 16 years. That isn't something I can agree with.

One conclusion of the nature paper that I do agree with is that COVID-19 is between 2 and 9 times worse than the average flu. This is far more realistic than the 16 years of life lost. Corona has filled the hospitals worldwide and does appear to be a bad cold indeed. Twice as bad as usual is optimistic. I would have guessed three times.

Using the formula from the literature, we get the following results for YLL.

Italy
YLL_75=2
YLL_85=6
YLL_95=14


Belgium
YLL_75=2
YLL_85=3.9
YLL_95=12.7

YLL_75 is normally used when discussing the years of lost life in other illnesses or situations like war, traffic accidents, etc.

Going against Nature

I have on my desk a paper from Nature , the most influential and highly ranked multidisciplinary science journal. This paper addresses the reduction in life expectancy due to COVID-19, a very important topic. It makes the following claim: The average years of life lost per death is 16 years.

I have addressed this problem on this blog and in "COVID-19: Observations from a world upside down" in March 2020. My conclusion was that the loss of life expectancy for each Corona death was about 2 years. In later discussions, I rounded this number to one, as it's easier to manipulate.

So, how can Nature claim 16?

Here I am revising the argument I put forward in March last year with some updated numbers. Before I looked at the average age at death of Italian Coronavirus victims and found it to be 81. The life expectancy in Italy is 83

Thus, my natural conclusion is that the people who died of COVID-19 lost, on average 2 years. Clinically, they don't seem to be too different from the cohort of people dying from other causes -- old, with preexisting conditions, etc.

The thesis that the life expectancy of COVID-19 victims is very short and, thus, the YLL (Years of Life Lost) is of order 1 and close to my estimate of 2 years is supported by the fact that the excess mortality drops below zero (mortality drops below average) in the middle of the Corona pandemic.

For example, in April 2021, Belgian mortality from all causes dropped to 20% below average, despite the Corona virus killing some people (few, as, in my view, the Belgian population was thoroughly infected before and had good herd immunity by April). Still, cases of long Covid and the few new cases of Covid should have increase mortality to something above average.

If COVID kills people with long life expectancy (16 years, according to the Nature paper), these deaths should affect the mortality in April. If, however, COVID kills people with short life expectancy, many of the COVID victims from the winter would have naturally died in April, and, as they are dead already, they don't die again and don't show up in the statistic.

To their credit, the authors do acknowledge that their YLL of 16 years may be an overestimate, due to Covid selectively killing people who are already sick and have low life expectancy. I very much believe it is indeed -- and very much do.

'However, our key results are not the total YLL but YLL ratios and YLL distributions which are relatively robust to the co-morbidity bias.'

These alternative claim in that, in the most affected countries, COVID-19 kills between 2 and 9 times more than the average flu. In Figure 1 in the paper, we see that, even if we restrict ourselves to the last relatively mild flu years, there is considerable variation in the severity of flu in different seasons. In severely affected countries, like Italy, US, Spain and Belgium, the most severe recent flu comes fairly close to Covid.

This is more consistent with my claim that COVID-19 is part of the natural dying process in humans. It is like a bad flu -- perhaps comparable to 1958 or 1967, and worse than the typical flu from the past few years. The impact on life expectancy on most victims is low, with most of the life lost being end-of-life care often in specialized institution.

An Economist article stated that in about half of the US states, over half of COVID deaths occurred in care homes and other kinds of end-of-life institutions. In April, the NY times counts the deaths from nursing homes to be about a third of the total COVID-19 deaths.

I thank Anna Bojds for useful discussion.

Sunday, May 2, 2021

The second wave in India

India is facing a massive wave of Covid-19. As about 1 in 5 people is Indian, this is a planetary problem as far as humans are concerned. Our survival depends on India. As a response, many conuntries have been closing borders with India. The US bans most travel to India with some extemptions for students, US citizens and permanent residents. Australia has been closed off for more than a year and continues with its strict policies. An Australian returning home from India can face 5 years in jail, if they don't cleanse themselves for 2 weeks in another country before joining the Australian quarantine. Will these new restrictions last? Let's look at the situation and then let's look at numbers.

The problem and the proposed way out?

As expected, despite having one year to prepare, India has failed to build sufficient capacity in the medical system to deal with the problem. Most other countries have done the same.

Several politicians, some rather prominent, have advised people to use readily available holy cow urine to treat COVID-19.

So, such statements beg the question, does cow urine kill people? Short answer: no! We routinely drink milk from cows, eat their meat, sometimes raw and we are generally safe. In India, people sometimes choose to drink cow urine or eat cow feces without notable negative consequences to their health. Thus, it is reasonable to assume that, when it comes to COVID-19, cow urine is a placebo. This means it will work just as well as holy water, a prayer, or a sugar pill. We know that, when it comes to common colds, we often have noting better. In fact, my father's favourite joke about the common colds is that they last a week without medication, and seven days with medication.

We do, however, have a lot of medicine that can do a lot of harm.

Especially now, I believe going to a hospital in India with Covid-19 can result in a lot of harm. Here's how:

Just like with common colds and flu, treatment for COVID-19 is largely supportive. It is used to temporarily relieve some of the symptoms. Doctors try to keep the patients alive and let the immune system take care of the virus. Most people -- and, when it comes to Indians, a lager fraction than in the West, will stay alive without any special measures when infected with COVID-19.

Supportive treatment starts with rest, warm tea and love. Just like with colds, the mind plays a big role in the evolution of the illness. Stress makes things worse. When we take someone to a hospital, we increase stress. The hospitals are stressful places in the best of times.

The hospitals are dangerous, dirty places. Sure, they look clean, but they are teeming with sick people and their germs -- a wide selection of viruses and bacteria that, when added to COVID, have the potential to make things much worse. Now, the hospitals are overcrowded, and require the patient and his family to put on a considerable fight to get in. Waiting doesn't help. All these make Covid worse. Thus, many people who would have survived at home die in hospitals.

If the lungs are affected, statistics show that changing position (i.e., turning the patient on their side or on their belly) increases survival more than being intubated. The former is more likely to happen at home. Doctors and nurses are overwhelmed. So, patients are often tied to their beds, which prevents movement and increases the probability of death and/or intubation. Intubation is a very sensitive process that can only happen in the hospital, but requires a lot of monitoring, which is simply unavailable in COVID times. Furthermore, hastily administered medication without monitoring its effects can be lethal.

The turning of the patient is called proning. It's a technique that has been used against respiratory infections for centuries. When we visited the Skansen museum in Sweden, I asked why their beds were so short. They said it was because respiratory infections were common, and if one laid down on a flat surface, they believed death would come. So, the bed was a short wooden structure on which there was not enough room to sleep lying flat like we do today.

Some people choose to go to a hospital when they have symptoms consistent with COVID, but are not sure they have COVID and not a normal cold or flu. If they don't have COVID, they will get it, and are more likely to die.

In some parts if India, hospitals only allow patients who bring their own oxygen. At home, one would get to use his oxygen bottle. In the hospital, it may get shared.

One should also consider the family. As hospitals are short of staff, often healthy family members are allowed to look after their loved ones. At home, these family members would be exposed only to the virus from their loved one. In the hospital, they have a wide choice of viruses and bacteria to get sick from. Added to this, is the stress that will make these people more vulnerable. Thus, going to the hospital may not kill only the patient, but his relatives as well.

So, to go or not to go to the hospital? It is a personal decision that should be taken by family and professionals on a case by case basis.

The Situation in India: From the beginning to now.

India had a relatively mild first wave of Corona, with mortality 20 times lower than the UK or 10 times lower than Germany. While in Europe, it looked like the virus stops after killing 0.2% of the population, in India, it seems to have stopped after only 0.01% were dead. While this is most likely an undercount, the numbers remain low. Furthermore, it looked like India had herd immunity and the decrease in infection rates and deaths was constant and solid -- until now.

In April 2021, a new wave of COVID infections sweeps over India. The deaths and incidence increase exponentially, as if there is no immunity at all. What could have India done wrong?

(1) The early, strict lockdown. While it did not seem to contain COVID-19, the lockdown lowered the incidence of the other harmless coronaviruses which are endemic in the Indian population. Infection with these harmless coronas provides a degree of immunity to COVID-19. This immunity isn't permanent. The longer the time since last exposure, and the lower the number of coronaviruses a patient was recently exposed to, the lower the immunity and the higher the potential of serious disease. Thus, by eliminating the harmless coronaviruses, the lockdown may have created the conditions for this new wave to take place and be deadly.

(2) Virus mutations. It could be that the COVID-19 has evolved in India in a way that it can evade immunity from the old version. The virus was under evolutionary pressure to do so. India may have been for a long time in a situation where COVID-19 was widespread and most people immune. Thus, if a variant of the virus evolves to be able to reinfect these immune people, it can have all of India and the world. The virus mutates randomly -- lots of infected people means lots of mutations. The Indian environment would then select the best variant that can cause an all-new pandemic worldwide.

I worry about (2). In this scenario, the whole world may follow India and experience a new wave of the COVID pandemic. This is common with other colds. The viruses mutate and reinfect. COVID-19 is more deadly and new, but should function on similar principles.

The Future as predicted by numbers

The new COVID wave won't last long in India. In a large part of India, 25-50% of tests carried out a positive. It can't last. The virus will run out of Indians soon. This new wave appears to have the dvcmic of New York or Belgium. The Indians no longer comply with lockdown rules and it doesn't appear to stop. Thus, in a short time, the entire population will be exposed to the virus. Rich people will be immunized by the vaccine, poor people naturally.

Given the structure of the Indian population, the overall mortality will remain well below Europe. Most Indians are young and healthy. In Europe, Corona generally kills people who are within about one year from their natural death. In India, these people have been killed a decade ago, by more deadly diseases that are endemic.

Sure, some people will die, but it won't be like Belgium or New York. I think it won't even reach Germany, or Sweden. May even stay below the most successful EU nations like Denmark and Norway.

India couldn't really hope for a better outcome.

Shockingly, it may even be that, overall, Indian life expectancy will continue to increase this year.

In 1900, the Indian life expectancy was only 22 years. It has increased almost every year since. The Spanish flu of 1918, which was about 10 times as deadly as Corona and it killed mostly young people, has lowered Indian life expectancy by 2.5 years from 23.5 in 1915 to about 21 in 1920. By 1925, it had recovered and increased to 25 and kept growing since. In 2020, it was the highest ever at nearly 69.27.

The current rate of increase in India's life expectancy is about 4 months a year. This rate was maintained since the Spanish flu.

In Europe COVID seems to kill 0.2% of the population one year earlier than normal. Thus, 2 lives and 2 years of life expectancy are lost for 1000 people. That amounts to a reduction in life expectancy by 1 day, for the entire population alive today. Indians are younger and less likely to die. Thus, a reduction of Indian life expectancy for of 1 day due to Covid appears an overestimate.

If we look only at the people dying tis year, they will be about 1% of the population dying of the usual causes, plus (at most!) 0.2% dying of Corona one year too soon. Thus, this year's deaths will be 20% more than last year and 2 months younger than they might otherwise have been due to COVID-19.

They are however, on average, due to be 4 months older than the people who died in India last year due to the normal increase in life expectancy seen for the entire past century. Thus, the people dying in India this year, will still be 2 months older than those who died last year.

It's not worth shutting the country down if people dying this year are only 2 months older than those that died last year.

Drinking cow pee may indeed be the best solution. Thus, India's politicians are right. I say this as a Caltech-educated scientist.

A fast moving and short pandemic is better for live and the economy than a deadly long lockdown.

The sun will raise tomorrow. The cows will pee. New babies will be born.

++++ Looking ahead: the problem of lower birth rates in India ++++

India has been through many pandemics. COVID-19 isn't the most deadly. The prospect of losing 0.2% of the population in addition to the 1% that die every year won't make India run out of people.

India will, however, be running out of people soon.

Indian brith rates have gone down just as living condition improved. Vast swathes of India a below replacement level and, India as a whole went below 3 children born per woman in 2005. They are under 2.18 today.

The lowest integer number of children a childless woman can aim for that is compatible with the existence of the human species is 3. Most Indian women aim for less and most don't reach this number.

If birth rates continue to drop at the same rate, they will reach replacement level within the next five years. It may temporarily settle after that at some value below two or it may continue to drop. If it continues to drop at the same rate, India will reach one child born per woman in the next 25 years and absolute zero in less than 50 years. Over time, the drop in birth rates should become a much bigger problem than diseases like COVID.

--------------------------------

I thank Anja Bojds inspiring discussions.