Thomas Wilckens (托馬斯)

MD #PrecisionMedicine 精密医学 thought & technology leader, Keynote Speaker, industry advisor 29.000+ Followers
15 articles 
 Prologue:
This analysis is ment to spur a discussion that definitely does not weigh one life against another, nor neglect humanistic thinking, but push to end the current actionism, return to rational, hypothesis driven good science and the application of the principle of logic thinking for decision making.
Hypothesis:
We are lost in speculations and not logic interpolations of data from earlier pandemics, interpretation of incomplete, fragmented data with a strong, social media and public driven bias towards a highly biased view on the pandemic, that does neglects essential facts.

Let’s start with what we do NOT know

1: Prevalence:
We have no idea how many infections there are in a given population at a given time point. Remember, testing capacities were scaled up only gradually and only in some countries in a massive effort for mass testing; i.e. infected patients may have been missed simply because they were tested too late or not at all, no matter if they had symptoms, had been exposed to infected persons or where at risk. Not even medical personnel are consequently being tested. In Vo, Italy, which was the first to be completely on lockdown, 43.2% (95% CI 32.2 -54. 7 %) of all confirmed SARS-CoV-2 infections across the two surveys were asymptomatic. Most interestingly, none of the children in the study tested positive, even those 13 living with infected relatives did not test positive. Suppression of COVID-19 outbreak in the municipality of Vo’, Italy published April 19th Will antibody tests for the coronavirus really change everything? "Touted as society’s way out of widespread lockdowns, scientists say the true potential of these rapidly developed tests is still unknown." Nature April 18th.
This contrasts with an earlier study from China Epidemiology and Transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts, where children were also infected, but showed no to little symptoms.
Update April 26th: Furthermore, the fist cases arriving us, may have gone unrecognized: First US COVID-19 Deaths Happened Weeks Earlier than Thought
It could well be that the first cases of pneumonia were regarded as influenza, not only the in the US, but also EU Early Santa Clara County coronavirus cases likely connected to China, microbiologist says
Update April 30th Genomic Epidemiology of SARS-CoV-2 in Guangdong, China - Analyses reveal multiple viral importations with limited local transmission - Effective control measures helped reduce and eliminate chains of viral transmission
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Update May 1st Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2) Again this is a simulation (see video and comments below) but provides some thoughtful considerations @Science
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"We estimate that 86% of all infections were undocumented [95% credible interval (CI): 82–90%] before the 23 January 2020 travel restrictions. The transmission rate of undocumented infections per person was 55% the transmission rate of documented infections (95% CI: 46–62%), yet, because of their greater numbers, undocumented infections were the source of 79% of the documented cases."

2: Immunity, antibodies and PCR testing:
We have no idea if and to what extent SARS-CoV-2 induces an antibody response, for how long and in how many infected people. I.e., there might be no scientific way to determine prevalence, even with the best assay available, since we do not understand the course of the infection. A Nature paper dated March 24th describes seroconversion of all after 14 days, but there was apparently no follow-up so far. Virological assessment of hospitalized patients with COVID-2019 So what are these figures from few patients telling?
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Update April 19th 140-Plus Coronavirus Survivors Retest Positive For Disease In South Korea, Raising Questions About Immunity "Similarly, about 5-10% of recovered patients in Wuhan, China re-tested positive for the virus at the end of March, according to data NPR obtained from Wuhan quarantine facilities that house COVID-19 patients after hospital discharge." @Forbes
Update April 26: German group reports some "background" immunity against SARS-Cov-2 " The presence of pre-existing SARS-CoV-2-reactive T cells in healthy donors is of high interest but larger scale prospective cohort studies are needed to assess whether their presence is a correlate of protection or pathology." Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors.
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Update April 30th: Experts: People Probably Aren’t Actually Catching COVID Again Reviewing the data experts feel that the PCR test may have identified "dead" particles from the virus lingering around in the body for several months
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"Try to reach it without a vaccine, and millions will die." This is another bold statement, which we must question, not least once we will learn how COVID-19 will impact on regions, that have not the priviledge for social distancing. Off note, the notion that hope resides in a vaccine are equally unlogic, since we know how difficult it is to predict a vaccine for influenza each year, and yet, we do not know the coronavirus and must not interpolate between different viruses; we are left in the dark.
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This paper suggest 100% seroconversion, while an early publications hints to the possibility some aysmptomatic carriers may not convert, albeit with just 4 of 5 asymptomatic infections in their cohort. Different longitudinal patterns of nucleic acid and serology testing results based on disease severity of COVID-19 patients
This is a question of utmost interest, but I cannot find more robust data; pls comment!
Update May 4th: Assay Techniques and Test Development for COVID-19 Diagnosis Good summary on emerging test and related challenges.
"Talk of licensing people with the right antibodies, always ahead of the science, has faded as experts warn that they are still studying what level offers protection and how long it lasts."
Roche’s COVID-19 antibody test receives FDA Emergency Use Authorization and is available in markets accepting the CE mark @ROCHE KUDOS: Can you pls help me with a question? Let's speculate there may be some genetic componant and/or "background immunity" re other coronavirus strains (common cold); an infected patient may then mount a response your specific test may not detect?

3: Who get's infected why and how?
What explains the differences in age, children being "spared", men more frequently hit? We do not know what virus load might be needed to induce severe disease courses, or if this is a relevant concept at all; some suggest severe cases in medical personnel may result from continuous massive exposure, but this is also only a hypothesis. Very recent evidence may not surprisingly hint that our genetics background my play a role.
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At same time children show no difference in viral load if infected Studie includes 37 children in a larger cohort of 3712 patients.
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4: Vaccination & Treatment:
There is a race for a vaccine, but will there be a good candidate anytime soon. Not if this is true Coronavirus’s ability to mutate has been vastly underestimated, and mutations affect deadliness of strains, Chinese study finds @April 20 @SCMP
What about treatments Effective treatments: Here are the drugs, vaccines and therapies in development to tackle COVID-19 April 21 @WEF
Update May 5th: Defense minister claims Israel’s biological institute developed virus antibody Since Israel is a leader in biodefense research, this may be a very early light at the end of the tunnel.
Why a coronavirus vaccine could take years - and may not be possible at all An increasing number of scientists are warning that finding an effective jab may take much longer than 18 months
5: How does the pandemic spread:
This is not a prepring or peer reviewed paper, yet very interesting analysis
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The figure relates to a publication quoted in this blogpost on spread of the virus in a Chinese restaurant in Guangzhou January 24th; airflow direction corresponds to the transmission of the virus.
6 Herd immunity and a future with COVID-19:
Upated April 28: Modeling infectious disease dynamics @Science
"SARS-CoV-2 and influenza virus are epidemiologically similar in that they are both highly transmissible by the respiratory route, they both cause acute infections, and they both infect and are transmitted by adults. This suggests that in the absence of widespread, carefully coordinated and highly effective interventions to stop SARS-CoV-2 transmission, the virus could persist through similar migratory patterns, assuming it is influenced by similar seasonal forces."
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"The high costs of current interventions underscore a need to quickly identify the most helpful measures to reduce transmission until healthcare capacity can be increased and immunity boosted through vaccination."
"Substantial asymptomatic and presymptomatic transmission make containment-based interventions, especially those depending on recognition of early symptoms or limited testing, more challenging and potentially infeasible alone."

6: What can the death rates aroung the world tell us?
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Considering the these puzzling numbers, one may speculate that many countries missed the timepoint, where interventions had an effect on the pandemic. It is unfortunate that there are no numbers on South Korea, Singapore, New Zealand etc. i.e. those countries that massively flattened the curve.

What do we know (as of today May 1st):

1: Testing in China and around the world:
Most infections in Wuhan went initially undiagnosed; the related study estimates 86 percent of coronavirus infections in China went undiagnosed prior to the travel ban; again testing capacities may not have been sufficient to identify all infected at all, even with symptoms at a given time point; serologic data are inconclusive. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2)
Even with massive scaling of testing we will not anytime soon be in a position to test everybody, in particular without symptoms within a short time interval to sceen for active infections and related pathways in a given population. In addition, there is evidence that California may have been hit long before anyone thought about testing New signs suggest coronavirus was in California far earlier than anyone knew COVID-19 Antibody Seroprevalence in Santa Clara County, California How to test everyone for the coronavirus
2: #Coronavirus strains, epidemiology and first patients:
There is new evidence that the epidemic in China may have started even in September and have its origin outside Hubei. Off note, there is also speculation that the virus may have hit the US already last year with infections being misinterpreted as influenza. Germany had its first official case January 28th, i.e. the one we detected because a Chinese women was tested positive after returning to Wuhan, that later informed her colleagues near Munich; in the following months however, very often patient 0 in a given cluster remained unknown. Coronavirus Outbreak May Have Started as Early as September, Scientists Say
3: Is there a second surge?
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In case link is dead, use "Coronavirus Update Finacial Times" to search for https://www.ft.com/coronavirus-latest - you may have to sign in, but this site is free...
We do see some signs of a second surge in China, but could that also be attributed to massively increased testing capabilities and earlier testing when symptoms and/or exposure occur?
Update May 2nd: A recent blogpost on Medium claim the ""truth" is, that we may simply postpone the diseaster to a second wave. A call to honesty in pandemic modeling Yet, since we do not know where we stand, we may also be hit much severely than we thought and underestimate the prevalence massively, see overall death rates around the world below.
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After all, this is one model of many, on the basis of most unreliable data!
4: In the age of Artificial Intelligence we can predict the future
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Definitely a good paper worth reading, yet its strength is its weakness; i.e. the data rely not on previous pandemic like SARS or MERS but the training set derive from Wuhan, South Korea, Italy and the US. Thus, per definition they do not reflect reality, since they only reflect what was tested in a certain cohort at a give time point. Can these data then be used to predict a possible outcome in the US just considering the very different testing capacities that were applied?
Obviously all models are only as good as the training set. They are useful to discuss various scenarios, but they are not telling us where we currently really are re prevalence, incidence and mortality in the time course of the pandemic. Most likely we will never know, also not post hoc, what really happened.

This is one of the simulation videos I like most!
4: The myths around number R ≤ 1
Data from the Robert-Koch Institute indicate R was already smaller 1 before the #lockdown in Germany took place; i.e. the data suggest the curve was flattening even without measures being in place starting March 20th. Lockdown Germany was March 23!
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5: Early Responders versus Late Responders:
Countries like the UK, the US, and Sweden did not respond to the pandemic early on, yet it seems their curves are flattening, even though they potentially acted too late. At the same time the death rate curve seems to bend in very different regions, i.e. with or without measures. Granted that the numbers from many countries vary greatly, not least due to lack of testing capabilities, differences in post mortem testing, etc.
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6: The Diamond Princess analysis:
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By the 20th of February, 619 of 3,700 passengers and crew (17%) were tested positive. The first patient tested positive on the 1st of February 2020, after he had left the cruise ship some days before. Thus, we have no idea how many patients were positive at that time, how many cleared the virus before being tested, and who was patient 0. Off note, we may anticipate that the population on a cruise ship may have an increased risk profile, which may explain the high fatalities. What the cruise-ship outbreaks reveal about COVID-19
7: USS Theodore Roosevelt and French flagship aircraft carrier Charles de Gaulle What the cruise-ship outbreaks reveal about COVID-19
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Since the outbreak began in late March, the Navy has tested 94% of the ship, a force of roughly 4,800 personnel. App 60% are asymptomatic. Among the infected sailors aboard the USS Theodore Roosevelt, more than half a dozen have been hospitalized. Two have been placed in the ICU. One died Monday, and the other remains in intensive care.
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More Than 1,000 French Sailors Test Positive For Coronavirus—On A Single Ship Nearly 60 percent of sailors from the flagship aircraft carrier, the Charles de Gaulle, tested positive for Covid-19, leading to questions, finger-pointing and investigations. How an Invisible Foe Slipped Aboard a French Navy Ship The vessel is “under quarantine” since March 16 when Charles de Gaulle left Brest; before there were stops at other EU locations. April 5, the captain got suspicious about COVID-19-like symptoms, while as of late January all other cases were attributed to some kind of flu.
Yet, it seems there are so far no fatalities with most sailors again being asymptomatic, patient 0 remaining obscure. I.e. whenever the virus got on board, chances are high that not all infected are even being tested when they were carrying the virus. App 25 are hospitalized, one sailor is in the ICU.
I wonder if there are any efforts being taken to analyse these well described cohorts, i.e. cruise ship and vessels for antibody presence?
8: Read yourself (updated April 22):
  • Projections by Chinese-US team indicate South Korea and New Zealand are among the best in the global crisis at balancing economics with disease controls
  • China has been effective in suppressing the epidemic quickly but the strategy comes at too high a cost, researchers say
What I find particularly puzzling is the fact, that the WHO admits that the evidence quality is low or very low for most measures currently imposed on our societies, i.e. social disantancing etc. In light of the analysis above, i.e. most countries are not in a position to implement rigid manners like countries in Asia and in particular China, we must reflect if we need not a completey different approach to contain the pandemic . Weak Evidence for Strong Pandemic Interventions. A 2019 WHO Warning for the Current COVID-19 Crisis
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Update May 1st: “MESSAGE IN A BOTTLE SOS: THE BLIND LEADING THE BLIND INTO THE TWILIGHT ZONE" SVP Morgan Stanley @Dave Jenny; guess where he suggest we might already be?
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Conclusions:

First of all it would be most arrogant to pretend that all "facts" I collected prior to my hypothesis are reliable and valid. In fact, this would be the same error in applying scientific principles and logic to data that are incomplete, fragmented and where the methodology is often obscure as is the timeframe when and how these data were collected, analyzed and reported! Yet science is all about generating hypotheses and testing them thereafter. The concept of this article is to put forward a hypothesis that I do not see reflected in any of the discussions I follow rigorously ever since I learned about the existence of a new mysterious and potentially deadly disease that the US intelligence concluded could be a cataclysmic event Intelligence report warned of coronavirus crisis as early as November

The anti-CONCLUSIONS - I have only one conclusion:

1: What if all our measures were coming too late to flatten the curve first hand, i.e., we have seen the real peak of the pandemic in most regions of the world already?
2: What if we underestimate the prevalence of SARS-CoV-2 since we do not understand the virus at all.
3: What if we are so shocked to be hit by a deadly virus where there is no herd immunity in our population, so it can kill that many people and spread limitlessly that we are blinded.
4: What if public pressure, press, polls, and social media were directing us to a state of one-dimensional thinking, so that all of us easily accepted only one scenario to be true in order to ease the process of decision making, selling the consequences to the public, pretending we play it safe on the best informed basis. After all, what scientist or politician wants to be held responsible for millions of deaths of beloved ones?
5: What is the role of social media in what some call the first infodemic? How to fight an infodemic Coronavirus lies are going viral. It’s essential we all fight back
6: What if tests, track and trace is illusive, given the many unkown unknowns, the fact that we too often cannot identify patient 0
7: Do we highly underestimate the detrimental mid- and long term consequences of the current lockdown? Op-Ed: We are losing ground on every other disease while fighting COVID-19
8: What if we must prepare for Scenarios of a superfluous crisis Added April 21st
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WE MUST ACCEPT THAT WE FLY BLIND

CONSEQUENCES:
Societies, scientists from all disciplines must reduce their ego, accept their given bias as well as lack of precise knowledge. Politicians must be better advised from various disciplines. We must abandon opinionated interpretation of sketchy limited data. Most importantly, we must look into all possible scenarios and related consequences! Not least the necessity to avoid the melt down of our societies as we know, love and miss.. We see the deterioration of general health due to lockdown, ranging from mental issues to long term physical damage due to lack of medical treatment. We see economic disaster emerge around the world with mostly unpredictable consequences that may include hunger, nationalism, war, you name it!
Off note, it might well be that the emerging regions that are now being hit with little or no way to escape the pandemic, flattening the curve via social distancing may be our best bet to learn faster what this killer is really doing to our world, our societies and future.

EPILOGUE
How could something like this happen? In 2002 Amos Tversky and Daniel Kahneman were awarded the Nobel Prize for their Prospect Theory which is outlined in more depth in Judgment under Uncertainty Heuristics and Biases Editors: Daniel Kahneman Paul Slovic Amos Tversky View all contributors Published: May 1982, see back cover:
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In their original article they investigated human decision-making, specifically what human brains tend to do when we are forced to deal with uncertainty or complexity. Based on experiments carried out with volunteers, Tversky and Kahneman discovered that humans make predictable errors of judgement when forced to deal with ambiguous evidence or make challenging decisions. These errors stem from ‘heuristics’ and ‘biases’ – mental shortcuts and assumptions that allow us to make swift, automatic decisions, often usefully and correctly, but occasionally to our detriment.
What we may have seen re COVID-19 is an unprecedented coincidence that created a vision of a reality that may not have existed at any time point; i.e. a complete misinterpretation of the current pandemic.
Thanks to @Maria-Elena Bernal for editing my German English and correcting some typos
For daily curated content and further discussions pls join the group Precision Medicine & Digital Health @LinkedIn; off note, did you know group content is searchable?
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Published by


Thomas Wilckens (托馬斯)
MD #PrecisionMedicine 精密医学 thought & technology leader, Keynote Speaker, industry advisor 29.000+ Followers
Published • 2w
15 articles
COVID19 – WHAT IF WE ARE ALL WRONG! Emering data may hint towards a very different interpretation of our current situation, but it seems there is currently only one mainstream thinking politically correct and being discussed. The concept of this article is simply to widen our horizon, hint to bias and enable new thinking pandemic coronavirus epidemiology heuristics biases politics goverments science research virology medicine healthcare diagnostics immunity virus covid19testing covid19research covid19vaccine