Medical What makes the current coronavirus different from the others?

[lavinia]

TL;DR Summary

What makes the current corona virus different than others?

An interview on NPR with virologists discussed the reasons that this current viral pandemic is different than others in the past.

Key differences were:

- Ability to make new viruses - apparently 1000 times more prolific than flu.
- Unlike flu viruses, it does not appear to mutate because it has a "proofreading enzyme" that repairs mistakes in replication of its RNA.
- If I remember this right, its "spike proteins" cling more strongly to the cell membrane.

I wonder if someone can give a detailed explanation of how these viruses work in general and connect that to the particular case of this one.

 

[atyy]

Why does the Coronavirus spread so easily between people?
Smriti Mallapaty
https://www.nature.com/articles/d41586-020-00660-x

The answer is not known, but the article gives an overview of ongoing research.

 

[berkeman]

This study suggests that the virus is shed by infected people (who do not yet have symptoms) at a high rate, which helps it to spread more quickly:

Clinical presentation and virological assessment of hospitalized cases of Coronavirus disease 2019 in a travel-associated transmission cluster

https://www.medrxiv.org/content/10.1101/2020.03.05.20030502v1

From the popular news article about the study:

https://www.statnews.com/2020/03/09...-likely-not-infectious-after-recovery-begins/

The researchers found very high levels of virus emitted from the throat of patients from the earliest point in their illness —when people are generally still going about their daily routines. Viral shedding dropped after day 5 in all but two of the patients, who had more serious illness. The two, who developed early signs of pneumonia, continued to shed high levels of virus from the throat until about day 10 or 11.

This pattern of virus shedding is a marked departure from what was seen with the SARS coronavirus, which ignited an outbreak in 2002-2003. With that disease, peak shedding of virus occurred later, when the virus had moved into the deep lungs.

Shedding from the upper airways early in infection makes for a virus that is much harder to contain. The scientists said at peak shedding, people with Covid-19 are emitting more than 1,000 times more virus than was emitted during peak shedding of SARS infection, a fact that likely explains the rapid spread of the virus. The SARS outbreak was contained after about 8,000 cases; the global count of confirmed Covid-19 cases has already topped 110,000.

 

[bhobba]

Modeler thinks Australia is stuffed because the virus is moving faster than we have pretty much ever encountered before - we needed to make decisions a lot earlier - but didn't - very sobering:
https://www.skynews.com.au/details/_6141726868001

The difference to other epidemics - IMHO lack of understanding of how exponential growth can suddenly 'spike'. Basic math - simple basic math.

Thanks
Bill

 

[Ygggdrasil]

Here's a new, non-peer reviewed pre-print which may explain why the new Coronavirus is different from others. It had been assumed that the SARS-CoV-2 virus that causes COVID-19 enters cells via the ACE2 receptor, like other related coronaviruses. However, the new study suggests that the virus may enter cells through a completely new route involving the host protein CD147:

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein
https://www.biorxiv.org/content/10.1101/2020.03.14.988345v1

Abstract:

Currently, COVID-19 caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 μg/mL and IC50 of 15.16 μg/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85E-07M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.

Meplazumab is manufactured by GSK under the name Nucala and was approved by the FDA in 2015 for the treatment of severe asthma (https://www.drugs.com/nucala.html). It appears that phase I clinical trials are underway to test Meplazumab as a treatment for COVID-19 (https://clinicaltrials.gov/ct2/show/NCT04275245).

 

[Orodruin]

Meplazumab is manufactured by GSK under the name Nucala and was approved by the FDA in 2015 for the treatment of severe asthma (https://www.drugs.com/nucala.html). It appears that phase I clinical trials are underway to test Meplazumab as a treatment for COVID-19 (https://clinicaltrials.gov/ct2/show/NCT04275245).

Revealing my huge ignorance in biomedicine: How long would clinical trials generally take for a drug that is already approved for other treatments?

 

[BWV]

- Unlike flu viruses, it does not appear to mutate because it has a "proofreading enzyme" that repairs mistakes in replication of its RNA.

Question - how speculative is this? this would be a big deal regarding the long term efficacy of a vaccine, correct?

 

[lavinia]

Question - how speculative is this? this would be a big deal regarding the long term efficacy of a vaccine, correct?

The virologist said that this could help for a vaccine because the virus genome is relatively fixed. Apparently DNA viruses also have proofreading enzymes (according to the Wikipedia article).However he did say that there are conditions under which the virus does change and rapidly, But still relative stability of the genome seemed to him to be a check in the plus column.

The interview was on "On Point" on NPR.

 

[Ygggdrasil]

Revealing my huge ignorance in biomedicine: How long would clinical trials generally take for a drug that is already approved for other treatments?

Likely, phase I trials (to determine safety and dosage) can be skipped or abbreviated, though the drug would still need to undergo Phase II and Phase III trials to test efficacy. The Meplazumab trial is a small (20 patient) combined Phase I/II trial that will likely give preliminary data as to whether it is worth investing in a large Phase III trial. I would guess that the trial could get enough data to make that determination in a month or two. Not sure how long a Phase III trial would take.

However, because the drug is FDA approved, doctors in the US have the ability to prescribe the drug off label for unapproved uses (https://www.fda.gov/patients/learn-...rstanding-unapproved-use-approved-drugs-label). I'm not sure about the availability of the drug and whether there would be enough of it or if manufacture could scale to meet demand if it is shown that the drug is helpful as a treatment.

Currently, all the data suggesting that the drug could be useful come from a single study done in cultured cells, so I would be skeptical about using this drug widely in people. However, if the clinical trial data look promising, that could lead doctors to begin using the drug as a last resort treatment in some of the most severe cases.

 

[Ygggdrasil]

Question - how speculative is this? this would be a big deal regarding the long term efficacy of a vaccine, correct?

Based on our experiences with other coronaviruses, infection by coronaviruses can produce immunity, but that immunity is not long lasting, so people can be re-infected multiple times throughout their lifetime (as opposed to a disease like chickenpox, where getting the disease once produces nearly life-long immunity).

STAT news has a nice discussion of the possibilities of the Covid-19 virus becoming endemic, and here is the relevant section regarding immunity to coronaviruses. The full piece is worth a read, however:

“There is some evidence that people can be reinfected with the four coronaviruses and that there is no long-lasting immunity,” Dr. Susan Kline, an infectious disease specialist at of the University of Minnesota. “Like rhinoviruses [which cause the common cold], you could be infected multiple times over your life. You can mount an antibody response, but it wanes, so on subsequent exposure you don’t have protection.” Subsequent infections often produce milder illness, however.

https://www.statnews.com/2020/02/04/two-scenarios-if-new-coronavirus-isnt-contained/

 

[BWV]

Based on our experiences with other coronaviruses, infection by coronaviruses can produce immunity, but that immunity is not long lasting, so people can be re-infected multiple times throughout their lifetime (as opposed to a disease like chickenpox, where getting the disease once produces nearly life-long immunity).

The issue with the annual flu vaccine is virus mutation, not fading immunity correct? Does one get lifetime immunity to a whatever particular strain of flu virus you get? either way, would an annual Coronavirus vaccine be workable?

 

[lavinia]

Here's a new, non-peer reviewed pre-print which may explain why the new Coronavirus is different from others. It had been assumed that the SARS-CoV-2 virus that causes COVID-19 enters cells via the ACE2 receptor, like other related coronaviruses. However, the new study suggests that the virus may enter cells through a completely new route involving the host protein CD147:

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein
https://www.biorxiv.org/content/10.1101/2020.03.14.988345v1

Abstract:Meplazumab is manufactured by GSK under the name Nucala and was approved by the FDA in 2015 for the treatment of severe asthma (https://www.drugs.com/nucala.html). It appears that phase I clinical trials are underway to test Meplazumab as a treatment for COVID-19 (https://clinicaltrials.gov/ct2/show/NCT04275245).

Can you explain the biology of the CD147 protein?

 

[atyy]

This study suggests that the virus is shed by infected people (who do not yet have symptoms) at a high rate, which helps it to spread more quickly:

Clinical presentation and virological assessment of hospitalized cases of Coronavirus disease 2019 in a travel-associated transmission cluster

https://www.medrxiv.org/content/10.1101/2020.03.05.20030502v1

From the popular news article about the study:

https://www.statnews.com/2020/03/09...-likely-not-infectious-after-recovery-begins/

Why do you think it shows that pre-symptomatic people shed virus at a high rate? The samples in the study are taken at earliest from the first day of symptoms, so I don't see how it would provide data about pre-symptomatics.

 

[berkeman]

Why do you think it shows that pre-symptomatic people shed virus at a high rate? The samples in the study are taken at earliest from the first day of symptoms, so I don't see how it would provide data about pre-symptomatics.

Good question. But the evidence seems to be increasing...

http://www.cidrap.umn.edu/news-perspective/2020/03/study-highlights-ease-spread-covid-19-viruses

 

[sqljunkey]

I have a question about this virus, according to this site about 7 people die per year in the US for every 1000 people. and in 2003 about 2.5 million people died during that year, that makes for about 6,800 people dying daily on average in the us alone. And I'm assuming most of these who died were the elderly.

This corona virus has killed around 10,000 people so far. At least 80 % of those who died of corona were elderly people. ( the percentage could be higher). In this same time span, 3 months let's say, about 500,000 people died in the us alone, probably of old age and age related diseases. and of that half a million only 10,000 had Coronavirus .

How are the doctors linking this virus to death? I mean what are they seeing in these patients who died, who were in their 90s might I add, that makes them think the virus was the cause?

 

[anorlunda]

How are the doctors linking this virus to death? I mean what are they seeing in these patients who died, who were in their 90s might I add, that makes them think the virus was the cause?

My guess is the pneumonia symptoms. Most deaths are not directly due to the virus but rather by the secondary infections triggered in victim's weakened states. A stethoscope can detect the symptoms of pneumonia.

 

[sqljunkey]

But other respiratory diseases can cause pneumonia too in the elderly. Flu, a cold, smoking, asthma, according to this website, and there are 3 million cases of pneumonia in the US alone every year. and this website, suggests that it's a serious disease for people over 65.

I mean has the daily global death rate increased? Does anyone know?

If this was a problem 100% of the people who tested positive for this disease would have died, and not 1% or less.If I test 100,000 people in a survey and ask them who has seen the movie the shinning and 8000 say they didn't and of that 8,000 only 80 die eventually, am I to say that because they didn't see the movie they died?

I'm not a doctor, but I find this casual link very weak to tell you the truth.

 

[Mary Conrads Sanburn]

National Center for Science Education

March 10, 2020

How deadly is COVID-19?

NCSE Executive Director Ann Reid, a research biologist who helped sequence the 1918 flu virus, wrote the following article which NCSE disseminated to science teachers in order to help them begin to answer students' questions about Coronavirus and resulting disease, COVID-19.

What is the mortality rate for COVID-19, the disease caused by the novel coronavirus, SARS-CoV-2?

This question is in the news a lot this week — you can see a typical example in this article from the Washington Post.

The first thing for your students to understand is that mortality rate is determined by a very simple bit of math:

Number of deaths / Number of cases = Case Specific Mortality Rate (CSM).

Have your students try some simple examples:

What is the CSM if there are 10 deaths out of 100 cases? What is the CSM if there are 10 deaths out of 1000 cases?

Now. What if there are 10 deaths and — at first — you think there were 100 cases? But later you find out there were actually 1000 cases! Then, the CSM turns out to be much lower than you thought. That would mean that the virus was 10 times less deadly than you thought. Good news!

The bottom line is that the question of how deadly the SARS-CoV-2 virus is can’t really be answered right now. But what your class should realize is that this isn’t a question of the virus becoming more or less deadly — it’s a matter of how many cases are being detected. The CSM is likely to drop as more-and-more mild, asymptomatic, infections are detected.

You can predict that the number of cases will go up in the next few weeks as doctors all around the country are going to be testing more people. The number of deaths caused by the virus will go up, too. You’ll see discussions about estimates of the mortality rate, but the actual number will not be known for a long time.

Here’s what we know for sure: COVID-19 can be a very serious disease, but almost exclusively among a certain demographic. People 60+ years of age, especially if they have other health conditions like heart disease, are most at-risk for getting seriously ill. Therefore, even if we later find out that the CSM is much lower than the currently estimated 2-3%, the more we can reduce the spread of the disease, the fewer people will get sick, or even die.

While, thankfully, the majority of media headlines are saying that the virus might not be as deadly as initially thought, that does not mean we shouldn’t do everything we can to keep it from spreading. We want to keep that denominator as low as possible!

Bonus question: Are there multiple strains of the virus?

Towards the end of the Washington Post article, Jeffery Taubenberger, a researcher at the National Institute of Health (and my colleague for many years on the 1918 flu project) is asked about new reports of different strains of the novel Coronavirus — one less deadly than the other.

Note his answer:

It’s certainly possible there’s more than one strain because viruses that jump from animals to humans, as this one is thought to have done, often do change because they face different selection pressures in the new host(evolution, for the win!).

BUT

It’s way too early to say for sure (in other words, this is a plausible claim, but we need more evidence: science, for the win!).

Short Bio
Ann Reid is the Executive Director of NCSE.
https://ncse.ngo/how-deadly-covid-19

 

[PAllen]

I have a question about this virus, according to this site about 7 people die per year in the US for every 1000 people. and in 2003 about 2.5 million people died during that year, that makes for about 6,800 people dying daily on average in the us alone. And I'm assuming most of these who died were the elderly.

This corona virus has killed around 10,000 people so far. At least 80 % of those who died of corona were elderly people. ( the percentage could be higher). In this same time span, 3 months let's say, about 500,000 people died in the us alone, probably of old age and age related diseases. and of that half a million only 10,000 had Coronavirus .

How are the doctors linking this virus to death? I mean what are they seeing in these patients who died, who were in their 90s might I add, that makes them think the virus was the cause?

What makes you think Covid 19 deaths aren’t tested for? That would make for absolute certainty as to attribution.

[edit: I should also add that there is a particular respiratory syndrome common to several corona viruses, e.g. SARS and MERS as well as Covid19. So seeing this plus virus identification confirms the cause of death.]

 

[sqljunkey]

Well in Wuhan the population is 11 million people, and in china 7 out of 1000 people die yearly. so if I was going to extrapolate that to Wuhan 77,000 people die on a yearly basis. if I divide that by 12 months and multiply it by 2 I get 12,833 people for the two months of the infection(jan and feb). Has the death rate exceeded what was expected in those two months to cause alarm?

To me it looks like some people who were going to die anyway, died, and it so happened they had an infectious disease when they did.

I mean the link between HIV and AIDS was 100% traceable back in the days.

I'm just asking what are the tests conducted at the moment of death that determines the cause of death was indeed the virus?

I mean I can see the media(Washington Post) saying that I died of covid19 even though I died of a heart attack, but because I was corona virus positive it did not matter that I suffered a cardiac arrest.

Not every nurse in nursing homes are going to practice rigor, right now they are probably just filling out a questionnaire. Did this person have covid19? Do you think he or she died of covid19?

 

[Ygggdrasil]

The issue with the annual flu vaccine is virus mutation, not fading immunity correct? Does one get lifetime immunity to a whatever particular strain of flu virus you get? either way, would an annual Coronavirus vaccine be workable?

Yes, mutation of the flu virus seems to be the primary reason why we need an annual flu vaccine (though I'm not sure how long immunity from the flu vaccine lasts).

I don't know if we have enough information to know about the COVID-19 virus to determine how a vaccine might work. We don't know how long immunity to the current Coronavirus lasts, and we don't know whether the Coronavirus could mutate to avoid immunity. Yes, the mutation rate of the virus is low, but if we get to the worst case scenario and ~60% of the world is infected (~4 billion people), that gives the virus plenty of opportunity to evolve. (Luckily, viruses generally evolve to become less virulent over time, as less virulent strains are better able to spread though individuals with no or mild symptoms).

Here's some of what we do know:
1) Preliminary studies in monkeys suggest that re-infection with COVID-19 is rare: https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1

2) People infected with SARS during the 2002-3 outbreaks show high levels of antibodies against SARS for 2 years, after which antibody levels decline: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851497/

This would suggest that (barring mutation of the virus), vaccination could work on the short term (1-2 years), but not the long term (>2 years), so an annual vaccine may be needed if the virus becomes endemic and persists.

 

[Ygggdrasil]

But other respiratory diseases can cause pneumonia too in the elderly. Flu, a cold, smoking, asthma, according to this website, and there are 3 million cases of pneumonia in the US alone every year. and this website, suggests that it's a serious disease for people over 65.

I'm just asking what are the tests conducted at the moment of death that determines the cause of death was indeed the virus?

People hospitalized with respiratory disease (at least in the US) are first tested for other viruses that cause respiratory disease (such as flu or other respiratory diseases), and if those are negative are then tested for the Covid-19 virus. Therefore, the people who are counted of dying from Covid-19 likely died due to infection with the Covid-19 virus, but not other viruses.

Not every nurse in nursing homes are going to practice rigor, right now they are probably just filling out a questionnaire. Did this person have covid19? Do you think he or she died of covid19?

A person with respiratory disease in a nursing home would be transported to a hospital for treatment, at which point they would be testing for Covid-19 and other respiratory viruses.

I mean I can see the media(Washington Post) saying that I died of covid19 even though I died of a heart attack, but because I was corona virus positive it did not matter that I suffered a cardiac arrest.

I'm not a doctor, but I find this casual link very weak to tell you the truth.

COVID-19 infection (like infection with other respiratory viruses) can progress to a condition called acute respiratory distress syndrome (ARDS). ARDS is well studied from our experiences with influenza, pneumoina and other conditions that can progress to ARDS, and it is known that ARDS can cause multiple organ failure (likely because damage to the lung from viral pneumonia impairs gas exchange, which leads to low blood oxygen levels and this can impair the functions of various organ systems in the body).

There is also evidence that the COVID-19 virus can infect other organs in the body like the gastrointestinal tract (gastrointestinal symptoms are seen in those with COVID-19) as well as heart, liver and kidney. These organs could be damaged directly by the virus or indirectly by the body's inflammatory responses to viral infection.

Well in Wuhan the population is 11 million people, and in china 7 out of 1000 people die yearly. so if I was going to extrapolate that to Wuhan 77,000 people die on a yearly basis. if I divide that by 12 months and multiply it by 2 I get 12,833 people for the two months of the infection(jan and feb). Has the death rate exceeded what was expected in those two months to cause alarm?

To me it looks like some people who were going to die anyway, died, and it so happened they had an infectious disease when they did.

This is a more valid point about the disease and echoes some points brought up in this article: https://www.statnews.com/2020/03/17...e-are-making-decisions-without-reliable-data/

I will note that a COVID-19 outbreak has the potential to overwhelm an area's healthcare capabilities (we are seeing signs of this in Italy and Washington State), which would increase the rates of death from all causes. If hospitals are overflowing with COVID-19 cases (and especially if hospitals run out of protective gear like masks so that healthcare workers begin to get sick and/or scared to do their jobs), then people who need medical care for other emergency issues (auto accidents, heart attacks, appendicitis, etc.) may not be able to get timely care and suffer increased mortality rates.

 

[anorlunda]

The following article claims that the death rate in the Lombardy province of Italy has increased from 300 deaths/day to 540 deaths/day. No word on the age distribution of those extra deaths.https://reason.com/2020/03/17/itali...of-coronavirus-lombardy-up-about-80/#comments

 

[Ygggdrasil]

Here's a nice paper that was just published noting some features unique to the SARS-CoV-2 virus (that causes COVID-19) among other coronaviruses:

Our comparison of alpha- and betacoronaviruses identifies two notable genomic features of SARS-CoV-2: (i) on the basis of structural studies7,8,9 and biochemical experiments1,9,10, SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2; and (ii) the spike protein of SARS-CoV-2 has a functional polybasic (furin) cleavage site at the S1–S2 boundary through the insertion of 12 nucleotides8, which additionally led to the predicted acquisition of three O-linked glycans around the site.

Andersen et al. The proximal origin of SARS-CoV-2. Nat Med 2020. Published online 17 Mar 2020
https://www.nature.com/articles/s41591-020-0820-9

The paper discusses how these features could influence viral replication and the potential evoutionary origins of these features. All around a good read if one is interested in this question.

 

[PAllen]

@sqljunkey ,

Where the infection rate is high it is impossible to miss the increased death rate:
https://khn.org/morning-breakout/it...rus-victims-as-loved-ones-mourn-in-isolation/

 

[sqljunkey]

@Ygggdrasil I'm not going to argue that pneumonia and other respiratory diseases caused by the corona virus will lead to death in the older population. But one thing I am going to point out however, is that older people suffer of many other diseases. heart disease, cancer, Alzheimer's disease, diabetes and more.And so far I have not heard anyone say with very much concreteness; " corona virus almost always ends up leading to pneumonia, and or ARDS, and this is then what weakens the elderly further and cause them to die. "

All I have heard so far, and correct me if I am wrong, is that the ones in the elderly population who died of the corona virus also had underlying pathogens.

The diseases I've listed above are all very deadly in elderly patients on their own to begin with. Now it could be that the Coronavirus does accentuate the ill effects of these diseases and aggravate them even more. I don't know that. But it could also be that these people were going to die of these very deadly diseases anyways and had the virus when they did.

I know we have to act quickly and ask questions later since this is potentially a fast spreading virus, but we need to probably be a bit more careful linking this virus with death, especially since when those who have died already were at incredibly high risk of dying anyways.

And as to nurses filling out questionnaires, that is not clear either, I don't know how it's happening, but I know in normal cases, after going to the hospitals patients get released and if terminally ill are put on hospice and are taken care of by nurses either at their home or at the nursing homes themselves. I should assume that patients with corona who have reached a state of terminal illness are kept in quarantine somewhere at the hospital but still are being put on hospice.

It's not like they die on the operating table with 60 doctors looking at their vitals. It is a nurse that gives them the morphine and lorazepam maneuver. This is a process, and along that process emotions might run a bit high and they might forget the 2 or 3 underlying pathogens that brought the patient to this process and blame it all on this "novel" virus. @PAllen regarding morgues filled up to the ceiling with corpses I think someone should do something about that, it is not safe.

 

[Majorana]

Unlike flu viruses, it does not appear to mutate because it has a "proofreading enzyme" that repairs mistakes in replication of its RNA [...] However he did say that there are conditions under which the virus does change and rapidly

It seems contradictory... I am not any biologist/virologist. I am just a very concerned guy from northern Italy (475 deaths in the last 24 hours). I would like to understand more about this aspect of mutate/doesn't mutate. Thank you very much.

 

[Ygggdrasil]

@Ygggdrasil I'm not going to argue that pneumonia and other respiratory diseases caused by the corona virus will lead to death in the older population. But one thing I am going to point out however, is that older people suffer of many other diseases. heart disease, cancer, Alzheimer's disease, diabetes and more.

And so far I have not heard anyone say with very much concreteness; " corona virus almost always ends up leading to pneumonia, and or ARDS, and this is then what weakens the elderly further and cause them to die. "

All I have heard so far, and correct me if I am wrong, is that the ones in the elderly population who died of the corona virus also had underlying pathogens.

The diseases I've listed above are all very deadly in elderly patients on their own to begin with. Now it could be that the Coronavirus does accentuate the ill effects of these diseases and aggravate them even more. I don't know that. But it could also be that these people were going to die of these very deadly diseases anyways and had the virus when they did.

I think you are vastly overestimating the death rate of the conditions you list. For example, the life expectancy for an 80-89 year olds in China is 6.58 years. Median time to death for fatal COVID-19 patients was observed to be about 20 days from the onset of symptoms, and for people over 80, the mortality rate was 14.8% in studies of the Chinese outbreak. I don't think 14.8% of all people >80 years of age are going to drop dead in the next three weeks. (There are 23 million 80+ year olds in China, so this would correspond to 3.4 million deaths over three weeks. Based on the previously quoted 7 out of 1000 people dying per year in China (pop 1.4 billion), you would only expect to see 0.56 million total deaths of all ages in China over three weeks.) Modeling survival as an exponential decay with a half-life of 6.58 years, we would only expect to see about 0.61% mortality among octogenerians over a three week span (even if you double the period to six weeks as 20 days is only the median time to death, you still only expect 1.2% of octogenerians to die of natural causes in that time span). Thus, COVID-19 may increase mortality among octogenerians by over an order of magnitude.

Does the 14.8% represent the proportion of the >80 year-olds that are worse off in health? The study of life expectancy among the elderly in China found that ~ 11.8% of octogenerians were disabled (they require assistance in the essential activities of daily living like bathing, dressing, eating, or going to the bathroom). Among disabled octogenerians, life expectancy is only 1.1 year. Still, you would only expect to see 3.6% of that population die over the course of three weeks, nowhere near the 14.8% mortality seem among all infected 80+ year olds (regardless of whether they have additional health problems). Even the 70-79 age group (mortality rate of 8%) has twice the expected death rate of disabled octogenerians.

The health conditions that pre-dispose COVID-19 patients to greater mortality do not come close to explaining the observed mortality of the disease.

 

[sqljunkey]

@Ygggdrasil

Well if the numbers from(communist) China are accurate then yes there would seem to be an increase in the rate of death of elderly patients with underlying diseases.

How did you get to the 3.6% for patients with health problems? If I used a fake population of people older than 80 with multiple chronic diseases of 1,000,000 and I expect them to live for 1.1 year on average I would divide that population with the amount of year it takes for them to pass away, 1,000,000/1.1 to get how many would pass away in one year. That gives me 909,090 that die in the first year, and dividing that with 52 weeks to get the weekly death rate I would get 17,482. and I multiply that by 3 weeks and I get 52,447. Which in turn is 0.05 or 5% of the initial one million.

We have to remember though that the winter months tends to be the deadliest. So there might be a slight skew in percentages towards the months we are considering right now.

Keeping all this in mind, we should not forget the rather more mild, but still alarmingly high death rates of countries like South Korea with only 7% of deaths of people over 80.

I think Iran reported a 100% death rate or something along those lines.

 

[berkeman]

Thread closed temporarily for Moderation...

 

[berkeman]

Thread reopened...

 

[PAllen]

@Ygggdrasil

Well if the numbers from(communist) China are accurate then yes there would seem to be an increase in the rate of death of elderly patients with underlying diseases.

How did you get to the 3.6% for patients with health problems? If I used a fake population of people older than 80 with multiple chronic diseases of 1,000,000 and I expect them to live for 1.1 year on average I would divide that population with the amount of year it takes for them to pass away, 1,000,000/1.1 to get how many would pass away in one year. That gives me 909,090 that die in the first year, and dividing that with 52 weeks to get the weekly death rate I would get 17,482. and I multiply that by 3 weeks and I get 52,447. Which in turn is 0.05 or 5% of the initial one million.

We have to remember though that the winter months tends to be the deadliest. So there might be a slight skew in percentages towards the months we are considering right now.

Keeping all this in mind, we should not forget the rather more mild, but still alarmingly high death rates of countries like South Korea with only 7% of deaths of people over 80.

I think Iran reported a 100% death rate or something along those lines.

You haven't responded to any information about Italy, which has been open in its reporting. You have villages where the the obituary page of the local newspaper jumped to 3 to 5 times normal size over a matter of weeks, and the cremation capacity which is fine for normal fluctuations of death rate is overwhelmed in a matter of weeks. It is really impossible to mistake the cause here, when all the excess deaths test positive for covid-19.

 

[Ygggdrasil]

How did you get to the 3.6% for patients with health problems? If I used a fake population of people older than 80 with multiple chronic diseases of 1,000,000 and I expect them to live for 1.1 year on average I would divide that population with the amount of year it takes for them to pass away, 1,000,000/1.1 to get how many would pass away in one year. That gives me 909,090 that die in the first year, and dividing that with 52 weeks to get the weekly death rate I would get 17,482. and I multiply that by 3 weeks and I get 52,447. Which in turn is 0.05 or 5% of the initial one million.

I am modeling survival as an exponential decay with half life 1.1 years.
$$S(t) = e^{-\frac{ln(2)}{1.1}t}$$
Plug in t= 3/52, and you should get a surviving fraction of 0.964 or a 3.6% death rate.

 

[Astronuc]

Andersen et al. The proximal origin of SARS-CoV-2. Nat Med 2020. Published online 17 Mar 2020
https://www.nature.com/articles/s41591-020-0820-9

The article mentions "Neither the bat betacoronaviruses nor the pangolin betacoronaviruses sampled thus far have polybasic cleavage sites. Although no animal Coronavirus has been identified that is sufficiently similar to have served as the direct progenitor of SARS-CoV-2, the diversity of coronaviruses in bats and other species is massively undersampled. "

An article from the World Economic Forum states, "However, genomic comparisons suggest that the SARS-Cov-2 virus is the result of a recombination between two different viruses, meaning the exact origin of the virus is still unclear." From where would they get the notion?
https://www.weforum.org/agenda/2020...-analysis-covid19-data-science-bats-pangolins
Besides pangolins, the WEF article mentions bats (genus Rhinolophus, e.g., Rhinolophus affinis) and palm civet (Paguma larvata).

Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission
https://jvi.asm.org/content/84/7/3134

The WEF article ends "Two questions remain unanswered: in which organism did this recombination occur? (a bat, a pangolin or another species?) And above all, under what conditions did this recombination take place?"

 

[sqljunkey]

@PAllen it is kinda hard to get data from that country, like rates and such. All I have seen so far is Washington Post reports.

Germany has a low death rate, we are just now starting to test for it. Me and you could have had it already, and since the symptoms are mild we might have thought it was a "simple" cold. We weren't testing for it since we didn't have the equipment. It was cold and flu season and I'm willing to bet 0.0000001 Dogecoins that sometime during the winter you might have had a runny nose, chills, cough, or some difficulty breathing(in severe cases), all symptoms of the virus.

Inconsistencies in the data between different countries is telling me we should wait and see because data might be incomplete. If we all reported total deaths per month, keeping a running count, this would be more obvious.

I'm still skeptical, since we haven't reached anywhere near what the influenza does in the US alone https://www.cdc.gov/flu/about/burden/2017-2018.htm#table1

It is not bad that now we are all washing our hands after we go number 2, so some good might have come out of this after all.

 

[TeethWhitener]

The Internet Book of Critical Care has a lot of good info for this thread:
https://emcrit.org/ibcc/covid19/
A few points relevant to the thread.
1) Novel Coronavirus phylogeny:
https://nextstrain.org/ncov
2) COVID-19 can directly induce ARDS via viral cytopathy:
https://www.thelancet.com/action/showPdf?pii=S2213-2600(20)30076-X

Edit: there is also some limited evidence that the Wuhan strain is significantly more virulent than the strain outside China.

 

[Ygggdrasil]

The article mentions "Neither the bat betacoronaviruses nor the pangolin betacoronaviruses sampled thus far have polybasic cleavage sites. Although no animal Coronavirus has been identified that is sufficiently similar to have served as the direct progenitor of SARS-CoV-2, the diversity of coronaviruses in bats and other species is massively undersampled. "

An article from the World Economic Forum states, "However, genomic comparisons suggest that the SARS-Cov-2 virus is the result of a recombination between two different viruses, meaning the exact origin of the virus is still unclear." From where would they get the notion?
https://www.weforum.org/agenda/2020...-analysis-covid19-data-science-bats-pangolins
Besides pangolins, the WEF article mentions bats (genus Rhinolophus, e.g., Rhinolophus affinis) and palm civet (Paguma larvata).

Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission
https://jvi.asm.org/content/84/7/3134

The WEF article ends "Two questions remain unanswered: in which organism did this recombination occur? (a bat, a pangolin or another species?) And above all, under what conditions did this recombination take place?"

Most of the SARS-CoV-2 genome resembles bat coronaviruses, expect for one protein encoded by the viral genome, the spike protein (which is the element that helps the virus bind to the host cells). The spike protein more closely resembles the spike protein from coronaviruses found in pangolins. Therefore, from this data, scientists infer that the SARS-CoV-2 virus resulted from recombination between a bat Coronavirus and a pangolin coronavirus. When and where this recombination took place remain yet to be understood.

Here are some preliminary, non-peer reviewed pre-prints that present genetic analysis of various Coronavirus sequences making the case that SARS-CoV-2 likely resulted from recombination of bat and pangolin coronaviruses:
https://www.biorxiv.org/content/10.1101/2020.02.07.939207v1
https://www.biorxiv.org/content/10.1101/2020.02.17.951335v1
https://www.biorxiv.org/content/10.1101/2020.02.13.945485v1

 

[Astronuc]

Therefore, from this data, scientists infer that the SARS-CoV-2 virus resulted from recombination between a bat Coronavirus and a pangolin coronavirus.

That's what I was thinking, but also, is it bat -> pangolin, or pangolin -> bat, or bat/pangolin -> human -> pangolin/bat. Is the recombination necessarily in the secondary or intermediate host?

Pagolins are from Malaya, and they are smuggled to China through Guangong, and then distributed to wet markets across China, but perhaps more in central China (?) to places like Wuhan, Hubei. Where would a pangolin encounter bats, in Malaya, Guangdong, or Wuhan, in the market?

And according to nextstrain.org/ncov, the virus is mutating in the human population as it spread from China to Europe and US, and between Europe and US.

 

[Ygggdrasil]

@PAllen it is kinda hard to get data from that country, like rates and such. All I have seen so far is Washington Post reports.

Germany has a low death rate, we are just now starting to test for it. Me and you could have had it already, and since the symptoms are mild we might have thought it was a "simple" cold. We weren't testing for it since we didn't have the equipment. It was cold and flu season and I'm willing to bet 0.0000001 Dogecoins that sometime during the winter you might have had a runny nose, chills, cough, or some difficulty breathing(in severe cases), all symptoms of the virus.

Inconsistencies in the data between different countries is telling me we should wait and see because data might be incomplete. If we all reported total deaths per month, keeping a running count, this would be more obvious.

I'm still skeptical, since we haven't reached anywhere near what the influenza does in the US alone https://www.cdc.gov/flu/about/burden/2017-2018.htm#table1

It is not bad that now we are all washing our hands after we go number 2, so some good might have come out of this after all.

Here's a good article with a counterpoint to your view: https://www.statnews.com/2020/03/18/we-know-enough-now-to-act-decisively-against-covid-19/

You're focusing too much on the death rate from the disease (which will definitely vary between locations due to how widespread testing is and due to readiness of health systems to take on an large influx of patients, see this article for a nice discussion). Essentially, we are already seeing in locations like Wuhan, Italy, and Washington State, where outbreaks have been very severe and have overwhelmed the local health care system (e.g. see this reporting from Italy). Under these conditions, death rates will increase because those with severe illness will not be able to get the proper treatment (e.g. due to lack of ICU beds or ventilators). This could be one reason why locations with severe outbreaks like Italy and Wuhan have reported death rates 5-10x higher than locations where the outbreak has not been so severe and the health care system is better prepared (e.g Germany and South Korea).

These problems can be compounded by shortages of protective equipment for nurses and doctors, which could lead to them getting sick or scared to go to work, further reducing hospitals' capacity to treat cases. An overwhelmed hospital system also increases mortality from non-coronavirus related deaths as hospitals would have reduced capacity to treat other emergencies (heart attacks, strokes, car accidents, apdendicitis, etc.).

As to why we have to take drastic actions now, even though the numbers are well below what we would see in a typical flu season. From the STAT News Op/Ed I cited above:

First, the number of severe cases — the product of these two unknowns — becomes fearsome in country after country if the infection is allowed to spread. In Italy, coffins of Covid-19 victims are accumulating in churches that have stopped holding funerals. In Wuhan, at the peak of the epidemic there, critical cases were so numerous that, if scaled up to the size of the U.S. population, they would have filled every intensive care bed in this country.

That is what happens when a community waits until crisis hits to try to slow transmission. Intensive care demand lags new infections by about three weeks because it takes that long for a newly infected person to get critically ill. So acting before the crisis hits — as was done in some Chinese cities outside Wuhan, and in some of the small towns in Northern Italy — is essential to prevent a health system overload.

Second, if we don’t apply control measures, the number of cases will keep going up exponentially beyond the already fearsome numbers we have seen. Scientists have estimated that the basic reproductive number of this virus is around 2. That means without control, case numbers will double, then quadruple, then be eight times as big, and so on, doubling with each “generation” of cases.

If we wait to stop the spread of infections until our healthcare capacity is even at 25% of its capacity to deal with new cases, a three week lag in new intensive care cases combined with a doubling time of 7-10 days means that, even if you could halt all new infections at that point, the number of cases are already on their way to becoming sever cases in the coming weeks is already enough to overwhelm the health care system.

 

[Ygggdrasil]

That's what I was thinking, but also, is it bat -> pangolin, or pangolin -> bat, or bat/pangolin -> human -> pangolin/bat. Is the recombination necessarily in the secondary or intermediate host?

Pagolins are from Malaya, and they are smuggled to China through Guangong, and then distributed to wet markets across China, but perhaps more in central China (?) to places like Wuhan, Hubei. Where would a pangolin encounter bats, in Malaya, Guangdong, or Wuhan, in the market?

Unsure. These questions likely require further study.

And according to nextstrain.org/ncov, the virus is mutating in the human population as it spread from China to Europe and US, and between Europe and US.

Edit: there is also some limited evidence that the Wuhan strain is significantly more virulent than the strain outside China.

@TeethWhitener do you have a source for the claim?

The only paper I've seen claiming two strains of the virus is from the journal National Science Review . This paper has been criticized by other researchers in the field:

An analysis of genetic data from the ongoing COVID-19 outbreak was recently published in the journal National Science Review by Tang et al. (2020) 84. Two of the key claims made by this paper appear to have been reached by misunderstanding and over-interpretation of the SARS-CoV-2 data, with an additional analysis suffering from methodological limitations. [...] Given these flaws, we believe that Tang et al. should retract their paper, as the claims made in it are clearly unfounded and risk spreading dangerous misinformation at a crucial time in the outbreak.

http://virological.org/t/response-to-on-the-origin-and-continuing-evolution-of-sars-cov-2/418

Observing mutations in the nextstrain data is expected. The real question is whether those mutations have any effect on the behavior of the virus, which can be difficult to determine just from the sequence data. Also, experts urge caution in interpreting sequencing data from the various viral isolates as sampling is quite sparse: https://www.sciencemag.org/news/202...-coronavirus-moves-they-re-easy-overinterpret

 

[Astronuc]

Does sampling method affect the sequencing tests? I ask this not as expert in the subject, but as one who has seen the preparation of metallography affect results leading to potential misinterpretation of surface characteristics (nanometer scale), e.g., grain boundaries of metal alloys with other phases.

 

[Ygggdrasil]

By sampling, I mean that relatively few viral isolates have been sequenced, which makes it difficult to build reliable phylogenetic trees that show the evolutionary relationship between viruses from different locations (similar to the problem in figuring out where the SARS-CoV-2 came from; if we had more sequences of bat and pangolin viruses, maybe we could observe a more direct ancestor to SARS-CoV-2 in bat, pangolin or another species that could tell us more about the origin of the virus).

 

[Astronuc]

By sampling, I mean that relatively few viral isolates have been sequenced, which makes it difficult to build reliable phylogenetic trees that show the evolutionary relationship between viruses from different locations (similar to the problem in figuring out where the SARS-CoV-2 came from; if we had more sequences of bat and pangolin viruses, maybe we could observe a more direct ancestor to SARS-CoV-2 in bat, pangolin or another species that could tell us more about the origin of the virus).

Yes, I saw that mentioned in the papers, that we do not have enough sequences from different species. The world has been unprepared probably because this was not considered a high priority, even though some scientists have been concerned for some time, and following previous outbreaks.

 

[TeethWhitener]

@TeethWhitener do you have a source for the claim?

I can’t recall; the Tang paper may well have been the source for that info. Thanks for pointing out the criticisms.

 

[sqljunkey]

I don't find the theory it is plugging up the healthcare situation very convincing either, according to this paper, https://www.sciencedirect.com/science/article/pii/S1201971219303285, about 20,000 people die over there too because of the flu, you still take these patients to the hospitals, ICUs etcetera. They had ample time over there to develop a remarkable healthcare system to cope with all the flu patients. I mean the numbers alone are crazy.

Or are you arguing somehow that the care cycle for a terminally ill patient that has the Covid is more intensive than the ones that have the influenza.

I don't find the theory that the Covid 19 could have been an ongoing epidemic before 2019 until someone in China isolated this novel virus, too outlandish. Given the rather mild symptoms and our very limited to non existent testing capabilities up to this point, it is possible.

All of a sudden the virus is everywhere, some of it cannot even be explained by travel or contact with traveling persons."The hospitals would have been plugged up with people trying to get in and out if the virus was present before 2019" is not a valid argument either.Until I get those death numbers(covid deaths + other deaths) and do some comparisons I won't know for sure...

I mean, seriously, they will eventually find a vaccine for the Covid that is as effective as the influenza vaccine, and we will all forget about it.

 

[BillTre]

Sometimes the first attempts to make a vaccine do not work out so well.
Its not a sure thing to be counted on.

 

[jim mcnamara]

I have stayed out of this because it seems political.

@sqljunkey However some points:
A vaccine may not be likely. Too many new Covid 19 serotypes have evolved. Herd immunity is probably not a viable opportunity. It is an RNA virus, you may want look up why that makes a difference.
https://jvi.asm.org/content/92/14/e01031-17
<edit fix typo 12:12 MDT>
Plus, I think you are confusing replacement mortality with excess mortality. Check Italy for what they are doing with the piles of caskets. If the mortality rate was net ~zero piles of caskets would not be a problem because the infrastructure would be there to handle them already.

You also may not be clear about why getting R₀ (transmission rate) well below 1 slows an epidemic. Estimates of Covid 19 R₀ are 2-3.5, lots higher higher than the flu.

BTW I am going to ask you to look up the number of people who died from the harmless(?) influenza problem of 1918. Flu is not a problem, right?

 

[PeterDonis]

the care cycle for a terminally ill patient that has the Covid is more intensive than the ones that have the influenza

My understanding is that ventilators are the scarce resource; a far smaller percentage of annual flu patients need them because the flu much more rarely causes respiratory distress than COVID-19 does. To the point where "shortness of breath" is listed as a symptom to watch for for COVID-19 but not for flu.

 

[snorkack]

You're focusing too much on the death rate from the disease (which will definitely vary between locations due to how widespread testing is and due to readiness of health systems to take on an large influx of patients, see this article for a nice discussion). Essentially, we are already seeing in locations like Wuhan, Italy, and Washington State, where outbreaks have been very severe and have overwhelmed the local health care system (e.g. see this reporting from Italy). Under these conditions, death rates will increase because those with severe illness will not be able to get the proper treatment (e.g. due to lack of ICU beds or ventilators). This could be one reason why locations with severe outbreaks like Italy and Wuhan have reported death rates 5-10x higher than locations where the outbreak has not been so severe and the health care system is better prepared (e.g Germany and South Korea).

One reason. And another reason is that testing gets overwhelmed so patients with mild cases do not get tested and identified (but keep spreading the infection).
Germany has another reason for low death rate. They test "for benefit of living"... meaning that people who die of Coronavirus at home without assistance do not get tested nor count into death rate,

 

[Motore]

Here in Slovenia we are testing only those who need hospitalization. There are several reasons:
1.) We are a small country and per capita our test numbers per day are still pretty high.
2.) Because of the incubation period is long, testing someone now can show negative result, even though he is infected (he would test positive in 4 days for example)
3.) Evereyone should act like he is already infected, which means work from home if possible or strictly follow social distancing rules.

This virus (as seen in Italy) can overhelm the health care system in 3 weeks. Even though the flu kills between 4 000 - 10000 people a year in Italy it is spread in space and time, which means it cannot overhelm the system as the new Coronavirus does. But the new Coronavirus is much more contagious, has cca 20-30x higher mortality rate, is localized and is hitting all at once. In three weeks the death tool in Italy is almost 5000!

If we don't follow the measures (social distancing, no gatherings, lockdowns, ...) the death toll could spike very very fast.