What makes the current coronavirus different from the others?

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lavinia
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Summary:

What makes the current corona virus different than others?

Main Question or Discussion Point

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.
 
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  • #2
atyy
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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/people-shed-high-levels-of-coronavirus-study-finds-but-most-are-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.
 
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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
 
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Ygggdrasil
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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).
 
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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?
 
  • #7
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- 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?
 
  • #8
lavinia
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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.
 
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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-about-expanded-access-and-other-treatment-options/understanding-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.
 
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Ygggdrasil
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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/
 
  • #11
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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?
 
  • #12
lavinia
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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?
 
  • #13
atyy
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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/people-shed-high-levels-of-coronavirus-study-finds-but-most-are-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.
 
  • #14
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  • #15
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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 lets 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?
 
  • #16
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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.
 
  • #17
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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.
 
  • #18
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
 
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  • #19
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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 lets 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.]
 
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  • #20
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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?
 
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  • #21
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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.
 
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  • #22
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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/a-fiasco-in-the-making-as-the-coronavirus-pandemic-takes-hold-we-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.
 
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  • #24
Ygggdrasil
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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.
 

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