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  1. BREAKING: New CDC Coronavirus Data Cuts American Death Toll Nearly In HALF · 66.8K Views · Share · Follow Jonathan Davis Posted May 2, 2020 in Politics , Source: edhub Despite the fact most media are reporting coronavirus that has killed more than 67,000 Americans, the official Centers for Disease Control and Prevention website shows nearly have as many deaths. As of this writing, the site says there have been 67,224 deaths thus far from the virus, and most media all week long have been reporting a figure of about 66,000. sponsor But according to the official CDC website, just 37,308 people have died from the disease in the United States. That figure includes confirmed and presumed coronavirus deaths, the site notes. In addition, the CDC data show that the pandemic peaked in the United States the week of April 11, now nearly three weeks ago — yet several states and cities are continuing or extending their current stay-at-home orders. Also, the number of COVID-19 deaths have been steadily decreasing since April 25, according to the listed data, with some 93 percent of all coronavirus deaths occurring in people 55 years old and older. And, as noted by Newsmax journalist John Cardillo, data reported on WorldInfo is most likely a “scam” for attributing other causes of death to the virus, in order to inflate the numbers. “I’m well aware of the CDC ‘lag times’ but this isn’t that, so stop with that excuse for these numbers. They’ve separated out other illnesses that were the actual causes of deaths and now the mortality rate is half of what it was last week. It’s been nothing but a scam,” he tweeted. Another Twitter user retweeted a CDC post that said hospitalization rates for COVID-19, “which are cumulative, have started to level off,” while noting that the rate of hospitalization “is highest among adults 65 and older and similar to what has been seen during a comparable time period during a recent high severity flu season.” That last part is important because the Left-wing pundit class keeps telling us we’re not allowed to compare coronavirus to ‘the flu.’ This new data further undermines the health experts’ coronavirus projection models. They claimed in March that more than 1 million people would die from the virus in the U.S. alone. In February, National Institute of Allergy and Infectious Diseases chief Dr. Anthony Fauci, one of President Donald Trump’s top coronavirus task force advisers, said in February after looking at the data it appeared that coronavirus was “acting more like bad pandemic influenza (efficient spread, overall lower mortality) than like SARS (less efficient spread, overall higher mortality),” according to an update posted by the American Medical Association.
  2. Common sense advice and understanding..... CL Making neural nets uncool again HomeAboutOur MOOCPosts by Topic © 2020. All rights reserved. Covid-19, your community, and you — a data science perspective Written: 09 Mar 2020 by Jeremy Howard and Rachel Thomas Translations Anyone is welcome to translate this article, to help their local communities understand these issues. Please link back to here with appropriate credit. Let us know on Twitter so we can add your translation to this list. French Spanish German Italian Polish Portuguese (Brazil) Chinese 中文简体 Thai Swahili Contents We need a working medical system This is not like the flu “Don’t panic. Keep calm.” is not helpful It’s not just about you We need to flatten the curve A community’s reaction makes all the difference We don’t have good information in the US In conclusion We need a working medical system Just over 2 years ago one of us (Rachel) got a brain infection which kills around 1/4 of people who get it, and leaves 1/3 with permanent cognitive impairment. Many others end up with permanent vision and hearing damage. Rachel was delirious by the time she crawled across the hospital parking lot. She was lucky enough to receive prompt care, diagnosis, and treatment. Up until shortly before this event Rachel was in great health. Having prompt access to the emergency room almost certainly saved her life. Now, let’s talk about covid-19, and what might happen to people in Rachel’s situation in the coming weeks and months. The number of people found to be infected with covid-19 doubles every 3 to 6 days. With a doubling rate of three days, that means the number of people found to be infected can increase 100 times in three weeks (it’s not actually quite this simple, but let’s not get distracted by technical details). One in 10 infected people requires hospitalization for many weeks, and most of these require oxygen. Although it is very early days for this virus, there are already regions where hospitals are entirely overrun, and people are no longer able to get the treatment that they require (not only for covid-19, but also for anything else, such as the life-saving care that Rachel needed). For instance, in Italy, where just a week ago officials were saying that everything was fine, now sixteen million people have been put on lock-down (update: 6 hours after posting this, Italy put the entire country on lock-down), and tents like this are being set up to help handle the influx of patients: A medical tent used in Italy Dr. Antonio Pesenti, head of the regional crisis response unit in a hard-hit area of Italy, said, “We’re now being forced to set up intensive care treatment in corridors, in operating theaters, in recovery rooms… One of the best health systems in the world, in Lombardy is a step away from collapse.” This is not like the flu The flu has a death rate of around 0.1% of infections. Marc Lipsitch, the director of the Center for Communicable Disease Dynamics at Harvard, estimates that for covid-19 it is 1-2%. The latest epedemiological modeling found a 1.6% rate in China in February, sixteen times higher than the flu1 (this might be quite a conservative number however, because rates go up a lot when the medical system can’t cope). Current best estimates expect that covid-19 will kill 10 times more people this year than the flu (and modeling by Elena Grewal, former director of data science at Airbnb, shows it could be 100 times more, in the worst case). This is before taking into consideration the huge impact on the medical system, such as that described above. It is understandable that some people are trying to convince themselves that this is nothing new, an illness much like the flu, because it is very uncomfortable to accept the reality that this is not familiar at all. Trying to understand intuitively an exponentially increasing growth in the number of infected people is not something that our brains are designed to handle. So we have to analyze this as scientists, not using our intuition. Where will this be in 2 weeks? 2 months? For each person that has the flu, on average, they infect 1.3 other people. That’s called the “R0” for flu. If R0 is less than 1.0, then an infection stops spreading and dies out. If it’s over 1.0, it spreads. R0 currently is 2-3 for covid-19 outside China. The difference may sound small, but after 20 “generations” of infected people passing on their infection, an R0 of 1.3 would result in 146 infections, but an R0 of 2.5 would result in 36 million infections! (This is, of course, very hand-wavy and ignores many real-world impacts, but it’s a reasonable illustration of the relative difference between covid-19 and flu, all other things being equal). Note that R0 is not some fundamental property of a disease. It depends greatly on the response, and it can change over time2. Most notably, in China R0 for covid-19 has come down greatly, and is now approaching 1.0! How, you ask? By putting in place measures at a scale that would be hard to imagine in a country such as the US—for instance, entirely locking down many giant cities, and developing a testing process that allows more than a million people a week to be tested. One thing which comes up a lot on social media (including from highly-followed accounts such as Elon Musk) is a misunderstanding of the difference between logistic and exponential growth. “Logistic” growth refers to the “s-shaped” growth pattern of epidemic spread in practice. Obviously exponential growth can’t go on forever, since otherwise there would be more people infected than people in the world! Therefore, eventually, infection rates must always decreasing, resulting in an s-shaped (known as sigmoid) growth rate over time. However, the decreasing growth only occurs for a reason–it’s not magic. The main reasons are: Massive and effective community response, or Such a large percentage of people are infected that there’s fewer uninfected people to spread to. Therefore, it makes no logical sense to rely on the logistic growth pattern as a way to “control” a pandemic. Another thing which makes it hard to intuitively understand the impact of covid-19 in your local community is that there is a very significant delay between infection and hospitalization — generally around 11 days. This may not seem like a long time, but when you compare it to the number of people infected during that time, it means that by the time you notice that the hospital beds are full, community infection is already at a level that there will be 5-10 times more people to deal with. Note that there are some early signs that the impact in your local area may be at least somewhat dependent on climate. The paper Temperature and latitude analysis to predict potential spread and seasonality for COVID-19 points out that the disease has so far been spreading in mild climates (unfortunately for us, the temperature range in San Francisco, where we live, is right in that range; it also covers the main population centers of Europe, including London.) “Don’t panic. Keep calm.” is not helpful One common response we’ve seen on social media to people that are pointing out the reasons to be concerned, is “don’t panic” or “keep calm”. This is, to say the least, not helpful. No-one is suggesting that panic is an appropriate response. For some reason, however, “keep calm” is a very popular reaction in certain circles (but not amongst any epidemiologists, whose job it is to track these things). Perhaps “keep calm” helps some people feel better about their own inaction, or makes them feel somehow superior to people who they imagine are running around like a headless chicken. But “keep calm” can easily lead to a failure to prepare and respond. In China, tens of millions were put on lock-down and two new hospitals were built by the time they reached the statistics that the US has now. Italy waited too long, and just today (Sunday March 😎 they reported 1492 new cases and 133 new deaths, despite locking down 16 million people. Based on the best information we’re able to ascertain at this stage, just 2-3 weeks ago Italy was in the same position that the US and UK are in today (in terms of infection statistics). Note that nearly everything about covid-19 at this stage is up in the air. We don’t really know it’s infection speed or mortality, we don’t know how long it remains active on surfaces, we don’t know whether it survives and spreads in warm conditions. Everything we have is current best guesses based on the best information people are able to put together. And remember, the vast majority of this information is in China, in Chinese. Currently, the best way to understand the Chinese experience so far is to read the excellent Report of the WHO-China Joint Mission on Coronavirus Disease 2019, based on a joint mission of 25 national and international experts from China, Germany, Japan, Korea, Nigeria, Russia, Singapore, the United States of America and the World Health Organization (WHO). When there’s some uncertainty, that perhaps this won’t be a global pandemic, and perhaps everything just might pass by without the hospital system collapsing, that doesn’t mean that the right response is to do nothing. That would be enormously speculative and not an optimal response under any threat modeling scenario. It also seems extremely unlikely that countries like Italy and China would effectively shut down large parts of their economy for no good reason. It’s also not consistent with the actual impacts we’re seeing on the ground in infected areas, where the medical system is unable to cope (for instance, Italy is using 462 tents for “pre-triage”, and still has to move ICU patients from infected areas). Instead, the thoughtful, reasonable response is to follow the steps that are recommended by experts to avoid spreading infections: Avoid large groups and crowds Cancel events Work from home, if at all possible Wash hands when coming and going from home, and frequently when out Avoid touching your face, especially when outside your home (not easy!) Disinfect surfaces and packages (it’s possible the virus may remain active for 9 days on surfaces, although this still isn’t known for sure either way). It’s not just about you If you are under 50, and do not have risk factors such as a compromised immune system, cardiovascular disease, a history of previous smoking, or other chronic illnesses, then you can have some comfort that covid-19 is unlikely to kill you. But how you respond still matters very much. You still have just as much chance of getting infected, and if you do, just as much chance of infecting others. On average, each infected person is infecting over two more people, and they become infectious before they show symptoms. If you have parents that you care about, or grandparents, and plan to spend time with them, and later discover that you are responsible for infecting them with covid-19, that would be a heavy burden to live with. Even if you are not in contact with people over 50, it is likely that you have more coworkers and acquaintances with chronic illnesses than you realize. Research shows that few people disclose their health conditions in the workplace if they can avoid it, for fear of discrimination. Both of us are in high risk categories, but many people who we interact with regularly may not have known this. And of course, it is not just about the people immediately around you. This is a highly significant ethical issue. Each person who does their best to contribute to controlling the spread of the virus is helping their whole community to slow down the rate of infection. As Zeynep Tufekci wrote in Scientific Amercian: “Preparing for the almost inevitable global spread of this virus… is one of the most pro-social, altruistic things you can do”. She continues: This has impacted us personally. The biggest and most important course we’ve ever created at, which represents the culmination of years of work for us, was scheduled to start at the University of San Francisco in a week. Last Wednesday (March 4), we made the decision to move the whole thing online. We were one of the first large courses to move online. Why did we do it? Because we realized early last week that if we ran this course, we were implicitly encouraging hundreds of people to get together in an enclosed space, multiple times over a multi-week period. Bringing groups together in enclosed spaces is the single worst thing that can be done. We felt ethically obliged to ensure that, at least in this case, this didn’t happen. It was a heart-breaking decision. Our time spent working directly with our students has been one of the great pleasures and most productive periods every year. And we had students planning to fly in from all over the world, who we really didn’t want to let down3. But we knew it was the right thing to do, because otherwise we’d be likely to be increasing the spread of the disease in our community4. We need to flatten the curve This is extremely important, because if we can slow down the rate of infection in a community, then we give hospitals in that community time to deal with both the infected patients, and with the regular patient load that they need to handle. This is described as “flattening the curve”, and is clearly shown in this illustrative chart: Staying under that dotted line means everything Farzad Mostashari, the former National Coordinator for Health IT, explained: “New cases are being identified every day that do not have a travel history or connection to a known case, and we know that these are just the tip of the iceberg because of the delays in testing. That means that in the next two weeks the number of diagnosed cases will explode… Trying to do containment when there is exponential community spread is like focusing on putting out sparks when the house is on fire. When that happens, we need to switch strategies to mitigation–taking protective measures to slow spread & reduce peak impact on healthcare.” If we can keep the spread of disease low enough that our hospitals can handle the load, then people can access treatment. But if the cases come too quickly, then those that need hospitalization won’t get it. Here’s what the math might look like, according to Liz Specht: A community’s reaction makes all the difference As we’ve discussed, this math isn’t a certainty—China has already shown that it’s possible to reduce the spread by taking extreme steps. Another great example of a successful response is Vietnam, where, amongst other things, a nationwide advertising campaign (including a catchy song!) quickly mobilized community response and ensured that people adjusted their behavior appropriately. This is not just a hypothetical situation — it was clearly displayed in the 1918 flu pandemic. In the United States two cities displayed very different reactions to the pandemic: Philadelphia went ahead with a giant parade of 200,000 people to help raise money for the war. But St Louis put in place carefully designed processes to minimize social contacts so as to decrease the spread of the virus, along with cancelling all large events. Here is what the number of deaths looked like in each city, as shown in the Proceedings of the National Academy of Sciences: Impact of differing responses to the 1918 Flu pandemic The situation in Philadelphia became extremely dire, even getting to a point where there were not enough funeral caskets or morgues to handle the huge number of dead from the flu. Richard Besser, who was acting director of the Centers for Disease Control and Prevention during the 2009 H1N1 pandemic, says that in the US “the risk of exposure and the ability to protect oneself and one’s family depends on income, access to health care, and immigration status, among other factors.” He points out that: The US Bureau of Labor Statistics shows that less than a third of those in the lowest income band have access to paid sick leave: Most poor Americans do not have sick leave, so have to go to work. We don’t have good information in the US One of the big issues in the US is that very little testing is being done, and testing results aren’t being properly shared, which means we don’t know what’s actually happening. Scott Gottlieb, the previous FDA commissioner, explained that in Seattle there has been better testing, and we are seeing infection there: “The reason why we knew early about Seattle outbreak of covid-19 was because of sentinel surveillance work by independent scientists. Such surveillance never got totally underway in other cities. So other U.S. hot spots may not be fully detected yet.” According to The Atlantic, Vice President Mike Pence promised that “roughly 1.5 million tests” would be available this week, but less than 2,000 people have been tested throughout the US at this point. Drawing on work from The COVID Tracking Project, Robinson Meyer and Alexis Madrigal of The Atlantic, said: Part of the problem is that this has become a political issue. In particular, President Donald Trump has made it clear that he wants to see “the numbers” (that as, the number of people infected in the US) kept low. This is an example of where optimizing metrics interferes with getting good results in practice. (For more on this issue, see the Ethics of Data Science paper The Problem with Metrics is a Fundamental Problem for AI). Google’s Head of AI Jeff Dean, tweeted his concern about the problems of politicized disinformation: It doesn’t look like there is the political will to turn things around, when it comes to transparency. Health and Human Services Secretary Alex Azar, according to Wired, “started talking about the tests health care workers use to determine if someone is infected with the new coronavirus. The lack of those kits has meant a dangerous lack of epidemiological information about the spread and severity of the disease in the US, exacerbated by opacity on the part of the government. Azar tried to say that more tests were on the way, pending quality control.” But, they continued: Other countries are reacting much more quickly and significantly than the US. Many countries in SE Asia are showing great results, including Taiwan, where R0 is down to 0.3 now, and Singapore, which is being proposed as The Model for COVID-19 Response. It’s not just in Asia though; in France, for instance, any gathering of >1000 people is forbidden, and schools are now closed in three districts. In conclusion Covid-19 is a significant societal issue, and we can, and should, all work to decrease the spread of the disease. This means: Avoiding large groups and crowds Canceling events Working from home, if at all possible Washing hands when coming and going from home, and frequently when out Avoiding touching your face, especially when outside your home. Note: due to the urgency of getting this out, we haven’t been as careful as we normally like to be about citing and crediting the work we’re relying on. Please let us know if we’ve missed anything. Thanks to Sylvain Gugger and Alexis Gallagher for feedback and comments. Footnotes (Click ↩ on a footnote to go back to where you were.) Epidemiologists are people who study the spread of disease. It turns out that estimating things like mortality and R0 are actually pretty challenging, so there is a whole field that specializes in doing this well. Be wary of people who use simple ratios and statistics to tell you how covid-19 is behaving. Instead, look at modeling done by epidemiologists. ↩ Well, not technically true. “R0” strictly speaking refers to the infection rate in the absence of response. But since that’s not really ever the thing that we care about, we’ll let ourselves be a bit sloppy on our definitions here. ↩ Since that decision, we’ve worked hard to find a way to run a virtual course which we hope will be even better than the in-person version would have been. We’ve been able to open it up to anyone in the world, and will be running virtual study and project groups every day. ↩ We’ve made many other smaller changes to our lifestyle too, including exercising at home instead of going to the gym, moving all our meetings to video-conference, and skipping night events that we’d been looking forward to. ↩ This post is tagged: [ ai-in-society ] (click a tag for more posts in that category). Related Posts Disinformation: what it is, why it's pervasive, and proposed regulations 26 Feb 2020 fastai—A Layered API for Deep Learning 13 Feb 2020 Tech Ethics Crisis: The Big Picture, and How We Got Here 09 Feb 2020
  3. Coronavirus Jul 23, 2015 - THE PIRBRIGHT INSTITUTE The present invention provides a live, attenuated coronavirus comprising a variant replicase gene encoding polyproteins comprising a mutation in one or more of non-structural protein(s) (nsp)-10, nsp-14, nsp-15 or nsp-16. The coronavirus may be used as a vaccine for treating and/or preventing a disease, such as infectious bronchitis, in a subject. Latest THE PIRBRIGHT INSTITUTE Patents: Attenuated African swine fever virus vaccine Stabilised FMDV capsids Stabilised FMDV Capsids Chicken cells for improved virus production Mutant spike protein extending the tissue tropism of infectious bronchitis virus (IBV) Skip to: Description · Claims · References Cited · Patent History · Patent History Description FIELD OF THE INVENTION The present invention relates to an attenuated coronavirus comprising a variant replicase gene, which causes the virus to have reduced pathogenicity. The present invention also relates to the use of such a coronavirus in a vaccine to prevent and/or treat a disease. BACKGROUND TO THE INVENTION Avian infectious bronchitis virus (IBV), the aetiological agent of infectious bronchitis (IB), is a highly infectious and contagious pathogen of domestic fowl that replicates primarily in the respiratory tract but also in epithelial cells of the gut, kidney and oviduct. IBV is a member of the Order Nidovirales, Family Coronaviridae, Subfamily Corona virinae and Genus Gammacoronavirus; genetically very similar coronaviruses cause disease in turkeys, guinea fowl and pheasants. Clinical signs of IB include sneezing, tracheal rales, nasal discharge and wheezing. Meat-type birds have reduced weight gain, whilst egg-laying birds lay fewer eggs and produce poor quality eggs. The respiratory infection predisposes chickens to secondary bacterial infections which can be fatal in chicks. The virus can also cause permanent damage to the oviduct, especially in chicks, leading to reduced egg production and quality; and kidney, sometimes leading to kidney disease which can be fatal. IBV has been reported to be responsible for more economic loss to the poultry industry than any other infectious disease. Although live attenuated vaccines and inactivated vaccines are universally used in the control of IBV, the protection gained by use of vaccination can be lost either due to vaccine breakdown or the introduction of a new IBV serotype that is not related to the vaccine used, posing a risk to the poultry industry. Further, there is a need in the industry to develop vaccines which are suitable for use in ovo, in order to improve the efficiency and cost-effectiveness of vaccination programmes. A major challenge associated with in ovo vaccination is that the virus must be capable of replicating in the presence of maternally-derived antibodies against the virus, without being pathogenic to the embryo. Current IBV vaccines are derived following multiple passage in embryonated eggs, this results in viruses with reduced pathogenicity for chickens, so that they can be used as live attenuated vaccines. However such viruses almost always show an increased virulence to embryos and therefore cannot be used for in ova vaccination as they cause reduced hatchability. A 70% reduction in hatchability is seen in some cases. Attenuation following multiple passage in embryonated eggs also suffers from other disadvantages. It is an empirical method, as attenuation of the viruses is random and will differ every time the virus is passaged, so passage of the same virus through a different series of eggs for attenuation purposes will lead to a different set of mutations leading to attenuation. There are also efficacy problems associated with the process: some mutations will affect the replication of the virus and some of the mutations may make the virus too attenuated. Mutations can also occur in the S gene which may also affect immunogenicity so that the desired immune response is affected and the potential vaccine may not protect against the required serotype. In addition there are problems associated with reversion to virulence and stability of vaccines. It is important that new and safer vaccines are developed for the control of IBV. Thus there is a need for IBV vaccines which are not associated with these issues, in particular vaccines which may be used for in ovo vaccination. SUMMARY OF ASPECTS OF THE INVENTION The present inventors have used a reverse genetics approach in order to rationally attenuate IBV. This approach is much more controllable than random attenuation following multiple passages in embryonated eggs because the position of each mutation is known and its effect on the virus, i.e. the reason for attenuation, can be derived. Using their reverse genetics approach, the present inventors have identified various mutations which cause the virus to have reduced levels of pathogenicity. The levels of pathogenicity may be reduced such that when the virus is administered to an embryonated egg, it is capable of replicating without being pathogenic to the embryo. Such viruses may be suitable for in ovo vaccination, which is a significant advantage and has improvement over attenuated IBV vaccines produced following multiple passage in embryonated eggs. Thus in a first aspect, the present invention provides a live, attenuated coronavirus comprising a variant replicase gene encoding polyproteins comprising a mutation in one or more of non-structural protein(s) (nsp)-10, nsp-14, nsp-15 or nsp-16. The variant replicase gene may encode a protein comprising one or more amino acid mutations selected from the list of: Pro to Leu at position 85 of SEQ ID NO: 6, Val to Leu at position 393 of SEQ ID NO: 7; Leu to Ile at position 183 of SEQ ID NO: 8; Val to Ile at position 209 of SEQ ID NO: 9. The replicase gene may encode a protein comprising the amino acid mutation Pro to Leu at position 85 of SEQ ID NO: 6. The replicase gene may encode a protein comprising the amino acid mutations Val to Leu at position 393 of SEQ ID NO: 7; Leu to Ile at position 183 of SEQ ID NO: 8; and Val to Ile at position 209 of SEQ ID NO: 9. The replicase gene may encodes a protein comprising the amino acid mutations Pro to Leu at position 85 of SEQ ID NO: 6; Val to Leu at position 393 of SEQ ID NO:7; Leu to Ile at position 183 of SEQ ID NO:8; and Val to Ile at position 209 of SEQ ID NO: 9. The replicase gene may comprise one or more nucleotide substitutions selected from the list of: C to T at nucleotide position 12137; G to C at nucleotide position 18114; T to A at nucleotide position 19047; and G to A at nucleotide position 20139; compared to the sequence shown as SEQ ID NO: 1. The coronavirus may be an infectious bronchitis virus (IBV). The coronavirus may be IBV M41. The coronavirus may comprise an S protein at least part of which is from an IBV serotype other than M41. For example, the S1 subunit or the entire S protein may be from an IBV serotype other than M41. The coronavirus according to the first aspect of the invention has reduced pathogenicity compared to a coronavirus expressing a corresponding wild-type replicase, such that when the virus is administered to an embryonated egg, it is capable of replicating without being pathogenic to the embryo. In a second aspect, the present invention provides a variant replicase gene as defined in connection with the first aspect of the invention. In a third aspect, the present invention provides a protein encoded by a variant coronavirus replicase gene according to the second aspect of the invention. In a fourth aspect, the present invention provides a plasmid comprising a replicase gene according to the second aspect of the invention. In a fifth aspect, the present invention provides a method for making the coronavirus according to the first aspect of the invention which comprises the following steps: (i) transfecting a plasmid according to the fourth aspect of the invention into a host cell; (ii) infecting the host cell with a recombining virus comprising the genome of a coronavirus strain with a replicase gene; (iii) allowing homologous recombination to occur between the replicase gene sequences in the plasmid and the corresponding sequences in the recombining virus genome to produce a modified replicase gene; and (iv) selecting for recombining virus comprising the modified replicase gene. The recombining virus may be a vaccinia virus. The method may also include the step: (v) recovering recombinant coronavirus comprising the modified replicase gene from the DNA from the recombining virus from step (iv). In a sixth aspect, the present invention provides a cell capable of producing a coronavirus according to the first aspect of the invention. In a seventh aspect, the present invention provides a vaccine comprising a coronavirus according to the first aspect of the invention and a pharmaceutically acceptable carrier. In an eighth aspect, the present invention provides a method for treating and/or preventing a disease in a subject which comprises the step of administering a vaccine according to the seventh aspect of the invention to the subject. Further aspects of the invention provide: the vaccine according to the seventh aspect of the invention for use in treating and/or preventing a disease in a subject. use of a coronavirus according to the first aspect of the invention in the manufacture of a vaccine for treating and/or preventing a disease in a subject. The disease may be infectious bronchitis (IB). The method of administration of the vaccine may be selected from the group consisting of; eye drop administration, intranasal administration, drinking water administration, post-hatch injection and in ovo injection. Vaccination may be by in ova vaccination. The present invention also provides a method for producing a vaccine according to the seventh aspect of the invention, which comprises the step of infecting a cell according to the sixth aspect of the invention with a coronavirus according to the first aspect of the invention. DESCRIPTION OF THE FIGURES FIG. 1—Growth kinetics of M41-R-6 and M41-R-12 compared to M41-CK (M41 EP4) on CK cells FIG. 2—Clinical signs, snicking and wheezing, associated with M41-R-6 and M41-R-12 compared to M41-CK (M41 EP4) and Beau-R (Bars show mock, Beau-R, M41-R 6, M41-R 12, M41-CK EP4 from left to right of each timepoint). FIG. 3—Ciliary activity of the viruses in tracheal rings isolated from tracheas taken from infected chicks. 100% ciliary activity indicates no effect by the virus; apathogenic, 0% activity indicates complete loss of ciliary activity, complete ciliostasis, indicating the virus is pathogenic (Bars show mock, Beau-R, M41-R 6, M41-R 12, M41-CK EP4 from left to right of each timepoint). FIG. 4—Clinical signs, snicking, associated with M41R-nsp10rep and M41R-nsp14,15,16rep compared to M41-R-12 and M41-CK (M41 EP5) (Bars show mock, M41-R12; M41R-nsp10rep; M41R-nsp14,15,16rep and M41-CK EP5 from left to right of each timepoint). FIG. 5—Ciliary activity of M41R-nsp10rep and M41R-nsp14,15,16rep compared to M41-R-12 and M41-CK in tracheal rings isolated from tracheas taken from infected chicks (Bars show mock; M41-R12; M41R-nsp10rep; M41R-nsp14,15,16rep and M41-CK EP5 from left to right of each timepoint). FIG. 6—Clinical signs, snicking, associated with M41R-nsp10, 15rep, M41R-nsp10, 14, 15rep, M41R-nsp10, 14, 16rep, M41R-nsp10, 15, 16rep and M41-K compared to M41-CK (Bars show mock, M41R-nsp10,15rep1; M41R-nsp10,14,16rep4; M41R-nsp10,15,16rep8; M41R-nsp10,14,15rep10; M41-K6 and M41-CK EP4 from left to right of each timepoint). FIG. 7—Clinical signs, wheezing, associated with M41R-nsp10, 15rep, M41R-nsp10, 14, 15rep, M41R-nsp10, 14, 16rep, M41R-nsp10, 15, 16rep and M41-K compared to M41-CK (Bars show mock, M41R-nsp10,15rep1; M14R-nsp10,14,16rep4; M41R-nsp10,15,16rep8; M41R-nsp10,14,15rep10; M41-K6 and M41-CK EP4 from left to right of each timepoint). FIG. 8—Ciliary activity of M41R-nsp10, 15rep, M41R-nsp10, 14, 15rep, M41R-nsp10, 14, 16rep, M41R-nsp10, 15, 16rep and M41-K compared to M41-CK in tracheal rings isolated from tracheas taken from infected chicks (Bars show mock, M41R-nsp10,15rep1; M41R-nsp10,14,16rep4; M41R-nsp10,15,16rep8; M41R-nsp10,14,15rep10; M41-K6 and M41-CK EP4 from left to right of each timepoint). FIG. 9—Growth kinetics of rIBVs compared to M41-CK on CK cells. FIG. 9A shows the results for M41-R and M41-K. FIG. 9B shows the results for M41-nsp10 rep; M41R-nsp14, 15, 16 rep; M41R-nsp10, 15 rep; M41R-nsp10, 15, 16 rep; M41R-nsp10, 14, 15 rep; and M41R-nsp10, 14, 16. FIG. 10—Position of amino acid mutations in mutated nsp10, nsp14, nsp15 and nsp16 sequences. FIG. 11—A) Snicking; Respiratory symptoms (wheezing and rales combined) and C) Ciliary activity of rIBV M41R-nsp 10,14 rep and rIBV M41R-nsp 10,16 rep compared to M41-CK (Bars show mock, M41R-nsp10,14rep; M41R-nsp10,16rep and M41-K from left to right of each timepoint). DETAILED DESCRIPTION The present invention provides a coronavirus comprising a variant replicase gene which, when expressed in the coronavirus, causes the virus to have reduced pathogenicity compared to a corresponding coronavirus which comprises the wild-type replicase gene. Coronavirus Gammacoronavirus is a genus of animal virus belonging to the family Coronaviridae. Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome and a helical symmetry. The genomic size of coronaviruses ranges from approximately 27 to 32 kilobases, which is the longest size for any known RNA virus. Coronaviruses primarily infect the upper respiratory or gastrointestinal tract of mammals and birds. Five to six different currently known strains of coronaviruses infect humans. The most publicized human coronavirus, SARS-CoV which causes severe acute respiratory syndrome (SARS), has a unique pathogenesis because it causes both upper and lower respiratory tract infections and can also cause gastroenteritis. Middle East respiratory syndrome coronavirus (MERS-CoV) also causes a lower respiratory tract infection in humans. Coronaviruses are believed to cause a significant percentage of all common colds in human adults. Coronaviruses also cause a range of diseases in livestock animals and domesticated pets, some of which can be serious and are a threat to the farming industry. Economically significant coronaviruses of livestock animals include infectious bronchitis virus (IBV) which mainly causes respiratory disease in chickens and seriously affects the poultry industry worldwide; porcine coronavirus (transmissible gastroenteritis, TGE) and bovine coronavirus, which both result in diarrhoea in young animals. Feline coronavirus has two forms, feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneous mutation of this virus can result in feline infectious peritonitis (FIP), a disease associated with high mortality. There are also two types of canine coronavirus (CCoV), one that causes mild gastrointestinal disease and one that has been found to cause respiratory disease. Mouse hepatitis virus (MHV) is a coronavirus that causes an epidemic murine illness with high mortality, especially among colonies of laboratory mice. Coronaviruses are divided into four groups, as shown below: Alpha Canine coronavirus (CCoV) Feline coronavirus (FeCoV) Human coronavirus 229E (HCoV-229E) Porcine epidemic diarrhoea virus (PEDV) Transmissible gastroenteritis virus (TGEV) Human Coronavirus NL63 (NL or New Haven) Beta Bovine coronavirus (BCoV) Canine respiratory coronavirus (CRCoV)—Common in SE Asia and Micronesia Human coronavirus OC43 (HCoV-OC43) Mouse hepatitis virus (MHV) Porcine haemagglutinating encephalomyelitis virus (HEV) Rat coronavirus (Roy). Rat Coronavirus is quite prevalent in Eastern Australia where, as of March/April 2008, it has been found among native and feral rodent colonies. (No common name as of yet) (HCoV-HKU1)  Severe acute respiratory syndrome coronavirus (SARS-CoV) Middle East respiratory syndrome coronavirus (MERS-CoV) Gamma Infectious bronchitis virus (IBV) Turkey coronavirus (Bluecomb disease virus) Pheasant coronavirus Guinea fowl coronavirus Delta Bulbul coronavirus (BuCoV) Thrush coronavirus (ThCoV) Munia coronavirus (MuCoV) Porcine coronavirus (PorCov) HKU15 The variant replicase gene of the coronavirus of the present invention may be derived from an alphacoronavirus such as TGEV; a betacoronavirus such as MHV; or a gammacoronavirus such as IBV. As used herein the term “derived from” means that the replicase gene comprises substantially the same nucleotide sequence as the wild-type replicase gene of the relevant coronavirus. For example, the variant replicase gene of the present invention may have up to 80%, 85%, 90%, 95%, 98% or 99% identity with the wild type replicase sequence. The variant coronavirus replicase gene encodes a protein comprising a mutation in one or more of non-structural protein (nsp)-10, nsp-14, nsp-15 or nsp-16 when compared to the wild-type sequence of the non-structural protein. IBV Avian infectious bronchitis (IB) is an acute and highly contagious respiratory disease of chickens which causes significant economic losses. The disease is characterized by respiratory signs including gasping, coughing, sneezing, tracheal rales, and nasal discharge. In young chickens, severe respiratory distress may occur. In layers, respiratory distress, nephritis, decrease in egg production, and loss of internal egg quality and egg shell quality are common. In broilers, coughing and rattling are common clinical signs, rapidly spreading in all the birds of the premises. Morbidity is 100% in non-vaccinated flocks. Mortality varies depending on age, virus strain, and secondary infections but may be up to 60% in non-vaccinated flocks. The first IBV serotype to be identified was Massachusetts, but in the United States several serotypes, including Arkansas and Delaware, are currently circulating, in addition to the originally identified Massachusetts type. The IBV strain Beaudette was derived following at least 150 passages in chick embryos. IBV Beaudette is no longer pathogenic for hatched chickens but rapidly kills embryos. H120 is a commercial live attenuated IBV Massachusetts serotype vaccine strain, attenuated by approximately 120 passages in embryonated chicken eggs. H52 is another Massachusetts vaccine, and represents an earlier and slightly more pathogenic passage virus (passage 52) during the development of H120. Vaccines based on H120 are commonly used. IB QX is a virulent field isolate of IBV. It is sometimes known as “Chinese QX” as it was originally isolated following outbreaks of disease in the Qingdao region in China in the mid 1990s. Since that time the virus has crept towards Europe. From 2004, severe egg production issues have been identified with a very similar virus in parts of Western Europe, predominantly in the Netherlands, but also reported from Germany, France, Belgium, Denmark and in the UK. The virus isolated from the Dutch cases was identified by the Dutch Research Institute at Deventer as a new strain that they called D388. The Chinese connection came from further tests which showed that the virus was 99% similar to the Chinese QX viruses. A live attenuated QX-like IBV vaccine strain has now been developed. IBV is an enveloped virus that replicates in the cell cytoplasm and contains an non-segmented, single-stranded, positive sense RNA genome. IBV has a 27.6 kb RNA genome and like all coronaviruses contains the four structural proteins; spike glycoprotein (S), small membrane protein (E), integral membrane protein (M) and nucleocapsid protein (N) which interacts with the genomic RNA. The genome is organised in the following manner: 5′UTR—polymerase (replicase) gene—structural protein genes (S-E-M-N)—UTR 3′; where the UTR are untranslated regions (each ˜500 nucleotides in IBV). The lipid envelope contains three membrane proteins: S, M and E. The IBV S protein is a type I glycoprotein which oligomerizes in the endoplasmic reticulum and is assembled into homotrimer inserted in the virion membrane via the transmembrane domain and is associated through non-covalent interactions with the M protein. Following incorporation into coronavirus particles, the S protein is responsible for binding to the target cell receptor and fusion of the viral and cellular membranes. The S glycoprotein consists of four domains: a signal sequence that is cleaved during synthesis; the ectodomain, which is present on the outside of the virion particle; the transmembrane region responsible for anchoring the S protein into the lipid bilayer of the virion particle; and the cytoplasmic tail. All coronaviruses also encode a set of accessory protein genes of unknown function that are not required for replication in vitro, but may play a role in pathogenesis. IBV encodes two accessory genes, genes 3 and 5, which both express two accessory proteins 3a, 3b and 5a, 5b, respectively. The variant replicase gene of the coronavirus of the present invention may be derived from an IBV. For example the IBV may be IBV Beaudette, H120, H52, IB QX, D388 or M41. The IBV may be IBV M41. M41 is a prototypic Massachusetts serotype that was isolated in the USA in 1941. It is an isolate used in many labs throughout the world as a pathogenic lab stain and can be obtained from ATCC (VR-21™). Attenuated variants are also used by several vaccine producers as IBV vaccines against Massachusetts serotypes causing problems in the field. The present inventors chose to use this strain as they had worked for many years on this virus, and because the sequence of the complete virus genome is available. The M41 isolate, M41-CK, used by the present inventors was adapted to grow in primary chick kidney (CK) cells and was therefore deemed amenable for recovery as an infectious virus from a cDNA of the complete genome. It is representative of a pathogenic IBV and therefore can be analysed for mutations that cause either loss or reduction in pathogenicity.
  4. Creator Of US BioWeapons Act Says Coronavirus Is Biological Warfare Weapon by Tyler Durden Mon, 02/03/2020 - 17:25 5 SHARES TwitterFacebookRedditEmailPrint Via, In an explosive interview Dr. Francis Boyle, who drafted the Biological Weapons Act has given a detailed statement admitting that the 2019 Wuhan Coronavirus is an offensive Biological Warfare Weapon and that the World Health Organization (WHO) already knows about it. Dr. Francis Boyle Creator Of BioWeapons Act Says Coronavirus Is Biological Warfare Weapon Francis Boyle is a professor of international law at the University of Illinois College of Law. He drafted the U.S. domestic implementing legislation for the Biological Weapons Convention, known as the Biological Weapons Anti-Terrorism Act of 1989, that was approved unanimously by both Houses of the U.S. Congress and signed into law by President George H.W. Bush. In an exclusive interview given to Geopolitics and Empire, Dr. Boyle discusses the coronavirus outbreak in Wuhan, China and the Biosafety Level 4 laboratory (BSL-4) from which he believes the infectious disease escaped. He believes the virus is potentially lethal and an offensive biological warfare weapon or dual-use biowarfare weapons agent genetically modified with gain of function properties, which is why the Chinese government originally tried to cover it up and is now taking drastic measures to contain it. The Wuhan BSL-4 lab is also a specially designated World Health Organization (WHO) research lab and Dr. Boyle contends that the WHO knows full well what is occurring. Dr. Boyle also touches upon GreatGameIndia‘s exclusive report Coronavirus Bioweapon – where we reported in detail how Chinese Biowarfare agents working at the Canadian lab in Winnipeg were involved in the smuggling of Coronavirus to Wuhan’s lab from where it is believed to have been leaked. Watch Dr. Francis Boyle’s interview with Geopolitics and Empire below: Dr. Boyle’s position is in stark contrast to the mainstream media’s narrative of the virus being originated from the seafood market, which is increasingly being questioned by many experts. Recently, American Senator Tom Cotton of Arkansas also dismantled the mainstream media’s claim on Thursday that pinned the coronavirus outbreak on a market selling dead and live animals. In a video accompanying his post, Cotton explained that the Wuhan wet market (which Cotton incorrectly referred to as a seafood market) has been shown by experts to not be the source of the deadly contagion. Cotton referenced a Lancet study which showed that many of the first cases of the novel coronavirus, including patient zero, had no connection to the wet market — devastatingly undermining mainstream media’s claim. Such concerns have also been raised by J.R. Nyquist, the well known author of the books “Origins of the Fourth World War” and “The Fool and His Enemy,” as well as co-author of “The New Tactics of Global War”. In his insightful article he published secret speechs given to high-level Communist Party cadres by Chinese Defense Minister Gen. Chi Haotian explaining a long-range plan for ensuring a Chinese national renaissance – the catalyst for which would be China’s secret plan to weaponiz viruses. Nyquist gave three different data points for making his case in analyzing Coronavirus. He writes: Meanwhile, the mainstream media’s narrative still maintains that the origin of the 2019 Coronavirus is the Wuhan Seafood Market. After GreatGameIndia published the story on Coronavirus Bioweapon – not only were our databse tinkered with and our reports blocked by Facebook on the flimsy reason that they could not find GreatGameIndia Facebook page, but the report itself was viciously attacked by Foreign Policy magazine, PolitiFact (known widely as Facebook’s propaganda arm) and BuzzFeedNews. NEVER MISS THE NEWS THAT MATTERS MOST ZEROHEDGE DIRECTLY TO YOUR INBOX Receive a daily recap featuring a curated list of must-read stories. It is not GreatGameIndia alone which is being viciously attacked. Zero Hedge, a popular alternate media blog was suspended by Twitter for publishing a story related to a study by Indian scientists finding 2019 Wuhan Coronavirus to be not naturally evolved, raising the possibility of it being created in a lab. Shockingly, the study itself came under intense online criticism by Social Media experts resulting in the scientists withdrawing the paper. In retaliation India has launched a full-scale investigation against China’s Wuhan Institute of Virology. The Indian government has ordered an inquiry into a study conducted in the Northeastern state of Nagaland (close to China) by researchers from the U.S., China and India on bats and humans carrying antibodies to deadly viruses like Ebola. The study came under the scanner as two of the 12 researchers belonged to the Wuhan Institute of Virology’s Department of Emerging Infectious Diseases, and it was funded by the United States Department of Defense’s Defense Threat Reduction Agency (DTRA). The study, conducted by scientists of the Tata Institute of Fundamental Research, the National Centre for Biological Sciences (NCBS), the Wuhan Institute of Virology, the Uniformed Services University of the Health Sciences in the U.S. and the Duke-National University in Singapore, is now being investigated for how the scientists were allowed to access live samples of bats and bat hunters (humans) without due permissions. The results of the study were published in October last year in the PLOS Neglected Tropical Diseases journal, originally established by the Bill and Melinda Gates Foundation. As the author J.R. Nyquist puts it:
  6. Focus Coronavirus underpins gold; $1,600 break would trigger chart buying Allen Sykora Monday January 27, 2020 10:01 Kitco News Share this article: (Kitco News) - Gold futures have risen to their highest level in nearly three weeks, drawing a safe-haven bid amid worries about China's coronavirus spreading and hurting the global economy, as well as a weekend attack on the U.S. embassy in Iraq, traders and analysts said. Look for momentum-based chart buying to add further steam to the rally should these factors push gold above $1,600 an ounce again, one strategist said. As of 9:57 a.m. EST, Comex February gold was $6.90, or 0.43%, higher to $1,578.50 an ounce. The metal peaked at $1,588.40, its most muscular level since Jan. 8 when worries about a possible war between the U.S. and Iran prompted a safe-haven bid. "A big part is that is the coronavirus hitting stocks and possibly spreading," said Daniel Pavilonis, senior commodities broker with RJO Futures. "The market is trying to factor in what type of dent in global GDP [gross domestic product] from a slowing down in the world's second-largest economy and [the virus] spreading into other countries. It could be pretty big." All three of the major U.S. stock indices opened at least 1.8% lower on Monday. George Gero, managing director with RBC Wealth Management, commented he often describes gold prices as a barometer of geopolitics and the economy, rising when conditions are worsening, and vice-versa. "Now it is also a barometer of our well-being," he said, referring to the health scare boosting gold. While the virus is capturing the bulk of the headlines in the financial press early Monday, traders also listed to still other factors prompting a bid in gold. Phil Flynn, senior market analyst with Price Futures Group, cited the rocket attack on the U.S. embassy in Iraq. "There is a mixture of geopolitical risks, along with concerns about the fallout from the coronavirus and how that will affect capital flows going forward," Flynn said. Uncertainty about the U.S. impeachment process and Brexit may also be lending some support to the precious metal, Gero said. Flynn looks for gold to maintain a bid while the market continues to monitor the factors currently underpinning prices. "We should see the strength at least until midweek until we get more answers about the virus and the response [to the attacks] from the U.S.," Flynn said. Should gold top $1,600, however, momentum-based buying would likely be triggered, Pavilonis said. "At $1,600, it would become more technical," said Pavilonis. "Then I think you would see buyers come in on [an expectation] for more of a longer-term trend and buy, whether this virus fizzles out or not. We're getting close to the old highs." While gold is higher so far Monday, Commerzbank did characterize the virus as both a "blessing and a curse" for the yellow metal. Risk aversion has risen, the bank pointed out. Thus, gold is being bought as a "crisis currency" and safe haven, Commerzbank said. But the virus also may be curbing gold purchases in China, the world's largest gold-consuming nation, analysts continued. "While gold is in demand as a kind of insurance for financial investors – as can be seen primarily from the ongoing ETF [exchange-traded-fund] inflows – the coronavirus could depress physical gold demand in China," Commerzbank said. "Because public life there is grinding more and more to a standstill, some market observers expect less gold to be bought around the Chinese New Year's festival this year, which is normally a period of high demand."
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