PCR is the workhorse technology of molecular biology, it takes hours not days, the only complication here is that you need to convert the RNA to DNA first, hence the RT bit of RT-pcr
I appreciate your opinion greatly, Its very hard to know if our concerns are warranted or are just over-reacting or just paranoia. My good sense would say it should be serious investigated as you suggest as well. The question is will the medical profession. He does not reside near me, I will insist he sees a dr. and i will try to make sure he advocates his case and travel contact history… Will keep you posted.
Treeplanter,
I’ve been thinking about this… I’m inclined to go early…
I’m not going to talk to many people about this - you get some funny looks from people. If I consider it likely that I will get a dose (of this, or the next one), then I’d sooner see if I’m able to recover sooner than later.
I guess this depends a good deal on how things develop. Does recovering from ncov19 generally leave us with resilience? Who knows?
I was going to post here this morning, asking if there are other Aussies reading this blog. Look at local news? Crickets. Nothing much seems to be developing. Of course, it’s early days and the weather (generally) warm.
I live near Brighton and I know Brighton well. The information on the local news about the Brighton case is worrying:
https://www.theargus.co.uk/news/18221431.coronavirus-timeline-hove-mans-movements-diagnosis/
https://www.brightonandhovenews.org/2020/02/10/several-pupils-at-different-schools-in-brighton-and-hove-told-to-self-isolate/
The man has been in a pub in a Saturday evening, when it’s most crowded and he may have infected any number of people that have no more connection to him than being in the same place at the same time. Worse, this particular pub is a rather big one, which makes it a favorite for family gatherings. It’s quite possible that some of those infected weren’t local but came for some sort of family event.
Also, there is a chance that pupils at several different schools were infected. And there was a report about an asymptomatic child in China that infected a number of relatives. Maybe children are more likely to be asymptomatic for longer?
In sort, I estimate the likelihood of an uncontrolled outbreak in Brighton is high. It strikes me as unlikely that they detect all the people that this man infected.
Large numbers of people in Brighton actually work in London and go there by train. So an uncontrolled outbreak in Brighton would likely spread to the London underground pretty fast.
I wonder whether the UK authorities would try to lock down Brighton if the number of cases went high enough. It would make sense to do in an effort to protect London, if it was spreading faster in Brighton than in London. But the logistics of attempting to do that would be a nightmare.
My boss actually lives pretty close to where this man lived. The pub is about a hundred yards from my boss’ home. I have advised him not to be sociable with his neighbors until he knows which way the wind blows. But of course there is no telling what might happen. Does anybody have any further advice? (My workplace isn’t in Brighton but a nearby town).
I think we are all wise enough, or cynical enough to realize the popular media are given marching orders on what/how to report.
The cruise ship bio-domes will, I hope, be too stark to go unnoticed.
As I have said, if this were a hurricane, every commercial would be Lowe’s, Generac Generators, or Home Depot.
There is no money to be made if people stay home.
When was the last time you saw a prime-time beans & rice commercial?
How much cash back will Capital One give you for not going on that vacation because flying is too risky?
Think about it.
Anderson Cooper and other “journalists” have been busted for dramaticizing storms by finding deep holes to stand in so as to make flooding seem worse.
Do you think any of them are begging to board one of those ships?
When we start seeing these pathetic Ernie Pyle wannabes wearing masks, then we will know the jig is up.
Hackers capitalizing on the fear… ugh!
U.S. cybersecurity firm Sophos said last week that it had learned of a scam that used fake emails pretending to be safety instructions from the World Health Organization.https://globalnews.ca/news/6533339/coronavirus-emails-cybersecurity-malware/ Be careful what you open or click on folks! Jan
I know some people have questioned one reason for slow growth outside of china. However lets look at the cruise ship, are these all chinese or asian? and how about those 5 britons in french alps ski resort. two of them are physicians in UK… are they not susceptible??
Trump confirmed again his believe that with warmer weather the virus will retreat.A coworker from Wuhan told me the Chinese leadership decided long ago not to heat homes during the winter south of the Yellow River. This includes Wuhan. I asked him if the windows were closed to maintain some heat, and he said the humidity will spike and mildew will take over. Windows are kept open all winter. This time of the year the temperatures are about -10C. He thought hospitals would vary on heat - some would have it, some won't. Cities north of the Yellow river (Beijing) utilize coal generated steam and pump it through pipes. The air quality is horrible after every November 2nd. Side note - he has visited family in Wuhan frequently and ALWAYS comes back to the states sick. My take is that Wuhan and large cities in China are a biological and chemical cesspools. And when you throw in no heat during the middle of winter, I can't image a decent survival rate. I don't know if the virus will retreat with warmer weather, but a case can be made for reduced mortality during warmer weather.
The charts with high SO2 output really bother me. Is that really from people’s bodies burning? There’s not much else that can account for those high SO2 levels. If so, how sad to have your loved ones burn in what must be a giant inferno.
If someone had the time, I’d think they could go through SO2 readings from the past year and see what levels correlate to massive burning of pigs from the pig virus in various areas of China. Perhaps the increased SO2 levels from a known number of pigs burned could be correlated to the mass of human bodies needed to reach certain SO2 levels. It wouldn’t give an absolute number, but it could give an order of magnitude estimate to know how far off are China’s reported deaths.
Ibuprofen is an NSAID, nonsteroidal anti-inflammatory drugs (NSAIDs) are members of a drug class that reduces pain, decreases fever, prevents blood clots, and in higher doses, decreases inflammation.
Don’t use ibuprofen if you aren’t in pain, too many will eat away your stomach lining. I’m not a doctor, and this isn’t medical advice, but if you have something that reduces inflammation, it’s better than not having it.
If you assume you are going to get the corona virus, then focus on things to keep you hydrated, things that are nutritional. Go an get 5 days of soup, something you can make easily if you are sick, something that will hydrate and provide nutrition.
Get another say 21 days of food for when you are quarantined.
I just watched Chris’ new video, "
Coronavirus: Up To 24 Days Before Symptoms Start Showing?
(Up on youtube, but not here yet - probably to reduce bandwidth problems). He discusses potential antibiotic supply chain interruptions since most of our antibiotics are manufactured in China or with Chinese manufactured precursors. Since secondary bacterial pneumonia is a fairly likely outcome of viral pneumonia, this could be a big problem.
So, may I suggest: Herbal Antibiotics by Stephen Harrod Buhner?
With the infection count already up to 130 there are suggestions that the entire ship be tested, something that in my opinion should have been started last week. As peakTheTruth said it’s not complicated and takes hours not days. In the olden days I used to run PCR in 2-3 hours using gel electrophoreis to detect products. Now the whole cocktail can be put in 96 or 384 well microtitre plates, produce a fluorescent signal if positive, be read by a plate reader and uploaded into a computer. It’s all automated. One protocol runs the reaction inside 30 minutes, the reading takes seconds. I don’t however understand the Chinese reports of negative tests on affected persons.
The contribution that the Diamond Princess cases will make to our knowledge should be the fraction of mild, moderate and severe cases and their resolution in a sophisticated medical setting. This ought to be our best source of information on the disease prognosis. It might be a little skewed since the cruise passenger demographic tends toward a more mature group.
I recently read that the half-life of bleach is about 1 year (if I remember correctly). So if my bleach is 1 year old (from purchase date? from manufacturing date?), I double the amount of bleach that I’m about to dilute. If 2 years old, I use quadruple the amount of bleach.
P.S. I’ve been marking the purchase date on bottles of bleach when I buy them, and since I get them at Costco (a big-box store), the turnover in inventory makes it likely that they’re about as fresh as one can get them.
Terry L
There is a fair amount of speculation about the apparent slow spread of the virus outside of China. I would like to point out that this is most likely an apparent change not a real phenomenon.
If we start with the great Wuhan diaspora of 5 million people before the quarantine on January 23 consider the following.
- Assuming that some people were infected and perhaps spent the next day flying internationally, what would you expect? The R0 is ~4. You don’t necessarily expect transmissions to happen all at once but for the sake of argument say it did on that flight.
- Now 4 new people are infected and head back to the rest of the world. If it take on average 5 days to even start getting sick you have some people getting what appears to be a mild flu around Jan 28.
- If they the infect 4 more people (for arguments sake on this day but a few might be earlier and a few later) there are now 4 new infections at whatever location they landed (e.g. New York).
- Five days later (Feb 2) those people start feeling ill and have spread the virus to 16 more people.
- By Feb 7, the New York (or any other location) outbreak has reached 64 new people but only 21 (16+4+1) appear ill with a flu like illness. Serious complications arise after the second week in 20% of the affected people so maybe a couple have gotten pneumonia-like symptoms and are in the hospital.
- Does anyone think that the medical staff is going to flag 1 or 2 new cases of pneumonia in NY as potential corona virus? Likely there is just one patient in any given hospital. They are not testing every patient in the country (any country) for corona virus even if they have pneumonia.
- Fast forward a couple day to Feb 12. 256 more people have been infected. Still just a handful with serious complications spread throughout NY. No one will notice anything unusual.
- It may be a few weeks yet before anyone notices that there is an unusual outbreak that can’t be explained by normal flu infections.
By the time there are enough cases to be flagged as unusual, chances are that there will be many hundreds of infected people circulating in the population. In short, by the time we realize we have a problem it will be far too late to actually do much about it. We don’t have the capacity to test everyone and so we will always be playing catch up. With an R0 of 4 or more that’s a fools game. Welcome to the pandemic…
This looks promising. I wonder how difficult/expensive this would be to ramp up dramatically if it proved effective in a clinical trial on humans.
2019-nCoV, which is a novel coronavirus emerged in Wuhan, China, at the end of 2019, has caused at least infected 11,844 as of Feb 1, 2020. However, there is no specific antiviral treatment or vaccine currently. Very recently report had suggested that novel CoV would use the same cell entry receptor, ACE2, as the SARS-CoV. In this report, we generated a novel recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. An ACE2 mutant with low catalytic activity was also used in the study. The fusion proteins were then characterized. Both fusion proteins has high affinity binding to the receptor-binding domain (RBD) of SARS-CoV and 2019-nCoV and exerted desired pharmacological properties. Moreover, fusion proteins potently neutralized SARS-CoV and 2019-nCoV in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they could have potential applications for diagnosis, prophylaxis, and treatment of 2019-nCoV. https://www.biorxiv.org/content/biorxiv/early/2020/02/02/2020.02.01.929976.full.pdfYikes David, I would hope people in this group would not consider it a meme, nor wish ill on anyone based on race, etc. I’m not sure I would want to be a part of such a group.
It’s good to remember, not everyone has been living and breathing this every day.
David, the raw stats point to Male greatly over Female in infections. Also, the fact that it seems that the growth outside of China is a factor. Honestly, I just don’t think we understand that 1 person, even with a 3 R0 is only going to infect so many… It takes time for that number to hockey stick. Also, there has been talk of it being much greater risk for smokers, and Chinese men out smoke women by a GREAT number. I assume we know less than we even think we know… and that’s not a lot.
Best all, be safe and be a sane and kind voice in the trying times we are in, and are coming
-Eric and Cindy
Just watched Chris’ latest video where he summarizes the best guesses on the numbers.
https://www.youtube.com/watch?v=DNArvGCBgJ4
He uses Neil Ferguson’s group’s numbers (here)
Asymptomatic and mild respiratory infection 80% Serious infection (viral pneumonia needing hospitalization) 15% Critical (ICU level care) 5% Death 1% (Range of 0.5% - 4%)*So you have a city like San Jose, California with a population of 1 million. What kind of medical care will be needed?
Hospital beds with IVs and Oxygen -- 150,000 ICU beds with ventilators/ECMO -- 50,000 Deaths** -- 10,000A very rough recollection of the numbers of hospital beds available in San Jose (where I used to work) is ~ 2,000 beds total with maybe 100 - 150 ICU beds. Normal hospital occupancy is ~90%+ and goes to 100%+ during the normal winter flu season. Almost all of the ICU beds are full all of the time. San Jose will have a big problem caring for these projected 50,000 ICU patients. -------------------- *CRF estimated at 18% in Wuhan! **with a range of deaths up to 100,000 in the setting of an overwhelmed medical system.
2019-Novel Coronavirus (2019-nCoV): estimating the case fatality rate – a word of caution
DOI: https://doi.org/10.4414/smw.2020.20203 Publication Date: 07.02.2020 Swiss Med Wkly. 2020;150:w20203
Battegay Manuela, Kuehl Richarda, Tschudin-Sutter Saraha, Hirsch Hans H.abc, Widmer Andreas F.a, Neher Richard A.d
Estimating and predicting the extent and lethality of the 2019-Novel Coronavirus (2019-nCoV) outbreak, originating in Wuhan/China is obviously challenging, reflected by many controversial statements and reports. Unsurpassed to date, an ever-increasing flow of information, immediately available and accessible online, has allowed the description of this emerging epidemic in real-time [1]. The first patients were reported in Wuhan on December 31st 2019 [2]. Only a few days later, Chinese researchers identified the etiologic agent now known as the 2019-nCoV and published the viral sequence [3]. New data on the virus, its characteristics and epidemiology become available 24/7 and are often shared via informal platforms and media [4]. Yet, key questions remain largely unanswered.
How is the virus transmitted, how long is the incubation period, what is the role of asymptomatic infected, what is the definite reproductive number R0, how long is viral shedding persisting after fading of symptoms, who is at risk for a severe course, and ultimately, how high is the case fatality rate?
Accurate answers are critical for predicting the outbreak dynamics, to tailor appropriate and effective prevention measures, and to prepare for a potential pandemic. Precise estimates of the case fatality rate and the fraction of infections that require hospitalization are critical to balance the socioeconomic burden of infection control interventions against their potential benefit for mankind. Hence, one of the most important figures to determine is the rate of asymptomatic and mild cases allowing to put severe courses and death rates into accurate context.
At present, it is tempting to estimate the case fatality rate by dividing the number of known deaths by the number of confirmed cases. The resulting number, however, does not represent the true case fatality rate and might be off by orders of magnitude. Diagnosis of viral infection will precede recovery or death by days to weeks and the number of deaths should therefore be compared to the past case counts – accounting for this delay increasing the estimate of the case fatality rate. On the other hand, cases in official statistics are likely a severe underestimate of the total – accounting for this underestimate will decrease the case fatality rate. The time between diagnosis and death/recovery and the degree of underreporting will vary over time as well as between cities and countries. A precise estimate of the case fatality rate is therefore impossible at present. Figure 1 illustrates how these uncertainties manifest themselves using currently available data.
fullscreenFigure 1Uncertainties of naive case count estimates. This graph shows how the ratio of the number of confirmed deaths and case counts changed over time. Case counts are corrected for 3-fold or 30-fold under-reporting (solid and dashed lines, respectively) and are taken 2, 4, and 7 days prior to the date of the count of confirmed death. The latter is meant to illustrate the effect of the delay between diagnosis and death or recovery. This actual delay is likely longer than one week. Data source: https://github.com/globalcitizen/2019-wuhan-coronavirus-data.
Better estimates could be derived from large-scale investigations, in particular, in the region of the epidemic’s origin. Still, population-based testing of respiratory secretions by nucleic acid amplification testing (NAT) for 2019-nCoV would most likely underestimate the scale of the outbreak, as asymptomatic patients or patients after recovery from infection may no longer be NAT-positive. A sensitive 2019-nCoV-specific serological assay is needed to firmly assess the rate of past exposure and may help to assess herd immunity.
One intriguing aspect of the outbreak so far is the discrepancy between the estimates of the case fatality rate reported from Hubei province, from different regions of China and from other countries. As of February 7, 2020, 30’536 have been confirmed. Thereof, 22’112 occurred in the Hubei province of China with a death toll of 619 (= 2.8%). This contrasts with 16 deaths among 8’702 recorded cases in other regions of China and further countries, suggesting at first glance a case fatality rate of 0.18%. The uncertainties and spatio-temporal variation discussed above could explain this divergence:
The higher case fatality rate reported from Wuhan may be overestimated
- The true number of exposed cases affected in Wuhan may be vastly underestimated. With a focus on thousands of serious cases, mild or asymptomatic courses that possibly account for the bulk of the 2019-nCoV infections might remain largely unrecognized, in particular during the influenza season.
- Under-detection of mild or asymptomatic cases may be further fueled after further growth of the outbreak, as healthcare-facilities and testing capacities in Wuhan have reached their limits.
Accordingly, the official numbers of both cases and deaths reported from Wuhan represent the “tip of the iceberg”, potentially skewing case fatality estimates towards patients presenting with more severe disease and fatal outcome. As the current measures in Wuhan aim at slowing the spread, other regions of China and countries gained critical time for preparations permitting to better track cases from the first occurrence of the virus in their populations. Thus, estimates deriving from these settings may be more accurate. That case fatality rates appear to decrease overall renders this hypothesis plausible.
The lower case fatality rates outside Wuhan may be underestimated
- As the epidemic arrived later in other regions and countries, there may be a delay of fatal cases arising and their reporting. The low number of documented recovered cases might indicate that days and weeks can pass until death occurs. Hence, the numbers, e.g. in Guangdong with 970 cases and no death occurring, might be false low because severe cases might still have a deadly outcome.
- Testing patients with severe respiratory diseases in outside of China might have been delayed so that unclear deaths are not yet being attributed to the coronavirus. This is unlikely at this point as international awareness has increased, but may have resulted in an underestimation of attributable deaths previously.
Case fatality rates may truly differ among different regions of the world
- Supportive care is crucial for severe respiratory disease. Differences in case fatality rates may be caused by differences in medical care during a large epidemic versus care for single cases. Hence, the large-scale capacities for medical care in the Hubei province, and specifically large-scale intensive care and extracorporeal membrane oxygenation (ECMO) may lag behind the epidemic. This hypothesis is supported by the construction of two hospitals in record time.
- There are different susceptibilities to the 2019-Novel Coronavirus in different regions of China as well as different regions of the world. However, as this is the second coronavirus emerging from China, it is unlikely that herd-immunity is lower in this region of the world, than in others. Immunogenetics and socioeconomic factors however, may potentially contribute to differences in susceptibilities to the disease.
Current authorities such as the World Health Organization, the Centers for Disease Control & Prevention (USA), the European Centers for Disease Control as well as renowned journals are challenged by the rapid generation and dissemination of data, largely published on social media platforms. Thus, new approaches will have to be defined to validate the accuracy of such posts in times where multiple tweets per second are published, sometimes with misleading, sometimes with important information. Modelling the 2019-nCoV epidemic remains challenging as relevant questions are still unanswered. So, despite the dramatic increase of rapidly available data, public health authorities remain torn back and forth between the options of overreacting and frightening the population or underreacting putting citizen at risk in their aim to provide advice to countries and individuals on measures to protect health and prevent the spread of this outbreak.
https://smw.ch/article/doi/smw.2020.20203All three coronaviruses induce excessive and aberrant non-effective host immune responses that are associated with severe lung pathology, leading to death.
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Similar to patients with SARS-CoV and MERS-CoV, some patients with 2019-nCoV develop acute respiratory distress syndrome (ARDS) with characteristic pulmonary ground glass changes on imaging. In most moribund patients, 2019-nCoV infection is also associated with a cytokine storm, which is characterised by increased plasma concentrations of interleukins 2, 7, and 10, granulocyte-colony stimulating factor, interferon-γ-inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1 alpha, and tumour necrosis factor α.
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In those who survive intensive care, these aberrant and excessive immune responses lead to long-term lung damage and fibrosis, causing functional disability and reduced quality of life.
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Specific drugs to treat 2019-nCoV will take several years to develop and evaluate. In the meantime, a range of existing host-directed therapies that have proven to be safe
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could potentially be repurposed to treat 2019-nCoV infection. Several marketed drugs with excellent safety profiles such as metformin, glitazones, fibrates, sartans, and atorvastin, as well as nutrient supplements and biologics could reduce immunopathology, boost immune responses, and prevent or curb ARDS.
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Zinc and other metal-containing formulations appear to have anti-viral activity,
are safe, cheap, and readily available. These formulations could be used as adjuncts to monotherapy or as combinational therapies with cyclosporine, lopinavir–ritonavir, interferon beta‑1b, ribavirin, remdesivir, monoclonal antibodies, and anti-viral peptides targeting 2019-nCoV.
Tocilizumab, a monoclonal antibody that targets the interleukin 6 receptor, has a good safety profile. Monoclonal and polyclonal antibodies to 2019-nCoV could be developed for post-exposure prophylaxis.
Ongoing trials of cellular therapies for treatment of ARDS could be expanded to treatment of seriously ill patients with 2019-nCoV infection. Cellular therapy,
using mesenchymal stromal cells from allogeneic donors, has been shown to reduce non-productive inflammation and affect tissue regeneration and is being evaluated in phase 1/2 trials in patients with ARDS (NCT02804945; NCT03608592). Infection with 2019-nCoV appears to be initially associated with an increased Th2 response,
which might reflect a physiological reaction to curb overt inflammatory responses, a clinical phenomenon that guided the optimal timing of interferon treatment in patients with sepsis, resulting in increased survival.
Interleukin 17 blockade might benefit those patients who have a 2019-nCoV infection and increased plasma concentration of interleukin 17.
The isolation and short-term expansion of anti-viral directed T cells has been proven to be a life-saving procedure in patients after autologous hematopoietic stem-cell transplantation with cytomegalovirus infection.
Expansion of anti-2019-nCoV-specific T cells, as cellular drugs, could aid to prepare T-cell products for the adjunct treatment of patients with severe 2019-nCoV infection.
Several unique opportunities to evaluate a range of treatment interventions at the peak of the SARS-CoV and MERS-CoV outbreaks were missed due to avoidable delays and subsequent decline of the numbers of cases, leaving numerous questions about coronavirus pathogenesis unanswered. Disappointingly, treatment trials registered for MERS-CoV are still not complete. As the 2019-nCoV continues to spread and evolve, and the numbers of deaths rise exponentially, advancing new therapeutic development becomes crucial to minimise the number of deaths from 2019-nCoV infection.
We declare no competing interests. AZ is co-principal investigator of the Pan-African Network on Emerging and Re-emerging Infections (PANDORA-ID-NET), funded by the European & Developing Countries Clinical Trials Partnership, supported under Horizon 2020, the EU's Framework Programme for Research and Innovation, and a National Institutes of Health Research senior investigator. MM is a member of the innate immunity advisory group of the Bill & Melinda Gates Foundation, and his work is funded by the Champalimaud Foundation.