Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
Manli Wang,
Ruiyuan Cao, et.al
“Our findings reveal that remdesivir and chloroquine are highly effective in the control of 2019-nCoV infection in vitro. Since these compounds have been used in human patients with a safety track record and shown to be effective against various ailments, we suggest that they should be assessed in human patients suffering from the novel coronavirus disease.”
“Human coronaviruses can remain infectious on inanimate surfaces for up to 9 days. Surface disinfection with 0.1% sodium hypochlorite or 62–71% ethanol significantly reduces coronavirus infectivity on surfaces within 1 min exposure time. We expect a similar effect against the SARS-CoV-2.”
https://www.journalofhospitalinfection.com/article/S0195-6701(20)30046-3/fulltext
Impact of non-pharmaceutical interventions (NPIs) to reduce COVID19 mortality and healthcare demand
Imperial College
UK and US projection models, plots below.
Ferguson, N
Laydon, D
Nedjati Gilani, G.
et.al.
"The global impact of COVID-19 has been profound, and the public health threat it represents is the most serious seen in a respiratory virus since the 1918 H1N1 influenza pandemic.
Here we present the results of epidemiological modelling which has informed policymaking in the UK and other countries in recent weeks. In the absence of a COVID-19 vaccine, we assess the potential role of a number of public health measures – so-called non-pharmaceutical interventions (NPIs) – aimed at reducing contact rates in the population and thereby reducing transmission of the virus.
In the results presented here, we apply a previously published microsimulation model to two countries: the UK (Great Britain specifically) and the US.
We conclude that the effectiveness of any one intervention in isolation is likely to be limited, requiring multiple interventions to be combined to have a substantial impact on transmission.
Two fundamental strategies are possible: (a) mitigation, which focuses on slowing but not necessarily stopping epidemic spread – reducing peak healthcare demand while protecting those most at risk of severe disease from infection, and (b) suppression, which aims to reverse epidemic growth, reducing case numbers to low levels and maintaining that situation indefinitely. Each policy has major challenges.
We find that that optimal mitigation policies (combining home isolation of suspect cases, home quarantine of those living in the same household as suspect cases, and social distancing of the elderly and others at most risk of severe disease) might reduce peak healthcare demand by 2/3 and deaths by half.
However, the resulting mitigated epidemic would still likely result in hundreds of thousands of deaths and health systems (most notably intensive care units) being overwhelmed many times over. For countries able to achieve it, this leaves suppression as the preferred policy option.
We show that in the UK and US context, suppression will minimally require a combination of social distancing of the entire population, home isolation of cases and household quarantine of their family members. This may need to be supplemented by school and university closures, though it should be recognised that such closures may have negative impacts on health systems due to increased absenteeism.
The major challenge of suppression is that this type of intensive intervention package – or something equivalently effective at reducing transmission – will need to be maintained until a vaccine becomes available (potentially 18 months or more) – given that we predict that transmission will quickly rebound if interventions are relaxed.
We show that intermittent social distancing – triggered by trends in disease surveillance – may allow interventions to be relaxed temporarily in relative short time windows, but measures will need to be reintroduced if or when case numbers rebound.
Last, while experience in China and now South Korea show that suppression is possible in the short term, it remains to be seen whether it is possible long-term, and whether the social and economic costs of the interventions adopted thus far can be reduced."
Issue Date: 16-Mar-2020
https://spiral.imperial.ac.uk:8443/bitstream/10044/1/77482/5/Imperial%20College%20COVID19%20NPI%20modelling%2016-03-2020.pdf
Happy Saint Patrick’s Day and Snake Oil.
They’re already coming out of the weeds. The snakes! And they’ve got a sure fire solution for whatever ails you. Already they are out there, using the Covid 19 virus pandemic and making specious claims!
But Wait! There’s More! If you buy my book, subscribe to my program, use my supplements, “It’ll Cure Your Diseases!!!” Just Look at the Testimonials. Proof? Just read my website. It’s Organic and Natural.
Where’s the random trial publication by independent reference test groups and response and adverse effects data?
DATA? We don’t need no stinkin’ data, we got slick web pages and tweets and infomercials and testimonials…(and if you hurry we’ll double the number of bottles, you just pay the $19.95 shipping and handling and sign up for our automatic replenishment program, no warranties expressed or implied, your results may vary).
"Over the centuries, the mythology surrounding the life of Saint Patrick has become ever more ingrained in the Irish culture. Patrick, the patron saint of Ireland, is credited with expelling all the snakes from Ireland, and today, not a single snake can be found there. But the true meaning of the casting away of all snakes runs much deeper.
Since snakes often represent evil in literature, “when Patrick drives the snakes out of Ireland, it is symbolically saying he drove the old, evil, pagan ways out of Ireland [and] brought in a new age,” said classics professor Philip Freeman of Luther College in Iowa."
These days we really need a St. Patrick to run off all the Snakes, and the Snake Oil they are peddling on unsuspecting and uniformed desperate Ill persons.
How many times have I heard it from well meaning neighbors, friends, and relatives, or from someone on the internet trying to make a quick buck by preying on a frustrated suffering patient.
Have you tried some Yoga, or Coffee Enemas, or Oils to stop those reactions?? My sister’s mother in laws cousin had…Detox you need to detox, obviously you kidneys and liver, evolved over million years of generations, isn’t as specialized as my $199.95 random chemical supplement diet that was never independently trialed, from some YouTube doctor who usually goes by one name.
Personally, If I can’t find three different groups, with independent double blind random trials, and a truck load of refereed papers, published in Reputable principal Scientific and Medical Journals (not the Eastern Slobovia Medical Journal and Goat Husbandry Quarterly), that crap isn’t touching the outside of my body, much less going on the inside.
“Science, bitches!!”, is made from failing repeatedly and reporting it until you think you got it right, and then putting it out there in publication, where you try to get other research groups to try their very best to show everyone in the research community what an complete idiot you are.
When at least three diverse groups can get your results in different ways, Then, and only Then, you get to try it on goats, or pigs, or your sweaty brother in law that you never really liked. After further review, and double blind test groups with humans, to see if they sprout feathers or hooves, real doctors and scientists go over the data from multiple rounds of testing, to determine risk and benefit. For “normal” sick people it’s safe and effective. For orphan “rare disease” meds it’s risks and benefits.
When these snakes, can find a hard to definitively diagnose malady, with suffering people, frustrated and desperate for help, and limited detailed medical knowledge, they have an easy target.
When the test tools available for that condition are limited in repeatability, not firmly and incontrovertibly definitive, for some evil spawn “medical” types, they have an easy mark, a money making machine on the back of their “patients”.
They frequently have no metric. If they can’t do quantitative tests before and after “treatment” and show a specific change in analytical quantities or qualities, look out for the worst of all, the not so rare duck-snake. It slithers on it’s belly amongst the slime and filth and quacks. Physician swear an oath “To do no harm”. Most of these folks want to be called doctor, and
They can tag you with any of these “conditions” where opinion is the final arbiter. If blood test, biopsy, genetic sequencing, RT-PCR can not give a definitive answer with confidence intervals, they got you.
When you feel their hand sympathetically patting you on the back, most of them are actually just hunting for your wallet.
No cure or amelioration comes without failure and pain, and head banging, in the research, development, test, trials, and approval process.
If something is natural and historical and ancient that’s amazing; so is the fact that in 1900, before modern antibiotics, male life expectancy was about 45 years, and a natural cure in Egypt was chiseling a hole in your skull, in England they would blow tobacco smoke up your arse, and in America native Americans rubbed raw petroleum on their wounds.
There is no magic, no silver bullets. If something is too good to be true is usually is. If reviewed analytical test data isn’t out there from multiple sources, no go. If it is incredibly good and successful therapy the there is usually big money in research funding and there is data and a refereed journal or conference paper trail. Scientists, not shamans or shysters.
Anything that can solve the impossibly hard, diverse, immune system biochemical and genetic problems; of the incredibly unique and complex machine that is You!; doesn’t come cheap, doesn’t come simple, doesn’t come fast, and never can address all the interrelated issues.
Beware. This isn’t the year 400AD, St. Patrick isn’t here running off the snakes, and they’re everywhere in the weeds, smuggling many different flavors of snake oil, to a web page, blog, infomercial, or cousin/neighbor/friend of a friend near you.
…
A parable
My vascular edema was acting up as I was next door trying to help out changing the oil and filter of a young ladies car. I was rubbing my painful, mast cell activated immune system, swollen hands and could feel the inside of my mouth and lips starting to swell from a familiar not unpleasant aroma. [1]
“Oils, you need some of my oils,” she says as I wash down a couple of Benadryl with the last swallow of Dr. Pepper.
As I wiped the axle grease from my hand, I looked her up and down and said, “Young lady, if it can’t be cured with a heavy application of Benadryl, WD40, Royal Purple, Rotella 15W40, or Marvel Mystery Oil, and a good coat of Ben-Gay or Icy-Hot, then that frou-frou stuff there isn’t ‘gonna’ touch this. And half of that stuff make my face and throat swell up like a pregnant puffer fish.”
“This is natural,” she says, “And it’s only $25 per ounce. It’s very concentrated, it takes over 3 pounds of flowers to make just one ounce."[2]
My neighbor, another retired scientist, a chemist, looks over at me with a grin, and I knew what was coming.
He said, “You know, we’re using similar very rare and special oils to fix your car.”
“Really!?” she asks, feigning interest.
"Yep,"he says, "A purely organic concentrated, highly catalyst refined and purified to rigid international specifications, made from purified blends of ancient marine organisms, extremely rare prehistoric plants, exotic flowers, algae, and seaweed. Over 98 tons of plants are processed and distilled go into each gallon, why that’s 153 pounds of plants per oz., much much more concentrated than yours. " [3]
He writes figures in the dust on the hood, “Let’s see then, Uhhh…tons per gallons, to pounds to gallon, and then pounds per ounce. 128 ounces per gallon times $25 per ounce.” He scratches his head, “Oh yeah, carry the 2.”
“Well young lady, you’re all set. Internationally controlled, standardized, rigorously specified, and tested oils made from the finest and rarest of plants and flowers has fixed what was wrong your car.”[4]
“Now, I’m only going to charge you the same, that’ll be $3200 for the gallon and I’ll throw in the precision 20 micrometer particle contaminant purification filter for free. This is just for limited time, these materials are difficult to extract and refine, and many of the plants and flowers used are now extinct.” [5]
“That’s ridiculous,” she says, “How can you charge that much a gallon just to fix my car?!!”
He looks at me and then down at his feet, running his boot toe back and forth in the grime on the floor. “Well” he says, not looking up, “Y’all got us there, for you, we’ll cut the price to $1000…that’s let’s see only $7.81 per ounce, but I’m telling your car will never make it home without it. It’s essential to safe operation and your car will have seizures without it.”[6]
“That’s still ludicrous,” she says, “But why such a big price drop??”
“Well,” he says with a slight grin and twinkle in his eye, “I heard tell this last batch was rejected by NASCAR, Kyle Busch’s guys opened a jug and sniffed it and they said this batch still had to much Dinosaur poop to their liking.”
Isao Ohsawa, et.al.;Clinical Features of Hereditary and Mast Cell-mediated Angioedema Focusing on the Differential Diagnosis in Japanese Patients; Intern Med. 2018 Feb 1; 57(3): 319–324. Published online 2017 Nov 1. doi: 10.2169/internalmedicine.8624-16. PMCID: PMC5827308
University Of Utah. “Bad Mileage: 98 Tons Of Plants Per Gallon – Study Shows Vast Amounts Of ‘Buried Sunshine’ Needed To Fuel Society.” ScienceDaily. ScienceDaily, 27 October 2003. <Bad Mileage: 98 Tons Of Plants Per Gallon -- Study Shows Vast Amounts Of 'Buried Sunshine' Needed To Fuel Society -- ScienceDaily>.
4.ISO 19291:2016(en) Lubricants — Determination of tribological quantities for oils and greases — Tribological test in the translatory oscillation apparatus. https://www.iso.org/obp/ui/#iso:std:iso:19291:ed-1:v1:en
K. Than; The Mysterious Origin and Supply of Oil; 2006 Redirect Notice
Loganathan, S., Esakkimuthu, P., Srivatsan, M., and Anand, M., “Performance Optimization of Single Cylinder Diesel Engine Oil Pump through PRV and Rotor System,” SAE Technical Paper 2015-26-0028, 2015, SAE MOBILUS.
New group, different result from the German group
"Transmission of SARS-CoV-2, which causes COVID-19, has quickly outstripped the pace of the 2003 SARS epidemic. “Superspread” of the earlier disease arose from infection during medical procedures, in which a single infected individual seeded many secondary cases. In contrast, the novel coronavirus appears to be spread more through human-to-human transmission in a variety of settings.
However, it’s not yet known the extent to which asymptomatic or presymptomatic individuals spread the new virus through daily routine.
To investigate how long SARS-CoV-2 remains infective in the environment, Neeltje van Doremalen, PhD, of the Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, in Hamilton, Montana, and colleagues conducted simulation experiments in which they compared the viability of SARS-CoV-2 with that of SARS-CoV-1 in aerosols and on surfaces.
Among patients infected with SARS-CoV-2, viral loads in the upper respiratory tract are high; as a consequence, respiratory secretion in the form of aerosols (<5 μm) or droplets (>5 mcm) is likely, the authors note.
van Doremalen and colleagues used nebulizers to generate aerosols. Samples of SARS-CoV-1 and SARS-CoV-2 were collecting at 0, 30, 60, 120, and 180 minutes on a gelatin filter. The researchers then tested the infectivity of the viruses on Vero cells grown in culture.
They found that SARS-CoV-2 was largely stable through the full 180-minute test, with only a slight decline at 3 hours. This time course is similar to that of SARS-CoV-1; both viruses have a median half-life in aerosols of 2.7 hours (range, 1.65 hr for SARS-CoV-1, vs 7.24 hr for SARS-CoV-2).
The researchers then tested the viruses on a variety of surfaces for up to 7 days, using humidity values and temperatures designed to mimic “a variety of household and hospital situations.” The volumes of viral exposures that the team used were consistent with amounts found in the human upper and lower respiratory tracts.
For example, they applied 50 mcL of virus-containing solution to a piece of cardboard and then swabbed the surface, at different times, with an additional 1 mcL of medium. Each surface assay was replicated three times.
The novel coronavirus was most stable on plastic and stainless steel, with some virus remaining viable up to 72 hours. However, by that time the viral load had fallen by about three orders of magnitude, indicating exponential decay. This profile was remarkably similar to that of SARS-CoV-1, according to the authors.
However, the two viruses differed in staying power on copper and cardboard. No viable SARS-CoV-2 was detectable on copper after 4 hours or on cardboard after 24 hours. In contrast, SARS-CoV-1 was not viable beyond 8 hours for either copper or cardboard.
“Taken together, our results indicate that aerosol and fomite transmission of HCoV-19 [SARS-CoV-2] are plausible, as the virus can remain viable in aerosols for multiple hours and on surfaces up to days,” the authors conclude.
Andrew Pekosz, PhD, codirector of the Center of Excellence in Influenza Research and Surveillance and director of the Center for Emerging Viruses and Infectious Diseases at the Johns Hopkins Center for Global Health, Baltimore, Maryland, applauds the real-world value of the experiments.
“The PCR [polymerase chain reaction] test used [in other studies] to detect SARS-CoV-2 just detects the virus genome. It doesn’t tell you if the virus was still infectious, or ‘viable.’ That’s why this study is interesting,” Pekosz said. “It focuses on infectious virus, which is the virus that has the potential to transmit and infect another person. What we don’t know yet is how much infectious (viable) virus is needed to initiate infection in another person.”
He suggests that further investigations evaluate other types of environmental surfaces, including lacquered wood that is made into desks and ceramic tiles found in bathrooms and kitchens.
One limitation of the study is that the data for experiments on cardboard were more variable than the data for other surfaces tested.
The investigators and Pekosz have disclosed no relevant financial relationships’
WASH YOUR HANDS!
GI symptoms
Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study
Lei Pan, MD, PhD, Mi Mu, MD, Hong Gang Ren MD, et.al.
FLASH:bangbang:
Nearly half of COVID-19 patients enrolled in the study conducted in the Hubei province of China presented digestive symptoms, such as diarrhea and anorexia, and cited it as their chief complaint. The study also reveals that patients with digestive symptoms had a longer gap between the onset of symptoms and hospital admission than patients presenting only respiratory symptoms and were less likely to be cured and discharged than those without digestive symptoms.
The authors recommend that “the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms rather than waiting for respiratory symptoms to emerge.”
If you do get infected, take appropriate measures to prevent spread of fecally shed virus. Sterilize soiled bedding and clothing as appropriate.
“The way that it worked against SARS was by preventing the attachment of the virus to the cells. Chloroquine interfered with the attachment to that receptor on the cell membrane surface," Len Horovitz, MD, a pulmonologist at Lenox Hill Hospital in New York City, told ABC News. “So it’s disrupting a lock and key kind of mechanism of attachment.”
Doctors in China who administered chloroquine to patients with COVID-19 noted that those patients were more likely to have shorter hospital stays and improved outcomes.
French investigators found that patients with COVID-19 who were treated with a combination of hydroxychloroquine and azithromycin were virologically cured after 6 days. "
Steroids, mainline for respiratory infections.not of much benefit in small sample study of recent outcomes
NEW.
"Previous studies indicate cytokine storm and inflammation induced by uncontrolled immunologic response to a virus is crucial in causing fatal pneumonia following infection with human coronavirus.10 11 Inhibition of the inflammation improved outcome in animal models infected with SARS and MERS.12 13 Corticosteroids are commonly used in severe acute respiratory infections of viral etiology due to its antiinflammatory effect.14 However, studies of the efficacy of corticosteroids during the SARS and MERS outbreaks showed no improvement in clinical outcomes, but delays in viral clearance and increases in the rates of secondary infections.8 15 16 A majority of the patients enrolled in these studies were critically ill with ARDS and such patients may have passed the point where adverse outcomes were modifiable with steroids. The World Health Organization (WHO) has recommended against the routine administration of systematic corticosteroids in patients with COVID-19.17 Despite this, a consensus statement by the Chinese Thoracic Society recommends the use of corticosteroids, albeit prudently,18 ideally undertaken in the context of a randomized controlled trial. To accomplish this during an ongoing epidemic is challenging. To facilitate study design, we report the impact of corticosteroid in patients with COVID19 from accumulated observational clinical data. "
Flash 18 March 2020
Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro
Jia Liu,
Ruiyuan Cao,
[…]
Manli Wang
Cell Discovery volume 6, Article number: 16 (2020)
"Clinical investigation found that high concentration of cytokines were detected in the plasma of critically ill patients infected with SARS-CoV-2, suggesting that cytokine storm was associated with disease severity12.
Other than its direct antiviral activity, HCQ is a safe and successful anti-inflammatory agent that has been used extensively in autoimmune diseases and can significantly decrease the production of cytokines and, in particular, pro-inflammatory factors.
Therefore, in COVID-19 patients, HCQ may also contribute to attenuating the inflammatory response. In conclusion, our results show that HCQ can efficiently inhibit SARS-CoV-2 infection in vitro. In combination with its anti-inflammatory function, we predict that the drug has a good potential to combat the disease. This possibility awaits confirmation by clinical trials.
We need to point out, although HCQ is less toxic than CQ, prolonged and overdose usage can still cause poisoning. And the relatively low SI of HCQ requires careful designing and conducting of clinical trials to achieve efficient and safe control of the SARS-CoV-2 infection."
Temperature Check for viruses.