Corona Virus Part 3

[re-tyred]

Ok guys I have had enough. I am not in the mood to deal with this at the moment so I hope another mod steps in.
Our daughter who is a front line worker, now has all the symptoms except respiratory distress. She has been in for her swab, a very unpleasant experience in her words. She has been sent home to isolate (with a husband and 3 kids and home schooling) she is a casual worker that does about 6 shifts a week. So zero income from today. Her husband also has zero income. If she tests positive she will get workers comp but at the normal rate not shift rate. If she tests negative she will get zero shifts till she is over what ever she has.

[4liters]

Well, time doesn't permit pointing out all the factual errors in your rant.
But guess what? ..... those are the measures that have saved thousands of lives! I for one am pleased that our politicians are demonstrating decisive and strong leadership for a change. You may not agree with their decisions but they are at least doing what they have been elected to do .... and that includes public safety.
Can't wait for what will be a rant-filled response

There are no factual errors in what I posted. Certainly not in the same league as the just released modelling that suggests another fictitious number of lives saved thanks to these measures. Let's remember the predicted modelling of 150 000 dead when all this kicked off in Aus. And no I don't accept at all the accusation that I must want old people to die because I don't like being under house arrest....that's just a cowardly slagging off of people with a different point of view.

The modeling predicted 150,000 dead people *if nothing changed*.

Things changed though.

We went into lockdown, non-essential businesses were closed, beaches etc were closed. That changes the assumptions of the modeling because the effective rate of transmission is reduced by those actions. If you reduce the rate of transmission, you reduce the number of people that catch it and the number of people that die.

Those old models are only relevant as long as their assumptions remain valid. If we were to unlock everything, the current models predicting we are on a path to eradicating the virus would suddenly be incorrect because the assumptions around social distancing and the effective rate of transmission would be wrong. As a result we'd go back to a model that as a 100,000 or so people dying again.

[4liters]

Anyway...

[Bugatti]

Thoughts and prayers to you and yours Mike.

Regards, Bill

[4liters]

Here's a cheery article about what you've got to look forward to if this thing hospitalises you.


https://www.sciencemag.org/news/2020/04 ... brain-toes#

How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes

By Meredith Wadman, Jennifer Couzin-Frankel, Jocelyn Kaiser, Catherine MatacicApr. 17, 2020 , 6:45 PM

Science’s COVID-19 reporting is supported by the Pulitzer Center.

On rounds in a 20-bed intensive care unit one recent day, physician Joshua Denson assessed two patients with seizures, many with respiratory failure and others whose kidneys were on a dangerous downhill slide. Days earlier, his rounds had been interrupted as his team tried, and failed, to resuscitate a young woman whose heart had stopped. All shared one thing, says Denson, a pulmonary and critical care physician at the Tulane University School of Medicine. “They are all COVID positive.”

As the number of confirmed cases of COVID-19 surges past 2.2 million globally and deaths surpass 150,000, clinicians and pathologists are struggling to understand the damage wrought by the coronavirus as it tears through the body. They are realizing that although the lungs are ground zero, its reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain.

“[The disease] can attack almost anything in the body with devastating consequences,” says cardiologist Harlan Krumholz of Yale University and Yale-New Haven Hospital, who is leading multiple efforts to gather clinical data on COVID-19. “Its ferocity is breathtaking and humbling.”

Understanding the rampage could help the doctors on the front lines treat the fraction of infected people who become desperately and sometimes mysteriously ill. Does a dangerous, newly observed tendency to blood clotting transform some mild cases into life-threatening emergencies? Is an overzealous immune response behind the worst cases, suggesting treatment with immune-suppressing drugs could help? What explains the startlingly low blood oxygen that some physicians are reporting in patients who nonetheless are not gasping for breath? “Taking a systems approach may be beneficial as we start thinking about therapies,” says Nilam Mangalmurti, a pulmonary intensivist at the Hospital of the University of Pennsylvania (HUP).


What follows is a snapshot of the fast-evolving understanding of how the virus attacks cells around the body, especially in the roughly 5% of patients who become critically ill. Despite the more than 1000 papers now spilling into journals and onto preprint servers every week, a clear picture is elusive, as the virus acts like no pathogen humanity has ever seen. Without larger, prospective controlled studies that are only now being launched, scientists must pull information from small studies and case reports, often published at warp speed and not yet peer reviewed. “We need to keep a very open mind as this phenomenon goes forward,” says Nancy Reau, a liver transplant physician who has been treating COVID-19 patients at Rush University Medical Center. “We are still learning.”

The infection begins
When an infected person expels virus-laden droplets and someone else inhales them, the novel coronavirus, called SARS-CoV-2, enters the nose and throat. It finds a welcome home in the lining of the nose, according to a preprint from scientists at the Wellcome Sanger Institute and elsewhere. They found that cells there are rich in a cell-surface receptor called angiotensin-converting enzyme 2 (ACE2). Throughout the body, the presence of ACE2, which normally helps regulate blood pressure, marks tissues vulnerable to infection, because the virus requires that receptor to enter a cell. Once inside, the virus hijacks the cell’s machinery, making myriad copies of itself and invading new cells.

As the virus multiplies, an infected person may shed copious amounts of it, especially during the first week or so. Symptoms may be absent at this point. Or the virus’ new victim may develop a fever, dry cough, sore throat, loss of smell and taste, or head and body aches.

If the immune system doesn’t beat back SARS-CoV-2 during this initial phase, the virus then marches down the windpipe to attack the lungs, where it can turn deadly. The thinner, distant branches of the lung’s respiratory tree end in tiny air sacs called alveoli, each lined by a single layer of cells that are also rich in ACE2 receptors.

Normally, oxygen crosses the alveoli into the capillaries, tiny blood vessels that lie beside the air sacs; the oxygen is then carried to the rest of the body. But as the immune system wars with the invader, the battle itself disrupts this healthy oxygen transfer. Front-line white blood cells release inflammatory molecules called chemokines, which in turn summon more immune cells that target and kill virus-infected cells, leaving a stew of fluid and dead cells—pus—behind. This is the underlying pathology of pneumonia, with its corresponding symptoms: coughing; fever; and rapid, shallow respiration (see graphic). Some COVID-19 patients recover, sometimes with no more support than oxygen breathed in through nasal prongs.

But others deteriorate, often quite suddenly, developing a condition called acute respiratory distress syndrome (ARDS). Oxygen levels in their blood plummet and they struggle ever harder to breathe. On x-rays and computed tomography scans, their lungs are riddled with white opacities where black space—air—should be. Commonly, these patients end up on ventilators. Many die. Autopsies show their alveoli became stuffed with fluid, white blood cells, mucus, and the detritus of destroyed lung cells.



Some clinicians suspect the driving force in many gravely ill patients’ downhill trajectories is a disastrous overreaction of the immune system known as a “cytokine storm,” which other viral infections are known to trigger. Cytokines are chemical signaling molecules that guide a healthy immune response; but in a cytokine storm, levels of certain cytokines soar far beyond what’s needed, and immune cells start to attack healthy tissues. Blood vessels leak, blood pressure drops, clots form, and catastrophic organ failure can ensue.

Some studies have shown elevated levels of these inflammation-inducing cytokines in the blood of hospitalized COVID-19 patients. “The real morbidity and mortality of this disease is probably driven by this out of proportion inflammatory response to the virus,” says Jamie Garfield, a pulmonologist who cares for COVID-19 patients at Temple University Hospital.

But others aren’t convinced. “There seems to have been a quick move to associate COVID-19 with these hyperinflammatory states. I haven’t really seen convincing data that that is the case,” says Joseph Levitt, a pulmonary critical care physician at the Stanford University School of Medicine.

He’s also worried that efforts to dampen a cytokine response could backfire. Several drugs targeting specific cytokines are in clinical trials in COVID-19 patients. But Levitt fears those drugs may suppress the immune response that the body needs to fight off the virus. “There’s a real risk that we allow more viral replication,” Levitt says.

Meanwhile, other scientists are zeroing in on an entirely different organ system that they say is driving some patients’ rapid deterioration: the heart and blood vessels.

Striking the heart
In Brescia, Italy, a 53-year-old woman walked into the emergency room of her local hospital with all the classic symptoms of a heart attack, including telltale signs in her electrocardiogram and high levels of a blood marker suggesting damaged cardiac muscles. Further tests showed cardiac swelling and scarring, and a left ventricle—normally the powerhouse chamber of the heart—so weak that it could only pump one-third its normal amount of blood. But when doctors injected dye in the coronary arteries, looking for the blockage that signifies a heart attack, they found none. Another test revealed why: The woman had COVID-19.

How the virus attacks the heart and blood vessels is a mystery, but dozens of preprints and papers attest that such damage is common. A 25 March paper in JAMA Cardiology documented heart damage in nearly 20% of patients out of 416 hospitalized for COVID-19 in Wuhan, China. In another Wuhan study, 44% of 36 patients admitted to the ICU had arrhythmias.

The disruption seems to extend to the blood itself. Among 184 COVID-19 patients in a Dutch ICU, 38% had blood that clotted abnormally, and almost one-third already had clots, according to a 10 April paper in Thrombosis Research. Blood clots can break apart and land in the lungs, blocking vital arteries—a condition known as pulmonary embolism, which has reportedly killed COVID-19 patients. Clots from arteries can also lodge in the brain, causing stroke. Many patients have “dramatically” high levels of D-dimer, a byproduct of blood clots, says Behnood Bikdeli, a cardiovascular medicine fellow at Columbia University Medical Center.

“The more we look, the more likely it becomes that blood clots are a major player in the disease severity and mortality from COVID-19,” Bikdeli says.

Infection may also lead to blood vessel constriction. Reports are emerging of ischemia in the fingers and toes—a reduction in blood flow that can lead to swollen, painful digits and tissue death.

In the lungs, blood vessel constriction might help explain anecdotal reports of a perplexing phenomenon seen in pneumonia caused by COVID-19: Some patients have extremely low blood-oxygen levels and yet are not gasping for breath. It’s possible that at some stages of disease, the virus alters the delicate balance of hormones that help regulate blood pressure and constricts blood vessels going to the lungs. So oxygen uptake is impeded by constricted blood vessels, rather than by clogged alveoli. “One theory is that the virus affects the vascular biology and that’s why we see these really low oxygen levels,” Levitt says.

If COVID-19 targets blood vessels, that could also help explain why patients with pre-existing damage to those vessels, for example from diabetes and high blood pressure, face higher risk of serious disease. Recent Centers for Disease Control and Prevention (CDC) data on hospitalized patients in 14 U.S. states found that about one-third had chronic lung disease—but nearly as many had diabetes, and fully half had pre-existing high blood pressure.

Mangalmurti says she has been “shocked by the fact that we don’t have a huge number of asthmatics” or patients with other respiratory diseases in HUP’s ICU. “It’s very striking to us that risk factors seem to be vascular: diabetes, obesity, age, hypertension.”

Scientists are struggling to understand exactly what causes the cardiovascular damage. The virus may directly attack the lining of the heart and blood vessels, which, like the nose and alveoli, are rich in ACE2 receptors. Or perhaps lack of oxygen, due to the chaos in the lungs, damages blood vessels. Or a cytokine storm could ravage the heart as it does other organs.

“We’re still at the beginning,” Krumholz says. “We really don’t understand who is vulnerable, why some people are affected so severely, why it comes on so rapidly … and why it is so hard [for some] to recover.”

Multiple battlefields
The worldwide fears of ventilator shortages for failing lungs have received plenty of attention. Not so a scramble for another type of equipment: dialysis machines. “If these folks are not dying of lung failure, they’re dying of renal failure,” says neurologist Jennifer Frontera of New York University’s Langone Medical Center, which has treated thousands of COVID-19 patients. Her hospital is developing a dialysis protocol with different machines to support additional patients. The need for dialysis may be because the kidneys, abundantly endowed with ACE2 receptors, present another viral target.

According to one preprint, 27% of 85 hospitalized patients in Wuhan had kidney failure. Another reported that 59% of nearly 200 hospitalized COVID-19 patients in China’s Hubei and Sichuan provinces had protein in their urine, and 44% had blood; both suggest kidney damage. Those with acute kidney injury (AKI), were more than five times as likely to die as COVID-19 patients without it, the same Chinese preprint reported.


Medical staff work to help a COVID-19 patient in an intensive care unit in Italy. ANTONIO MASIELLO/GETTY IMAGES
“The lung is the primary battle zone. But a fraction of the virus possibly attacks the kidney. And as on the real battlefield, if two places are being attacked at the same time, each place gets worse,” says Hongbo Jia, a neuroscientist at the Chinese Academy of Sciences’s Suzhou Institute of Biomedical Engineering and Technology and a co-author of that study.

Viral particles were identified in electron micrographs of kidneys from autopsies in one study, suggesting a direct viral attack. But kidney injury may also be collateral damage. Ventilators boost the risk of kidney damage, as do antiviral compounds including remdesivir, which is being deployed experimentally in COVID-19 patients. Cytokine storms also can dramatically reduce blood flow to the kidney, causing often-fatal damage. And pre-existing diseases like diabetes can increase the chances of kidney injury. “There is a whole bucket of people who already have some chronic kidney disease who are at higher risk for acute kidney injury,” says Suzanne Watnick, chief medical officer at Northwest Kidney Centers.

Buffeting the brain
Another striking set of symptoms in COVID-19 patients centers on the brain and central nervous system. Frontera says neurologists are needed to assess 5% to 10% of coronavirus patients at her hospital. But she says that “is probably a gross underestimate” of the number whose brains are struggling, especially because many are sedated and on ventilators.

Frontera has seen patients with the brain inflammation encephalitis, with seizures, and with a “sympathetic storm,” a hyperreaction of the sympathetic nervous system that causes seizurelike symptoms and is most common after a traumatic brain injury. Some people with COVID-19 briefly lose consciousness. Others have strokes. Many report losing their sense of smell. And Frontera and others wonder whether in some cases, infection depresses the brain stem reflex that senses oxygen starvation. This is another explanation for anecdotal observations that some patients aren’t gasping for air, despite dangerously low blood oxygen levels.

ACE2 receptors are present in the neural cortex and brain stem, says Robert Stevens, an intensive care physician at Johns Hopkins Medicine. But it’s not known under what circumstances the virus penetrates the brain and interacts with these receptors. That said, the coronavirus behind the 2003 severe acute respiratory syndrome (SARS) epidemic—a close cousin of today’s culprit—could infiltrate neurons and sometimes caused encephalitis. On 3 April, a case study in the International Journal of Infectious Diseases, from a team in Japan, reported traces of new coronavirus in the cerebrospinal fluid of a COVID-19 patient who developed meningitis and encephalitis, suggesting it, too, can penetrate the central nervous system.

But other factors could be damaging the brain. For example, a cytokine storm could cause brain swelling, and the blood’s exaggerated tendency to clot could trigger strokes. The challenge now is to shift from conjecture to confidence, at a time when staff are focused on saving lives, and even neurologic assessments like inducing the gag reflex or transporting patients for brain scans risk spreading the virus.

Last month, Sherry Chou, a neurologist at the University of Pittsburgh Medical Center, began to organize a worldwide consortium that now includes 50 centers to draw neurological data from care patients already receive. The early goals are simple: Identify the prevalence of neurologic complications in hospitalized patients and document how they fare. Longer term, Chou and her colleagues hope to gather scans, lab tests, and other data to better understand the virus’ impact on the nervous system, including the brain.

Chou speculates about a possible invasion route: through the nose, then upward and through the olfactory bulb—explaining reports of a loss of smell—which connects to the brain. “It’s a nice sounding theory,” she says. “We really have to go and prove that.”

Most neurological symptoms “are reported from colleague to colleague by word of mouth,” Chou adds. “I don’t think anybody, and certainly not me, can say we’re experts.”

Reaching the gut

In early March, a 71-year-old Michigan woman returned from a Nile River cruise with bloody diarrhea, vomiting, and abdominal pain. Initially doctors suspected she had a common stomach bug, such as Salmonella. But after she developed a cough, doctors took a nasal swab and found her positive for the novel coronavirus. A stool sample positive for viral RNA, as well as signs of colon injury seen in an endoscopy, pointed to a gastrointestinal (GI) infection with the coronavirus, according to a paper posted online in The American Journal of Gastroenterology (AJG).

Her case adds to a growing body of evidence suggesting the new coronavirus, like its cousin SARS, can infect the lining of the lower digestive tract, where the crucial ACE2 receptors are abundant. Viral RNA has been found in as many as 53% of sampled patients’ stool samples. And in a paper in press at Gastroenterology, a Chinese team reported finding the virus’ protein shell in gastric, duodenal, and rectal cells in biopsies from a COVID-19 patient. “I think it probably does replicate in the gastrointestinal tract,” says Mary Estes, a virologist at Baylor College of Medicine.

Recent reports suggest up to half of patients, averaging about 20% across studies, experience diarrhea, says Brennan Spiegel of Cedars-Sinai Medical Center in Los Angeles, co–editor-in-chief of AJG. GI symptoms aren’t on CDC’s list of COVID-19 symptoms, which could cause some COVID-19 cases to go undetected, Spiegel and others say. “If you mainly have fever and diarrhea, you won’t be tested for COVID,” says Douglas Corley of Kaiser Permanente, Northern California, co-editor of Gastroenterology.

The presence of virus in the GI tract raises the unsettling possibility that it could be passed on through feces. But it’s not yet clear whether stool contains intact, infectious virus, or only RNA and proteins. To date, “We have no evidence” that fecal transmission is important, says coronavirus expert Stanley Perlman of the University of Iowa. CDC says that based on experiences with SARS and with the virus that causes Middle East respiratory syndrome, another dangerous cousin of the new coronavirus, the risk from fecal transmission is probably low.

The intestines are not the end of the disease’s march through the body. For example, up to one-third of hospitalized patients develop conjunctivitis—pink, watery eyes—although it’s not clear that the virus directly invades the eye. Other reports suggest liver damage: More than half of COVID-19 patients hospitalized in two Chinese centers had elevated levels of enzymes indicating injury to the liver or bile ducts. But several experts told Science that direct viral invasion isn’t likely the culprit. They say other events in a failing body, like drugs or an immune system in overdrive, are more likely driving the liver damage.

This map of the devastation that COVID-19 can inflict on the body is still just a sketch. It will take years of painstaking research to sharpen the picture of its reach, and the cascade of cardiovascular and immune effects it might set in motion. As science races ahead, from probing tissues under microscopes to testing drugs on patients, the hope is for treatments more wily than the virus that has stopped the world in its tracks.

*Correction, 20 April, 12:25 p.m.: This story has been updated to correct the description of a sympathetic storm. It has also been updated to more accurately describe the geographic locations of the patients found to have protein and blood in their urine.

They mention that ACE2 receptor a lot, you know where else that protein is found..?
Your balls!

(Note that this is a pre-print and has not been peer reviewed. I couldn't find any studies that have proven the link, most scientists are focusing their efforts on organs that you need to survive)
https://www.medrxiv.org/content/10.1101 ... 20022418v1

In December 2019 and January 2020, novel coronavirus (2019-nCoV) - infected pneumonia (NCIP) occurred in Wuhan, and has already posed a serious threat to public health. ACE2 (Angiotensin Converting Enzyme 2) has been shown to be one of the major receptors that mediate the entry of 2019-nCoV into human cells, which also happens in severe acute respiratory syndrome coronavirus (SARS). Several researches have indicated that some patients have abnormal renal function or even kidney damage in addition to injury in respiratory system, and the related mechanism is unknown. This arouses our interest in whether coronavirus infection will affect the urinary and male reproductive systems. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicate that ACE2 highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts in testis. Therefore, virus might directly bind to such ACE2 positive cells and damage the kidney and testicular tissue of patients. Our results indicate that renal function evaluation and special care should be performed in 2019-nCoV patients during clinical work, because of the kidney damage caused by virus and antiviral drugs with certain renal toxicity. In addition, due to the potential pathogenicity of the virus to testicular tissues, clinicians should pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility.

[Boonanza]

Ok guys I have had enough. I am not in the mood to deal with this at the moment so I hope another mod steps in.
Our daughter who is a front line worker, now has all the symptoms except respiratory distress. She has been in for her swab, a very unpleasant experience in her words. She has been sent home to isolate (with a husband and 3 kids and home schooling) she is a casual worker that does about 6 shifts a week. So zero income from today. Her husband also has zero income. If she tests positive she will get workers comp but at the normal rate not shift rate. If she tests negative she will get zero shifts till she is over what ever she has.

Hopefully she is ok mate and it's just a bit under the weather, our Front line workers are doing so much hard work at the moment and we are lucky we have the best in the world.

[laneends]

As a byproduct of all this:

In Australia, influenza on average causes 1,500 to 3,000 deaths,3 about 18,000 hospitalisations and 300,000 GP consultations each year.

With the current COVID restrictions and added pressure to get flu shots, it is likely that there could be a huge reduction in number of cases this year.

[Stumpjumper]

Here's a cheery article about what you've got to look forward to if this thing hospitalises you.

Cool story bro.Over 98% of Australians who contract this virus exhibit mild or no symptoms and get over it without medical intervention. Most don't even know they've had it. Fatality rate is 2 per million head of population. Not models, these are the actual numbers so far.

[4liters]

Surprised they aren’t routinely testing frontline health workers given people can spread it while asymptomatic or presymptomatic.

I hope you get some good news and it’s all clear.

Apparently you can have it for a couple of days before the test picks it up. It has to have time to incubate. They are just introducing a new testing protocol in Tassie as they expand their testing.

It depends on the type of testing. There's two types, reagent and antibody testing. Reagent is more reliable, can indicate infection at any stage but is in limited supply and takes longer. Antibody testing was recently introduced but falls short because of the period in which you can be positive but antibody tests will not detect anything, by which if you are symptomatic it will be obvious you are infected anyways.

I’ve heard the antibody tests so far have really bad specificity so the false positives are... significant

That's true. Universally the antibody tests just aren't reliable but we still purchased heaps of them despite advice from leading virology officials. Reagent tests are really the only good option but it's a shame that we are forced into these options because of limited supply.

Heh, speaking of which, look what I found... I thought the bolded bit was intersting

https://www.mercurynews.com/2020/04/20/ ... n-apology/

Feud over Stanford coronavirus study: ‘The authors owe us all an apology’


Researchers are engaged in a fierce debate over the startling estimates in a Stanford study that suggested as many as 81,000 people could already have been infected with coronavirus in Santa Clara County, with some of the world’s top number crunchers calling the study sloppy, biased and an example of “how NOT to do statistics.”

“I think the authors owe us all an apology… not just to us, but to Stanford,” wrote Andrew Gelman, a professor of statistics and political science and director of the Applied Statistics Center at Columbia University.

Yet after a weekend of attacks on the paper, a study announced Monday out of the University of Southern California on a sampling of residents in Los Angeles reached a very similar conclusion: It found hundreds of thousands of adults there may have already been infected. As of Monday, Los Angeles County had recorded fewer than 13,000 cases.

The Santa Clara County study concluded that the virus had infected 2.5% to 4.2% of residents here; in LA, the estimated infection rate ranged from 2.8% to 5.6%.

The early studies set off a firestorm — not only among academics taking to Twitter to debate sampling methods, false positives and Bayesian inferences with a furor reminiscent of the banning of @BabyYodaBaby — but critics who believe the numbers show that COVID-19 is merely a partisan-driven flu hoax.

The showdown over a few percentage points has captured our cultural zeitgeist, sheltering at home in fear of both a virus and an economic meltdown.

In response, on Sunday, the Stanford study’s authors said they are planning to soon release a detailed appendix that addresses many of the “constructive comments and suggestions” the team has received.

“This is exactly the way peer-review should work in scientific work, and we are looking forward to engaging with other scholars as we proceed in this important work,” said Dr. Jayanta Bhattacharya, professor of medicine at Stanford University, who along with colleague Dr. Eran Bendavid, also assisted with the USC study.

The estimate, posted on the website medRxiv, comes from a first-in-the-nation community study of newly available antibody tests of 3,300 Santa Clara County residents in early April. Like all other emerging COVID-19 research papers, the work had not been peer reviewed prior to its release.


Based on those tests, the authors contend that between 48,000 and 81,000 of the county’s 1.9 million residents had been infected with the virus as of the first week of April. That’s 50 to 85 times more than the official count of cases at the time.

If true, it suggests that the large majority of people who contract COVID-19 recover without ever knowing they were infected. If undetected infections are that widespread, then the death rate in the county could be less than 0.2%, making the virus far less lethal than authorities have assumed. Los Angeles authorities also peg their death rate at 0.2% based on the USC study.

Santa Clara County Executive Dr. Jeff Smith remains steadfast in his interpretation of the study’s findings: It suggests that asymptomatic people spread the virus, and that more than 95% of the population remains susceptible to infection.

“That all means that there is more risk than we initially were aware of,” said Smith, lamenting how some are using the study to challenge Bay Area health officials’ unprecedented stay-home orders.

Similarly, Los Angeles Department of Public Health’s chief science officer Dr. Paul Simon said Monday that the LA study “suggests that many folks out there have infections and aren’t aware of it, or have mild symptoms….I think it is really important to continue the social distancing at least for the next month.”

The Los Angeles study was smaller than the Santa Clara County study, testing fewer than 1,000 people. This puts it at greater risk of distorted results. Researchers there plan to repeat the study to improve the accuracy of their results and track the virus’ spread.

However, researchers in LA took a more representative sample of residents than the Stanford team, using a market research firm rather than recruiting study subjects through Facebook, and including more minority groups.

They both used the same test kit, which is not FDA approved and has a 90 to 95% accuracy rate.

The Stanford study’s authors said they adjusted for the test kit’s performance and their limited sampling techniques to estimate the prevalence of the virus in Santa Clara County.

But over the weekend, some of the nation’s top number crunchers said their extrapolation of the results rests on a flimsy foundation.


They contended the Stanford analysis is troubled because it draws sweeping conclusions based on statistically rare events, and is rife with sampling and statistical imperfections.

Gelman of Columbia University called the conclusions “some numbers that were essentially the product of a statistical error.”

“They’re the kind of screw-ups that happen if you want to leap out with an exciting finding,” he wrote, “and you don’t look too carefully at what you might have done wrong.”

From the lab of Erik van Nimwegen of the University of Basel came this: “Loud sobbing reported from under Reverend Bayes’ grave stone,” referring to a famed statistician. “Seriously, I might use this as an example in my class to show how NOT to do statistics.”

“Do NOT interpret this study as an accurate estimate of the fraction of population exposed,” wrote Marm Kilpatrick, an infectious disease researcher at the University of California Santa Cruz. “Authors have made no efforts to deal with clearly known biases and whole study design is problematic.”


Others accused the authors of having agendas before going into the study. Back in March, Bhattacharya and Bendavid wrote an editorial in the Wall Street Journal arguing that a universal quarantine may not be worth the costs. Their colleague John Ioannidis has written that we lack the data to make such drastic economic sacrifices.

One major problem with the Santa Clara County study relates to test specificity. It used a kit purchased from Premier Biotech, based in Minneapolis with known performance data discrepancies of two “false positives” out of every 371 true negative samples. Although it was the best test at the time of the study, that’s a high “false positive” rate that can skew results, critics say — especially with such a small sample size.

With that ratio of false positives, a large number of the positive cases reported in the study — 50 out of 3320 tests — could be false positives, critics note. To ensure a test is sensitive enough to pick up only true SARS-CoV-2 infections, it needs to evaluate hundreds of positive cases of COVID-19 among thousands of negative ones.

This potential error in the test can easily dominate the results, they said.

Statistician John Cherian of D. E. Shaw Research, a computational biochemistry company, made his own calculations given the test’s sensitivity and specificity — and estimated the proportion of truly positive people in the Stanford study to range from 0.5% to 2.8%.

Adjusting for demographics, Cherian’s calculations suggest that prevalence could plausibly be under 1% and the mortality rate could be over 1%.

The “confidence intervals” in the paper – that is, the range around a measurement that conveys how precise the measurement is – “are nowhere close to what you’d get with a more careful approach,” he noted.

Even if the test were completely accurate, there would still be sampling problems in the Stanford study, critics said.

Biostatistician Natalie E. Dean of the University of Florida called it a “consent problem.” The Facebook ad might have attracted people who thought they were exposed to the virus and wanted testing.

“The prevalence drops off quickly when adjusted for even a small self-selection bias,” wrote Lonnie Chrisman, chief technical officer at the Los Gatos data software company Lumina Decision Systems.

Addressing the critics, Stanford’s Ioannidis, professor of medicine and biomedical data science at Stanford University, promised an expanded version of their study will be posted soon. “The results remain very robust,” he said.

In the end, no single study is going to answer the question of how prevalent COVID-19 is in our communities, scientists said. More studies with different technologies and analytic approaches are needed.

That’s coming. A UC Berkeley project, which will begin in May, will test a large and representative swath of 5,000 East Bay residents. Scientists will take saliva, swab and blood samples from volunteers between the ages of 18 and 60 around the region.

Starting Monday, UC San Francisco and a privately-funded operation will test all 1,680 residents of rural Bolinas for evidence of the virus. UCSF will launch a similar effort Saturday in San Francisco’s densely populated and largely Latino Mission District, where it hopes to test 5,700 people.

Results are expected soon from seroprevalence surveys run by other groups around the world, including teams in China, Australia, Iceland, Italy and Germany

“This pandemic,” wrote research scientist Ganesh Kadamur, “has been one giant Stats class for everyone.”

[croe04]

Here's a cheery article about what you've got to look forward to if this thing hospitalises you.

Cool story bro.Over 98% of Australians who contract this virus exhibit mild or no symptoms and get over it without medical intervention. Most don't even know they've had it. Fatality rate is 2 per million head of population. Not models, these are the actual numbers so far.

source ?????