Is this no longer a non-political thread?
COVID-19 Pandemic: Transmissions, Deaths, Treatments, Vaccines, Interventions and More...
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Is this no longer a non-political thread?
you went back pages to find a political post to complain that the thread is political ?
Agree on HCQ, but will remain skeptical on leronlimab until we see more data, since one very small uncontrolled trial is nowhere near enough to deserve the hype. In the trial, 4 of 10 critically ill patients died vs. ~57% of COVID ICU patients in general, which is intriguing, at best. Need to wait for results from controlled randomized clinical trials before jumping on the bandwagon (as for everything else), short of an obvious breakthrough in an observational study. Was also a red flag to me when Cytodyn's CEO sold half of his stock recently, while trying to court investors, which raised eyebrows all over Wall Street.
Also, how would you know clinical results from a mild/moderate trial that, in theory, should be blinded or at least not available to anyone not on the clinical study IRB (institutional review board)?
https://www.statnews.com/2020/05/04...covid-19-as-winner-while-its-ceo-sells-stock/
There's obviously some political content in this thread, which is unavoidable during a pandemic where political decisions have great import. However, the mods are at least trying to prevent it from becoming a CE-board style pissing match, which can happen very easily around here, so probably not worth arguing this particular point any more. Just my two cents.
http://cbs12.com/news/local/woman-w...-dashboard-has-been-removed-from-her-position
makes you wonder how accurate FL’s numbers are.
makes you wonder how accurate FL’s numbers are.
Strange, we have Georgia and Florida opening up despite statistics which lead to believe they shouldn't. Then we have Georgia's numbers being fudged to appear like they are better than reality. Now we have the designer of Florida's statistical website removed from her position because she refused to "manually change data to drum up support for the plan to reopen." These two states will be interesting to track going forward. I wonder if those responsible for these deliberate f-ups will be held accountable.
For the most part (with one notable exception) this thread has reminded me of why I am so proud to be an alumni of Rutgers University.
Because like RU#s, I believe in the rule of science and also Murphy's law. There is no solid unbiased proof of the HCQ other than theory and my anecdotal experience that I cannot deny. I don't like that kind of science. For instance, I started it on Sunday on the two patients I described and then they said they were feeling better yesterday but the male said he had some new GI symptoms. It could be the infection or it could be a side effect from the meds. And I always worry about the cardiac side effects and something we call the QT interval and to protect my butt and the patients, I tell people to buy this little home EKG device on Amazon. It's really a cool device, Kardia, when it works right.
It's very unlikely to have a significant QT effect in most relatively well patients. I also don't like to be part of the propagation of science that has not undergone unbiased blinded controlled studies. But we are all human beings and I do believe in the mind-body connection and even a placebo effect is a real effect. So there's a number of little things that go on into evaluating any particular case. Also, we have a 62-year-old guy who had very mild symptoms for 2 weeks and went into respiratory arrest and he's pretty much stuck on the vent & i'm a little bit haunted about not giving HCQ right up front and wondering well what if ? I would not have done that when I was a young, much brighter physician because I was much more rigid and black and white then. I used to burn a lot of bridges but now I just sleep under them. :)
I don't if this will help you sleep a little better:
Also, Dr Boulware already knows the data from his completed study on early treatment using HCQ. His study is currently being peer reviewed prior to publication. If it had no positive benefit I don't think he would have posted this an hour ago.
I read MDs are hoarding hydro so that's an up-vote right there.
https://www.propublica.org/article/...escriptions-for-themselves-and-their-families
Chris Martensen did a pre CV19 check on all the dire warnings about hydro, but apparently nobody at the agencies were concerned. CDC website called hydro "relatively well tolerated." It mentioned risk of retinopathy at high dosages and "years" of usage.
I'm not a clinician, but I went through 7 years of Lyme, and various heroes/villains trying to help/hinder. I know what its like to be stuck between waring factions in health area. There are people who will knowingly flush you down the potty while smiling at you, and saying its for "your own good."
I saw how ultra quick/hard the financial interests came down on cheap hydro while juicing the more expensive Remdesivir.
Pre CV19 CDC site:
Last edited:
In my post right above yours I shared the the safety review of 1290 patients in the UMN study. No serious incidents, None as in zero.I read MDs are hoarding hydro so that's an up-vote right there.
https://www.propublica.org/article/...escriptions-for-themselves-and-their-families
Chris Martensen did a check on all the dire warnings about hydro, but apparently nobody at the agencies were concerned. CDC website called hydro "relatively well tolerated." It mentioned risk of retinopathy at high dosages and "years" of usage.
I'm not a clinician, but I went through 7 years of Lyme, and various heroes/villains trying to help/hinder. I know what its like to be stuck between waring factions in health area. There are people who will knowingly flush you down the potty while smiling at you, and saying its for "your own good."
I saw how ultra quick/hard the financial interests came down on cheap hydro while juicing the more expensive Remdesivir.
Pre CV19 CDC site:
So that's kind of the point of the HCQ discussion. We know it doesn't do much if anything in advanced disease. That's fine. The question which remains unanswered is, can it be used early on to prevent people from developing advanced disease? There is a lot of anecdotal evidence that suggests it could be quite useful used that way. The ongoing trials should give us an idea if that holds up within a couple of weeks. And as for the side effects, people have been taking HCQ for a long time, side effect profile is well known and everything I've read suggests that if used short term the risk is pretty small. The big question is, is that side effect risk smaller than the risk of any particular individual who gets covid progressing to severe disease or death without treatment?
Ideally we find out that it can help prevent disease progression if given as soon as symptoms start (kind of like tamiflu for influenza). Then doctors can prescribe it to the appropriate patients and we have less people winding up in hospitals, ICUs, or morgues.
As for leronlimab, the jury remains out. The data/results I saw certainly didn't scream "game changer" to me but hopefully with more studies it is found to be an excellent treatment option.
Nope. Not even a tiny bit better. junk science is all over the place now, and it's like wild west Covid Dodge City. Let's throw it against the wall and see if it sticks. And I've been doing this a long time and I am always seemingly the one running into thatthat 1% who is supposed to not have an adverse reaction or so forth.
Let's create a narrative. And then let's go prove that narrative. Pretty much anybody can do that. That's why we have peer review and a lot of stuff gets retracted in the aftermath.
Don’t you take this as preventative for malaria?
Meaning you don’t take it once you get it. Or do you? I don’t know.
Like if you’re going to an area that has it, you take it before you go.
Dr. in Detroit (not to be confused with Dr. Detroit) is trying to study HCQ but having patients sign up because of the bad press around it.
https://fox42kptm.com/news/nation-w...f-politicized-medicine-in-the-age-of-covid-19
Cardiologist Dr. William O’Neill is a medical director at the Henry Ford Health System in Detroit, Michigan where they’re studying both remdesivir and hydroxychloroquine.
“I've never seen science [so] politicized in 40 years of practice,” Dr. O’Neill told me.
“President Trump touted [hydroxychloroquine] early and so then the media set out to disprove and discredit it without any regard for science. I think those of us that are actually involved in the scientific endeavor feel that there is some value to it and it has to be tested.”
Dr. O’Neill says he’s prescribed hydroxychloroquine to help numerous coronavirus patients and saw improvement in all of them. He’s less impressed, so far, by remdesivir, calling the data on that drug (so far) “a big Ho Hum.”
The biggest promise of hydroxychloroquine, he says, could be as a medicine to prevent Covid-19. He’s leading a study to find out if it works but says the bad press generated about the drug is making it difficult to get answers.
“Now people are scared to use the drug, without any scientifically valid concern. We've talked with our colleagues at the University of Minnesota who are doing a similar study, and at the University of Washington, we've treated 400 patients that haven't seen a single adverse event. And what's happening is because of this fake news and fake science, the true scientific efforts are being harmed because people now are so worried that they don't want to enroll in the trials,” says Dr. O’Neill.
This just in:Annie Glenn,wife of John Glenn,has died in a Minneapolis nursing home at the age of 100.The cause of death will be listed as COVID-19.No comment.
I had to look it up as you sparked my curiosity.
It sounds like there are now many malarial strains that are resistant to HCQ, so it can only be used for travel to certain areas.
Dose according to cdc is one 300 mg (or so) pill per week starting 1 week before travel, continuing during travel and for 4 weeks after return. So that is a lot less than they'd be using for covid.
People who take it for lupus take much larger doses for long time periods, something like 400 mg/day according to the lupus foundation website. People taking those kinds of long term treatments are at increased risk of a particular retinal disease that can cause blindness, and thus require regular eye exams.
Thanks for posting that. Very interesting. Strange times we live in.
Hopefully the ongoing clinical trials will put the issue to bed one way or the other.
People saying Plaquenil has no side effects are simply not paying attention. It's always had them and always will, like many drugs. My wife was prescribed HCQ for her RA and had quite a bad reaction to it (nauesea, headache, and dizziness) and stopped taking it. These weren't life threatening, but we know the QT issues can be, especially at higher doses.
https://www.drugs.com/sfx/plaquenil-side-effects.html
None of this means it might not work as a preventative or in those with mild symptoms - we need to await the data. However, with mildly symptomatic patients, detecting a statistically meaningful difference between HCQ treatment and no treatment is going to be difficult, given the very high rate of people with mild symptoms who get better on their own. Prevention will likely be even harder to demonstrate.
Then, fkr's post should be deleted.
If not, it can ignite the typical CE type of banter
Numbers, do your homework! The selling of his warrants had to do with raising money to pay Samsung to ratchet up production to scale because of prior agreement payment was due a day or 2 later. CEO has poured his life and soul and his own money into the company and is doing so not to dilute shareholder value. Remember this is a small company that will shortly be approved by the FDA as treatment for AIDS and triple breast cancer ( probably many other cancers as well) and COVID use was experimental.
They are seeking right now an investment bank to uplift to Nasdaq from the OTC.
Regarding the Montefiore Ny 11 patients, all who had multiple system failure and were going to die, and the most severe and critical patients there, Leronlimab saved 4 lives , which was remarkable on its own. The science and the identifying of the Rantes CcLR pathway by Dr. Bruce Johnson , their consulting doctor will prove exactly how the virus is killing so many and how Leronlimab does everything safely to stop it.
Here we are on May 19, and "still not enough testing" is happening.
- You still need a prescription to get tested at most testing centers
- Most testing is still the invasive & uncomfortable swab shoved into the back of your nasal cavity
- The few places that offer the less invasive & more convenient saliva test are only for Middlesex County residents (and also require a doctor's prescription)
I know I haven't gotten tested yet because if I'm asymptomatic and have not knowingly been directly exposed, I'm not voluntarily getting the test done. I do work in a location that has had cases allegedly tied to workplace spread. I know I'm not the only one who feels this way. Does anyone know what the holdup could be here? If we're going to start relaxing work restrictions, you're now going to force folks to get their brains swabbed twice a week?
- You still need a prescription to get tested at most testing centers
- Most testing is still the invasive & uncomfortable swab shoved into the back of your nasal cavity
- The few places that offer the less invasive & more convenient saliva test are only for Middlesex County residents (and also require a doctor's prescription)
I know I haven't gotten tested yet because if I'm asymptomatic and have not knowingly been directly exposed, I'm not voluntarily getting the test done. I do work in a location that has had cases allegedly tied to workplace spread. I know I'm not the only one who feels this way. Does anyone know what the holdup could be here? If we're going to start relaxing work restrictions, you're now going to force folks to get their brains swabbed twice a week?
The testing restrictions are a concern of mine, as well. Last week I had a routine telemed appointment with my doctor and asked about getting a Covid test. My doctor told me that since I don't have an Covid symptoms now, I can't get a Covid test. (I also asked about an antibody test, since I had a respiratory illness earlier this year, and I was told that I should wait on that, until there is better data around the accuracy of antibody tests, as well as data around antibodies and immunity.)
I think NJ really needs to ramp up availability of the Rutgers saliva test, in order to make testing easy and widespread. Then it will be much easier to spot small Covid outbreaks as social distancing is relaxed.
I have. Pourhassan's actions and explanation are at least questionable, as per the article. But that's largely irrelevant compared to the importance of whether or not leronlimab will be shown to be effective in COVID patients. Let's hope so - even if it's not a "breakthrough" (which seems doubtful), but is still somewhat to moderately effective, that would be fantastic.
we pretty much now have enough supplies to test anybody we want within reason but I won't do the antibody test without getting the antigen at least once.
And I still believe if you're going to get a swab for the virus that you really got to do it the right way I mean I stick that sucker in a good 6-inch. -And I leave it there for a while and then I twirl it around and rotate it for a bit. Sounds kind of pornographic I know.We're starting to get some evidence that that's really the right way to get it early on before it starts migrating to the lungs. I had a case where a guy had two negative swabs and we only got it from the lungs on the third try. In fact I just emailed him that I want to test his family. They've been asymptomatic but they need to be tested for antigen and antibody. The hard reality is that after 30% of swabs can be negative and that can be a combination of virus migration and poor technique. Couple that with a very questionable antibody test as far as thethe utility of it in any given individual as opposed to population studies. Sure we would all like to have a positive IGG antibody and say to ourselves that you escaped the ventilator but we really don't know that for sure yet. there's a number of people who can't make antibodies for some reason or they don't hang around or they're too low of titer. I find a good use for it on people that I strongly suspected had covid 19 in February and March and I couldn't test them but made the diagnosis anyway and now I'm going back and testing them with the antibody So I find that useful as a complimentary tool.
Came across this article that NJ authorizes 18000 pharmacists to conduct coronavirus tests without prescriptions.
From the article:
More than 18,000 licensed pharmacists across New Jersey have been granted permission to administer tests for the coronavirus as officials continue to expand the amount testing needed to lift restrictions put in place to slow the spread, state officials announced Tuesday.
The announcement gives pharmacists in the state at more than 2,200 pharmacies the green light to test people for COVID-19, though Gov. Phil Murphy said test would more likely be done at pharmacies with drive-thrus. Two major chains, Rite Aid and CVS, have moved forward with testing. Residents won’t need to have symptoms of the virus or need a referral from a doctor.
https://www.nj.com/coronavirus/2020...-coronavirus-tests-without-prescriptions.html
News > Medscape Medical News
COVID-19 Test Results: Don't Discount Clinical Intuition
Heather Boerner
May 16, 2020
- Coronavirus Resource Center.
Recently, a patient arrived at the UC San Diego Health medical center with what are now classic symptoms of COVID-19: a history of coughs, pneumonia, and severe respiratory distress that required immediate intubation.
What he didn't have was a positive SARS-CoV-2 test — neither the first nor the second time clinicians swabbed the back of his throat. SARS-CoV-2 is the virus that causes COVID-19.
"The two negative tests didn't convince anybody," said Davey Smith, MD, a virologist and chief of the division of infectious diseases and global public health at UC San Diego School of Medicine. It was only on the third test, when they sampled fluid from a bronchial wash, that they were able to find the virus.
Smith's patient is not alone. Though almost all experts agree that broad testing for SARS-CoV-2 will be critical to understanding, containing, and eventually treating COVID-19, the effort is hampered by limitations of current tests.
The tests today, experts say, are so new that it's unclear how reliable they are. Anecdotally, clinicians report false negative rates of anywhere from 2% to 30%, depending on what part of the body is being tested and what means they are using to get a sample, as well as epidemiological and clinical factors.
And the US Food and Drug Administration issued an alert earlier this week warning of false negatives with one of the most commonly used tests, Abbott Labs' ID NOW rapid test for COVID-19.
Data published earlier this week in the Annals of Internal Medicine show that test accuracy varies widely over the course of the disease in a mixed population of inpatients and outpatients. On the day symptoms appear, the median false negative rate was 38%. That figure dropped to 20% on the third day after symptom onset, but climbed again to 66% about 2 weeks later.
But test results should only be part of the picture. The key is clinical suspicion informed by all the above factors, said Joshua Metlay, MD, PhD, chief of the division of internal medicine at Massachusetts General Hospital, and coauthor of a series of articles on clinical decision-making in the Annals of Internal Medicine.
"How we treat patients is going to depend on understanding this concept," Metlay told Medscape Medical News. "It isn't one number. It's actually much more complicated and very nuanced." If clinicians don't understand that, he added, "We're really going to make mistakes about how to use all these negative tests."
When Hope Outstrips Reason
A positive SARS-CoV-2 test sets off a cascade of actions, in and out of clinical settings: In patients with symptoms, it triggers a set of protocols, as recommended by the National Institutes of Health and individual hospitals, around use of personal protective equipment (PPE) for staff, whether patients are placed in rooms with others or singly, and specific treatment choices, such as which ventilator protocol to use. By contrast, a negative test, in an ideal situation, should lead a clinician to keep looking for a causative agent or underlying problem. Quality care, in other words, relies on accurate diagnosis.
In patients without symptoms, a positive test means suggesting quarantine and isolation for two weeks, said Colin West, MD, PhD, professor of medicine and biostatistics at the Mayo Clinic in Rochester, Minnesota.
But because of the relatively high rate of false negatives, a negative test in an asymptomatic person can't confer the kind of relief patients, the public, or policymakers would like it to, West said.
"People can't relax their physical distancing, their handwashing, their surface hygiene, their mask-wearing" even with a negative test, he said, because they still could be carrying the virus.
"When hope outstrips reason, we sometimes prematurely pin our hopes on tests that aren't as good as we want them to be," said West, who wrote a perspective for Mayo Clinic Proceedings warning about the dangers of false negatives. "Smart clinicians all around the country are not believing the test results when their clinical suspicion is high enough."
Calculating Clinical Suspicion
With false negative rates ranging from 3.2% in a cohort of seriously ill COVID-19 inpatients in New York City, to 66% in the mixed population in the Annals of Internal Medicine study, it's understandable that clinicians might be skeptical of the results in front of them.
The first thing to understand, Metlay said, is that the sensitivity of the test isn't the same as the rate of false negatives. Sensitivity only describes the absolute ability of a given test to detect SARS-CoV-2 when it's present.
A false negative is a combination of the accuracy of the test itself and its handling, along with clinical symptomology, local epidemiology, and the individual behavior of the person in front of you.
"This is why people don't usually report false negative rates as one number — because that number can only be calculated or interpreted in the context of the group that you're talking about," Metlay said. "Two hospitals could report completely different false negative rates and that's completely reasonable. Even within the same hospital, the false negative rate in the clinic could be different than the false negative rate in the emergency room."
That is to say, people showing up with symptoms in an emergency department should be met with a higher pre-test probability of having COVID-19 than well people who show up for drive-through testing, he said.
The same holds true for the background rate of COVID-19 in a community.
"If you get into a community where almost no one is infected and you tested everybody, your false-negative rates are going to be very low, because almost everybody there is negative," he said. In Boston, where Metlay practices, the community rates of COVID-19 are substantial, so even those with mild symptoms might be met with higher suspicion of having SARS-CoV-2. And that's even before the patient opens their mouth and explains where they've been or who they've been in contact with.
This helps explain why Rajesh Gandhi, MD, Metlay's colleague at Mass General, said the inpatient false negative rate there is between 2% and 3%, while Smith from UC San Diego reported that their false negative rates are no more than 10% — or that unpublished data first reported by NPR found that the most commonly used, fastest turnaround tests also churned out 15% false negatives.
No Gold Standard
Another factor in all of this are the tests themselves. Back in March, Chinese researchers at Central South University in Changsha, Hunan province, lamented that "existing PCR methods have very good specificity but low sensitivity, meaning that negative test results cannot exclude the presence of SARS-CoV-2."
PCR stands for polymerase chain reaction, a means of testing for viral genetic material, currently most commonly used in a nasopharyngeal swab.
But we don't know how inaccurate the tests actually are, said Stephen Rawlings, MD, PhD, an infectious disease fellow at UC San Diego's Center for AIDS Research, who has been helping to validate RT-PCR tests for SARS-CoV-2 since repatriated Americans were held in isolation at military bases starting in March.
For one thing, we have nothing to compare current tests with.
"To truly determine false negatives, you need a gold standard test, which is essentially as close to perfect as we can get," Rawlings said. "But there just isn't one yet for coronavirus."
For another, the studies that have been done on the accuracy of the tests themselves are filled with flaws, said Mayo Clinic's West.
Sensitivity estimates are usually based on testing the tests against people who they already know have COVID-19. But that's a bias — you know what you're looking for, West said. Without control groups or blinded testing, it's impossible to get "good information about where these imperfections lie, or even the magnitude of those imperfections," said West, who conducted a tweetorial on how to understand the accuracy of current RT-PCR tests.
A recent non-peer reviewed preprint meta-analysis of five COVID-19 studies comprising 957 patients found that the underlying poor quality of data made it impossible to judge how effective the tests in the nation's labs are at all.
"We're trying to have informed conversations about how good are these tests, and how helpful are they in ruling in or ruling out diagnosis, when the source literature is so poor," West said.
This is where the Centers for Disease Control and Prevention should step in, according to UCSD's Smith. Local labs are doing their best to validate tests on their own, but if they could send their results in a blinded way to the CDC, he'd have a lot more confidence in every test.
"We really need these panels to help with the quality assurance internally," Smith said. "It's not about the nasal swabs or not. It's about the potential sources of error within the lab."
Human Error and Biological Process
Now add in the human piece of gathering, transporting, and reading an RT-PCR test, said Daniel Griffin, MD, PhD, an infectious disease physician and associate research scientist in the department of biochemistry and molecular biophysics at Columbia University in New York City.
"Basically, I tell my patients that unless you feel like they were trying to biopsy your brain, it wasn't done correctly," he said. And the less well done the test, the less likely the results will be reliable.
But even if all that is correct, there's one more hurdle: What part of the body should be sampled and at what point in the illness? A viewpoint published in JAMA earlier this month synthesized known data on the accuracy of different tests at different points in the disease process.
For instance, it shows that within the first week of exposure before symptoms and in the first week of symptoms, nasopharyngeal swabs are most accurate. But by the end of week 2 of symptoms, bronchoalveolar lavage/sputum is most accurate.
This conforms to what clinicians report anecdotally. The number of copies of the virus in the nose and pharynx is highest in the early days infection, just like the flu, said Columbia University's Griffin. And that may mean the RT-PCR tests of the nose and pharynx work best in the first few days of infection — when patients still have mild or moderate symptoms.
"If you do the test that first day or so when you're sick, you're going to have pretty good sensitivity" with nasopharyngeal swabs, said Griffin, who often provides COVID-19 updates on the podcast "This Week in Virology."
"The interesting thing is, when people get admitted to the hospital, now they've been feeling crummy for a week or more," he said. "Now it's day 13 or day 14, and now the virus is actually starting to get to a lower level of activity" in the upper respiratory tract.
And that means, said Griffin, "there's not as much virus around" the nose and pharynx to test.
That's when UC San Diego's Rawlings said they've found that passing a catheter through the tracheal tube of someone who's already intubated can "often find [the virus] there at very high levels."
This may explain the phenomenon that Smith described, as well as what Neera Ahuja, MD, of Stanford University, said in a "Medicine and the Machine" podcast recently, that "this virus actually moves from proximal upper airway nasal-pharyngeal down to the lower lungs."
"If you catch it in a stage where it's already progressed, you may have a false negative," she said.
Using Clinical Judgment
It's a lot to take in for a single clinician interpreting a single test result. The good news is that clinicians are literally trained for this, said Carlos del Rio, MD, of Emory University and coauthor with Gandhi of a recent article on mild or moderate COVID-19.
"We as clinicians use our brains," he said. "We don't say, 'Oh the person doesn't have the disease' — we use the test in the context of our clinical expertise."
So clinicians should ask: Are the patients sick themselves? What are their symptoms? Have they traveled to or from COVID-19-endemic areas recently? Have they been in touch with someone they know has COVID-19? Have they been practicing physical distancing, mask-wearing, and other protective behaviors? said Metlay.
They may even want to consider other questions, said Gregorio Millett, MPH, vice president and director of public policy at the American Foundation for AIDS Research (amfAR). Millett and colleagues have unpublished data showing that although disproportionately black counties account for just 22% of US counties overall, they make up 52% of counties with COVID-19 cases and 58% of counties with COVID-19 deaths. In those communities, lack of insurance and living in crowded households were associated with increased risk for acquiring COVID-19 — opening another potential data point to consider in those communities.
The bottom line is that "nobody can integrate all this math in their head every single time" they see a patient, Metlay said. Still, keeping all these factors in mind will help clinicians look at that negative result with clear eyes.
"This," he said, "is what helps people not get tricked by these tests."
Sounds like that NBC virologist expert contributor who caught it. He tested negative 4 times even though he got it so bad he had to go to hospital for some days.
News > Medscape Medical News
COVID-19 Test Results: Don't Discount Clinical Intuition
Heather Boerner
May 16, 2020
- Coronavirus Resource Center.
Recently, a patient arrived at the UC San Diego Health medical center with what are now classic symptoms of COVID-19: a history of coughs, pneumonia, and severe respiratory distress that required immediate intubation.
What he didn't have was a positive SARS-CoV-2 test — neither the first nor the second time clinicians swabbed the back of his throat. SARS-CoV-2 is the virus that causes COVID-19.
"The two negative tests didn't convince anybody," said Davey Smith, MD, a virologist and chief of the division of infectious diseases and global public health at UC San Diego School of Medicine. It was only on the third test, when they sampled fluid from a bronchial wash, that they were able to find the virus.
Smith's patient is not alone. Though almost all experts agree that broad testing for SARS-CoV-2 will be critical to understanding, containing, and eventually treating COVID-19, the effort is hampered by limitations of current tests.
The tests today, experts say, are so new that it's unclear how reliable they are. Anecdotally, clinicians report false negative rates of anywhere from 2% to 30%, depending on what part of the body is being tested and what means they are using to get a sample, as well as epidemiological and clinical factors.
And the US Food and Drug Administration issued an alert earlier this week warning of false negatives with one of the most commonly used tests, Abbott Labs' ID NOW rapid test for COVID-19.
Data published earlier this week in the Annals of Internal Medicine show that test accuracy varies widely over the course of the disease in a mixed population of inpatients and outpatients. On the day symptoms appear, the median false negative rate was 38%. That figure dropped to 20% on the third day after symptom onset, but climbed again to 66% about 2 weeks later.
But test results should only be part of the picture. The key is clinical suspicion informed by all the above factors, said Joshua Metlay, MD, PhD, chief of the division of internal medicine at Massachusetts General Hospital, and coauthor of a series of articles on clinical decision-making in the Annals of Internal Medicine.
"How we treat patients is going to depend on understanding this concept," Metlay told Medscape Medical News. "It isn't one number. It's actually much more complicated and very nuanced." If clinicians don't understand that, he added, "We're really going to make mistakes about how to use all these negative tests."
When Hope Outstrips Reason
A positive SARS-CoV-2 test sets off a cascade of actions, in and out of clinical settings: In patients with symptoms, it triggers a set of protocols, as recommended by the National Institutes of Health and individual hospitals, around use of personal protective equipment (PPE) for staff, whether patients are placed in rooms with others or singly, and specific treatment choices, such as which ventilator protocol to use. By contrast, a negative test, in an ideal situation, should lead a clinician to keep looking for a causative agent or underlying problem. Quality care, in other words, relies on accurate diagnosis.
In patients without symptoms, a positive test means suggesting quarantine and isolation for two weeks, said Colin West, MD, PhD, professor of medicine and biostatistics at the Mayo Clinic in Rochester, Minnesota.
But because of the relatively high rate of false negatives, a negative test in an asymptomatic person can't confer the kind of relief patients, the public, or policymakers would like it to, West said.
"People can't relax their physical distancing, their handwashing, their surface hygiene, their mask-wearing" even with a negative test, he said, because they still could be carrying the virus.
"When hope outstrips reason, we sometimes prematurely pin our hopes on tests that aren't as good as we want them to be," said West, who wrote a perspective for Mayo Clinic Proceedings warning about the dangers of false negatives. "Smart clinicians all around the country are not believing the test results when their clinical suspicion is high enough."
Calculating Clinical Suspicion
With false negative rates ranging from 3.2% in a cohort of seriously ill COVID-19 inpatients in New York City, to 66% in the mixed population in the Annals of Internal Medicine study, it's understandable that clinicians might be skeptical of the results in front of them.
The first thing to understand, Metlay said, is that the sensitivity of the test isn't the same as the rate of false negatives. Sensitivity only describes the absolute ability of a given test to detect SARS-CoV-2 when it's present.
A false negative is a combination of the accuracy of the test itself and its handling, along with clinical symptomology, local epidemiology, and the individual behavior of the person in front of you.
"This is why people don't usually report false negative rates as one number — because that number can only be calculated or interpreted in the context of the group that you're talking about," Metlay said. "Two hospitals could report completely different false negative rates and that's completely reasonable. Even within the same hospital, the false negative rate in the clinic could be different than the false negative rate in the emergency room."
That is to say, people showing up with symptoms in an emergency department should be met with a higher pre-test probability of having COVID-19 than well people who show up for drive-through testing, he said.
The same holds true for the background rate of COVID-19 in a community.
"If you get into a community where almost no one is infected and you tested everybody, your false-negative rates are going to be very low, because almost everybody there is negative," he said. In Boston, where Metlay practices, the community rates of COVID-19 are substantial, so even those with mild symptoms might be met with higher suspicion of having SARS-CoV-2. And that's even before the patient opens their mouth and explains where they've been or who they've been in contact with.
This helps explain why Rajesh Gandhi, MD, Metlay's colleague at Mass General, said the inpatient false negative rate there is between 2% and 3%, while Smith from UC San Diego reported that their false negative rates are no more than 10% — or that unpublished data first reported by NPR found that the most commonly used, fastest turnaround tests also churned out 15% false negatives.
No Gold Standard
Another factor in all of this are the tests themselves. Back in March, Chinese researchers at Central South University in Changsha, Hunan province, lamented that "existing PCR methods have very good specificity but low sensitivity, meaning that negative test results cannot exclude the presence of SARS-CoV-2."
PCR stands for polymerase chain reaction, a means of testing for viral genetic material, currently most commonly used in a nasopharyngeal swab.
But we don't know how inaccurate the tests actually are, said Stephen Rawlings, MD, PhD, an infectious disease fellow at UC San Diego's Center for AIDS Research, who has been helping to validate RT-PCR tests for SARS-CoV-2 since repatriated Americans were held in isolation at military bases starting in March.
For one thing, we have nothing to compare current tests with.
"To truly determine false negatives, you need a gold standard test, which is essentially as close to perfect as we can get," Rawlings said. "But there just isn't one yet for coronavirus."
For another, the studies that have been done on the accuracy of the tests themselves are filled with flaws, said Mayo Clinic's West.
Sensitivity estimates are usually based on testing the tests against people who they already know have COVID-19. But that's a bias — you know what you're looking for, West said. Without control groups or blinded testing, it's impossible to get "good information about where these imperfections lie, or even the magnitude of those imperfections," said West, who conducted a tweetorial on how to understand the accuracy of current RT-PCR tests.
A recent non-peer reviewed preprint meta-analysis of five COVID-19 studies comprising 957 patients found that the underlying poor quality of data made it impossible to judge how effective the tests in the nation's labs are at all.
"We're trying to have informed conversations about how good are these tests, and how helpful are they in ruling in or ruling out diagnosis, when the source literature is so poor," West said.
This is where the Centers for Disease Control and Prevention should step in, according to UCSD's Smith. Local labs are doing their best to validate tests on their own, but if they could send their results in a blinded way to the CDC, he'd have a lot more confidence in every test.
"We really need these panels to help with the quality assurance internally," Smith said. "It's not about the nasal swabs or not. It's about the potential sources of error within the lab."
Human Error and Biological Process
Now add in the human piece of gathering, transporting, and reading an RT-PCR test, said Daniel Griffin, MD, PhD, an infectious disease physician and associate research scientist in the department of biochemistry and molecular biophysics at Columbia University in New York City.
"Basically, I tell my patients that unless you feel like they were trying to biopsy your brain, it wasn't done correctly," he said. And the less well done the test, the less likely the results will be reliable.
But even if all that is correct, there's one more hurdle: What part of the body should be sampled and at what point in the illness? A viewpoint published in JAMA earlier this month synthesized known data on the accuracy of different tests at different points in the disease process.
For instance, it shows that within the first week of exposure before symptoms and in the first week of symptoms, nasopharyngeal swabs are most accurate. But by the end of week 2 of symptoms, bronchoalveolar lavage/sputum is most accurate.
This conforms to what clinicians report anecdotally. The number of copies of the virus in the nose and pharynx is highest in the early days infection, just like the flu, said Columbia University's Griffin. And that may mean the RT-PCR tests of the nose and pharynx work best in the first few days of infection — when patients still have mild or moderate symptoms.
"If you do the test that first day or so when you're sick, you're going to have pretty good sensitivity" with nasopharyngeal swabs, said Griffin, who often provides COVID-19 updates on the podcast "This Week in Virology."
"The interesting thing is, when people get admitted to the hospital, now they've been feeling crummy for a week or more," he said. "Now it's day 13 or day 14, and now the virus is actually starting to get to a lower level of activity" in the upper respiratory tract.
And that means, said Griffin, "there's not as much virus around" the nose and pharynx to test.
That's when UC San Diego's Rawlings said they've found that passing a catheter through the tracheal tube of someone who's already intubated can "often find [the virus] there at very high levels."
This may explain the phenomenon that Smith described, as well as what Neera Ahuja, MD, of Stanford University, said in a "Medicine and the Machine" podcast recently, that "this virus actually moves from proximal upper airway nasal-pharyngeal down to the lower lungs."
"If you catch it in a stage where it's already progressed, you may have a false negative," she said.
Using Clinical Judgment
It's a lot to take in for a single clinician interpreting a single test result. The good news is that clinicians are literally trained for this, said Carlos del Rio, MD, of Emory University and coauthor with Gandhi of a recent article on mild or moderate COVID-19.
"We as clinicians use our brains," he said. "We don't say, 'Oh the person doesn't have the disease' — we use the test in the context of our clinical expertise."
So clinicians should ask: Are the patients sick themselves? What are their symptoms? Have they traveled to or from COVID-19-endemic areas recently? Have they been in touch with someone they know has COVID-19? Have they been practicing physical distancing, mask-wearing, and other protective behaviors? said Metlay.
They may even want to consider other questions, said Gregorio Millett, MPH, vice president and director of public policy at the American Foundation for AIDS Research (amfAR). Millett and colleagues have unpublished data showing that although disproportionately black counties account for just 22% of US counties overall, they make up 52% of counties with COVID-19 cases and 58% of counties with COVID-19 deaths. In those communities, lack of insurance and living in crowded households were associated with increased risk for acquiring COVID-19 — opening another potential data point to consider in those communities.
The bottom line is that "nobody can integrate all this math in their head every single time" they see a patient, Metlay said. Still, keeping all these factors in mind will help clinicians look at that negative result with clear eyes.
"This," he said, "is what helps people not get tricked by these tests."
Only read the beginning of this, but is South Korea's tests that much better then ours?
News > Medscape Medical News
COVID-19 Test Results: Don't Discount Clinical Intuition
Heather Boerner
May 16, 2020
- Coronavirus Resource Center.
Recently, a patient arrived at the UC San Diego Health medical center with what are now classic symptoms of COVID-19: a history of coughs, pneumonia, and severe respiratory distress that required immediate intubation.
What he didn't have was a positive SARS-CoV-2 test — neither the first nor the second time clinicians swabbed the back of his throat. SARS-CoV-2 is the virus that causes COVID-19.
"The two negative tests didn't convince anybody," said Davey Smith, MD, a virologist and chief of the division of infectious diseases and global public health at UC San Diego School of Medicine. It was only on the third test, when they sampled fluid from a bronchial wash, that they were able to find the virus.
Smith's patient is not alone. Though almost all experts agree that broad testing for SARS-CoV-2 will be critical to understanding, containing, and eventually treating COVID-19, the effort is hampered by limitations of current tests.
The tests today, experts say, are so new that it's unclear how reliable they are. Anecdotally, clinicians report false negative rates of anywhere from 2% to 30%, depending on what part of the body is being tested and what means they are using to get a sample, as well as epidemiological and clinical factors.
And the US Food and Drug Administration issued an alert earlier this week warning of false negatives with one of the most commonly used tests, Abbott Labs' ID NOW rapid test for COVID-19.
Data published earlier this week in the Annals of Internal Medicine show that test accuracy varies widely over the course of the disease in a mixed population of inpatients and outpatients. On the day symptoms appear, the median false negative rate was 38%. That figure dropped to 20% on the third day after symptom onset, but climbed again to 66% about 2 weeks later.
But test results should only be part of the picture. The key is clinical suspicion informed by all the above factors, said Joshua Metlay, MD, PhD, chief of the division of internal medicine at Massachusetts General Hospital, and coauthor of a series of articles on clinical decision-making in the Annals of Internal Medicine.
"How we treat patients is going to depend on understanding this concept," Metlay told Medscape Medical News. "It isn't one number. It's actually much more complicated and very nuanced." If clinicians don't understand that, he added, "We're really going to make mistakes about how to use all these negative tests."
When Hope Outstrips Reason
A positive SARS-CoV-2 test sets off a cascade of actions, in and out of clinical settings: In patients with symptoms, it triggers a set of protocols, as recommended by the National Institutes of Health and individual hospitals, around use of personal protective equipment (PPE) for staff, whether patients are placed in rooms with others or singly, and specific treatment choices, such as which ventilator protocol to use. By contrast, a negative test, in an ideal situation, should lead a clinician to keep looking for a causative agent or underlying problem. Quality care, in other words, relies on accurate diagnosis.
In patients without symptoms, a positive test means suggesting quarantine and isolation for two weeks, said Colin West, MD, PhD, professor of medicine and biostatistics at the Mayo Clinic in Rochester, Minnesota.
But because of the relatively high rate of false negatives, a negative test in an asymptomatic person can't confer the kind of relief patients, the public, or policymakers would like it to, West said.
"People can't relax their physical distancing, their handwashing, their surface hygiene, their mask-wearing" even with a negative test, he said, because they still could be carrying the virus.
"When hope outstrips reason, we sometimes prematurely pin our hopes on tests that aren't as good as we want them to be," said West, who wrote a perspective for Mayo Clinic Proceedings warning about the dangers of false negatives. "Smart clinicians all around the country are not believing the test results when their clinical suspicion is high enough."
Calculating Clinical Suspicion
With false negative rates ranging from 3.2% in a cohort of seriously ill COVID-19 inpatients in New York City, to 66% in the mixed population in the Annals of Internal Medicine study, it's understandable that clinicians might be skeptical of the results in front of them.
The first thing to understand, Metlay said, is that the sensitivity of the test isn't the same as the rate of false negatives. Sensitivity only describes the absolute ability of a given test to detect SARS-CoV-2 when it's present.
A false negative is a combination of the accuracy of the test itself and its handling, along with clinical symptomology, local epidemiology, and the individual behavior of the person in front of you.
"This is why people don't usually report false negative rates as one number — because that number can only be calculated or interpreted in the context of the group that you're talking about," Metlay said. "Two hospitals could report completely different false negative rates and that's completely reasonable. Even within the same hospital, the false negative rate in the clinic could be different than the false negative rate in the emergency room."
That is to say, people showing up with symptoms in an emergency department should be met with a higher pre-test probability of having COVID-19 than well people who show up for drive-through testing, he said.
The same holds true for the background rate of COVID-19 in a community.
"If you get into a community where almost no one is infected and you tested everybody, your false-negative rates are going to be very low, because almost everybody there is negative," he said. In Boston, where Metlay practices, the community rates of COVID-19 are substantial, so even those with mild symptoms might be met with higher suspicion of having SARS-CoV-2. And that's even before the patient opens their mouth and explains where they've been or who they've been in contact with.
This helps explain why Rajesh Gandhi, MD, Metlay's colleague at Mass General, said the inpatient false negative rate there is between 2% and 3%, while Smith from UC San Diego reported that their false negative rates are no more than 10% — or that unpublished data first reported by NPR found that the most commonly used, fastest turnaround tests also churned out 15% false negatives.
No Gold Standard
Another factor in all of this are the tests themselves. Back in March, Chinese researchers at Central South University in Changsha, Hunan province, lamented that "existing PCR methods have very good specificity but low sensitivity, meaning that negative test results cannot exclude the presence of SARS-CoV-2."
PCR stands for polymerase chain reaction, a means of testing for viral genetic material, currently most commonly used in a nasopharyngeal swab.
But we don't know how inaccurate the tests actually are, said Stephen Rawlings, MD, PhD, an infectious disease fellow at UC San Diego's Center for AIDS Research, who has been helping to validate RT-PCR tests for SARS-CoV-2 since repatriated Americans were held in isolation at military bases starting in March.
For one thing, we have nothing to compare current tests with.
"To truly determine false negatives, you need a gold standard test, which is essentially as close to perfect as we can get," Rawlings said. "But there just isn't one yet for coronavirus."
For another, the studies that have been done on the accuracy of the tests themselves are filled with flaws, said Mayo Clinic's West.
Sensitivity estimates are usually based on testing the tests against people who they already know have COVID-19. But that's a bias — you know what you're looking for, West said. Without control groups or blinded testing, it's impossible to get "good information about where these imperfections lie, or even the magnitude of those imperfections," said West, who conducted a tweetorial on how to understand the accuracy of current RT-PCR tests.
A recent non-peer reviewed preprint meta-analysis of five COVID-19 studies comprising 957 patients found that the underlying poor quality of data made it impossible to judge how effective the tests in the nation's labs are at all.
"We're trying to have informed conversations about how good are these tests, and how helpful are they in ruling in or ruling out diagnosis, when the source literature is so poor," West said.
This is where the Centers for Disease Control and Prevention should step in, according to UCSD's Smith. Local labs are doing their best to validate tests on their own, but if they could send their results in a blinded way to the CDC, he'd have a lot more confidence in every test.
"We really need these panels to help with the quality assurance internally," Smith said. "It's not about the nasal swabs or not. It's about the potential sources of error within the lab."
Human Error and Biological Process
Now add in the human piece of gathering, transporting, and reading an RT-PCR test, said Daniel Griffin, MD, PhD, an infectious disease physician and associate research scientist in the department of biochemistry and molecular biophysics at Columbia University in New York City.
"Basically, I tell my patients that unless you feel like they were trying to biopsy your brain, it wasn't done correctly," he said. And the less well done the test, the less likely the results will be reliable.
But even if all that is correct, there's one more hurdle: What part of the body should be sampled and at what point in the illness? A viewpoint published in JAMA earlier this month synthesized known data on the accuracy of different tests at different points in the disease process.
For instance, it shows that within the first week of exposure before symptoms and in the first week of symptoms, nasopharyngeal swabs are most accurate. But by the end of week 2 of symptoms, bronchoalveolar lavage/sputum is most accurate.
This conforms to what clinicians report anecdotally. The number of copies of the virus in the nose and pharynx is highest in the early days infection, just like the flu, said Columbia University's Griffin. And that may mean the RT-PCR tests of the nose and pharynx work best in the first few days of infection — when patients still have mild or moderate symptoms.
"If you do the test that first day or so when you're sick, you're going to have pretty good sensitivity" with nasopharyngeal swabs, said Griffin, who often provides COVID-19 updates on the podcast "This Week in Virology."
"The interesting thing is, when people get admitted to the hospital, now they've been feeling crummy for a week or more," he said. "Now it's day 13 or day 14, and now the virus is actually starting to get to a lower level of activity" in the upper respiratory tract.
And that means, said Griffin, "there's not as much virus around" the nose and pharynx to test.
That's when UC San Diego's Rawlings said they've found that passing a catheter through the tracheal tube of someone who's already intubated can "often find [the virus] there at very high levels."
This may explain the phenomenon that Smith described, as well as what Neera Ahuja, MD, of Stanford University, said in a "Medicine and the Machine" podcast recently, that "this virus actually moves from proximal upper airway nasal-pharyngeal down to the lower lungs."
"If you catch it in a stage where it's already progressed, you may have a false negative," she said.
Using Clinical Judgment
It's a lot to take in for a single clinician interpreting a single test result. The good news is that clinicians are literally trained for this, said Carlos del Rio, MD, of Emory University and coauthor with Gandhi of a recent article on mild or moderate COVID-19.
"We as clinicians use our brains," he said. "We don't say, 'Oh the person doesn't have the disease' — we use the test in the context of our clinical expertise."
So clinicians should ask: Are the patients sick themselves? What are their symptoms? Have they traveled to or from COVID-19-endemic areas recently? Have they been in touch with someone they know has COVID-19? Have they been practicing physical distancing, mask-wearing, and other protective behaviors? said Metlay.
They may even want to consider other questions, said Gregorio Millett, MPH, vice president and director of public policy at the American Foundation for AIDS Research (amfAR). Millett and colleagues have unpublished data showing that although disproportionately black counties account for just 22% of US counties overall, they make up 52% of counties with COVID-19 cases and 58% of counties with COVID-19 deaths. In those communities, lack of insurance and living in crowded households were associated with increased risk for acquiring COVID-19 — opening another potential data point to consider in those communities.
The bottom line is that "nobody can integrate all this math in their head every single time" they see a patient, Metlay said. Still, keeping all these factors in mind will help clinicians look at that negative result with clear eyes.
"This," he said, "is what helps people not get tricked by these tests."
Work with a guy who was in the hospital but tested negative, meanwhile his mother tested positive but had no symptoms.
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Treatment Response to Hydroxychloroquine, Lopinavir–Ritonavir, and Antibiotics for Moderate COVID-19: A First Report on the Pharmacological Outcomes from South Korea
https://www.medrxiv.org/content/10.1101/2020.05.13.20094193v1.full.pdf
https://www.medrxiv.org/content/10.1101/2020.05.13.20094193v1.full.pdf
Here’s the article.
https://www.statnews.com/2020/05/19...-data-critical-to-assessing-covid-19-vaccine/
https://www.statnews.com/2020/05/19...-data-critical-to-assessing-covid-19-vaccine/
Edit: they also announced they intend to raise over $1.3B in cash via a public share offering - price of shares to be offered less than where they closed yesterday
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What are you talking about.
I was able to get an antibody test scheduled for a few day’s after my call to summit medical group (lab Corp was similar as was my kids pediatrician).
Rite aid in PARSIPPANY has a drive through no Rx needed covid 19 test. Not sure where you live.
testing seems abundantly available here in N.J.
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