Dr. Seth Corey is Professor, Pediatrics and Molecular Medicine, and on staff in the Departments of Pediatrics, Cancer Biology, and Translational Hematology and Oncology Research at the Cleveland Clinic. He sends along this Facebook post under the heading Day 27+. Slow the spread. I have lightly edited Dr. Coreys post. He writes:

This Wuhan pandemic is Peaking.

Surreal, these times have been, as suggested by the parody of one of Magrittes paintings (at figure at right). If only one could say this is not a pandemic. Magrittes pictures show a distorted reality. Or groups of objects which seemingly have no narrative unity. Magritte forces the viewer to construct his own explanation. There may be multiple truths. Scientific research is not so dissimilar. Lessons are to be learned.

Sometimes the models are right, as we have been informed for the past week at the daily White House press briefings: there is evidence that the new US cases and deaths are peaking at Easter time. Yesterday, there were 33,752 new cases; today 30,003. Yesterday, there were 2035 deaths; today 1830.

A study not yet published from Germany suggests that infection is indeed more widespread and fatality rates lower than expected [see our post Maybe some good news]. Using antibody testing, 15 percent of individuals had been infected with 2 percent having a current SARS-CoV2 infection. The case fatality rate was 0.37 percent whereas that of Germany was 1.98 percent. This is preliminary and should be taken as such.

Ohios numbers are reassuring, and may serve as an example of flattening the peak the purpose was to prepare hospitals for the surge. The model keeps getting flatter and flatter. Hospitalized patients were 1755 yesterday, 1788 today. The hospitals are more than sufficiently prepared. Even New York Citys hospitalization, ICU, and ventilator usage are way under the estimates.

According to the flatter, revised model there should be about 1200 new cases today in Ohio; instead there are 372 cases. Time to revise the model and make it even flatter. This of course means that infections will last longer. Please note 247 deaths include 5 deaths under CDC expanded death definition. Please note that 63 of 6250 cases are defined as CDC expanded case definition. The median age of death in Ohio is 79 yrs (which agrees with Israel and Italy). The deaths in New York follow closely what is observed in Ohio.

Lesson to be learned, especially by New York leaders: the metropolitan NYC (NJ/CT) area needs to be better prepared for the next epidemic. It has the population density, center of international travel, and cultural/economic/ethnic diversity (but so does Houston, which is a minority majority city-but nowhere near the health crisis of New York City with COVID-19).

It is possible that the next pandemic could come from outside New York City, but that would require an extremely more contagious infection (high R0). In addition to comparing COVID-19 to past influenza epidemics, we should restudy the measles outbreaks (measles far more contagious than coronavirus or influenza but there is greater herd immunity due to childhood vaccination).

Lesson to be learned by all: healthcare workers need to be considered high risk. For Ohio, 21 percent of confirmed cases were in healthcare workers.

One needs to ask why the models were so off. One way is for models to be explained more explicitly. What assumptions were used? Where did the data come from? What are the confidence intervals? If models are going to affect 325,000,000 Americans then it is incumbent upon the modelers to provide explicit details so that other scientists can verify or repudiate or revise the models.

Lesson to be learned by all: All models are wrong, but some are useful.

Either one is dead or alive (none of the Schrodingers cat business). Either one is employed or not.Lesson to be learned not soon enough: economic and mental health concerns need to be factored into public health policy. This is not just an infectious disease pandemic.

Keep calm. Wash your hands. Avoid sick people. Avoid physical contact with high risk people. Get rest. Eat well. Keep hydrated. Take zinc. Wear a mask. Support your local businesses. Thank a healthcare worker. Be kind.

I wish a Happy and Healthy Easter to my friends at this surreal time.

Read this article:
Seth Corey: The pandemic is peaking - Power Line

As scientists race to find specific treatments for COVID-19, the colourless gas nitric oxide has emerged as a candidate.

Nitric oxide works as a signalling molecule in the cardiovascular, nervous and immune systems of animals, and is mostly produced in the inner layer of blood vessels called the endothelium. The compound relaxes muscle cells, which in turn prompts blood vessel walls to widen, boosting blood flow and decreasing blood pressure.

As such, physicians have used it for a range of conditions, and it was first approved for use by the U.S. Food and Drug Administration in 1999.

Warren Zapol, emeritus anesthetist-in-chief at Massachusetts General Hospital and a professor at Harvard Medical School, told Gizmodo nitric oxide is used to treat babies born blue, as well as adults with cardiac surgery, and patients with what is known as acute respiratory distress syndrome, where the oxygen supply to lungs are cut off by bodily fluids. "About a half-million Americans have breathed in NO [nitric oxide]," Zapol told the outlet.

Nitric oxide was also central to the creation of the erectile dysfunction drug Viagra in the 1990s, as the pill's main ingredient sildenafil makes the relaxing effect of nitric oxide in the body more potent and increases blood flow.

Now, Zapol is among scientists exploring whether nitric oxide could be harnessed to help COVID-19 patients. Currently, there are no specific drugs for the disease. He and colleagues at the Massachusetts General Hospital have launched two clinical trials to see if the gas can help patients with mild to moderate COVID-19, and others with severe respiratory distress.

Zapol told Gizmodo his team is also awaiting approval to start a trial to see if dosing healthcare workers with the gas would prevent them from being infected by the new coronavirus

Dr. Lorenzo Berra, critical-care specialist at Massachusetts General Hospital who is leading the trials, told Los Angeles Times he wanted to try the gas on COVID-19 patients after it showed promise during the SARS epidemic.

Read more

Meanwhile, a team of scientists at Tongji Hospital in China have launched a clinical trial to investigate whether sildenafil can help COVID-19 patients.

Ian Hall, professor of molecular medicine at the University of Nottingham who is not involved in the projects, explained to Newsweek: "Nitric oxide works mainly by relaxing the blood vessels which supply blood to the lungs from the heart, and has been used to treat patients with other conditions where the pressure in these blood vessels is too high.

"Some patients with more severe COVID-19 disease have abnormal pressures in these blood vessels (the pulmonary arteries) and hence nitric oxide might help relieve this increased pressure, and hence improve gas exchange in the lung."

It is hoped the treatment would reduce the number of patients who need treatment in an intensive care unit or a ventilator, said Hall.

However, he stressed "whilst there is some anecdotal evidence this may work in patients with COVID19, there has been no formal clinical trial to date."

Hall warned any such experimental treatments could have unwanted side effects.

"Hence I think it is critical that these interventions are studied in a formal clinical trial setting. As such it is encouraging to see that this is exactly the approach being suggested in these studies," he said.

Putting the trials into the wider context of the COVID-19 pandemic, Hall said: "There are a lot of clinical trials which are underway or being planned for patients with COVID-19. Most of these target hospital patients with more severe disease."

"At present we don't know which drugs work, but we will soon get information on this from studies such as RECOVERY in the U.K. which is comparing a range of different agents," Hall said. That trial focuses on a HIV drug and a steroid.

Unapproved anti-viral remdesivir is also being tested as a COVID-19 treatment, as are the antimalarial drugs chloroquine and hydroxychloroquine. Last month the World Health Organization launched a multi-country clinical study of four potential combinations, including remdesivir and chloroquine.

Four months in to the COVID-19 pandemic, 1.3 million cases have been confirmed, almost 76,000 people have died, and over 289,000 have recovered, according to Johns Hopkins University. As shown in the Statista map below, every continent except Antarctica is affected.

Hygiene advice

Medical advice

Mask and glove usage

Read the original post:
What Is Nitric Oxide? How the Gas That Gave Us Viagra Could Help Treat Coronavirus Patients - Newsweek

Most people with coronavirus will recover within about a week of getting symptoms and will not need medical care.

But some people will need to be treated in hospital - as the prime minister was.

Boris Johnson, who is 55, has been discharged from St Thomas' hospital in London after being in intensive care.

He was given oxygen, but didn't need a ventilator machine to help his breathing.

Some people are at higher risk of complications.

This includes people over the age of 70, regardless of whether they have a medical condition or not, and people of any age with underlying health conditions such as heart disease.

There are more than 1.5 million people in the UK who are at the greatest risk of needing hospital treatment if they catch coronavirus.

This includes people with cancer who have been receiving chemotherapy, and they are being asked to stay at home all of the time to shield themselves from the virus.

Coronavirus also appears to disproportionately affect men in their 50s and 60s to a certain degree, although they are not singled out as a high risk group. But it's not that clear-cut. Correlation isn't necessarily cause.

Scientists are unsure.

UK data from intensive care hospital wards shows the average patient who is critically ill is aged 60. Most are men and many have other health conditions that could put them at increased risk, such as heart problems and obesity.

Of the 647 coronavirus-related deaths registered by the Office for National Statistics in England and Wales up to the week ending 27th March, 44 were aged 45-65 - around 7% of the total.

Death rates go up with age in both men and women, but men tend to outstrip women across the ages.

Data from China, where the pandemic began, also suggests men are at greater risk than women, although experts caution there could be factors other than gender, such as smoking habits, that could explain the link.

Prof Ian Hall, Professor of Molecular Medicine, University of Nottingham, said: "I am not convinced this completely explains the increased risk of severe disease in men, so it seems possible there may be some other as yet unidentified factor playing a role."

Men are more likely than women to have heart disease, diabetes and chronic lung disease.

Some have suggested genes and sex hormones might be involved too.

Prof Philip Goulder, an expert in immunology at University of Oxford, said: "It is becoming increasingly recognised that there are substantial differences in the immune system between males and females and that these have significant impact on outcome from a wide range of infectious diseases.

"The immune response throughout life to vaccines and infections is typically more aggressive and more effective in females compared to males."

This could be down to women carrying two copies of the X chromosome, compared to the single X and a Y that men have.

A number of critical immune genes are located on the X chromosome, he says.

Every year, about 600,000 people in the UK die. People with underlying health conditions and the elderly are most at risk, just as they are if they have coronavirus.

Nearly 10% of people aged over 80 will die in the next year, Prof Sir David Spiegelhalter, at the University of Cambridge, points out, and the risk of them dying if infected with coronavirus is almost exactly the same.

Stay as fit and healthy as you can by exercising and eating a balanced diet.

If you smoke, now is a good time to quit.

Men are more likely than women to:

Coronavirus spreads when an infected person coughs or sneezes small droplets - packed with the virus - into the air. These can be breathed in, or cause an infection if you touch a surface they have landed on, then your eyes, nose or mouth.

So, coughing and sneezing into tissues, not touching your face with unwashed hands, and avoiding close contact with infected people are important.

If you have a new, continuous cough or a fever you should stay at home and self-isolate for at least seven days.

If you, or someone you live with, develop symptoms, the entire household needs to isolate for 14 days to monitor for signs of the disease.

The main reason people need hospital treatment is difficulty breathing.

In the UK, the NHS 111 website will guide you through what you need to do.

If you are so breathless that you are unable to speak more than a few words then you will be told to call 999 as this is a medical emergency.

If you become so ill that you've stopped doing all of your usual daily activities then the website will advise speaking to a nurse by dialling NHS 111.

Link:
Coronavirus: What is the risk to men over 50? - BBC News

HAMILTON, Ontario The outbreak of coronavirus around the globe is stretching medical supplies to their limits. Growing demand for advanced medical masks are leaving healthcare workers in desperate situations, but is hi-tech equipment really needed to keep you safe from COVID-19? Researchers now say the most popular type of respirator masks should be saved for medical workers treating patients with severe cases of coronavirus.

According to McMaster University in Canada, a basic, loose-fitting medical mask works just as well for protecting against the spread of COVID-19. Researchers say the popular N95 respirator mask should be used by healthcare workers who carry out tasks like inserting tubes into a patients throat.

There is not convincing evidence that the loose-fitting medical masks are inferior to N95 respirators, Dr. Mark Loeb, a professor of pathology and molecular medicine at McMaster said in a statement. But the N95 respirators are unanimously recommended by national and international guidelines for aerosol generating procedures.

Loeb, an infectious disease doctor, notes that N95 respirators are most needed for those high-risk procedures that see patients coughing up more of the virus into the air around them. The professor sides with the World Health Organization and Canadian Public Health Agency, saying a standard face mask is fine for anyone treating non-emergency coronavirus patients.

Although COVID-19 transmission is not fully understood, its believed to be mainly through respiratory droplets, and the medical masks provide barrier protection for that, and prevent hand to face contact, Loeb explained.

Not all experts are convinced that a regular medical mask is good enough when treating people infected with COVID-19. The McMaster University study notes that both the U.S. Centers for Disease Control and Prevention and the European Centre for Disease and Prevention both urge people to wear the N95, even during routine medical work.

Loeb and others hope the research will convince the public to conserve the shrinking supplies of the tight-fitting respirators.

This evidence to support the relative effectiveness of medical masks compared to N95 respirators in routine care, might help preserve stockpiles of N95 respirators, Jessica Bartoszko, one of the papers authors said.

Loeb and a team of researchers are now expanding their work. They are testing the effectiveness of standard masks versus N95 respirators in several locations where patients with respiratory illnesses are being treated.

This study is critical to ensure were using personal protective equipment correctly during this, and any future infectious disease outbreak, Loeb concluded.

The studys findings are published in the journalInfluenza and Other Respiratory Viruses.

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View post:
Popular N95 Masks Only Needed For Workers Treating Extreme Coronavirus Cases, Researchers Say - Study Finds

As more people are tested for COVID-19, experts are warning the results might not be 100 percent accurate.

Preliminary research from China that is yet to be peer reviewed suggests the most common form of COVID-19 test produces false negatives up to 30 percent of the time.

The issue with the tests for the SARS-CoV-2 virus is that there has not been time to test them rigorously before deploying them in the field, Dr. Gary L. LeRoy, FAAFP, president of the American Academy of Family Physicians, told Healthline.

Most polymerase chain reaction (PCR) and antibody tests have years of laboratory testing before they are used. We just dont have that kind of time, LeRoy said. The major concern for false negatives is someone who tests negative, thinking they are not infected, could unknowingly spread the virus into the community.

In the United States, the most common form of test used for COVID-19 is a molecular test known as a reverse transcriptase polymerase chain reaction (RT-PCR) test.

For these tests, specimens are taken from the back of the nose and mouth.

The notion is that this is a virus that likes to implant itself on the mucous membranes high up in the back of the throat behind the nose, Dr. William Schaffner, an infectious disease specialist at Vanderbilt University Medical Center in Tennessee, told Healthline. So you have to put a swab, not at the front of the nose, but rather far back. Then you have the small mucus on the end of that specimen, it gets sent to the laboratory, its extracted from the specimen, then using molecular technology you determine whether the virus is there.

You can have a false negative if you have very little virus up there or perhaps the specimen was taken inappropriately. It didnt get up high enough to actually get to the place where the virus was located. Thats another possibility, Schaffner added.

Dr. Lee Harold Hilborne is a professor of pathology and laboratory medicine at the University of California Los Angeles.

He says no test is faultless and the high rate of false negatives is likely due to collection rather than testing in a laboratory.

Tests have different sensitivity and specificity. Its important to recognize that none are perfect. The 30 percent rate is based on collection, not the analytic performance of the test, Hilborne told Healthline.

The majority of issues contributing to error in diagnostic testing are pre-analytic, he added. These occur during specimen order, collection, and transport, before the specimen ever reaches the lab. We know that collection methods do not always pick up the virus. Studies suggest current swab collection may have sensitivity in the range of 60 to 75 percent. That means the specimen submitted to the laboratory from a patient with the infection will not contain the virus roughly 25 to 40 percent of the time.

Hilborne describes a hypothetical scenario in which a drive-thru collection center sees 100 patients who are unwell enough to warrant a test.

Specimens are collected using a technique that has a 65 percent chance of picking up the virus. Of the 100 people tested at the drive through, 20 percent test positive. Thats 20 patients.

But what about the remainder who tested negative?

If the collection success rate is 65 percent, then there will be an additional roughly 10 to 11 patients who are infected but who have a negative test. That is, one-third of infected patients in this scenario who have the infection will test negative even though the test itself is analytically extremely good, Hilborne explained.

The World Health Organization (WHO) estimates that one person with COVID-19 will pass the virus on to at least two people.

Given this, experts say that if a person with symptoms receives a negative test result, they should still self-isolate.

If a patient presents with symptoms of COVID-19 cough, fever, shortness of breath but they test negative, they should self-isolate out of an abundance of caution to stop the potential spread of the disease, LeRoy said. The tests used are not 100 percent accurate and a negative test does not always equate to not having the disease.

The Centers for Disease Control and Prevention (CDC) notes that even if a person tests negative, that doesnt guarantee they wont become ill.

If you test negative for COVID-19, you probably were not infected at the time your specimen was collected. However, that does not mean you will not get sick. It is possible that you were very early in your infection at the time of your specimen collection and that you could test positive later, or you could be exposed later and then develop illness. In other words, a negative test result does not rule out getting sick later, the CDC website states.

Early indications suggest that people may be most infectious before they become ill and experts say it is important people do their part to contain the spread of the virus.

The current physical distancing measures are in place to help slow the spread of the disease, especially from those who are currently not showing symptoms, LeRoy said.

Many who are later diagnosed with COVID-19 had actually been infected and spreading the virus for several days, he said. Staying home and wearing cloth masks in public, especially when physical distancing is more difficult, will help slow the spread from those who might currently be asymptomatic but who are actually infected.

The rest is here:
'False Negatives' in COVID-19 Tests: Have Symptoms, Assume Illness - Healthline

In the age of the coronavirus, when nothing is certain and we must plot our every move with the utmost caution, some people are wondering if they need not worry quite as much. What if, they ask, I already had COVID-19 weeks ago but didn't realize or couldn't confirm it?

The search terms "did I have coronavirus" spiked in Google Trends early last month, when it became clear the United States was on the cusp of major outbreaks. People also Googled "did I have coronavirus in January" and "did I have coronavirus in February."

Soccer star Carli Lloyd wondered as much on Twitter in late March, detailing symptoms similar to those caused by COVID-19, including a fever, cough, and shortness of breath.

"Beginning to think my husband and I had the Coronavirus back in mid February," she wrote. "A sickness we have never felt before."

Her replies were full of people wondering about the same scenario in their lives.

It's a simultaneously compelling, legitimate thing to ask and a kind of fantasy that we might indulge in because the alternative constantly worrying about contracting a highly infectious, potentially fatal disease is exhausting. The anxiety of extreme social distancing and panic buying might be more tolerable if people knew they'd already survived asymptomatic, mild, or moderate cases of COVID-19.

Unfortunately, the answer to this question is elusive, which means, as far as we know, the risk of contracting COVID-19 remains high. This is particularly true because people who are asymptomatic can infect others, undermining a key assumption about how viruses are transmitted.

There are now more than 370,000 known cases and 12,000 fatalities in the U.S., and public health authorities stress that the only way to stem infections and prevent more deaths is to continue practicing social distancing, hand washing, and other preventive measures.

In order to know how many people in the U.S. have been infected with COVID-19, we'd need widespread availability of highly accurate tests that detect the presence of antibodies against the disease. We also need more scientific information about how long immunity to the disease lasts once someone acquires it. Immunity to common colds, which are caused by coronaviruses, is temporary. Even if someone accurately suspected they'd come down with COVID-19 earlier this year, it doesn't necessarily mean they'd continue to be immune to the virus in the coming months or years.

Then there's the question of whether the timeline makes sense. Prior to the known outbreaks, could people have developed mild or moderate cases of COVID-19 without a simultaneous uptick in severe cases that would've required hospitalization?

Nicholas Reich, an associate professor of biostatistics at the University of Massachusetts in Amherst whose lab focuses on understanding and modeling infectious disease, has been looking for evidence of this happening, and so far sees little data to support that possibility.

He and his lab members noticed influenza-like illnesses increase in December and January and thought perhaps coronavirus had been silently circulating for months. They decided to look at the rate of influenza-like illnesses alongside the rate of negative flu tests as a potential signal of community spread of COVID-19; if illnesses rose but more flu tests came back negative, it could suggest another pathogen playing an unexpected role. By late February, the lab's analysis showed trends that were consistent with historical norms.

Since then, when the lab looked at patterns in March, they saw deviations from the historical norms but it was difficult to draw strong conclusions from that data.

More people went to the doctor with respiratory illnesses and also tested negative for the flu, but Reich said that could be the result of people changing their behavior as media coverage of coronavirus ramped up. In other words, more people sought medical attention for various symptoms because of alarming headlines about COVID-19 but may not have had the disease. The researchers couldn't rule out COVID-19 spreading earlier than thought, but the data also suggested that if the coronavirus had been present, it would've been relatively limited.

Reich believes it's plausible that someone in the vicinity of a hot spot like Seattle or New York could've developed COVID-19 in mid-February, as the disease began to spread throughout communities. (In fact, after this story was published, new research emerged suggesting that the coronavirus began spreading in New York in mid-February.)

"Outbreaks like this take time to build up steam and really start to burn," Reich said.

Still, given the severity of COVID-19, Reich believes it's unlikely that coronavirus was widespread prior to late February and early March. That would've been accompanied by what we're seeing now, and saw in Italy: a fraction of patients streaming into emergency rooms with respiratory distress.

"Outbreaks like this take time to build up steam and really start to burn."

"Based on everything thats been coming out, Ive been increasingly feeling as though it wouldve been really hard to miss a large outbreak," said Reich. "Data points like [what's happening in Italy] make it clearer to me just how this is really different from seasonal flu."

Reich also points to genomic analyses of the coronavirus conducted by Trevor Bedford, a computational biologist at the Fred Hutchinson Cancer Research Center in Seattle, which suggest that the first known COVID-19 case in the U.S. occurred in mid-January, in Washington state. That research looked at minor mutations in the virus' genome to analyze when it might have emerged in the U.S. If that analysis is accurate, it would make it far less likely that the disease caused mysterious respiratory illnesses in late 2019 or early 2020.

Ruth Collins, an associate professor of molecular medicine at Cornell University, said it's very likely that a different, nasty virus could've been circulating this winter. Since the symptoms caused by coronaviruses overlap significantly, it would make sense that some people experienced an awful illness that wasn't actually caused by COVID-19 but still produced similar symptoms like coughing, fever, and aches and pains.

Collins said that wondering about whether an illness experienced prior to the coronavirus outbreak was in fact COVID-19 is a form of highly relatable wishful thinking.

"It's part of human psychology," she said. "We always want to think were better than we are, that we got lucky, that we escaped it somehow."

It doesn't help, either, that tests to diagnose COVID-19 have been difficult to get.

In the absence of diagnostic testing, we need widespread individual and epidemiological testing to determine who contracted COVID-19 and developed antibodies to the disease. That requires highly accurate serology tests, or blood-based tests, that detect the presence of antibodies against COVID-19. Such testing is being rolled out by the Centers for Disease Control and Prevention, but the government agency is focusing on areas that became hot spots. Antibody tests are not widely available, and though there are efforts to make them accessible to the public, it's not clear when they will be.

Collins also said that antibody tests, like any other test, can be unreliable, producing both false negatives and false positives. Tests, for example, might not pick up antibodies present in small amounts because immunity declined, even if the person was infected.

What we need is more conclusive medical and scientific research on how COVID-19 is transmitted, particularly through asymptomatic people, and a more precise tally of how many people have been infected. Individual access to accurate antibody tests will be important to answering the lingering question about potential infection, but it's still unclear how long immunity lasts.

In the meantime, suspicion of a COVID-19 infection without confirmation is no reason to relax social distancing or hygiene practices.

"This thing is not going to go away fast," said Collins. "Weve got to know more about how the disease spreads. The idea of testing will give some level of confidence, but it wont be enough until we know more about how the disease is transmitted."

UPDATE: April 9, 2020, 8:48 a.m. PDT This story was updated to include information about new genomic research suggesting that COVID-19 was beginning to spread in New York in mid-February.

Link:
'Did I already have coronavirus?': People wonder if they previously had COVID-19, but the answer isn't easy - Mashable

There was a time when waking up with a scratchy throat or a dry cough didnt elicit such a sense of dread, but Covid-19 has made us all hyper-aware of its symptoms. Many people have been left wondering if they are asymptomatic carriers of the disease, or if a slight cold they may have recently experienced was actually something more menacing.

These fears are not unfounded: More than a million patients around the world have confirmed cases of coronavirus, but the real number of infections is far higherthough nobody yet knows by how much.

Thats why medical professionals are rushing to develop tests for antibodies that might reveal if a patient ever contracted Covid-19, regardless of whether they experienced symptoms. These tests may even be able to determine individual immunities to the virus, which has led to speculation that some people could reenter the workforce or resume normal activities if they have the right antibodies.

While this proposed solution may provide a sense of hope, it is far from a certain outcome at this point in time. Theres no clear consensus about the immunological response to Covid-19, and murky ethical problems undergird the idea of lifting restrictions on some populations, while isolating others, especially based on unsettled science.

Heres what you need to know about these tests, their development, and their potential to influence the global Covid-19 response.

Antibody tests, also known as serological tests, differ from the diagnostic swab tests that have been in high demand since the pandemic gained momentum.

Swab tests, or PCR tests, are designed to directly detect the virus by searching for its RNA, which is a genetic signature of its presence. These tests require collection of mucus samples from patients, typically sourced from deep within the nasal cavity, which are then sent to a laboratory to be examined. If the results come back positive, the patient is considered an active carrier of Covid-19 who could potentially infect other people.

Antibody tests, in contrast, dont look for the virus itself, but rather our immunological response to it. When our bodies are invaded by antigens such as the coronavirus, our immune systems react by creating a type of blood protein called an antibody. Antibodies flow through the blood, attacking the alien antigens by binding to them, which can neutralize the spread of infection. Many known antibodies can be detected with a quick blood test.

The idea is that you have volunteers who have recovered from infection, and you look to see what antibodies theyre expressing and test that against samples of the virus, basically, to see what are the circulating antibodies that recognize your virus, said Ruth Collins, professor of molecular medicine at Cornell University College of Veterinary Medicine, in a call.

It can take several weeks for the immune system to develop antibodies to fight a virus, which means positive serological tests may not indicate an active infection. Instead, the presence of coronavirus antibodies demonstrates if a patient ever had Covid-19, whether or not they experienced symptoms.

While it is common for an exposed person to develop immunity to other known viruses, it is important to emphasize that nobody knows yet whether the presence of Covid-19 antibodies indicates that a patient has either temporary or permanent immunity to the infection.

We dont know yet exactly how peoples immune systems respond to the infection, so wed have to find something that would mark everybodys response to the virusthe universal human response to the virusand to make sure that it was specific to this virus, Collins said.

These things are doable, she added, they just take a long time to work out.

Short answer: We have no idea.

Countless teams of scientists around the world are developing serological tests to detect antibodies related to Covid-19, including researchers at the Centers for Disease Control (CDC). Last Thursday, the US Food and Drug Administration approved the first test for antibodies test for Covid-19, though it is intended as a diagnostic test for active infections.

Last week, a team of scientists at Stanford University conducted finger-prick blood tests on 3,200 volunteers to help refine their antibody test. Likewise, in Italy, an entire town of 3,000 people that already received swab tests is now in the process of providing blood samples to follow-up on the diagnostic data with antibody studies.

Regardless, there have also been setbacks with the roughly 100 test kits for these antibodies that are already in development. None of these tests are close to reaching the high bar required for public distribution.

"Theres so much we really dont know"

Youd have to have a very high specificity and sensitivity, so you would be able to pick up even small amounts of those antibodies or the evidence of infection in people's blood, Collins said. Without that, you could well have people that have been infected without knowing about it, she continued, or people who might think they were still naive, immunologically, when in fact they werent.

In other words, antibody tests not only need to be good enough to yield reliable positive results, they also need to clearly show who does not have Covid-19 antibodies. Finding the right balance requires making sure that antibodies linked to viruses that arent Covid-19 do not produce false positives, and ensuring that the antibodies that are specifically linked to this particular coronavirus cannot evade detection.

Its hard to predict how long this process will take, given that so many teams are actively working on it, but its probably optimistic to expect they will take weeks or even months to be widely available to the public.

This timeline might be further delayed by new revelations about Covid-19. For instance, its possible that some carriers may never develop symptoms, but could still remain infectious to others for months.

Theres not even a consensus that everybody will completely clear the virus from their system, Collins noted. Some people may be asymptomatic shedders for a while. Theres so much we really dont know.

The phrase immunity passport has been floated by the government of the United Kingdom, and others, as a potential way to allow people with immunity to Covid-19 to return to regular work and travel routines.

Assuming that widespread serological testing is achievable, the idea is that people with antibodies linked to Covid-19 would be cleared of social distancing measures because they are theoretically immune to the virus and cannot actively spread it. This would bring back some normalcy for some of the population, and it would also enable scientists to better estimate the total number of Covid-19 cases, as opposed to confirmed cases involving patients who were sick enough to receive a swab test.

On the flip side, antibody tests for this purpose raise concerns about privacy rights and employment inequities, given that authorities would be using medical information to judge whether patients can return to work and normal life.

In the United States, the Americans with Disabilities Act (ADA) and the Genetic Information Act (GINA) prevent employers from discriminating on the basis of disability or genetic information. But discrimination for health reasons remains legal in many contexts in the United States, according to Jessica Roberts, director of the Health Law and Policy Institute at the University of Houston Law Center.

"We can go some way towards knowing who has been infected, but the idea of it being used as employment criteria is somewhat dystopian

Both laws would likely permit employers to screen employees for antibodies, Roberts said in an email. She noted that GINA only applies to genetic test results and family medical history, which are not likely to apply to antibody tests, which do not look for individual genetic information.

Moreover, the ADA actually allows employers to discriminate if employing a person with a disability could threaten the safety of the workplace, Roberts added. Assuming that ADA protection applies to people with Covid-19 (which a court would have to ask whether having Covid-19 constitutes a legally recognized disability), the employer could still prohibit an employee from coming to work if the employer could show that the employee would pose a significant risk.

The notion of planning a staggered reopening of society, in which restrictions are lifted on people judged immune to Covid-19, is inherently risky on both an epidemiological and ethical level.

While it may be soothing to daydream about receiving an immunity passport that allows you to return to your "normal" life, it is probably better to invest your energy in adapting to the restrictions, following health guidelines until more information is available, and working towards a better "normal" in whatever way you can.

It sounds good because it gives us what we want, which is definitive answers, Collins said.

But we dont know enough to be able to provide those definitive answers. We can go some way towards knowing who has been infected, but the idea of it being used as employment criteria is somewhat dystopian.

This article originally appeared on VICE US.

This article originally appeared on VICE US.

Original post:
What Are Antibody Tests, and Can They Prove Coronavirus Immunity? - VICE

Lung injury and acute respiratory distress syndrome have taken center stage as the most dreaded complications of COVID-19, the disease caused by the new coronavirus, SARS-CoV-2. But heart damage has recently emerged as yet another grim outcome in the virus'srepertoire of possible complications.

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COVID-19 is a spectrum disease, spanning the gamut from barely symptomatic infection to critical illness. Reassuringly, for the large majority of individuals infected with the new coronavirus, the ailment remains in the mild-to-moderate range.

Yet, a number of those infected develop heart-related problems either out of the blue or as a complication of preexisting cardiac disease. A report from the early days of the epidemic described the extent of cardiac injury among 41 patients hospitalized with COVID-19 in Wuhan, China: Five, or 12 percent, had signs of cardiovascular damage. These patients had both elevated levels of cardiac troponina protein released in the blood by the injured heart muscleand abnormalities on electrocardiograms and heart ultrasounds. Since then, other reports have affirmed that cardiac injury can be part of coronavirus-induced harm. Moreover, some reports detail clinical scenarios in which patients initial symptoms were cardiovascular rather than respiratory in nature.

How does the new coronavirus stoke cardiac damage?

The ways in which the new coronavirus provokes cardiac injury are neither that new nor surprising, according to Harvard Medical School physician-scientists Peter Libby and Paul Ridker. The part that remains unclear is whether SARS-CoV-2 is somehow more virulent toward the heart than other viruses.

Libby and Ridker, who are practicing cardiologists at Brigham and Womens, say COVID-19-related heart injury could occur in any several ways.

First, people with preexisting heart disease are at a greater risk for severe cardiovascular and respiratory complications from COVID-19. This is hardly a surprise. Research has shown that infection with the influenza virus poses a more severe threat for people with heart disease than those without cardiac problems. Research also shows that heart attacks can actually be brought on by respiratory infections such as the flu.

Second, people with previously undiagnosed heart disease may be presenting with previously silent cardiac symptoms unmasked by the viral infection. In people with existing heart-vessel blockages, infection, fever and inflammation can destabilize previously asymptomatic fatty plaques inside the heart vessels. Fever and inflammation also render the blood more prone to clotting, while also interfering with the bodys ability to dissolve clotsa one-two punch akin to throwing gasoline on smoldering embers.

Its like one big stress test for the heart, said Ridker, who is the Eugene Braunwald Professor of Medicine at Brigham and Womens Hospital.

Third, some people may experience heart damage that mimics heart attack injury even if their arteries lack the fatty, calcified flow-limiting blockages known to cause classic heart attacks. This scenario, called myocardial infarction type 2, can occur when the heart muscle is starved for oxygen, which in the case of COVID-19 may be triggered by a mismatch between oxygen supply and oxygen demand. Fever and inflammation accelerate heart rate and increase metabolic demands on many organs, including the heart. That stress is compounded if the lungs are infected and incapable of exchanging oxygen and carbon dioxide optimally. This impaired gas exchange can further diminish oxygen supply to the heart muscle.

Finally, there is a subset of people with COVID-19some of them previously healthy and with no underlying cardiac problemswho develop fulminant inflammation of the heart muscle as a result of the virus directly infecting the heart. This type of inflammation could lead to heart rhythm disturbances and cardiac muscle damage as well as interfere with the hearts ability to pump blood optimally.

The propensity of certain viruses to attack the heart muscle and cause viral myocarditis is well known, Libby said, adding that the most notorious viral offender has been the Coxsackie B virus. Nonetheless, a recent case report from Italy underscores the notion that the new coronavirus could also infect the heart and affect heart muscle function in healthy adults even after the acute phase of the infection has resolved and even in the absence of lung damage.

There are definitely some people who develop acute fulminant myocarditisin which the virus infects the heart muscle itself or the cells within the heartand causes a horrible inflammatory reaction, said Libby, who is also the Mallinckrodt Professor of Medicine at Brigham and Womens Hospital. This can be life threatening, and it can happen in people who don't have any preexisting risk factors.

Libby and Ridker, however, say this out-of-the-blue scenario in otherwise healthy individuals is likely rare relative to the overall number of people with COVID-19 who experience heart problems.

The frenemy within

For Ridker and Libby, who have studied the immune pathways of cardiovascular disease for decades, the cardiac involvement in COVID-19 is yet another striking example of the widespread effects of inflammation on multiple organs and systems.

Inflammation is a critical defense response during infection, but it has a dark side. Infections can set off a cascade of immune signals that affect various organs.

Libby and Ridker hypothesize that any infection in the bodya festering boil, an injured joint, a viruscan become a source of inflammation that activates the release of inflammatory proteins known as cytokines and calls up armies of white blood cells and other messenger molecules that, in an effort to fight the infection, disrupt normal processes. When these inflammatory molecules reach the welcoming soil of a fatty deposit in the blood vessel wallone that is already studded with resident inflammatory white blood cellsthe cytokines can boost the local inflammatory response and trigger a heart attack.

Our work has shown that cytokines can impinge on these cells in the plaque and push it through a round of further activation, Libby said.

The inflammatory chemicals released during infection can also induce the liver to ramp up the production of important proteins that defend the body from infection. These proteins, however, make the blood more prone to clotting, while also reducing the secretion of natural clot-dissolving substances. The tiny clots that may form can clog the small blood vessels in the heart and other organs, such as the kidneys, depriving them of oxygen and nutrients and setting the stage for the multisystem failure that can occur in acute infection.

Thus, immune-mediated injury to the heart and other organs could be collateral damage because of the bodys overwhelming systemic immune responsea condition known as cytokine storm, which is marked by the widespread release of cytokines that can cause cellular demise, tissue injury and organ damage.

COVID-19 and blood pressure medications

SARS-CoV-2 invades human cells by latching its spike protein onto the ACE2 receptor found on the surface of cells in the airways, lungs, heart, kidneys and blood vessels. The ACE2 protein is an important player in the renin-angiotensin-aldosterone system, which regulates blood vessel dilation and blood pressure. Two classes of drugs widely used to treat high blood pressure and heart diseaseACE inhibitors and angiotensin receptor blockersinteract with the ACE2 receptor. A possible concern related to COVID-19 stems from the notion that these blood pressure medications could increase the number of ACE2 receptors expressed on cells, possibly creating more molecular gates for the virus to enter. Some experts have wondered whether the use of such drugs could render people who take them more susceptible to infection. Conversely, others have postulated that the abundance of ACE2 receptors may enhance cardiovascular function, exercising a protective effect during infection.

The answer is far from clear, but a recent review suggests these medicines may play a dual role in COVID-19on the one hand, enhancing susceptibility to infection and, on the other, protecting the heart and ameliorating lung damage from the disease.

Libby and Ridker cautioned that patients who take such life-saving medications should stay on them or at least have a careful discussion with their cardiologists. This is because these drugs have clear and well-established benefits in hypertension and certain forms of heart disease, while their propensity to make humans more susceptible to SARS-CoV-2 remains speculative for the time being.

But what remains speculative today will crystalize in the weeks and months to come, Ridker and Libby said, because the science is moving forward rapidly, with new papers coming out daily and a growing pool of patients to draw observations from.

In 12 to 18 months we're going to have a great deal of information, but right now our job is to, number one, keep people from getting COVID-19 by strict adherence to now-familiar containment measures, Libby said. Then, we need to get people who get the disease through this acute phase.

The need for rigorous randomized trials done quickly and effectively is acute, they said. Until the evidence from these trials begins to coalesce, clinicians will have to navigate the uncharted territory of delivering cardiac care in the time of pandemic with caution but also with resolve.

We don't have the comfort of our usual databases, so we have to rely on our clinical skills and judgment. But we have to do so in all humility because often data dont bear out our logical preconceptions, Libby said. Yet, we must act.

RelatedEnding the Pandemic

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Coronavirus and the Heart - Harvard Medical School

Immunotherapies have revolutionized treatment for people with a variety of cancers. But when given to those with triple-negative breast cancer (TNBC), a particularly aggressive form of the disease, less than 20% respond.

A big question in the field has been, Why are the rest not responding? says Rumela Chakrabarti, an assistant professor at Penns School of Veterinary Medicine.

In a new paper in Nature Cell Biology, Chakrabarti and colleagues illuminate the molecular details at play. They found a signaling pathway which could be exploited in TNBC patients to better target therapies in the future. Using a mouse model of the disease that mimics key characteristics of human disease, they showed that losing the activity of the protein ELF5 promotes the activity of another protein, interferon-gamma receptor 1. Stabilized Interferon-gamma receptor 1 leads to activated interferon gamma signaling, which in turn leads to increases in tumor aggression and spread, which could be mitigated with therapeutics that block interferon gamma signaling.

This was an eye-opener, says Chakrabarti, because often interferon gamma has a protective effect in cancer and is commonly given as a cancer therapy to some patients. It works well in certain cancer types, but for particular subtypes of triple-negative breast cancer we see that blocking interferon gamma may be the best strategy for patients.

Chakrabarti had a deep familiarity with the biology of the ELF5 protein. She began studying it more than a decade ago as a postdoctoral researcher at the State University of New York at Buffalo, finding that its normal function supported pregnancy and lactation. More recently, in 2012 she and colleagues published a previous report in Nature Cell Biology showing that ELF5 could suppress a key transition that occurs to enable breast cancers to spread.

That earlier work, however, did not focus on TNBC specifically, in part because scientists had lacked an effective mouse model. Over the course of three years, Chakrabartis team developed a preclinical TNBC model that recapitulated two hallmarks of the disease: its propensity to spread and the influx of immune cells that accompanies tumor growth.

In the current study, the researchers found that, when these TNBC mices tumors also lost the function of the ELF5 protein, their disease course resembled that of human patients even more closely. Losing ELF5 made the disease very metastatic and very aggressive, says Chakrabarti.

To elucidate the molecular happenings that resulted in a more dangerous form of TNBC, Chakrabarti and colleagues examined the RNA that was being expressed in tumor cells of the TNBC mice whose tumors lost ELF5 expression. They found increased activity of the interferon-gamma pathway, caused, they believe, by an increase in expression of that proteins receptor. This loss also led to an accumulation of neutrophils, a type of immune cell, which has immune suppressive function. In contrast, normal mammary cells that retained ELF5 had low levels of interferon gamma signaling.

Blocking this signaling using an antibody against the interferon gamma receptor 1, or by genetically manipulating tumor cells to express lower levels of the receptor caused tumors to grow and spread more slowly.

Finally, to determine whether these findings in a mouse model may be relevant to humans, the research team looked at genetic and protein data from patients to determine their level of ELF5 and interferon gamma receptor expression. Patients with lower ELF5 and higher receptor levels, they observed, fared poorer; their cancers tended to spread sooner around their bodies.

The findings, Chakrabarti says, should be considered carefully by clinicians who are using interferon gamma and immunotherapies to treat cancer patients.

This is telling us that we need to target patients more selectively when we treat them, says Chakrabarti. It could be that if someone has low ELF5, they should be given an interferon-gamma signaling blocking therapy in addition to their immunotherapy.

In future work, Chakrabartis group will be diving in deeper into the immunology of TNBC, examining the role that different immune cells are playing in driving cancer metastasis and aggression. They also hope to see whether what they found regarding interferon gamma signaling in TNBC holds true in other tumor types, such as kidney and ovarian cancers.

Rumela Chakrabarti is an assistant professor of biomedical sciences at the University of Pennsylvania School of Veterinary Medicine.

Chakrabartis coauthors on the paper were first author Snahlata Singh, Sushil Kumar, Ratnesh Kumar Srivastava, Ajeya Nandi, Gatha Thacker, Hemma Murali, Sabrina Kim, Mary Baldeon, Mario Andres Blanco, and Serge Fuchs of Penn Vet; John Tobias, Rizwan Saffie, and Luca Busino of Penn s Perelman School of Medicine; Temple Universitys M. Raza Zaidi; and Satrajit Sinha of the State University of New York at Buffalo.

The work was supported by the National Cancer Institute (grants CA193661 and CA237243).

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Tailoring treatment for triple-negative breast cancer - Penn: Office of University Communications