This Might Explain Something Very Odd About Covid-19

One of the strange things about this virus is how patients can suddenly deteriorate, sometimes to the point of death. A highly-experienced emergency room doctor named Richard Levitan may have just explained why — he also suggests a way we might easily keep more people alive.

He lives in New Hampshire but volunteered to work ten days at New York City’s Bellevue Hospital, where he trained. This is from his article in today’s New York Times:

Here is what really surprised us: These patients did not report any sensation of breathing problems, even though their chest X-rays showed diffuse pneumonia and their oxygen was below normal. How could this be?

We are just beginning to recognize that Covid pneumonia initially causes a form of oxygen deprivation we call “silent hypoxia” — “silent” because of its insidious, hard-to-detect nature.

Pneumonia is an infection of the lungs in which the air sacs fill with fluid or pus. Normally, patients develop chest discomfort, pain with breathing and other breathing problems. But when Covid pneumonia first strikes, patients don’t feel short of breath, even as their oxygen levels fall. And by the time they do, they have alarmingly low oxygen levels and moderate-to-severe pneumonia (as seen on chest X-rays). Normal oxygen saturation for most persons at sea level is 94 percent to 100 percent; Covid pneumonia patients I saw had oxygen saturations as low as 50 percent.

To my amazement, most patients I saw said they had been sick for a week or so with fever, cough, upset stomach and fatigue, but they only became short of breath the day they came to the hospital. Their pneumonia had clearly been going on for days, but by the time they felt they had to go to the hospital, they were often already in critical condition.

In emergency departments we insert breathing tubes in critically ill patients for a variety of reasons. In my 30 years of practice, however, most patients requiring emergency intubation are in shock, have altered mental status or are grunting to breathe. Patients requiring intubation because of acute hypoxia are often unconscious or using every muscle they can to take a breath. They are in extreme duress. Covid pneumonia cases are very different.

A vast majority of Covid pneumonia patients I met had remarkably low oxygen saturations at triage — seemingly incompatible with life — but they were using their cellphones as we put them on monitors. Although breathing fast, they had relatively minimal apparent distress, despite dangerously low oxygen levels and terrible pneumonia on chest X-rays.

We are only just beginning to understand why this is so. The coronavirus attacks lung cells that make surfactant. This substance helps keep the air sacs in the lungs stay open between breaths and is critical to normal lung function. As the inflammation from Covid pneumonia starts, it causes the air sacs to collapse, and oxygen levels fall. Yet the lungs initially remain “compliant,” not yet stiff or heavy with fluid. This means patients can still expel carbon dioxide — and without a buildup of carbon dioxide, patients do not feel short of breath.

Patients compensate for the low oxygen in their blood by breathing faster and deeper — and this happens without their realizing it. This silent hypoxia, and the patient’s physiological response to it, causes even more inflammation and more air sacs to collapse, and the pneumonia worsens until their oxygen levels plummet. In effect, the patient is injuring their own lungs by breathing harder and harder. Twenty percent of Covid pneumonia patients then go on to a second and deadlier phase of lung injury. Fluid builds up and the lungs become stiff, carbon dioxide rises, and patients develop acute respiratory failure.

By the time patients have noticeable trouble breathing and present to the hospital with dangerously low oxygen levels, many will ultimately require a ventilator.
Silent hypoxia progressing rapidly to respiratory failure explains cases of Covid-19 patients dying suddenly after not feeling short of breath. (It appears that most Covid-19 patients experience relatively mild symptoms and get over the illness in a week or two without treatment.)

A major reason this pandemic is straining our health system is the alarming severity of lung injury patients have when they arrive in emergency rooms. Covid-19 overwhelmingly kills through the lungs. And because so many patients are not going to the hospital until their pneumonia is already well advanced, many wind up on ventilators, causing shortages of the machines. And once on ventilators, many die.

There is a way we could identify more patients who have Covid pneumonia sooner and treat them more effectively — and it would not require waiting for a coronavirus test at a hospital or doctor’s office. It requires detecting silent hypoxia early through a common medical device that can be purchased without a prescription at most pharmacies: a pulse oximeter.

Pulse oximetry is no more complicated than using a thermometer. These small devices turn on with one button and are placed on a fingertip. In a few seconds, two numbers are displayed: oxygen saturation and pulse rate. Pulse oximeters are extremely reliable in detecting oxygenation problems and elevated heart rates.

Pulse oximeters helped save the lives of two emergency physicians I know, alerting them early on to the need for treatment. When they noticed their oxygen levels declining, both went to the hospital and recovered (though one waited longer and required more treatment). Detection of hypoxia, early treatment and close monitoring apparently also worked for Boris Johnson, the British prime minister.

Widespread pulse oximetry screening for Covid pneumonia — whether people check themselves on home devices or go to clinics or doctors’ offices — could provide an early warning system for the kinds of breathing problems associated with Covid pneumonia.
People using the devices at home would want to consult with their doctors to reduce the number of people who come to the E.R. unnecessarily because they misinterpret their device. There also may be some patients who have unrecognized chronic lung problems and have borderline or slightly low oxygen saturations unrelated to Covid-19.

All patients who have tested positive for the coronavirus should have pulse oximetry monitoring for two weeks, the period during which Covid pneumonia typically develops. All persons with cough, fatigue and fevers should also have pulse oximeter monitoring even if they have not had virus testing, or even if their swab test was negative, because those tests are only about 70 percent accurate. A vast majority of Americans who have been exposed to the virus don’t know it.

Unquote.

This is a pulse oximeter. You may have stuck your finger in one at your doctor’s office, without really knowing why. I have one that looks like this.

thumbnail_CCI-BLACK-OX-DLX-2T

This little device measures the oxygen in your blood by sending infrared light through your finger. You can buy one for as little as $30. Some cost up to $60. If Dr. Levitan is right, they’re going to become very popular.

“Devs” Is an Excellent Series, Except…

Devs is a science fiction series that’s streaming on the Hulu service. You have to pay for Hulu, but they usually have a free trial for new subscribers. If you have the right kind of Spotify account, Hulu is free.

The people who made Devs have done a brilliant job. The scripts are intelligent, the actors are talented. One thing that sets it apart is that it’s visually stunning. It’s a TV show that looks better than most big-budget movies. One reason it’s so good is that it’s written and directed by Alex Garland, the filmmaker hugely responsible for 28 Days Later, Ex Machina and Annihilation.

Another thing that sets Devs apart is that it concerns the nature of reality. Is the universe deterministic? What is the correct interpretation of quantum mechanics? Are there multiple worlds? Do you and I have free will? Should we be held morally responsible for our decisions if we couldn’t have chosen otherwise?

I haven’t finished the series yet. Maybe when it’s over, my opinion will have changed. I think Aristotle said we should judge a work of art as a whole.

What motivated me to write this post, however, was that one of the characters, Lily Chan, is now faced with what might turn out to be a truly momentous decision, possibly the biggest decision anyone has ever made. (A determinist would say I had no choice — the history of the universe made me start writing.) It isn’t giving much away about the show to say that Lily has been told she will be at a certain place later tonight and, assuming she is, things are going to go terribly wrong. She and her friend both think it’s crazy to think anybody could reliably predict such a thing, but at the same time she wants to make sure the prediction doesn’t come true. How should she make sure of that?

Here are two options:

(a) She and her friend, who are in the beautiful city of San Francisco, should get some cash, turn off their phones and start driving. They should drive as far away as possible from the place she’s predicted to be later tonight. They should definitely not stay in San Francisco, since it’s only a few miles from where the big, bad event is supposed to happen. Come on, Lily! Run away!

(b) Lily and her friend should stay in her apartment in San Francisco, but not go outside. That should be good enough.

If you were in her situation and you wanted to prove the prediction wrong, which option would you choose? Would you choose (a) or (b) to make sure the very, very bad thing didn’t happen?

This is a TV show. Which option does she choose?

I think we all know the answers to these questions.

People Have Said This Is the Best Article About the Virus

A science and health reporter, Donald McNeill, who specializes in “plagues and pestilences”, consulted “more than 20 experts in public health, medicine, epidemiology and history” and then wrote a long article for The New York Times. It’s called “ The Coronavirus in America: The Year Ahead”. It’s received a lot of praise. These are the parts (2,200 words or so) I found most interesting. The article has many links that aren’t included below.

What follows is divided into sections:

How Many Will Die
The Lockdowns Will End, But Haltingly
Immunity Will Become an Advantage in Society
A Vaccine Is Not Coming Soon
Treatments Are Likely To Arrive First
We Will Need International Cooperation

[ How Many Will Die ]

In fast-moving epidemics, far more victims pour into hospitals or die at home than doctors can test; at the same time, the mildly ill or asymptomatic never get tested. Those two factors distort the true fatality rate in opposite ways. If you don’t know how many people are infected, you don’t know how deadly a virus is.

Only when tens of thousands of antibody tests are done will we know how many silent carriers there may be in the United States. The C.D.C.  has suggested it might be 25 percent  of those who test positive. Researchers in Iceland  said it might be double that.

China is also revising its own estimates. In February, a  major study  concluded that only 1 percent of cases in Wuhan were asymptomatic.  New research  says  perhaps 60 percent  were. Our knowledge gaps are still wide enough to make epidemiologists weep.

“All models are just models,” Dr. Anthony S. Fauci, science adviser to the White House coronavirus task force, has said. “When you get new data, you change them.”

There may be good news buried in this inconsistency: The virus may also be mutating to cause fewer symptoms. In the movies, viruses become more deadly. In reality, they usually become less so, because asymptomatic strains reach more hosts. Even the 1918 Spanish flu virus eventually  faded into the seasonal H1N1 flu.

At the moment, however, we do not know  exactly how transmissible  or lethal the virus is. But refrigerated trucks parked outside hospitals tell us all we need to know: It is far worse than a bad flu season.

[ The Lockdowns Will End, But Haltingly ]

The next two years will proceed in fits and starts, experts said. As more immune people get back to work, more of the economy will recover.

But if too many people get infected at once, new lockdowns will become inevitable. To avoid that, widespread testing will be imperative.

Dr. Fauci has said “the virus will tell us” when it’s safe. He means that once a national baseline of hundreds of thousands of daily tests is established across the nation, any viral spread can be spotted when the percentage of positive results rises.

Detecting rising fevers as they are mapped by … smart thermometers may give an earlier signal…

But diagnostic testing has been troubled from the beginning. Despite assurances from the White House, doctors and patients continue to complain of delays and shortages.

To keep the virus in check, several experts insisted, the country also must start isolating all the ill — including mild cases.

In this country, patients who test positive are asked to stay in their homes, but keep away from their families.

Television news has been filled with recuperating personalities like CNN’s Chris Cuomo, sweating alone in his basement while his wife left food atop the stairs…

But even Mr. Cuomo ended up illustrating why the W.H.O. strongly opposes home isolation. On Wednesday, he revealed that his wife had the virus.

“If I was forced to select only one intervention, it would be the rapid isolation of all cases,” said Dr. Bruce Aylward, who led the W.H.O. observer team to China.

In China, anyone testing positive, no matter how mild their symptoms, was required to immediately enter an infirmary-style hospital — often set up in a gymnasium or community center outfitted with oxygen tanks and CT scanners.

There, they recuperated under the eyes of nurses. That reduced the risk to families, and being with other victims relieved some patients’ fears…

Still, experts were divided on the idea of such wards. [One called for] mandatory but “humane quarantine processes.”

By contrast, [a Harvard epidemiologist] opposed the idea, saying: “I don’t trust our government to remove people from their families by force.”

Ultimately, suppressing a virus requires testing all the contacts of every known case. But the United States is far short of that goal.

Someone working in a restaurant or factory may have dozens or even hundreds of contacts. In China’s Sichuan Province, for example, each known case had an average of 45 contacts.

The C.D.C. has about 600 contact tracers and, until recently, state and local health departments employed about 1,600, mostly for tracing syphilis and tuberculosis cases.

China hired and trained 9,000 in Wuhan alone. [It’s been] estimated that the United States will need at least 300,000.

[ Immunity Will Become an Advantage in Society ]

Imagine an America divided into two classes: those who have recovered from infection with the coronavirus and presumably have some immunity to it; and those who are still vulnerable.

“It will be a frightening schism,” … a World Health Organization special envoy on Covid-19, predicted. “Those with antibodies will be able to travel and work, and the rest will be discriminated against.”

Already, people with presumed immunity are very much in demand, asked to donate their blood for antibodies and doing risky medical jobs fearlessly.

Soon the government will have to invent a way to certify who is truly immune. A test for IgG antibodies, which are produced once immunity is established, would make sense… Many companies are working on them.

Dr. Fauci has said the White House was discussing certificates like those proposed in Germany. China uses cellphone QR codes linked to the owner’s personal details so others cannot borrow them….

As Americans stuck in lockdown see their immune neighbors resuming their lives and perhaps even taking the jobs they lost, it is not hard to imagine the enormous temptation to join them through self-infection, experts predicted. Younger citizens in particular will calculate that risking a serious illness may still be better than impoverishment and isolation.

“My daughter, who is a Harvard economist, keeps telling me her age group needs to have Covid-19 parties to develop immunity and keep the economy going,” said Dr. Michele Barry…

It would be a gamble [since] even slim, healthy young Americans have died of Covid-19.

[ A Vaccine Is Not Coming Soon ]

Even though limited human trials of three candidates — two here and one in China — have already begun, [Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases] has repeatedly said that any effort to make a vaccine will take at least a year to 18 months.

All the experts familiar with vaccine production agreed that … that timeline was optimistic… The record is four years, for the mumps vaccine.

Researchers differed sharply over what should be done to speed the process. Modern biotechnology techniques using RNA or DNA platforms make it possible to develop candidate vaccines faster than ever before.

But clinical trials take time, in part because there is no way to rush the production of antibodies in the human body.

Also, for unclear reasons, some previous vaccine candidates against coronaviruses like SARS have triggered “antibody-dependent enhancement,” which makes recipients more susceptible to infection, rather than less….

A new vaccine is usually first tested in fewer than 100 young, healthy volunteers. If it appears safe and produces antibodies, thousands more volunteers — in this case, probably front-line workers at the highest risk — will get either it or a placebo in what is called a Phase 3 trial.

It is possible to speed up that process with “challenge trials.” Scientists vaccinate small numbers of volunteers, wait until they develop antibodies, and then “challenge” them with a deliberate infection to see if the vaccine protects them.

Challenge trials are used only when a disease is completely curable, such as malaria or typhoid fever. Normally, it is ethically unthinkable to challenge subjects with a disease with no cure, such as Covid-19.

But in these abnormal times, several experts argued that putting a few Americans at high risk for fast results could be more ethical than leaving millions at risk for years….

As arduous as testing a vaccine is, producing hundreds of millions of doses is even tougher, experts said.

Most American vaccine plants produce only about 5 million to 10 million doses a year, needed largely by the 4 million babies born and 4 million people who reach age 65 annually…

But if a vaccine is invented, the United States could need 300 million doses [assuming 30 million of us are immune] — or 600 million if two shots are required. And just as many syringes.

“People have to start thinking big,” [one doctor] said. “With that volume, you’ve got to start cranking it out pretty soon.”

Flu vaccine plants are large, but those that grow the vaccines in chicken eggs are not suitable for modern vaccines…

European countries have plants but will need them for their own citizens. China has a large vaccine industry, and may be able to expand it over the coming months. It might be able to make vaccines for the United States…

India and Brazil also have large vaccine industries. If the virus moves rapidly through their crowded populations, they may lose millions of citizens but achieve widespread herd immunity well before the United States does. In that case, they might have spare vaccine plant capacity.

Alternatively, [another doctor said] the government might take over and sterilize existing liquor or beer plants, which have large fermentation vats: “ any distillery could be converted”.

[ Treatment Is Likely To Arrive First ]

In the short term, experts were more optimistic about treatments than vaccines. Several felt that so-called convalescent serum could work.

The basic technique has been used for over a century: Blood is drawn from people who have recovered from a disease, then filtered to remove everything but the antibodies. The antibody-rich immunoglobulin is injected into patients.

The obstacle is that there are now relatively few survivors to harvest blood from [note: in New Jersey at least, you have to be under 60, among other requirements]….

[A treatment involving] monoclonal antibodies … recently came very close to conquering the Ebola epidemic in eastern Congo, [and] are the most likely short-term game changer…

The most effective antibodies are chosen, and the genes that produce them are spliced into a benign virus that will grow in a cellular broth.

But, as with vaccines, growing and purifying monoclonal antibodies takes time. In theory, with enough production, they could be used not just to save lives but to protect front-line workers….

Having a daily preventive pill would be an even better solution, because pills can be synthesized in factories far faster than vaccines or antibodies can be grown and purified.

But even if one were invented, production would have to ramp up until it was as ubiquitous as aspirin, so 300 million Americans could take it daily.

[Some keep suggesting] hydroxychloroquine and azithromycin… All the experts agreed … that no decision should be made until clinical trials are completed.

Some recalled that in the 1950s inadequate testing of thalidomide caused thousands of children to be born with malformed limbs. More than one hydroxychloroquine study has been halted after patients who got high doses developed abnormal heart rhythms.

“I doubt anyone will tolerate high doses, and there are vision issues if it accumulates,” [one doctor] said. “But it would be interesting to see if it could work [like pills used to prevent H.I.V.].

Others were harsher… “It’s total nonsense,” said … a former director of medical and biodefense preparedness at the National Security Council. “I told my family, if I get Covid, do not give me this combo.”

Chloroquine might protect patients hospitalized with pneumonia against lethal cytokine storms because it damps down immune reactions, several doctors said.

That does not, however, make it useful for preventing infections, as [some have] implied it would be, because it has no known antiviral properties.

Several antivirals, including remdesivir, favipiravir and baloxavir, are being tested against the coronavirus; the latter two are flu drugs.

Trials of various combinations in China are set to issue results by next month, but they will be small and possibly inconclusive…

[ We Will Need International Cooperation ]

A public health crisis of this magnitude requires international cooperation on a scale not seen in decades. Yet [the president] is moving to defund the W.H.O., the only organization capable of coordinating such a response.

And he spent most of this year antagonizing China, which now has the world’s most powerful functioning economy and may become the dominant supplier of drugs and vaccines. China has used the pandemic to extend its global influence, and says it has sent medical gear and equipment to nearly 120 countries [including the United States]….

“If [the president] cares about stepping up the public health efforts here, he should look for avenues to collaborate with China and stop the insults,” said … an economic historian… [A doctor added:] “What if they come up with the first vaccine? They have a choice about who they sell it to. Are we top of the list? Why would we be?”

Once the pandemic has passed, the national recovery may be swift…

The psychological fallout will be harder to gauge. The isolation and poverty caused by a long shutdown may drive up rates of domestic abuse, depression and suicide.

Even political perspectives may shift…. In the periods after both wars, society and incomes became more equal. Funds created for veterans’ and widows’ pensions led to social safety nets, measures like the G.I. Bill and V.A. home loans were adopted, unions grew stronger, and tax benefits for the wealthy withered.

If a vaccine saves lives, many Americans may become less suspicious of conventional medicine and more accepting of science in general…

 

Poor Grammar Leads to Justified Ridicule

One of the worst members of Congress expressed himself on Twitter last night with these words:

The United States has tested more than anyone in the world by far. Txxxx is the greatest testing President God has ever created.

You could read the second sentence as suggesting that President God — whoever that might be — created Txxxx as the greatest testing ever. This president has certainly tested us in many ways. But a Republican member of Congress would never acknowledge that reality.

Instead, thousands of Twitter-based smart alecks seized on the words “President God” as a great opportunity to express themselves. As well they should have.

Now, we sticklers will point out that the congressman should have put in a hyphen and used lower case, making it “the greatest-testing president” or maybe “the greatest testing-president”. He could have avoided some of the justified ridicule, but not completely.

Of the few replies I looked at, this was my favorite:

EV4kxNuXgAIETCA

A perhaps more apt reply was this:

Every time President God brags about how well he has done combating COVID-19, remember these FACTS:

The United States has just 1/23 of the world’s population.

The United States has had 1/4 of all COVID-19 deaths.

Actually, it’s 1/5 of all deaths (based on the available statistics), but the point remains.

Warren Even Endorses Well

Sen. Elizabeth Warren endorsed Joe Biden for president today. It’s a terrific little video with a nice moment at the end.