The Second Punch

In another Wall Street Journal op-ed Jeff Colyer reports on the progress in the second punch in the one-two punch I mentioned above—the search for an effective treatment beyond supportive care for people with COVID-19:

What is the treatment?

Physicians are using two drugs in combination—hydroxychloroquine and azithromycin, which I’ll abbreviate HC and AZ—to treat patients with advanced Covid-19 symptoms. We use a regimen reported in a recent open-label trial in Marseille, France, which was updated March 26, and which doctors may modify in any given case.

What is the evidence?

For HC, two bodies of evidence support its potential in treating Covid-19: in vitro (test tube) studies and initial clinical reports from the field. After the 2002-03 global outbreak of SARS, a coronavirus related to the one that causes Covid-19, an in vitro study conducted by doctors from the Centers for Disease Control and Prevention identified chloroquine (a relative of HC) as an attractive option for prevention and treatment. If added before the virus was introduced, the drug was highly effective in preventing cellular infection. Even later application markedly inhibited infection. Another contemporaneous study showed similar results. As for Covid, a Chinese study published March 9 showed HC has excellent in vitro effects. Other recent information suggests potential antiviral mechanisms of HC and chloroquine.

The bedrock of all infectious medicine, from developing treatments for specific infections to treating individual patients, is in vitro laboratory testing and patient trials. Covid-19 is no exception. Current laboratory data suggest that HC should work.

Clinical information has also emerged from Covid treatment. During the initial Chinese outbreak, Wuhan doctors observed that patients with lupus—a disease for which HC is a common treatment—did not seem to develop Covid-19. Of 178 hospital patients who tested positive, none had lupus and none were on HC. None of this Wuhan hospital’s dermatology department’s 80 lupus patients were infected with the novel coronavirus. The Wuhan doctors hypothesized that this may be due to long-term use of HC. They treated 20 Covid-19 patients with HC. Their result: “Clinical symptoms improve significantly in 1 to 2 days. After five days of chest CT examination, 19 cases showed significant absorption improvement.”

Second, consider AZ—the antibiotic marketed as Z-Pak—combined with HC. The French study showed that 57% of 14 Covid-19 patients receiving HC without AZ tested negative for the virus on a nasal swab on day six. But 100% of the six patients who received both HC and AZ tested negative on day six. Compare that with 16 infected patients at another hospital who didn’t receive either treatment: only 12% tested negative on day six. These are small samples, but significant.

HC has been approved by the FDA and in use since 1955 and Z-Pak since 1988. Given the field experience in South Korea in using the two in combination to treat COVID-19, I’m not sure why American physicians would be reluctant.

Finding an effective treatment for COVID-19 is the sine qua non for stemming the epidemic. As long as people continue to contract the disease which in my opinion is likely to be forever, new cases will continue to threaten the health care system with collapse.

It should be carefully noted that HC+Z-Pak or any other treatment will not be prophylactic and will not be a substitute for limiting the spread of the disease. Testing will need to be increased by several orders of magnitude, especially epidemiological testing and serological testing.

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The First Punch

I think this prescription by Scott Gottlieb and Lauren Silvis in an op-ed at the Wall Street Journal makes sense:

How do we crack the current outbreak, develop a plan to return to normal life, and ensure that the virus never poses the same threat again? That will require a system that can detect when the virus is spreading. The system would have three components:

First, a sentinel surveillance system, which collects high-quality data from specific locations and can test a statistically representative sample of patients to detect where and when the virus may be spreading. Such a system could help find small pockets of infection before they multiply into larger outbreaks.

Second, rapid and reliable diagnostic tools. Insurance coverage should be mandatory, and the Centers for Disease Control and Prevention should give flexible guidance that encourages doctors to test liberally. If you have any signs or symptoms of Covid-19, you get a test right away with no out-of-pocket payment.

Third, coronavirus serology tests, which screen blood for the antibodies that confer immunity after exposure to a pathogen. This is essential for tailoring interventions to stop local spread. If you know that a large percentage of people have been exposed and developed some immunity, it may allow for less-restrictive measures. These tests can be added to routine blood draws with no additional hassle for the patient.

This should be implemented with all due haste and whatever can be done to expedite the process should be done. That’s the first punch in the one-two punch that will enable all of these “stay at home” directives to be lifted prudently.

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Father of the Year

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COVID-19 + Power Failure = Double Disaster

Paul Steidler is right in his piece at Inside Sources. COVID-19-induced power failure is a “double disaster” we really need to avoid:

The electric grid is essential for all aspects of modern life — including hospital care, food preservation, computer operations (i.e., many people’s ability to work), and at-home medical devices for the sick, elderly and disabled.

When countries attack one another, there is an excellent reason the grid is typically a top target. By knocking out electric power, an adversary is thrown into disarray.

To make sure our grid stays up, we need to make sure the people managing the grid stay healthy. Indeed, this must be a priority.

The highly-skilled, hard-to-replace and experienced professionals in the energy profession seldom can work from home. In fact, there is no record of a power line ever having been replaced remotely.

There are also significant limits to “social distancing” in power production. Line workers often must be near one another.

The engineers and other professionals in the control rooms of power plants and transmission facilities must be able to communicate immediately, directly and close to one another.

Think things are tough now? Imagine being trapped in your house with your kids for a week without electricity.

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Re-Infected?

At NPR Emily Feng presents some accounts of people in Wuhan who were pronounced recovered from COVID-19 who reportedly have it again:

NPR has spoken by phone or exchanged text messages with four individuals in Wuhan who are part of this group of individuals testing positive a second time in March. All four said they had been sickened with the virus and tested positive, then were released from medical care in recent weeks after their condition improved and they tested negative.

Two of them are front-line doctors who were sickened after treating patients in their Wuhan hospitals. The other two are Wuhan residents. They all requested anonymity when speaking with NPR because those who have challenged the government’s handling of the outbreak have been detained.

One of the Wuhan residents who spoke to NPR exhibited severe symptoms during their first round of illness and was eventually hospitalized. The second resident displayed only mild symptoms at first and was quarantined in one of more than a dozen makeshift treatment centers erected in Wuhan during the peak of the outbreak.

But when both were tested a second time for the coronavirus on Sunday, March 22, as a precondition for seeking medical care for unrelated health issues, they tested positive for the coronavirus even though they exhibited none of the typical symptoms, such as a fever or dry cough. The time from their recovery and release to the retest ranged from a few days to a few weeks.

Read the whole thing.

We don’t know whether these were the results of false negatives, false positives, some combination, or something else. Take it for what it’s worth.

Basically, I don’t believe any reports coming out of China these days but if individuals who’ve had COVID-19 don’t gain immunity it’s pretty much a worst case scenario.

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South Korea’s COVID-19 Timeline

The Center for Strategic & International Studies has produced a timeline of South Korea’s response to COVID-19 which I commend to your attention. Their response has been hailed as a model for other countries but, unfortunately, at this point we just don’t know. More than anything I think it demonstrates what a small, compact country with high social cohesion and a recent history of authoritarian rule can accomplish.

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Why Physicians May Go Out of Business

An article at 24/7 Wall Street makes the argument I’ve been putting forward in much greater detail:

The doctors who face severe financial shortfalls in their business fall into two groups. Just over 100,000 doctors are primary care physicians. Some will shutter their offices out of concern for doctor, staff and patient safety. Doctors who work in certain specialties, of which there are about 40, may be unable to treat patients at all. There are almost 20,000 ophthalmologists, 13,000 neurologists, 57,000 pediatricians and 7,000 plastic surgeons. Among these and several other specialties, office visits will drop to near zero as the number of sick and dead people multiplies.

Telemedicine has been suggested as one means to treat patients somewhat. However, the means to bill for these “visits” are ill-defined. And in some cases, the doctor needs to examine and see the patient physically. Areas under lockdown make this impossible. Doctors using telemedicine still need to pay office rents and insurance and sometimes staff members.

Some private doctors have volunteered to treat COVID-19 patients by volunteering at hospitals. Some hospitals require private doctors who have privileges to admit patients under normal circumstances to help their hospitals to treat COVID-19 patients onsite, but without pay. These doctors do not have time to see their own patients, even with the use of telemedicine.

I don’t know whether my circle of friends is typical or not but many of the physicians of my acquaintance aren’t great savers. I don’t know how long a “stay at home” directive they’ll be able to sustain.

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Why Epidemiological Testing Is Important

I encourage you to read this post by Luigi Zingales at City Journal:

The Italian experience suggests that locking down towns is a necessary but insufficient condition to stop the spread of Covid-19. If 50 percent of the infected are asymptomatic, there is no hope of containing the disease unless we subject ourselves to massive testing. On February 22, 89 inhabitants of Vò Euganeo, a small town close to Padua, were found to be infected. Weeks later, the town is free of infection. The lesson of Vò Euganeo is of value to the world as it confronts this unimaginable crisis.

Vò Euganeo is a small town of 3,341 people located on the hills just outside of Padua, where I grew up. It came to international prominence on February 21, when Adriano Trevisan, a 77-year-old inhabitant, died of coronavirus. What will ensure Vò Euganeo a place in the history of medicine is the decision made by the Governor of the Veneto region (which includes Padua, Venice, and Verona) to test all 3,341 inhabitants of the town twice: the first time before closing it off from the rest of Italy, and a second time two weeks later.

In this respect, Vò Euganeo resembles the Diamond Princess, the ship that was quarantined in the port of Yokohama with about 3,700 passengers, making it comparable in size to the town. In both cases, we can observe an entire population exposed to the virus over time, with comprehensive testing. This is different from all other cases, where only a fraction of the population—usually symptomatic—is tested.

To understand what works in containing the spread of the disease, we need to have an accurate count of the infected. Reported infection numbers differ wildly from actual rates of infection and this gap might change over time, as regions expand their testing protocols differently. The experience of Vò and the Diamond Princess demonstrate how various testing approaches can have radically different results. On February 22, 3 percent of the inhabitants of Vò were infected. After two weeks, during which the town was locked down, only 0.25 percent were infected. Once these few infected people were isolated, the town reopened and has experienced no new cases. Compare this strategy with the one adopted in the Diamond Princess. Initially, passengers and crew members were tested when they showed symptoms, and only after that were they taken off the boat. Only toward the end did the authorities test all the passengers. As a result, what started with the infection of one passenger eventually contaminated 20 percent of the people on board. Thus, in one case we go from 3 percent to 0 percent infections, while in the other case from 1 percent to 20 percent.

Read the whole thing.

There are actually two messages here. The first is that the type of testing we’re doing now cannot achieve the objective of reducing the spread of the disease. The second is that epidemiological testing can. That can either be accomplished by sampling, universal testing, or a combination of the two.

Just as is the case with perfect compliance, completely universal testing will remain beyond our reach. We can’t even get everybody to immunize their kids against chickenpox or measles, for goodness sake. We can do better than we are but that will require many, many more tests with quicker results than are presently available and more reliance on epidemiological testing even if it means a reduction in diagnostic testing.

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Predictions

It isn’t too early to start making a few, tentative predictions. I welcome your own predictions in comments. Here are some of mine.

  • Even with the strenuous avoidance measures that have been put in place the peak of the curve of active COVID-19 cases in the U. S. won’t be reached in two or three weeks. It may take months.
  • There will be plenty of kvetching and even some lawsuits about the attempts by governors, like the governor of Rhode Island, to reduce the flow of people from states with larger numbers of diagnosed cases into their states. Governors do have that power under states of emergency, the Privileges and Immunities clause of the U. S. Constitution notwithstanding. There is plenty of case law to support it. It’s century-old case law but it’s unlikely to be overturned.
  • The shortages of materiel (face masks, respirators, ventilators, etc.) will ease over the next few weeks if federal, state, and local officials allow them to. Lots and lots of people want to and are contributing to the effort against COVID-19. It will become a valence issue.
  • As testing increases the number of diagnosed cases will increase rapidly.
  • U. S. GDP will take a 10% hit. That will ripple across the world. If the strenuous measures presently in place and which will be put in place over the next couple of weeks continue past the end of April, the decline in U. S. GDP will be much, much greater. They sky’s the limit.
  • The number of personal and corporate bankruptcies will soar. There will be what amounts to a full employment program for attorneys.
  • Enough people in the top 10% of income earners are, effectively, living beyond their means, i.e. month to month, that defaults on loans that were thought to be secure will start happening.
  • As I’ve said before anyone who earns their livings through performing personal services will take an enormous hit to their incomes. That doesn’t just include people like beauticians and barbers. It includes dentists and physicians. Physicians who are still sole practitioners won’t be able to pay their malpractice insurance bills. After the dust has settled there will be calls to reorganize the way health care is delivered.
  • Companies that will face enormous headwinds due to the “stay at home” directives and fear of contagion include airlines, cruise ship companies, and oil companies. There will be pleas to bail out the airlines. They should be resisted. I don’t know whether Disney’s loss of revenue due to the shutting down of its parks and experiences segment will be outweighed by increased revenue from Disney+.
  • COVID-19 will be the straw that broke the camel’s back for the city of Chicago. It is presently spending money in vast amounts that it doesn’t actually have. Its bonds, already rated the worst of any major city in the country, will be reduced to junk which effectively means the city will be unable to borrow. Same with the CPS. There will be calls to bail out Chicago and other cities. These calls should be resisted.
  • Urban real estate will decline in value at least in relative terms.
  • Amazon and other online retailers will actually benefit from COVID-19. Small retailers other than grocery stores will take an enormous hit. Lots of bankruptcies.
  • Zoom’s stock has doubled in price. That will continue to rise. It’s one of the prime beneficiaries of the “stay at home” directives.
  • The longer the “stay at home” directives continue, the more workers from Mexico and Central America will return to their native countries. This will evoke a second wave of COVID-19 cases in these countries in the Americas. The same thing may happen in Africa and the Middle East as well but European countries’ more expansive welfare systems may stem that.
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COVID-19 Status 3/29/2020

I wanted to draw your attention to the table above, sampled from this article at the Associated Press, depicting the number of cases of COVID-19, deaths due to the disease, and number recovered by county. If I could embed the table, I would. It’s interesting for a number of reasons.

You should take note of a few things. The most important thing is that these are just diagnosed cases. I believe that the actual number of cases not just in the United States but everywhere is much, much larger. Maybe an order of magnitude larger. Notice that in the United States, Western Europe, and Canada the number of deaths as a percentage of diagnosed cases the number of deaths is in single digits (or less). Here in the U. S. it’s 1.65%. In Germany it’s less than 1%. In Italy (10.8%) and Spain (8%) are seeing much higher rates. Why that is will undoubtedly be the subject of much study in the years to come. Diagnosed cases and deaths will continue to increase. As testing expands beyond those who definitely show symptoms to include those who show no symptoms, the diagnosed cases will increase substantially. I strongly suspect that the number of deaths attributed to COVID-19 will not increase proportionally, i.e. deaths as a percentage of diagnosed cases will decrease substantially.

Consider that last column: recoveries. Those are the statistics I’m worried about. Even if the rise of new cases is slowed the very slow pace of recovery from COVID-19 could overwhelm the health care system.

I believe you could construct a model that demonstrates, at least as a first order approximation, that the number of cases can be predicted based on variables including population, population density, and how connected a country is to the world economy (maybe just to China).

Many, many major unknowns remain. Among them are whether reinfection is possible or even likely, whether the prevalence of the virus abates as the weather warms, whether the avoidance strategy being used here can work even with society-wide testing, whether there are effective treatments for COVID-19, whether a vaccine can be developed for it in the foreseeable future, and just how credible the stats that China is reporting are.

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