22 April 2020 – Wednesday – #38

One of the most useful Covid-19 online trackers I’ve seen for US states is at rt.live.

Current Covid-19 R value for every US state (at 21 April 2020).

For an infectious disease, “R” refers to the number of people an infected person infects. If an infected person infects two people, R = 2. When R > 1, there is an outbreak. When R < 1, an infection is attenuating in a population and, assuming no further outbreaks, will be eradicated.

None other than German Chancellor Merkel explains how tiny changes in R can make huge difference to a country’s healthcare system.

Chacellor Merkel explains the relationship of R to Germnay’s healthcare system (subtitled in English).

Parenthentically, wouldn’t it be great if the resident of the White House could articulate Covid-19 policy issues so clearly?

For Covid-19, the current methods to reduce R are either to isolate populations or, if enough Covid-19 test kits are available, to test, quarantine infected people, and track their contacts for testing. Let’s call those the isolation and quarantine methods. The quarantine method is preferable because fewer people die and the economy can run reasonably well.

Presumably some day there will be a treatment or a vaccine. In the absence of treatments or vaccines, we know these two methods work. And there’s bad news on vaccines (see below), which is why we need to pay attention to what is working now.

In the chart above, 21 US states have R values greater than one, so Covid-19 is spreading. In the other 29 states, Covid-19 infections are coming under control. Checkout the site. It also shows historical R values for each state. Five states are preparing to relax Covid-19 restrictions: Georgia (R = 0.60), South Carolina (R = 0.76), Tennessee (R = 0.91), Texas (R = 0.52), and Vermont (R = 0.46). I would take these R values with a grain of salt given the overall quality of Covid-19 data at this point, but I think the trend lines on the site are indicative.

The question, of course, is whether this is the right time for these five US states to relax their Covid-19 restrictions. It’s the same question in Europe. I reported yesterday the Spanish government was going to allow children to go outside. Well, after I reported that, the government went back and forth about lifting these restrictions. We were supposed to go to our windows and bang our pots to protest in favor of “liberating” the kids, but the heavy rain got the better part of that protest. Yesterday evening, the government decided to let children out starting 26 April. This small tempest in a teapot is indicative of how hard it is for governments to make even incremental Covid-19 policy changes.

What is the cost of relaxing Covid-19 restrictions? In my mind, Sweden continues to be an example of what the costs of relaxed Covid-19 restrictions might be. Unlike its neighbors, Sweden has prioritized its economy over a tight Covid-19 lockdown.

Swedish per capita Covid-19 mortality versus neighboring countries with greater Covid-19 restrictions.

Swedish per capita Covid-19 mortality has been running about double that of its neighbors (Denmark, Finland, and Norway) that have strict Covid-19 lockdowns. In recent days, Sweden’s mortality continues to increase, heading towards triple the per capita mortality of its neighbors, while its neighbors mortality is leveling off (R < 1). We probably won’t know the benefits to Sweden of it’s lighter Covid-19 restrictions until Q2 financial reports come in July, but we can tell retrospectively from increasing deaths that Sweden’s R is going the wrong direction.

I want to take a step back for a moment to ask the question, how many tests would a country need to relax all Covid-19 restrictions and get back to “normal.” Nobel prize winning economist Paul Romer has an answer. If a country tests its entire population every 14 days, it can beat down R without Covid-19 restrictions. In the US, that means 22 million tests per day. Per DAY. As Ezra Klein has pointed out, that’s a wartime effort.

How close is the US to 22 million tests per day? A volunteer effort called the Covid Tracking Project tracks US testing by state and territory, presumably because no one in the federal government is tracking critical statistics like this. Right now the US tests about 150,000 people daily for Covid-19. To put this in perspective, South Korea had about 10x this per capita Covid-19 testing capacity at the beginning of the pandemic. With about 5 tests per 1,000 daily, it was able to contain its Covid-19 outbreak using the quarantine method.

So the US isn’t just way short of the 22 million daily Covid-19 tests Romer says are needed to relax all Covid-19 restrictions entirely. If the South Korean number of 5 per 1,000 is what it takes to get to the quarantine method of controling R, the US is still short by 10x its current Covid-19 testing capacity to achieving the quarantine method. It’s likely this late in the game that the US would need much more than 5 per 1,000 tests per day to get to the quarantine method.

In light of all this, should these five US states lift their Covid-19 restrictions. Probably not until there is enough testing to understand very quickly the effect of lifting restrictions on R. In theory, a state or country would change one aspect of its Covid-19 restrictions, measure change in R, and revert the change if R increases.

I’m not sure what amount of testing is required to see changes in R quickly enough, but I’m guessing it’s north of 0.5 per 1,000, which is where the US is today. In the absence of adequate testing, the way these states will measure R is through hosptial beds and deaths, both of which are lagging indicators. In other words, by the time these states see a problem, R is out of control again. My guess is that Dr. Fauci wants at least for all states to have R < 1 before any states relax their Covid-19 restrictions. That gives the US a little more time to ramp up testing and keeps the balance of states in the R < 1 column.

US testing has been behind from the beginning because the CDC failed to follow its own protocols when generating the first Covid-19 test kits. And because test kits weren’t available early, it wasn’t until this week that public health officials realized the first US cases of Covid-19 were not in Kirkland, WA at the end of February, as previously thought, but in Santa Clara County on 6 February and 17 February.

One reason the US and other countries are so far behind in Covid-19 RNA testing is a lack of reagents needed during the RNA extraction process. A group at the University of Vermont College of Medicine and their collaborators at the University of Washington have issued a pre-print of a method of RNA testing that skips the extraction step. A North Carolina company called BioSkryb has developed a different way to avoid RNA extraction, using a stabilization buffer that inactivates the virus but preserves the viral RNA. There are similar efforts in Denmark and Chile to design Covid-19 RNA tests without an extraction step. If any of these method works and scales, then there is no need for reagents and Covid-19 RNA tests would process faster.

In other testing news, the FDA has granted the first EUA for the first Covid-19 home collection test from LabCorp. Home testing is more error-prone than in-person testing, but is safer for healthcare workers and may increase testing rates.

By the way, it’s not just the US that’s figuring out what to do next. As Shane reminds me, the entire world is figuring out how to relax Covid-19 restrictions.

Every country should be concerned about ramping up Covid-19 testing. It’s the one thing that can get the world back to normal without a treatment or vaccine. There are, unfortunately, good reasons to be concerned about a Covid-19 vaccine.

First is this informative Twitter thread from David States, Chief Medical Officer of Affigen, Inc. Essentially, States says it looks like human immune response to Covid-19 is weak. This seems consistent with South Korean reports of recurrences of Covid-19.

Second, Chinese scientists are warning about mutations of Covid-19. In the 28 March entry, I reported that Italian researchers measured few Covid-19 mutations over the course of the Italian epidemic. That seemed like good news for a vaccine. Now, however, it looks like the there are significant mutations in the virus. Accordding to Chinese researchers, “The most aggressive strains created up to 270 times as much viral load as the least potent type.” This implies significant variation in mortality rates depending on the strain of the virus. More mutations of Covid-19, of course, make it harder to develop a single vaccination.

My social feeds have debates going on about CFR / IFR. Brad passed on this Twitter thread about French rates.

French IFR rates.

A couple points about this. First, as one of the commenters in the thread notes, “Again raises the question of why everyone argues about death rates (which are broadly consistent), when what is really remarkable is how effective lock-downs have been?” Second, as Chinese researchers noted above, I suspect we’re going to start finding that CFRs / IFRs are not broadly consistent as different strains promulgate around the globe.

Not to beat a dead horse, but on the hydroxychloroquine front, another study from the Veterans Administration confirms an earlier French study that showed the malaria drug provides no benefit to Covid-19 patients and increases risk of damage to internal organs. I noted the French hydroxychloroquine study results last week. The French study measured results of patients receiving hydroxychloroquine against a control group. The VA did a retrospective study looked at outcomes of 368 male patients. Of those receiving hydroxychloroquine, 22% died. Of the others, 11% died. Neither study has been peer reveiwed yet. As far as I know, no one in the Trump administration has acknowledged these studies.

Finally, is it just me, or are everyone’s social media feeds full of offers for shavers, razors, scissors, dyes, gels, creams, lotions, and all other form of hair treatment? For more than you’ve ever wanted to know about cutting your own hair, Brad found this in Wired.

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