4 June 2020 – Thursday – #81

As I wrote yesterday, things Covid-19 are going well in Spain. Barcelona is marching toward Phase 2 of the Spanish relaxation of Covid-19 restrictions.

So, how is the world doing this morning with Covid-19?

The first wave of Covid-19 has wound down in Asia (notable exceptions: Indonesia and Philippines). It is winding down in Spain and most of Europe (notable exceptions: UK and Sweden).

US numbers are trending the right way nationally, but about ten states have increasing cases (R > 1) and it won’t be clear for 7-10 days whether the George Floyd protests start another wave of Covid-19 infections. Parenthetically, the protests have closed down about 70 Covid-19 testing locations across the country.

South America, Russia, India, Pakistan and other parts of the developing world have trend lines that have not clearly inflected down yet. Brazil is particularly worrisome because of its population and lack of leadership. The only silver lining is that the Brazil currently is a good place to study Covid-19 vaccines. Africa and the Middle East are a mixed bag.

Covid-19 per capita mortality for US, Brazil, Russia, and India, 3 June 2020.

A good question now for parts of the world that are cooling off from Covid-19 is whether they will have additional waves of Covid-19 outbreaks. The short answer is probably.

Here’s one reason why.

The European countries in this chart have a measured Covid-19 exposure of 5% or less. That means 95%+ of the population is susceptible to Covid-19 infection. It’s not clear yet how long those who have been exposed to Covid-19 maintain immunity. There is a small silver lining that many cities have higher Covid-19 infection rates, so less than 95% of those cities’ populations is susceptible to Covid-19 infection.

In short, the world is a long way from 60% exposure needed for herd immunity from Covid-19.

From the numbers in the chart, it’s possible to infer an IFR for Covid-19. I’ve noted Spain’s implied Covid-19 IFR of 1.15%. The other country’s infection numbers look close enough that I’m going to assume (rather than calculate) that other countries have Covid-19 IFRs similar to Spain and that Covid-19 has a similar virulence to the Spainsh Flu.

Not to say that Covid-19 will follow the same path as Spanish Flu, but the UK had three distinct Spanish Flu outbreaks.

Spanish Flu mortality in the UK.

If history is a guide, we should expect more Covid-19 outbreaks. There are, however, things that we can do now to mitigate future outbreaks that people couldn’t do during the Spanish Flu.

Vaccines would create herd immunity in a safe way. I wrote about Covid-19 vaccines last Sunday.

Better clinical procedures and treatments would reduce Covid-19 mortality rates so that future outbreaks have smaller health and economic impacts than the first wave. On the treatment front there is good news (IL-6), not so good news (Remdesivir), and expected bad news with a twist (hydroxychloroquine—again).

In a Michigan study of 154 intubated patients with a control group, the anti IL-6 antibody tocilizumab had promising results, with some qualifications.

It has to be said that the treatment group was slightly younger and slightly less likely to have underlying pulmonary disease, so the results should probably be trimmed down a bit. But the results were good: 45% lower likelihood of death (the preprint’s Figure 2). The secondary endpoint of the trial was assessment on a 6-point disease severity scale, and the treatment group looks better on that one, too (the preprint’s Figure 3A)

Science, “Coronavirus Therapy Update (Remdesivir and Tocilizumab),” 3 June 2020.

Too early to take tocilizumab to the bank, but encouraging to see results from an early study that has a control group. In his article, Derek Lowe notes some important caveats about how tocilizumab may suppress the immune system and encourage pneumonia. However, Covid-19 patients experiencing cytokine storms don’t have any targeted pharmaceutical treatment options at this point and they are at very high risk of death. If tocilizumab pans out, it could reduce Covid-19 mortality significantly.

There’s not much to say about the most recent Remdesivir except that it’s a bigger and better study than previous Remdesivir studies and Remdesivir still won’t put a dent in Covid-19 mortality.

Unfortunately, hydroxychloroqine is back in the news. At least it’s easier to type than tocilizumab.

First, there is yet another study, this one with over 800 patients from the US and Canada, that shows hydroxychloroquine has no benefit for Covid-19 patients.

Then there is a previous hydroxychloroquine study that finds itself in the hot seat because of its data source, a company called Surgisphere. In fact, not only is the study in the hot seat, but so is Lancet, the publication that vetted the study. No one seems to know who Surgisphere is and where it acquires its data.

In case you missed the clumsy transition, I just moved on from the status of Covid-19 treatments part of this entry to the Covid-19 misinformation part of this entry.

Surgisphere data also was used for a paper pubished by the New England Journal of Medicine, claiming ACE inhibitors were safe for Covid-19 patients. Similarly to Lancet, NEJM finds itself in the hot seat for failing to vet Surgisphere.

Surgisphere is not the only questionable data source in our Covid-19 misinformation story. Another questionable source of Covid-19 data is Worldometer.

Despite Worldometer not being a good enough source for Wikipedia editors, it was for the UK government. From 30 March to 14 April, Worldometer figures were cited in the slide showing global comparison of deaths at the daily press conference. But perhaps because Worldometer didn’t explicitly note the difference in forms of reporting processes between countries and was bundling the death figure together even if it excluded care home deaths at the time, as Health Service Journal pointed out on 14 April, the comparison was flawed.

NewStatesman, “The story of Worldometer, the quick project that became one of the most popular sites on the internet,” 7 May 2020.

These three examples of Covid-19 data source failures are unfortunate because they expose what probably is a larger systematic failure of researchers, publications, and government policy makers to vet sources. The failures are understandable to a degree because the Covid-19 landscape is changing so quickly and people want answers in a hurry, but they lead to the institutionalization of misinformation.

Which brings me to my next topic, a story about Covid-19 losing its virulence that’s spreading on my social feeds quicker than you can say “Covid-19.”

“In reality, the virus clinically no longer exists in Italy. The swabs that were performed over the last 10 days showed a viral load in quantative terms that was absolutely infinitesimal compared to the ones carried out a month or two ago.

Dr. Alberto Zangrillo, San Raffaele Hospital, Milano.

Like anyone else, I would like to hear news that Covid-19 has become less virulent. Who knows? Maybe it has. This article quotes two Italian doctors, one from a television interview, as its source. It has given friends on social media permission to say that, yes, viruses get weaker and Covid-19 probably won’t come back as strong the second time.

First, it’s not a rule that viruses get weaker. Human populations adapt to them, but that doesn’t mean they are weaker.

Second, please remember the Spanish Flu chart above.

Third, consider the source. It could be true these doctors are measuring a real reduction in Covid-19 virulence. It seems to me just as likely they are seeing less critical cases than they saw a month ago because the healthcare system isn’t swamped.

While some friends seem convinced Covid-19 will weaken, the science is very unclear on whether Covid-19 will attenuate in any way. Unfortunately, the articles about this are long and complex. They don’t spread around social media the way short articles full of hope do.

One reason we shouldn’t expect Covid-19 to weaken is that it doesn’t mutate very quickly.

Coronaviruses are also one of the few RNA viruses with a genomic proofreading mechanism — which keeps the virus from accumulating mutations that could weaken it. That ability might be why common antivirals such as ribavirin, which can thwart viruses such as hepatitis C, have failed to subdue SARS-CoV-2. The drugs weaken viruses by inducing mutations. But in the coronaviruses, the proofreader can weed out those changes.

Nature, “Profile of a killer: the complex biology powering the coronavirus pandemic,” 4 May 2020.

Some researchers hope Covid-19 will weaken with mutation, but no one has measured that weakening yet.

Some researchers hope that the virus will weaken over time through a series of mutations that adapt it to persist in humans. By this logic, it would become less deadly and have more chances to spread. But researchers have not yet found any sign of such weakening, probably because of the virus’s efficient genetic repair mechanism. “The genome of COVID-19 virus is very stable, and I don’t see any change of pathogenicity that is caused by virus mutation,” says Guo Deyin, who researches coronaviruses at Sun Yat-sen University in Guangzhou.


So, yes, maybe the two doctors in Italy have seen what researchers haven’t found yet, a weaker Covid-19. Given what science knows about how the Covid-19 virus mutates and the mutation rate it has measured, the Italian doctors sound a little too good to be true to me. I’m waiting for a better source than a news report with quotes from two doctors before I believe it.

I’m going to end today with a way you can help science end Covid-19. Stanford scientists are asking people to provide a little bit of information about themselves every day. From that, they hope to predict Covid-19 outbreaks. Unfortunately for me, Stanford is looking for people in the US. Sign up here. Seriously. It will take 2-3 minutes the first day, and less than a minute every day after.

Don’t spread misinformation. Help scientists. Be part of the solution.

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