COVID Transmissions for 8-25-2020

The first confirmed case of reinfection

Aug 25, 2020

Greetings from an undisclosed location in my apartment.

It has been 282 days since the first documented human case of COVID-19.

Housekeeping note:

I have been meaning to write a continuation of the in-depth from last week, but there has been a lot of news this week that has been derailing that. Specifically, today I would like to cover in-depth the report of a case of reinfection from Hong Kong, which is not quite what it seems. In fact, it is some of the best news I have seen about this virus yet.

Glossary terms are bolded words with links to the running newsletter glossary.

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Now, let’s talk COVID.

The first reinfected patient

The New York Times, among other outlets, reported on the first confirmed case of reinfection with COVID-19 today: https://www.nytimes.com/2020/08/24/health/coronavirus-reinfection.html

I will have more details in the in-depth analysis later on.

Remdesivir looking weaker in latest data

Recent data from a randomized clinical trial in 533 hospitalized COVID-19 patients receiving remdesivir is brought to us from CIDRAP: https://www.cidrap.umn.edu/news-perspective/2020/08/remdesivir-scant-benefit-hospitalized-covid-patients-study-finds

In this study, patients who received remdesivir had a greater improvement in clinical severity score than patients who did not. Two remdesivir patient groups were used; one that received the treatment for 5 days and one that received it for 10. While both groups did better than the standard of care, there was no difference between the 5- and 10-day groups, and the effect vs standard of care was notable, but not extremely impressive.

51% of patients had some kind of safety event, with nausea being most common. No patient deaths were attributed to receipt of remdesivir therapy, though there were deaths in the study in all arms. Fewer patients receiving remdesivir died than in the standard of care group.

This is a modestly impressive result, but it is not suggestive of a strong effect. Still, it indicates the possibility of a growing clinical armamentarium for the treatment of COVID-19.

What am I doing to cope with the pandemic? This:

Playing

I’ve always been interested in the science fiction MMORPG EVE:Online, but I found it unapproachable because it has existed for so long and I figured it would be a huge chore to catch up with longstanding players.

Recently, EVE:Echoes launched for mobile devices, and I decided to try it out. It is one of the best economic and investment simulators I’ve ever encountered, and there’s space combat. So I’m having fun with that this week.

The first confirmed case of reinfection

As reported in the NYT story linked above, there was an announcement from Hong Kong yesterday that the first confirmed case of reinfection with SARS-CoV-2 in a human had been detected. Let’s explore what that means.

This patient had been ill with a mild case of COVID-19 some 4.5 months before testing positive a second time. The second infection appears to have been entirely asymptomatic.

There are quite a few things that need to be addressed based on those two sentences.

First—how do we know that this patient was reinfected, when people continue to test positive for virus RNA for months after recovery?

The team that worked with this patient has shown that the two infections were with different virus lineages. They demonstrated that there were notable enough differences between the first virus that infected this patient compared with the second one, to be convincing that these were viruses of different origins. No case has been this well documented before, so this represents the first confirmation of a person becoming infected a second time.

I’d like to note that I have been very careful with my language here—these are not different species of virus, or different strains. The words “strain” and “species” are terms with meaningful and impactful definitions in virology. While the virus lineages isolated from this patient were different in their genome sequence, they were not different enough to represent a new strain or species. I don’t want anyone reading this running around using the words “different strains” to describe what was detected in this patient.

The next thing to address is what this actually means. This patient got sick during their first infection, but had an asymptomatic case during the second infection. In the past, when “reinfection” has been discussed in the media, it has been under the banner of whether or not you can get COVID-19 twice. This patient did not get COVID-19 twice, because they were asymptomatic in their second infection. COVID-19 is a disease. What happened to this patient was that they got COVID-19 once, but they became infected with SARS-CoV-2 twice.

What I believe we may have seen here is a patient who had a protective immune response to the first infection, and that immune response prevented them from developing COVID-19 when they became infected with the virus a second time. It is possible that he simply received a much lower dose of virus the second time, but that is not the prevailing opinion of researchers who have looked at the data.

Part of the reason for this belief is that the patient had no antibodies to SARS-CoV-2 during their first infection, but upon reinfection a rapid induction of SARS-CoV-2-specific antibodies was observed. This suggests a meaningful immune memory response, and in this case that immune memory response coexisted with an asymptomatic infection. This looks an awful lot like protection.

If you remember my in-depth article “What can a vaccine do, anyway?” from a little while back, you’ll remember that I made a point of establishing the difference between sterilizing immunity and protective immunity. If you’ll recall, sterilizing immunity is something that neutralizes an incoming pathogen before it is ever able to establish infection, whereas protective immunity is just the prevention of disease. The reality is that it is possible to be infected with a pathogen and not get sick—as we know well from the term “asymptomatic infection.”

This is because our immune systems are often quite effective at containing, stopping, or otherwise managing many pathogens that we encounter. Every infection is different, but pathogen-host interactions can play out in several ways that can involve infection without a noticeable disease resulting. 2 billion people in the world are walking around with essentially asymptomatic tuberculosis infections, for example, with the immune system having contained the bacteria within the lungs, keeping them from causing disease without eradicating them entirely—and that’s just one example.

Returning to COVID-19, in this patient’s case, we see that they got the disease and seem to have then developed a protective immune response that was not sterilizing. They still produced detectable amounts of virus RNA during the second infection, but did not get sick. I can’t stress that enough. Having established that, though, I want to go a little further: this is fantastic news.

Previously, when I considered reports of potential reinfection, something that came to mind for me was that some people who had COVID-19 would not produce an effective memory immune response in the first place, but might still recover. I expected that our first confirmed reinfection case would be something like that scenario. We know that this is not what happened here, because the patient’s immune memory worked.

Instead of an inadequate immune response, we now have some evidence of a protective immune memory response that prevented disease in this patient. Until this point we have had extremely limited evidence, based on an absence of evidence of reinfection with new disease as well as animal work, that someone who had been previously infected with COVID-19 could be protected from future infection.

This patient changes all that. For the first time, we have confirmed human evidence of the possibility that a person who has had COVID-19 before could be protected from future disease.

Of course, I wouldn’t be a good scientist if I didn’t put some limitations on that. It’s possible that this patient didn’t get infected with enough virus to cause disease, and that his immune response was meaningless. It’s possible that this patient has an incredible immune system that has created a protective response while most people would not be able to. There are a lot of possibilities, because this is just a single patient. This story is a case report, an anecdote. It is not data, but it is encouraging.

Building on this story’s encouraging facts, I’d like to see evidence of a hundred or a thousand such situations. I look forward to a paper reporting that many patients who received, say, an experimental COVID-19 vaccine have experienced an asymptomatic infection with SARS-CoV-2 and were protected from COVID-19. This would show quite definitively that it is possible to have a protective immune response, in the average person, with the average community-acquired exposure to SARS-CoV-2. It is also, as you’ll have guessed, something that is actively being looked after in clinical trials of COVID-19 vaccines. What this report from Hong Kong does, for me at least, is suggest that we can expect that one of those clinical trials will actually work.

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