Coronavirus May ‘Reactivate’ in Cured Patients, Korean CDC Says | Hacker News Reader

Coronavirus May ‘Reactivate’ in Cured Patients, Korean CDC Says

bloomberg.com

52 pointssci_prog64 comments

This came up since the beginning in January. The number of people that were reported to reinfect like this seem to lie well within the expected rate of false positives. I don’t understand how this claim is made repeatedly, without a thorough statistical analysis of what is expected.

It's not just tests. All symptoms disappear - we had health workers coming back to hospital and days later symptoms reappeared

EDIT: to clarify: in my hospital there were colleagues who tested positive, isolated, had no symptoms, went back to work, still no symptoms. After a few days symptoms are back and they tested positive again

It's flu season, it's quite possible they have had both flu and Coronavirus. My wife had the flu in Feb & early March and the symptoms are identical to the Coronavirus.

They're working in a hospital so they'll catch everything.

Stupid question does being infected with some virus helps if a second pathogen infects you ? As in 'immune system globally more active' or not at all ?

Not a stupid question, but pretty much not at all. In fact, you are slightly immune compromised by the first pathogen against the second pathogen because your adaptive immune system is highly active against the first pathogen. The body has two systems, an innate immune system that has mechanisms to innately attack bacterial and viral pathogens in general and an adaptive immune system that adapts to each specific pathogen. The innate system is a first line of defense but is like a form of combined suicide bomber and cannon fodder throwing cell after cell to overwhelm the pathogen with death and there is significant collateral damage. The adaptive immune system takes time to ramp up to each new pathogen and if it's working on one pathogen doesn't really switch to working on the other. Rather older cells are/have adapted to the first pathogen and newly born cells begin to work on adapting a defense to the new pathogen. This takes time and there are, at the beginning, very few cells adapting to the new pathogen.

Could it be that the first test was false positive then and the first symptoms where actually not corona virus?

Not if they were tested with PCR. PCR can have false negative, but false positive is extremely unlikely.

As someone also said, one of the biggest enemies of PCR is contamination, or perhaps the samples had conservation / handling problems which meant the RNA ended up degraded.

Given the (currently) very low numbers of these "apparently relapsed" cases versus the total recovered cases, I think it is most likely.

What about the symptoms?

I can think of two ideas on top of my head:

- Similar sympthoms but different disease (flu?)

- False negatives, and so people were still actually sick

In addition, I wonder if those patients had distinct clinical features compared to others. In absence of more data (and these cases are very uncommon) it is hard to tell.

Probably a good idea would be to do a study with periodical follow up of a large cohort of discharged patients. This would probably give better indication.

It’s the other way around. It’s very easy to get a false positive due to DNA contamination.

Globally we are running 100-thousands of tests per week, we must expect to see some false positives under these circumstances.

There is a video of the head of a hospital in Korea talking about reactivation occurring.

I feel that the “false positive” answer is often quickly given, without considering that it is likely that some people that get the virus have it flair up again. Perhaps it is caused by wishful thinking: reactivation is scary so let’s find a less scary reason?

Correction as per video at 8 minutes: https://youtu.be/gAk7aX5hksU

What is the false positive rate for these tests?

I wouldn't read too much into this yet. Coronavirus tests are notoriously flaky and Korea has thousands of recovered people, so it's entirely possible that people either get false negatives twice (so they appear cured but aren't), or get true negatives followed by a false positive later (so they appear sick but aren't).

If there are patients who test negative for several weeks but then relapse and get clinically sick with COVID-19, we'll have cause to worry. On the other hand, if this was a common phenomenon, it'd be happening in China already.

Whether the tests are flaky or not, we shouldn't really discard the fact that virologists don't generally say that infected people do not get reinfected, but rather that infected people will have milder symptoms and therefore less lethal diseases. There was a really good episode on the immune system on TWIV recently.

https://www.microbe.tv/twiv/twiv-597/

Will COVID-19 become another cold? Were the 4 other coronaviruses that cause colds just as deadly when they first appeared? Interesting to ponder.

Actually yes. The virus that caused the 1918 "Spanish flu" is now one of the seasonal flu viruses that afflict us every year.

Possible. A pre-print paper from 3 weeks ago describes how the researchers already found a large deletion in populations in Singapore. The authors theorize that the virus is sacrificing strength in order to keep up the infection rate. The same deletion also occurred in SARS and MERS, effectively ending their runs.

https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....

It doesn't seem like there's much evolutionary pressure given both the estimated R0 and the asymptomatic transmission to make this disease learn to become less deadly. It transmits just fine despite killing people. I suppose our immune systems will just get better at learning about it (similar epitopes) as we continue to be exposed year after year.

Possibly, but it will take many years for this to happen.

I'm hoping it's just bad tests in the first place.

https://covid19usa.io/

Edit: Adding my website for tracking coronavirus cases over time in USA state and counties. Original Show HN here: https://news.ycombinator.com/item?id=22778152

Most likely. You need to develop antibodies to defeat a viral infection and, once you do, they don't just disappear overnight.

Well, as far as I know, the antibodies do disappear at some point, but now your immune system knows the virus and can quickly produce new antibodies again, if it finds the virus again. But I think over time the immune system also forgets.

But to the patients that got sick again. "Bad test" would be the best outcome yes, but I know, that with herpes virus for example, you can never really get rid of them. Your immune system defeats them, but some virus cells remain in stasis somewhere sleeping - and resurface, if your stress level is high enough. So it would not surprise me, if this coronavirus might have similar traits.

https://en.wikipedia.org/wiki/Herpes_simplex

Something I read recently is that the immune system is complex containing both an innate immune system an adaptive immune system. It's possible that in mild cases of Covid-19, it may be successfully handled by the innate immune system, which doesn't confer additional immunity. A mild case my occur if the initial infection is by a relatively small number of virus particles.

Also possible yes. The killer cells (do not know the proper english name) are general purpose defense cells against anything that the body does not know. Only if there are too many unkown cells of similar type, they get categorized by other cells in the lymphs of the immune system and then other cells finally produce antibodies. But that process takes time.

>The big "eating" cells (do not know the proper english name)

macrophage

Ok, I edited eating cells to killer cells, before you replied. Because with a quick look on english and german wikipedia, I found a bit contradicting information. Anyway, my first post was more right as the macrophage cells are indeed a first line of the defense and killer cells come later (ca. 3 days).

So .. I leave this debate to more knowing persons.

>macrophage

That's arguably Greek ;-)

The problem with defending the purity of the English language is that English is about as pure as a cribhouse whore. We don't just borrow words; on occasion, English has pursued other languages down alleyways to beat them unconscious and rifle their pockets for new vocabulary.

— James Davis Nicoll

Not really. THe innate immune system "talks" to the adaptive system. Innate immune cells are often incredibly proficient at displaying antigens to the adaptive immune system and initiating the adaptive immune response.

Innate immunity is not going to learn about Covid-19. That adapts on an evolutionary time scale.

We share Toll Like Receptors (TLRs) homology with drosophila. That's how ancient innate immunity is.

Herpes virus are entirely different from COVID and remain "sleeping" via a mechanism that simply cannot happen with a coronavirus.

Good to know, but is this secured knowledge? I thought there is too much not understood about COVID?

We don't know a lot about the pathology of COVID, like why is it so much worse than the coronaviruses that already circulate around the world and cause mild flu-like symptoms. We know a ton about coronaviruses in general, especially basic issues about how they replicate. Herpes viruses use a number of different genes to regulate latent infections. These genes are simply not found in COVID or any coronaviruses. This is not something we could be misunderstanding/missing. It's possible, but would be HIGHLY unlikely, that COVID has some, as yet undiscovered and never before seen in any other coronavirus studied to date, method of achieving latent infection and reactivation.

How come you can get the flu twice?

This makes no sense. It's not the antibodies, it's the virus itself - it can mutate.

> About 51 patients classed as having been cured in South Korea have tested positive again

So does this mean they're symptomatic again, or just testing positive?

A friend of mine fell ill with COVID-like symptoms; bad enough to be unable to work remotely, but not bad enough to go to the hospital and be tested (in the UK). He was sick for 5-6 days, then felt better, and thought he'd completely recovered. One week later, his symptoms returned for 2 days, and now he's feeling better again.

Was it COVID the first time? Was it COVID the second time? Was it stress, or his body adjusting to being in the same environment 24/7 (rather than spending half his day outside the home)? We may never know. An antibody test would show if he'd had it at least once, but that could well have been 2 back-to-back colds with asymptomatic SARS-CoV-2.

If it is only a few days later, it might be the normal covid19 pattern. I have been warned by a doctor of this two steps pattern when I got it, which I understand corresponds to infection by the virus first, then bacterial infection as a result of the damage caused by the virus.

Not a doctor, but just my understanding from [1] though I start seeing people challenge that pattern [2].

[1] https://www.youtube.com/watch?v=BtN-goy9VOY

[2] see responses to: https://news.ycombinator.com/item?id=22786656

Is it unusual to seemingly recover from a disease, and then relapse into more severe symptoms? I've seen that happen hundreds of times with less serious illnesses (colds, etc). Especially if the sick person stops taking it seriously and starts doing things like drinking alcohol, etc.

Stands to reason that it would apply to COVID-19 too.

Sometimes it doesnt matter what the person does.

HIV - https://upload.wikimedia.org/wikipedia/commons/thumb/0/0e/Hi...

It takes time as someone above said to work out whats happening and what to do - https://www.youtube.com/watch?v=Z48SZykpQeY

People forget a flu (especially in the past) could take weeks to recover from. Easily 2-3 weeks.

I Wonder if a virus could create waves inside one's body

From what I've picked up separate waves describe what is happening in typical Covid-19 patients: immune reactions that are good enough against the virus in the throat are insufficient to defeat it elsewhere so you get a first wave in the throat and if the virus spread into the lungs before that wave is over there's a second wave in the lungs. That wave then requires a different or stronger immune reaction.

For the flu, absolutely. It mutates rapidly and one can get the virus, mount an effective defense, and then the virus mutates and escapes the immune defense. This happens. It is known that coronaviruses mutate much more slowly than influenza for fundamental reasons. It is highly probably but not proven that this much slower rate is sufficient to preclude the "waves" you refer to.

It is a totally unrelated virus, but if you get chickenpox you may get many years later shingles, the virus may remain inactive in nerve cells fo a long time. https://en.wikipedia.org/wiki/Shingles

What a strange game of life

Or the reverse, tests returning to negative before symptoms kick in: the tests only check for presence in the accessible part of the throat and that area is known to get negative after a few days (apparently the virus is easy to defeat there). An infection down in the lungs could still be in early stages and growing at that time so symptoms would later appear as if out of a (recently clearedh clear sky.

Or were one or both tests a false positive?

Is it me or are Bloomberg articles in general panic stricken? I've been observing this over a number of articles lately, almost all of them are adjusted to sound like they want us to be more afraid and tensed, maybe my subconscious bias dunno.

I remember a thread about their writers being rewarded when moving the market.

https://outline.com/n8cTuW

IMHO I'm fairly skeptical of these claims. There have been a lot of scrambling to get testing online worldwide, so I'm fairly certain that Pr(False Positive) and Pr(False Negative) are reasonably high given circumstances. I don't have the numbers on me right now, but I think sensitivity is only 70%... So it's not hard to imagine a situation where a combination.

The thing that in my mind sorta kills this "reinfection" argument is our previous experience with SARS virus [1]. Figure 1 of the paper shows IgG reactivity for up to 3 years. Anecdotally, I've heard from my immunity bioinformatics colleagues that the spike protein that is recognized by the immune system is very well conserved.

I haven't seen a ton of great evidence that have really pushed my priors against the conclusion that these handful of cases are better explained somehow by faulty testing/some other combination of complication. As always, willing to adjust these priors if given compelling evidence. :)

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851497/

It is unclear whether these patients are shedding viral RNA particles from their prior infection or actual infectious virus from an ongoing infection. The way to tell the difference would be to perform viral cultures instead of the PCR-based test.

Your post makes little sense to me. viral RNA particles are virus no? You distinguish between viral RNA particles and "actual infectious virus". What is the difference between the two?

PCR tests will still detect signature bits of RNA even when the virus is physically broken and no danger at all. Virions are not alive like bacteria are, but they are still more than the pure RNA ("data"). To be infective they need the whole, intact package of RNA and a set of tooling molecules that the parent cell created created alongside the RNA copy (or that were taken from regular cell stocks).

In year 2000 computer terms, the virus doesn't just need the bytes of the VBS file, it also needs the email header that says "ILOVEYOU".

Not really though. Naked RNA is incredibly unstable when just out in the environment or floating around in blood, mucus, etc. Sure, if you dump a pot of naked RNA on the floor, mop it up and analyze it that second your PCR test will pick it up, but you would have to be right quick about it.

I think the OP means the actual, infective and complete virus (fully assembled) as opposed to the RNA of the virus, which can also be released by degraded/inactivated viruses.

But he says "viral particles" which is a term of art and means an assembled shell (envelope for enveloped viruses like corona). If there is viral RNA in the viral particle, its an assembled shell and thus a virus. Sure some people make viral particles in the lab to package other things, but that's certainly not what OP is referring to.

Sorry, I could have been clearer and said something like RNA fragments (non-infectious residue of the virus). It's true that in a clinical situation, you need to treat the positive PCR as infectious until proven otherwise. But from a research standpoint, it seems possible that someone who previously had a high viral load in their lungs, and is now recovering, could have detectable Sars-Cov2 RNA fragments for a period of time despite the presence of endogenous RNAse. And they might not be contagious.

>viral RNA particles are virus no?

Only in the same way as blood is people. Viruses are a DNA/RNA core packaged in proteins plus a borrowed disguise that acts like an envelope and would put the crownb part in coronavirus. Some are naked and lack the envelope, other (i.e coronavirus) not.

I am not sure whether this has to do with testing accuracy, however we had a similar case [0] recently in India.

> A 60-year-old woman from Pune who tested negative for coronavirus died three days after being discharged.

> However, on April 4, she was rushed to Sassoon Hospital in Pune, where she died even before admission. When her sample was tested again, it turned out to be positive.

[0] https://economictimes.indiatimes.com/news/politics-and-natio...

Correction: This isn’t a case of reinfection/reactivation as the woman in context was never tested positive when she was alive.

Reply on news.ycombinator.com