9 ms·

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

52 points by sci_prog 6y ago

sci_prog 6y ago
I'm hoping it's just bad tests in the first place. https://covid19usa.io/ 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 https://news.ycombinator.com/item?id=22778152
- Fragoel2 6y ago
  Most likely. You need to develop antibodies to defeat a viral infection and, once you do, they don't just disappear overnight.
  - hutzlibu 6y ago
    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 https://en.wikipedia.org/wiki/Herpes_simplex
    - incompatible 6y ago
      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.
      - hutzlibu 6y ago
        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.
        frank2 6y ago
        >The big "eating" cells (do not know the proper english name) macrophage
        imagine99 6y ago
        >macrophage That's arguably Greek ;-)
        teddyh 6y ago
        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
        hutzlibu 6y ago
        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.
      - hcknwscommenter 6y ago
        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.
    - hcknwscommenter 6y ago
      Herpes virus are entirely different from COVID and remain "sleeping" via a mechanism that simply cannot happen with a coronavirus.
      - hutzlibu 6y ago
        Good to know, but is this secured knowledge? I thought there is too much not understood about COVID?
        deleted 6y ago
        [deleted]
        hcknwscommenter 6y ago
        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.
  - tomp 6y ago
    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.
gnicholas 6y ago
> 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?
- lostlogin 6y ago
  Or were one or both tests a false positive?
- gwd 6y ago
  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.
  - nicoburns 6y ago
    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.
    - prox 6y ago
      People forget a flu (especially in the past) could take weeks to recover from. Easily 2-3 weeks.
    - op03 6y ago
      Sometimes it doesnt matter what the person does. HIV - https://upload.wikimedia.org/wikipedia/commons/thumb/0/0e/Hiv-timecourse_copy.svg/1280px-Hiv-timecourse_copy.svg.png 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 https://www.youtube.com/watch?v=Z48SZykpQeY
unsrsly 6y ago
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.
- hcknwscommenter 6y ago
  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?
  - lbeltrame 6y ago
    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.
    - hcknwscommenter 6y ago
      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.
      - unsrsly 6y ago
        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.
  - 6y ago
9nGQluzmnq3M 6y ago
https://outline.com/n8cTuW https://outline.com/n8cTuW
nil-sec 6y ago
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.
- space_fountain 6y ago
  What is the false positive rate for these tests?
- yread 6y ago
  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
  - nil-sec 6y ago
    Could it be that the first test was false positive then and the first symptoms where actually not corona virus?
    - hdjrork 6y ago
      Not if they were tested with PCR. PCR can have false negative, but false positive is extremely unlikely.
      - nil-sec 6y ago
        It’s the other way around. It’s very easy to get a false positive due to DNA contamination.
      - lbeltrame 6y ago
        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.
9nGQluzmnq3M 6y ago
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.
rjzzleep 6y ago
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/ https://www.microbe.tv/twiv/twiv-597/
- LordHumungous 6y ago
  Will COVID-19 become another cold? Were the 4 other coronaviruses that cause colds just as deadly when they first appeared? Interesting to ponder.
  - hdjrork 6y ago
    Possibly, but it will take many years for this to happen.
  - bobosha 6y ago
    Actually yes. The virus that caused the 1918 "Spanish flu" is now one of the seasonal flu viruses that afflict us every year.
  - echelon 6y ago
    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.
  - snapetom 6y ago
    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.full.pdf https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....
graposaymaname 6y ago
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.
- hexl 6y ago
  I remember a thread about their writers being rewarded when moving the market.
rajnathani 6y ago
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-nation/pune-womans-death-due-to-covid-19-puzzles-authorities/articleshow/75003417.cms https://economictimes.indiatimes.com/news/politics-and-natio...
- rajnathani 6y ago
  Correction: This isn’t a case of reinfection/reactivation as the woman in context was never tested positive when she was alive.
skwb 6y ago
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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851497/

52 points by sci_prog 6y ago

I'm hoping it's just bad tests in the first place. https://covid19usa.io/ 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 https://news.ycombinator.com/item?id=22778152

Fragoel2 6y ago
Most likely. You need to develop antibodies to defeat a viral infection and, once you do, they don't just disappear overnight.
- hutzlibu 6y ago
  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 https://en.wikipedia.org/wiki/Herpes_simplex
  - incompatible 6y ago
    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.
    - hutzlibu 6y ago
      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.
      - frank2 6y ago
        >The big "eating" cells (do not know the proper english name) macrophage
        imagine99 6y ago
        >macrophage That's arguably Greek ;-)
        teddyh 6y ago
        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
        hutzlibu 6y ago
        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.
    - hcknwscommenter 6y ago
      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.
  - hcknwscommenter 6y ago
    Herpes virus are entirely different from COVID and remain "sleeping" via a mechanism that simply cannot happen with a coronavirus.
    - hutzlibu 6y ago
      Good to know, but is this secured knowledge? I thought there is too much not understood about COVID?
      - deleted 6y ago
        [deleted]
      - hcknwscommenter 6y ago
        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.
- tomp 6y ago
  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.

gnicholas 6y ago

> 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?

lostlogin 6y ago
Or were one or both tests a false positive?
gwd 6y ago
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.
- nicoburns 6y ago
  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.
  - prox 6y ago
    People forget a flu (especially in the past) could take weeks to recover from. Easily 2-3 weeks.
  - op03 6y ago
    Sometimes it doesnt matter what the person does. HIV - https://upload.wikimedia.org/wikipedia/commons/thumb/0/0e/Hiv-timecourse_copy.svg/1280px-Hiv-timecourse_copy.svg.png 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 https://www.youtube.com/watch?v=Z48SZykpQeY

unsrsly 6y ago

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.

hcknwscommenter 6y ago
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?
- lbeltrame 6y ago
  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.
  - hcknwscommenter 6y ago
    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.
    - unsrsly 6y ago
      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.
- 6y ago

9nGQluzmnq3M 6y ago

https://outline.com/n8cTuW https://outline.com/n8cTuW

nil-sec 6y ago

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.

space_fountain 6y ago
What is the false positive rate for these tests?
yread 6y ago
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
- nil-sec 6y ago
  Could it be that the first test was false positive then and the first symptoms where actually not corona virus?
  - hdjrork 6y ago
    Not if they were tested with PCR. PCR can have false negative, but false positive is extremely unlikely.
    - nil-sec 6y ago
      It’s the other way around. It’s very easy to get a false positive due to DNA contamination.
    - lbeltrame 6y ago
      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.

9nGQluzmnq3M 6y ago

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.

rjzzleep 6y ago

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

LordHumungous 6y ago
Will COVID-19 become another cold? Were the 4 other coronaviruses that cause colds just as deadly when they first appeared? Interesting to ponder.
- hdjrork 6y ago
  Possibly, but it will take many years for this to happen.
- bobosha 6y ago
  Actually yes. The virus that caused the 1918 "Spanish flu" is now one of the seasonal flu viruses that afflict us every year.
- echelon 6y ago
  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.
- snapetom 6y ago
  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.full.pdf https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....

graposaymaname 6y ago

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.

hexl 6y ago
I remember a thread about their writers being rewarded when moving the market.

rajnathani 6y ago

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-nation/pune-womans-death-due-to-covid-19-puzzles-authorities/articleshow/75003417.cms https://economictimes.indiatimes.com/news/politics-and-natio...

rajnathani 6y ago
Correction: This isn’t a case of reinfection/reactivation as the woman in context was never tested positive when she was alive.

skwb 6y ago

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