8 ms·

Covid-19, duration of viral shedding, and infectiousness: meta-analysis

97 points by Manheim 6y ago

anon9001 6y ago
> Maximum shedding duration was 83 days in the upper respiratory tract So covid-19 is transmissible for up to 83 days once infected?
- krona 6y ago
  PCR tests detect fragments of a virus, not necessarily an active/viable virus.
- _Microft 6y ago
  Their interpretation does not make it sound like this is the case: "Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2."
- zelos 6y ago
  But: > no live virus was isolated from culture beyond day 9 of symptoms despite persistently high viral RNA loads. > This finding is supported by several studies demonstrating an association between viral load and viability of virus, with no successful culture from samples below a certain viral load threshold. So the amount shed is too low to infect anyone beyond 9-10 days (I think, I am not a virologist, etc.)
  - Aerroon 6y ago
    >So the amount shed is too low to infect anyone beyond 9-10 days (I think, I am not a virologist, etc.) Is it possible to acquire immunity against the virus (in a similar way that vaccines work) by being in contact with someone at say day 20+?
    - lnsru 6y ago
      If it would be possible, pandemic would be over months ago and there would be no need to develop any vaccine.
      - kadoban 6y ago
        It could be possible, just unlikely enough that immunity doesn't spread fast enough.
    - Geeflow 6y ago
      Sounds reasonable - but I'd still prefer to stay away from people who are shedding the virus. There is also a similar theory that cloth masks might have the unintended positive side effect of building immunity. They are not perfect, so the virus might still reach its target. But the viral load could be reduced enough that instead of infection it leads to immunity.
wojcikstefan 6y ago
If I'm reading this right, the RNA of SARS-CoV-2 can be found in the upper respiratory tract for a very long time (even 83 days in the extreme case), but the live virus (capable of infecting others) was not discovered by any study beyond day 9. Self-isolating/quarantining for 10 days after a positive test result, which many regions enforce, seems consistent with these findings (again, if I'm interpreting the results correctly).
- 2sk21 6y ago
  I agree but the key is to get test results quickly. A five day delay in getting test results (which is common) seems to imply that an infectious patient may have already done their worst spreading by the time they start quarantining.
  - wojcikstefan 6y ago
    I agree accessibility and speed of testing is critical.
  - JulianMorrison 6y ago
    Unless they quarantine preemptively from the time they're tested.
  - geden 6y ago
    In the UK, if you have a test, you are required to quarantine until you get the results. Is it not the case elsewhere??
    - Jedd 6y ago
      In Australia that's the standard response too - if you're symptomatic (of anything vaguely resembling the wide range of COVID19 symptoms) then you a) isolate, and b) get a test, and c) isolate at least until the test results come back.
    - evandijk70 6y ago
      It's probably the rules everywhere, but I imagine that compliance is a lot lower for people waiting for a test result than it is for people that received a positive test (especially those with mild symptoms)
sradman 6y ago
> data on the shedding of infectious virus in asymptomatic individuals are too scarce to quantify their transmission potential in order to inform policy on quarantine duration in the absence of testing. This has long been a key question: how much of community transmission is due to truly asymptotic individuals? Michael Mina style Lick-a-Stick daily tests could answer this question and remove the potential errors surrounding symptom self-assessment.
- nradov 6y ago
  That question was answered in a study published last week. "There were no positive tests amongst 1,174 close contacts of asymptomatic cases." https://www.nature.com/articles/s41467-020-19802-w https://www.nature.com/articles/s41467-020-19802-w
  - sradman 6y ago
    Interesting paper but I'm not convinced that these are asymptomatic cases. I think these are primarily recovered cases that still have trace amounts of non-infectious viral RNA. The originally linked Lancet paper makes a distinction between "viral shedding" and "viral RNA shedding". I think the unanswered question involves individuals in the first week of their newly acquired infection (EDIT: after the incubation period). I hope that doesn't come across as nit picking; the scale and scope of the Wuhan study is impressive but an equivalent study is needed in an area with ongoing community transmission.
thinkingemote 6y ago
Do tests test for the RNA or the live virus?
- westwing 6y ago
  The PCR test amplifies RNA fragments. If after a certain amount of replication cycles the amount of detected RNA crosses a threshold, it is considered a positive. A positive PCR test does not imply infectiousness. Many people who have a positive test are not just asymptomatic, they are not really infected to begin with. A negative PCR test does not rule out disease. Some people who have a clinical diagnosis of COVID may produce a negative PCR result.
jansan 6y ago
Can this be interpreted as most people who test positive for COVID-19 are not infectious anymore?
- bjarneh 6y ago
  I don't think they drew that conclusion as it is probably difficult to say in which phase of the illness people get tested. Some have mild (or no) symptoms and probably go through their active 9-day period without getting tested at all. Others can have severe symptoms from an early onset, and probably get tested quite fast (hopefully). Some may get severe symptoms after an incubation period, only to get ill when their active 9-day period was over. It should mean that a 10-day isolation for positive cases, combined with high frequency testing should have a massive impact on the spread of the virus. That the virus can be found in your body much much later, in an "inactive" state should not have much impact on the spread.
zby 6y ago
"No study detected live virus beyond day 9 of illness, despite persistently high viral loads," - is it possible that IgA antibodies in the mucosa neutralizes the virus even before it gets spread? That could also explain the strange heterogenity of the virus spreading - maybe some people have more IgA or have IgA earlier and don't really spread a live virus?
Jedd 6y ago
I know enough about viruses to know that they're not alive by any meaningful definition, but not enough to understand how this use of 'live virus' is used in these kinds of studies. I'm assuming it means a full, viable string of RNA, rather than (presumably harmless) fragments of same -- and the fragments we're finding being described here are definitely non-viable. Is that roughly right?
- flobosg 6y ago
  “Live” in this context seems to mean “active”.
- mensetmanusman 6y ago
  Live means that it is readable by the ribosome.
- svara 6y ago
  Whether viruses are alive or not is purely a matter of definition. Alive in this context means that it can infect host cells and replicate. Contrary to what the sibling posts say, that doesn't just require intact viral RNA, which by itself is not infectious, but an intact viral assembly, i.e in this case a lipid hull with various accessory proteins, such as the nucleocapsid that packs the RNA and the spike protein that binds to host cells.
SomeoneFromCA 6y ago
There many studies contradicting this. I need to find the links gain (check BNO reinfection tracker, it is one the most recent), but a recent Korean study showed a case of reinfection (or as I am often told to be a "relapse") when a healthy women had shown symptoms again 10 days after recovery, although genetically different. After that in 10 days (or similar time period, do not remember) she showed the symptoms again, third time, with the virus of the first serotype. Also, immunocompromised people keep shedding viruses for months, not only that, the viruses also mutate very rapidly in them.
- gregwebs 6y ago
  This study says live virus has only been confirmed to be seen for at most 9 days. However, (presumably inactive) virus particles can be shed for months afterwards and can show up as PCR positive. This meta analysis only includes studies of multi patients so there's pretty much a guarantee that there are individual case studies that differ from this.
  - westwing 6y ago
    > This study says live virus has only been confirmed to be seen for at most 9 days. However, (presumably inactive) virus particles can be shed for months afterwards and can show up as PCR positive. The paper cites 34 replication cycles as the lower bound to obtain viable viral cultures. Whether a PCR test is reported as "positive" depends on the chosen replication cycle threshold (Ct value). As far as I'm aware, this "magic number" is usually chosen to be 35. Beyond that, it is possible to do more cycles to demonstrate the existence of trace amounts of PCR fragments, but such a test would not be considered "PCR positive".
    - gregwebs 6y ago
      The issue is that a PCR test does not actually tell us if a virus particle is live or inactive. A shed virus particle can still have intact RNA for the region tested by PCR. There are published case reports where someone has tested PCR positive during an infection, then PCR negative, and then PCR positive again later and the explanation given has been that they did not get re-infected and their infection did not flare back up but just that virus had been continually shed and the later test was able to capture that. edit: s/DNA/RNA. The PCR process actually operates on DNA so the virus RNA is converted to DNA as the first step of RT-PCR.
egberts1 6y ago
It’s good to know that we can now file assault charges on those maskless mouth breathers. https://www.cbsnews.com/news/trump-backer-charged-with-assault-after-exhaling-twice-on-protesters/ https://www.cbsnews.com/news/trump-backer-charged-with-assau...
scotty79 6y ago
How did they test if virus is 'live' (able to infect)?
- zby 6y ago
  In cell cultures.
zug_zug 6y ago
To clarify, if I'm reading this correctly, when they say "day 9" they're referring to day 9 of illness, not day 9 after exposure. Does anybody know what the data says about how long to wait for symptoms after being in contact with somebody who has it?
- donclark 6y ago
  ^^^THIS. I have a friend that believes that if everyone invited to an indoor house party goes and gets a test, the test comes back negative, and if they have quarantined since the test, that they can then party in the same room together with zero risk.

97 points by Manheim 6y ago

> Maximum shedding duration was 83 days in the upper respiratory tract So covid-19 is transmissible for up to 83 days once infected?

krona 6y ago
PCR tests detect fragments of a virus, not necessarily an active/viable virus.
_Microft 6y ago
Their interpretation does not make it sound like this is the case: "Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2."
zelos 6y ago
But: > no live virus was isolated from culture beyond day 9 of symptoms despite persistently high viral RNA loads. > This finding is supported by several studies demonstrating an association between viral load and viability of virus, with no successful culture from samples below a certain viral load threshold. So the amount shed is too low to infect anyone beyond 9-10 days (I think, I am not a virologist, etc.)
- Aerroon 6y ago
  >So the amount shed is too low to infect anyone beyond 9-10 days (I think, I am not a virologist, etc.) Is it possible to acquire immunity against the virus (in a similar way that vaccines work) by being in contact with someone at say day 20+?
  - lnsru 6y ago
    If it would be possible, pandemic would be over months ago and there would be no need to develop any vaccine.
    - kadoban 6y ago
      It could be possible, just unlikely enough that immunity doesn't spread fast enough.
  - Geeflow 6y ago
    Sounds reasonable - but I'd still prefer to stay away from people who are shedding the virus. There is also a similar theory that cloth masks might have the unintended positive side effect of building immunity. They are not perfect, so the virus might still reach its target. But the viral load could be reduced enough that instead of infection it leads to immunity.

wojcikstefan 6y ago

If I'm reading this right, the RNA of SARS-CoV-2 can be found in the upper respiratory tract for a very long time (even 83 days in the extreme case), but the live virus (capable of infecting others) was not discovered by any study beyond day 9. Self-isolating/quarantining for 10 days after a positive test result, which many regions enforce, seems consistent with these findings (again, if I'm interpreting the results correctly).

2sk21 6y ago
I agree but the key is to get test results quickly. A five day delay in getting test results (which is common) seems to imply that an infectious patient may have already done their worst spreading by the time they start quarantining.
- wojcikstefan 6y ago
  I agree accessibility and speed of testing is critical.
- JulianMorrison 6y ago
  Unless they quarantine preemptively from the time they're tested.
- geden 6y ago
  In the UK, if you have a test, you are required to quarantine until you get the results. Is it not the case elsewhere??
  - Jedd 6y ago
    In Australia that's the standard response too - if you're symptomatic (of anything vaguely resembling the wide range of COVID19 symptoms) then you a) isolate, and b) get a test, and c) isolate at least until the test results come back.
  - evandijk70 6y ago
    It's probably the rules everywhere, but I imagine that compliance is a lot lower for people waiting for a test result than it is for people that received a positive test (especially those with mild symptoms)

sradman 6y ago

> data on the shedding of infectious virus in asymptomatic individuals are too scarce to quantify their transmission potential in order to inform policy on quarantine duration in the absence of testing. This has long been a key question: how much of community transmission is due to truly asymptotic individuals? Michael Mina style Lick-a-Stick daily tests could answer this question and remove the potential errors surrounding symptom self-assessment.

nradov 6y ago
That question was answered in a study published last week. "There were no positive tests amongst 1,174 close contacts of asymptomatic cases." https://www.nature.com/articles/s41467-020-19802-w https://www.nature.com/articles/s41467-020-19802-w
- sradman 6y ago
  Interesting paper but I'm not convinced that these are asymptomatic cases. I think these are primarily recovered cases that still have trace amounts of non-infectious viral RNA. The originally linked Lancet paper makes a distinction between "viral shedding" and "viral RNA shedding". I think the unanswered question involves individuals in the first week of their newly acquired infection (EDIT: after the incubation period). I hope that doesn't come across as nit picking; the scale and scope of the Wuhan study is impressive but an equivalent study is needed in an area with ongoing community transmission.

thinkingemote 6y ago

Do tests test for the RNA or the live virus?

westwing 6y ago
The PCR test amplifies RNA fragments. If after a certain amount of replication cycles the amount of detected RNA crosses a threshold, it is considered a positive. A positive PCR test does not imply infectiousness. Many people who have a positive test are not just asymptomatic, they are not really infected to begin with. A negative PCR test does not rule out disease. Some people who have a clinical diagnosis of COVID may produce a negative PCR result.

jansan 6y ago

Can this be interpreted as most people who test positive for COVID-19 are not infectious anymore?

bjarneh 6y ago
I don't think they drew that conclusion as it is probably difficult to say in which phase of the illness people get tested. Some have mild (or no) symptoms and probably go through their active 9-day period without getting tested at all. Others can have severe symptoms from an early onset, and probably get tested quite fast (hopefully). Some may get severe symptoms after an incubation period, only to get ill when their active 9-day period was over. It should mean that a 10-day isolation for positive cases, combined with high frequency testing should have a massive impact on the spread of the virus. That the virus can be found in your body much much later, in an "inactive" state should not have much impact on the spread.

zby 6y ago

"No study detected live virus beyond day 9 of illness, despite persistently high viral loads," - is it possible that IgA antibodies in the mucosa neutralizes the virus even before it gets spread? That could also explain the strange heterogenity of the virus spreading - maybe some people have more IgA or have IgA earlier and don't really spread a live virus?

Jedd 6y ago

I know enough about viruses to know that they're not alive by any meaningful definition, but not enough to understand how this use of 'live virus' is used in these kinds of studies. I'm assuming it means a full, viable string of RNA, rather than (presumably harmless) fragments of same -- and the fragments we're finding being described here are definitely non-viable. Is that roughly right?

flobosg 6y ago
“Live” in this context seems to mean “active”.
mensetmanusman 6y ago
Live means that it is readable by the ribosome.
svara 6y ago
Whether viruses are alive or not is purely a matter of definition. Alive in this context means that it can infect host cells and replicate. Contrary to what the sibling posts say, that doesn't just require intact viral RNA, which by itself is not infectious, but an intact viral assembly, i.e in this case a lipid hull with various accessory proteins, such as the nucleocapsid that packs the RNA and the spike protein that binds to host cells.

SomeoneFromCA 6y ago

There many studies contradicting this. I need to find the links gain (check BNO reinfection tracker, it is one the most recent), but a recent Korean study showed a case of reinfection (or as I am often told to be a "relapse") when a healthy women had shown symptoms again 10 days after recovery, although genetically different. After that in 10 days (or similar time period, do not remember) she showed the symptoms again, third time, with the virus of the first serotype. Also, immunocompromised people keep shedding viruses for months, not only that, the viruses also mutate very rapidly in them.

gregwebs 6y ago
This study says live virus has only been confirmed to be seen for at most 9 days. However, (presumably inactive) virus particles can be shed for months afterwards and can show up as PCR positive. This meta analysis only includes studies of multi patients so there's pretty much a guarantee that there are individual case studies that differ from this.
- westwing 6y ago
  > This study says live virus has only been confirmed to be seen for at most 9 days. However, (presumably inactive) virus particles can be shed for months afterwards and can show up as PCR positive. The paper cites 34 replication cycles as the lower bound to obtain viable viral cultures. Whether a PCR test is reported as "positive" depends on the chosen replication cycle threshold (Ct value). As far as I'm aware, this "magic number" is usually chosen to be 35. Beyond that, it is possible to do more cycles to demonstrate the existence of trace amounts of PCR fragments, but such a test would not be considered "PCR positive".
  - gregwebs 6y ago
    The issue is that a PCR test does not actually tell us if a virus particle is live or inactive. A shed virus particle can still have intact RNA for the region tested by PCR. There are published case reports where someone has tested PCR positive during an infection, then PCR negative, and then PCR positive again later and the explanation given has been that they did not get re-infected and their infection did not flare back up but just that virus had been continually shed and the later test was able to capture that. edit: s/DNA/RNA. The PCR process actually operates on DNA so the virus RNA is converted to DNA as the first step of RT-PCR.

egberts1 6y ago

It’s good to know that we can now file assault charges on those maskless mouth breathers. https://www.cbsnews.com/news/trump-backer-charged-with-assault-after-exhaling-twice-on-protesters/ https://www.cbsnews.com/news/trump-backer-charged-with-assau...

scotty79 6y ago

How did they test if virus is 'live' (able to infect)?

zby 6y ago
In cell cultures.

zug_zug 6y ago

To clarify, if I'm reading this correctly, when they say "day 9" they're referring to day 9 of illness, not day 9 after exposure. Does anybody know what the data says about how long to wait for symptoms after being in contact with somebody who has it?

donclark 6y ago
^^^THIS. I have a friend that believes that if everyone invited to an indoor house party goes and gets a test, the test comes back negative, and if they have quarantined since the test, that they can then party in the same room together with zero risk.