4 ms·

In general PCR tests are highly sensitive. Even smallest viral loads can be detected (Edit) added in general above due to valid points in the comments below

by baxtr 7y ago

hprotagonist 7y ago
if: - you do them right - your reagents are good - the kit was assembled properly - there's no contamination in the machines - you got a good sample - ... The capability for a highly sensitive and accurate test in no way guarantees that a randomly sampled administration of that test is going to meet the high standard that the test may be capable of.
- twic 7y ago
  And if you swabbed an infected part of the body in the first place! In 205 patients with proven COVID-19 [...] bronchoalveolar lavage fluid was positive in 14/15 (93%), sputum 75/104 (72%), nasal swabs 5/8 (63%), brush biopsy 6/13 (46%), pharyngeal swabs 126/398 (32%), feces 44/153 (29%), blood 3/307 (1%), and urine 0/72 (0%). https://www.jwatch.org/na51116/2020/03/17/pharyngeal-and-nasal-swabs-may-not-have-adequate https://www.jwatch.org/na51116/2020/03/17/pharyngeal-and-nas...
  - hinkley 7y ago
    Hol' up. > blood 3/307 (1%) Why isn't their blood rotten with virus?
    - gojomo 7y ago
      I suspect it's because this virus is optimized to enter cells that line the lungs/respiratory tract, then also sheds back that same way. Meanwhile, cells in, and along, the bloodstream aren't infected – and are most-trafficked by the body's immune response, including virus-destroying antibodies. (Why are rodents more prevalent in the walls/crawlspaces of a dwelling, rather than the hallways?)
      - hinkley 7y ago
        But the lungs are full of blood, that's how we breath. So it's spreading mucosally or through connective tissue?
        gojomo 7y ago
        Sure, but if an initially-infected respiratory cell releases its "baby coronaviruses" out to the respiratory linings, away from the blood, they'll find lots more of the respiratory cell surfaces they're optimized to infect, and maybe get a ride out to other hosts on sputum. To the extent an infected cell releases its "baby coronaviruses" into the blood stream, they find a hot, chemically active environment – which is already inhospitable to their continued survival – plus a relative dearth of the respiratory cell-walls they're optimized to enter, plus a growing number of hostile antibodies. (I don't know if a coronavirus-hijacked cell can direct its fresh viruses one way or the other, but it'd probably prefer to do that if it could, and I can understand why viruses wouldn't persist long in blood compared to respiratory-membranes.) The coronaviruses are definitely active in mucosal surfaces, and carried by mucus. I haven't seen anything about, nor do I think any activity is necessarily implied, in other connective tissues.
        dmm10 7y ago
        As far as I know the route of SARS-Cov-2 spreading in the human body isn't known beyond the change in locality of symptomatic expression with progression of Covid-19 (upper respiratory tract to lower respiratory tract.) Research has shown (1) the distribution of ACE2 protein, the functional receptor for SARS-Cov and SARS-Cov-2 (2), to include various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain) along with arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. And ACE2 mRNA has been found in virtually all organs. So there is definitely the potential for cells in the circulatory system binding viruses. What may be significant here is the concentration of ACE2 protein in cell membranes. One Chinese analysis of a group of 170 Covid-19 fatalities(3) found half of the cases suffered from hypertension. ACE inhibitors are a class of medication prescribed for lowering blood pressure and according to models they increase the concentration of ACE2 protein in lower respiratory tract cells. Given that fatality results from respiratory distress originating in the lower respiratory tract and that not all cases progress to the lower respiratory tract it seems possible that the spread of the virus within the body may be related to concentration of ACE2 protein in cells. The disease progression would also support mucosal transport of the virus within individuals the same as between them. (1) Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. https://www.ncbi.nlm.nih.gov/pubmed/15141377 https://www.ncbi.nlm.nih.gov/pubmed/15141377 (2) Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein https://www.sciencedirect.com/science/article/pii/S0092867420302622 https://www.sciencedirect.com/science/article/pii/S009286742... (3) Controversial Study Links COVID-19 Severity to ACEIs and ARBs (Newsweek, March 24, 2020)
    - seraphsf 7y ago
      Because it’s a respiratory disease
    - frenchy 7y ago
      If you're looking for a chemical explaination, I don't know, but the virus can work it's way around quite fine using the lymphatic system, so there's no "fitness" reason that would make it need to hang out in the blood.
- Kye 7y ago
  Or with a well-known phrase: garbage in, garbage out.
- usrusr 7y ago
  Even if you do everything perfectly a PCR test will still not be able to tell working virus copies from shattered remains.
im3w1l 7y ago
The PCR can detect if there is virus in the swab. But the swab may not have scooped up any virus even though the person had some.
- baxtr 7y ago
  That’s right!
- hprotagonist 7y ago
  my longstanding argument against theranos, by the way (like, since 2005), was "look. if i go down to the beach with a bucket and take a bucket of water and put it in my super accurate shark detector van, it doesn't mean the beach is safe to swim at!"
  - daotoad 7y ago
    Unless you dilute the water until it becomes homeopathic anti-shark water.
  - zerocrates 7y ago
    To be fair at some level that's an argument against blood testing in general.
    - hprotagonist 7y ago
      not really. it's just an admission that sampling frequency matters.
aqme28 7y ago
Even a 99.9% sensitivity will miss a few times when you're testing millions of people.
omnipugent 7y ago
Can't PCR tests detect damaged RNA and report that as a positive? https://www.aim-med.org/hiv-rna-test/ https://www.aim-med.org/hiv-rna-test/
bewaretheirs 7y ago
They're highly sensitive to the presence of the target DNA or RNA sequence in the sample well. But they can't easily tell if the target sequence they amplified came from the patient's sample or from other potential sources of contamination in the lab (the test, after all, makes billions of copies of the target DNA sequence), whether from other positive tests or from positive controls.
- W4ldi 7y ago
  But that doesn't explain false negatives, does it?
  - bewaretheirs 7y ago
    They typically do one swab of the nasopharynx (upper back of the throat, up above the soft palate). You might have the virus elsewhere but not there. Saw reports that bronchoalveolar lavage (introducing and then suctioning out fluid from a branch of the lung) is better at picking up virus if it's present -- but it's much more time consuming, more invasive, and much less pleasant for the patient than sticking a swab up your nose. Not something you're going to do in a parking lot in a drive through testing center for someone only showing mild symptoms. There are always compromises.
    - baxtr 7y ago
      It depends on the time of the illness. Roughly my understanding is: 1st week - high virus load in the nasopharyngeal area. 2nd - almost no virus load in the nasopharyngeal area, high virus load in the lungs

In general PCR tests are highly sensitive. Even smallest viral loads can be detected (Edit) added in general above due to valid points in the comments below

by baxtr 7y ago

In general PCR tests are highly sensitive. Even smallest viral loads can be detected (Edit) added in general above due to valid points in the comments below

hprotagonist 7y ago

if: - you do them right - your reagents are good - the kit was assembled properly - there's no contamination in the machines - you got a good sample - ... The capability for a highly sensitive and accurate test in no way guarantees that a randomly sampled administration of that test is going to meet the high standard that the test may be capable of.

twic 7y ago
And if you swabbed an infected part of the body in the first place! In 205 patients with proven COVID-19 [...] bronchoalveolar lavage fluid was positive in 14/15 (93%), sputum 75/104 (72%), nasal swabs 5/8 (63%), brush biopsy 6/13 (46%), pharyngeal swabs 126/398 (32%), feces 44/153 (29%), blood 3/307 (1%), and urine 0/72 (0%). https://www.jwatch.org/na51116/2020/03/17/pharyngeal-and-nasal-swabs-may-not-have-adequate https://www.jwatch.org/na51116/2020/03/17/pharyngeal-and-nas...
- hinkley 7y ago
  Hol' up. > blood 3/307 (1%) Why isn't their blood rotten with virus?
  - gojomo 7y ago
    I suspect it's because this virus is optimized to enter cells that line the lungs/respiratory tract, then also sheds back that same way. Meanwhile, cells in, and along, the bloodstream aren't infected – and are most-trafficked by the body's immune response, including virus-destroying antibodies. (Why are rodents more prevalent in the walls/crawlspaces of a dwelling, rather than the hallways?)
    - hinkley 7y ago
      But the lungs are full of blood, that's how we breath. So it's spreading mucosally or through connective tissue?
      - gojomo 7y ago
        Sure, but if an initially-infected respiratory cell releases its "baby coronaviruses" out to the respiratory linings, away from the blood, they'll find lots more of the respiratory cell surfaces they're optimized to infect, and maybe get a ride out to other hosts on sputum. To the extent an infected cell releases its "baby coronaviruses" into the blood stream, they find a hot, chemically active environment – which is already inhospitable to their continued survival – plus a relative dearth of the respiratory cell-walls they're optimized to enter, plus a growing number of hostile antibodies. (I don't know if a coronavirus-hijacked cell can direct its fresh viruses one way or the other, but it'd probably prefer to do that if it could, and I can understand why viruses wouldn't persist long in blood compared to respiratory-membranes.) The coronaviruses are definitely active in mucosal surfaces, and carried by mucus. I haven't seen anything about, nor do I think any activity is necessarily implied, in other connective tissues.
      - dmm10 7y ago
        As far as I know the route of SARS-Cov-2 spreading in the human body isn't known beyond the change in locality of symptomatic expression with progression of Covid-19 (upper respiratory tract to lower respiratory tract.) Research has shown (1) the distribution of ACE2 protein, the functional receptor for SARS-Cov and SARS-Cov-2 (2), to include various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain) along with arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. And ACE2 mRNA has been found in virtually all organs. So there is definitely the potential for cells in the circulatory system binding viruses. What may be significant here is the concentration of ACE2 protein in cell membranes. One Chinese analysis of a group of 170 Covid-19 fatalities(3) found half of the cases suffered from hypertension. ACE inhibitors are a class of medication prescribed for lowering blood pressure and according to models they increase the concentration of ACE2 protein in lower respiratory tract cells. Given that fatality results from respiratory distress originating in the lower respiratory tract and that not all cases progress to the lower respiratory tract it seems possible that the spread of the virus within the body may be related to concentration of ACE2 protein in cells. The disease progression would also support mucosal transport of the virus within individuals the same as between them. (1) Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. https://www.ncbi.nlm.nih.gov/pubmed/15141377 https://www.ncbi.nlm.nih.gov/pubmed/15141377 (2) Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein https://www.sciencedirect.com/science/article/pii/S0092867420302622 https://www.sciencedirect.com/science/article/pii/S009286742... (3) Controversial Study Links COVID-19 Severity to ACEIs and ARBs (Newsweek, March 24, 2020)
  - seraphsf 7y ago
    Because it’s a respiratory disease
  - frenchy 7y ago
    If you're looking for a chemical explaination, I don't know, but the virus can work it's way around quite fine using the lymphatic system, so there's no "fitness" reason that would make it need to hang out in the blood.
Kye 7y ago
Or with a well-known phrase: garbage in, garbage out.
usrusr 7y ago
Even if you do everything perfectly a PCR test will still not be able to tell working virus copies from shattered remains.

im3w1l 7y ago

The PCR can detect if there is virus in the swab. But the swab may not have scooped up any virus even though the person had some.

baxtr 7y ago
That’s right!
hprotagonist 7y ago
my longstanding argument against theranos, by the way (like, since 2005), was "look. if i go down to the beach with a bucket and take a bucket of water and put it in my super accurate shark detector van, it doesn't mean the beach is safe to swim at!"
- daotoad 7y ago
  Unless you dilute the water until it becomes homeopathic anti-shark water.
- zerocrates 7y ago
  To be fair at some level that's an argument against blood testing in general.
  - hprotagonist 7y ago
    not really. it's just an admission that sampling frequency matters.

aqme28 7y ago

Even a 99.9% sensitivity will miss a few times when you're testing millions of people.

omnipugent 7y ago

Can't PCR tests detect damaged RNA and report that as a positive? https://www.aim-med.org/hiv-rna-test/ https://www.aim-med.org/hiv-rna-test/

bewaretheirs 7y ago

They're highly sensitive to the presence of the target DNA or RNA sequence in the sample well. But they can't easily tell if the target sequence they amplified came from the patient's sample or from other potential sources of contamination in the lab (the test, after all, makes billions of copies of the target DNA sequence), whether from other positive tests or from positive controls.

W4ldi 7y ago
But that doesn't explain false negatives, does it?
- bewaretheirs 7y ago
  They typically do one swab of the nasopharynx (upper back of the throat, up above the soft palate). You might have the virus elsewhere but not there. Saw reports that bronchoalveolar lavage (introducing and then suctioning out fluid from a branch of the lung) is better at picking up virus if it's present -- but it's much more time consuming, more invasive, and much less pleasant for the patient than sticking a swab up your nose. Not something you're going to do in a parking lot in a drive through testing center for someone only showing mild symptoms. There are always compromises.
  - baxtr 7y ago
    It depends on the time of the illness. Roughly my understanding is: 1st week - high virus load in the nasopharyngeal area. 2nd - almost no virus load in the nasopharyngeal area, high virus load in the lungs