People may have noticed I'm quite keen on serology and am rather less than enthusiastic about PCR for test, track and trace in a situation where the SARS-CoV-2 virus is present throughout the country, as it is here in the UK. Stupid is as stupid does.
However, serology is not quite as straight forward as I might like either.
There are a number of serology tests coming on to the market, and many have a 100% sensitivity and 98% specificity. It difficult to express how phenomenally accurate these test are. If I submit a blood sample for some routine analysis I accept that 95% for these sorts of accuracy assessments is pretty good, we're dealing with biological systems, there is room for grey zones.
So presently serology has a 100% sensitivity. That means it will always pick up seropositive people. If you have antibodies, this test will find them. Always. Getting a negative needs some thought.
This is addressed by specificity. A 98% specificity means that a negative on the test will be correct 98 times out of 100. If the test says you don't have antibodies, it is also most likely correct, a one in fifty error rate there.
It is difficult to over emphasise quite how good these values for sensitivity and specificity are for a lab test. They are very, very good.
At detecting antibodies.
If antibodies are found in a healthy person it is, with a test this good, pretty well certain that they have been exposed to the disease and, in the absence of illness, that they are immune. Or at least they were at the time of exposure.
Sadly human immune systems can be recalcitrant in cooperating with serology.
The Royal College of Pathologists short presentation on serology is now up on Youtube
The COVID 19 pandemic: testing – serological diagnostics for COVID 19
and here is a screenshot from just after 18 minutes in:
The dotted red line is the lower limit of the serology assay used. All of the patients have had known, absolutely certain, clinical disease. If you use a serology test which is 100% sensitive and 98% specific, you will pick up everyone over the red dashed line. A negative result will be correct 98% of the time. That is what a highly sensitive, highly specific test does. To put that in a more visually clear image here is another screenshot:
Again, below the red dotted line you will be classified as seronegative, you are seronegative. That does not mean that you have not been exposed. It doesn't matter how good your test is. The test cannot see below the red line, above the red line the test is phenomenal. This not a problem with the test, the test is not for exposure/recovery from the disease. It is just for antibodies above a certain level. This is the limit of serology testing, it is undermined by the ability to recover from this infection without seroconverting. It happens, it's on the graphs. It's not the test's fault.
To a large extent recovery without seroconversion suggest that the innate immune system is at work (or you are simply unable to become infected) and that would fit nicely with the reports suggesting that hyperglycaemia over 10mmol/l is bad news and hyperglycaemia below 10mmol/l gives a slightly better outlook in severely ill patients. Hyperglycaemia is a good way of suppressing the innate immune system.
Passthecream put an interesting link in the comments of the last serology post which suggests the innate immune system is also adaptive, it remembers, no antibodies needed...
Adaptation in the Innate Immune System and Heterologous Innate Immunity
Sadly, at our rudimentary level of understanding of the immune system, we are in no position to assess whether a given person might be seronegative but still immune.
Having said all of this, it's worth remembering that being seropositive without having being ill suggests you are immune. It's interesting to see the WHO position on this. The WHO currently suggests that there is no evidence that having antibodies confers immunity.
That is interesting and absolutely, currently, technically correct. Thus far seropositive people have never been challenge-tested with virulent virus, so there can be no evidence that antibodies are protective (try getting that one through ethics committee review!). It is theoretically possible that a person could have been exposed to virulent virus, have never been ill, have developed antibodies, and yet is still be susceptible to the virus. You can imagine that this might be the case.
Well, actually, I can't.
So, if you are the head of an ITU in a UK district general hospital in London and you find you are one of those lucky people who are solidly IgG seropositive without ever having been ill, what would you do as regards PPE for yourself?
As the WHO says, there is no evidence that being seropositive is protective, as yet. But for antibodies produced in vivo, by someone who was never unwell, for these antibodies not to be protective would have to be a first of a kind as regards immunology (vaccine induced seropositivity is a whole different ball game).
I love this guy:
COVID-19: ICU care, long-term effects and immunity with Dr Richard Breeze
(Hat tip to Unknown for the link and no, Breeze didn't use any PPE while treating the large wave of COVID-19 patients which passed through Lewisham District General Hospital's upgraded ITU)
Knowledge over protocol. He also strikes me as the sort of person who might look at a patient on a ventilator who was developing barotrauma because "protocol" suggest "Xml/kg" as the "correct" tidal volume setting and who might reach over and reduce (gasp) the tidal volume setting. Just my guess. Or avoid intubated ventilation if at all possible (which was what they did).
You have to contrast this with the hospital managers who discharged SARS-CoV-2 positive patients in to unprotected nursing homes because "it's protocol".
I get the impression that good medics (and there are some excellent ones out there) don't seem to be the sort of people that become the politico-medics who guide the government...
Peter
Aside: I just can't get over Dr Breeze working without PPE. Sort of thing I might have done under the circumstances. I can't believe it was allowed nowadays!
