UKC

I've done some internet research on this but I'm no wiser. Perhaps those with expertise on here can add to my understanding. 

My son is in his 40s very fit and healthy normally and has just had an unpleasant 10 days of covid. For months he had worked at home in full compliance with all the rules . He only goes out to get the odd shopping. Yet his wife is a primary teacher and has pretty much been working at school the whole time. She has recently been testing twice a week and has no positive result and no symptoms. Both the kids have no symptoms nor positive test in spite of their own class teacher getting it. So in short my son has had a right dose of infection and illness in spite of being mostly distanced from the world and his wife and both kids have no signs of infection whilst cooped up in the same house and being exposed daily to the school and all that goes with it. How can this be? If it is so infectious, which I am not casting doubt on , how come he's the only one in the house to get it? 

This is a genuine question. How come four people who live closely together don't all pass it to each other?

Has he had a positive test for covid? (To rule out the obvious)

My friends husband was positive for COVID antibodies but she was negative. 

Yep. Pcr test at the local NHS test centre. They were really quick btw. Tested at about 4:00 pm and got a text back with the result in the middle of the night !! 

1. My cousin's son infected her, his dad and his brother - everybody in household was a bit ill but recovered. All tested positive.
2. A mate and his son both tested positive with no symptoms. They got tested because they thought his wife had Covid but she tested negative.

It's weird is my only conclusion.

Presumably once he was feeling ill he followed the guidelines and slept and isolated in another room from wife and kids? 

He obviously isn't asymptomatic so the risk to his family is reduced because he is obviously ill and they can take care not to be near him.  

As for why him and not the others, who knows.  He must have caught it from someone, has he been taking social distancing seriously while out shopping?  Has he been wearing a good mask?  I can see how it would be easy for him to take the risk less seriously because he is working from home and expecting his wife and kids to bring it home if anything.  

Probably just unlucky.  

We don't yet understand but there's quite possibly some inherent immunity. It's possibly his wife has some sort of immunity and passed that immunity onto the kids. I think we'll know more in time. However Covid isn't that contagious and it's not a certainty that others in the house get infected.

Re how he got it, he could have just walked down an aisle an infected person had coughed or sneezed on. It could be anything.

It is very infectious, but not everyone is a good spreader of infection. A minority of people (10-20%) provide the majority of spreading. If you're unlucky enough to be a good spreader then you'll give it to everyone else in the house. If you're a good spreader in contact with lots of people then you've got the potential to infect dozens rapidly.

(Hence why allowing mass gatherings to occur in March last year was retrospectively a very bad idea)

This seems to be how things go, from anecdotal evidence/experience.

I don't believe the test results too much. I had covid, got it off a guy at work. He had symptoms, got a PCR, was negative, so he came to work. Gave it to me and another colleague. He felt worse, got another test, it was positive. I got symptoms, got tested, was positive. Colleague tested negative, next few days felt worse, tested again positive.

I work in another practice, same thing happened there. Colleague started with symptoms, tested negative, got worse, then tested positive.

I'm convincedThose PCR tests are not as accurate as they're cracked up to be, from a small sample of direct experience, which tell a consistent story.

So I think in your situation you've got a combination of asymptomatic transmission and false negative PCR tests (which are more common than is published). That provides a sensible explanation IMO.

This does seem to happen. Studies looking at student households last year showed that a COVID positive but largely asymptomatic student in the house did not mean that the others showed a positive reaction. What is slightly different here is that you say your son was ill, so likely was excreting decent amounts of virus. I wonder if you have all (except your son) asymptomatically had the virus before and that is why there was no transmission at this stage.

Hope this makes sense

PCRs are pretty accurate, definitely better than the lateral flow test, but the sample quality can be a problem. People often gag a little when the swab is on their tonsils and that leads to a poorer compliance and effort in sampling. Saliva testing does offer a way around this, but is less usually employed. 

Presumably when you say kids were negative, that was lateral flow? That's really helpful test and has helped reduce Covid spread in schools (my eldest 2 are doing it) but it's not actually that reliable, quite a few false negatives 42% as the accuracy is "58% when used by self-trained members of the public" (source https://www.gov.uk/government/publications/evidence-on-the-accuracy-of-late...)

Perfectly possible one of your kids had Covid for a while but was asymptotic. Pure speculation though..

Thing is we'll never know how most people caught theirs. People do catch it...

https://www.healthline.com/health-news/how-fast-covid-19-can-spread-in-a-ho....

There was this study recently showing it's possible to live with someone and not contract covid.

I guess a third possibility, next to the tests not being so accurate, or the accuracy depending on how well people swab (both of which may overlap), could be that something happens within the mouth/back of throat where people swab in line with how they feel, so that when they swab again once feeling worse, they get a different result?

Trouble is, to measure the accuracy of a test, you need a "gold standard". The PCR test is the "gold standard" for covid testing, so I don't know quite what they're measuring it (sensitivity and specificity) against.

Yes, they're better than LFTs no doubt. But if the PCR is the best test, and as far as I can see PCRs keep have a good chance of telling people they're negative when they're positive, then we don't really have much of a "gold standard".

That's a possible explanation of why the PCR test isn't so great - it's wrapped up in the accuracy of the test, not separate from it.

I'm not making any conjecture about why/how the PCRs generate false -ves, I'm just pretty certain from repeated anecdotal experience that they do.

If anybody on here works in a related field, it might be something to look into, quite interesting and possibly helpful.

I think I had in mind the tests being accurate, but only if carried out a certain point in the illness, which possibly becomes about how the test and illness 'interact' (for want of a better word) without the mechanism itself of the test being inaccurate, but this is probably straying into the area of people thinking in different ways about the same thing, like 'tomarto' and 'tomaeto'.

There are some nice illustrations around of PCR & LFT likely outcomes versus time from infection. Early on both tests usually give a false negative but the window of a correct positive starts earlier and is much wider for the PCR. Most of the testing differences seem to be explained by that. There are obvious implications if exposed to someone you know was positive... self isolate for a few days and don't get PCR tested immediately.

The PCR is the most sensitive test we have and that is with a high specificity so at present this is 'the gold standard'. Sampling error through timing and sampling technique apart, PCRs are very good at detecting very low numbers of copies of virus. In a study you might sample before during and after infection and combine that with antibody and possibly non-specific, but supportive cytokine changes to add further information and sensitivity. I am concerned that your message to this board is that PCRs are not effective and often produce false negatives which is not borne out by current evidence. 

However, it does seem to depend which method you use e.g. Performance Characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 RT-PCR Tests in a Single Health System: Analysis of >10,000 Results from Three Different Assays doi: 10.1016/j.jmoldx.2020.11.008

In contrast a UK Lab is saying 'Our assay has been measured as having a sensitivity (chance of producing true negatives) of 96% and a specificity (chance of producing true positives) of 96%.  The LOD (Limit of Detection) of our assay is 30 copies per ul which means our assay can detect very small levels of the virus.' https://www.dbth.nhs.uk/news/test-covid-19-dbth/ accessed 4/21.

Medicine is a bit messy.  The OP asserted that his son's clinical signs were related to COVID, but actually we can't say that. He had respiratory disease and presumably tested positive for COVID which is not the same. 

Bayesian people are putting out the occasional paper claiming to create a gold standard against which to evaluate PCR by Bayesian methods.

I don’t know how the clinical community feels about that sort of thing...?

Remember that's there's a fairly high rate of false negative results (result says "no Covid" when actually the patient does have Covid). Last  I heard it was about 30% false negative rate, but that was a good while ago and I don't know if they've been able to improve it.

Good post thanks!

Yes, as Timmd points out, I think the problem I'm highlighting is how well the test has been done, not how good the test is when done perfectly in a research setting.

That's useful info on how you make the PCR into a useful gold standard. The problem as I see it is that the published info on the accuracy of PCR, while justified by research, doesn't seem to be how it turns out in the real world. The consequences of this are important: out of 4 people who got covid in a helathcare setting, 2 of them came into work with mild symptoms following a false neg PCR (another got a false -ve but stayed at home), allowing the infection to spread. This is a problem!

We had a kid at school who had a cold and tested positive for covid. She ended up with a pretty chesty cough but recovered quick. Her whole family tested negative repeatedly. Nobody in her friendship group tested positive either. She'll never know where she got it from. But in a big house (again money offers protection), with separate bathrooms it's quite possible the rest of the family don't contract it. 

My wife also had a 87 year old patient with cancer, his great grand daughter he lived with got covid, and he never did. They were pretty sure he'd not survive but everyone just masked and stayed separate, but they had one shared bathroom.

woman at work ended up in hospital, she'd been sharing cigarettes (one between two) with her daughter for two days before, only she had it and didn't pass it on.

Friend in Poland caught it at a wedding, passed it on to his mam and dad, they passed it on to another family, both incidents consisted of meetings of less than 1 hour.

My mates mam, had covid early on, she 70+, she had both jabs and caught it again 2 weeks ago!

Something between ignorance, bemusement and ROFLMAO..

A very common observation of infectious diseases, including SARS-CoV-2, is that transmission is not guaranteed, and you are best thinking about it in terms of probability (stochasticity), rather than a deterministic, fatalistic process. Within household secondary attack rates (the proportion of residents, excluding the index case, that get infected) are hardly ever binary, where a household either has no onward infection or everyone gets infected. 

Figure 1, page 20 of this paper illustrates the variety quite nicely: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab237/620940...

The operational FPR was fairly clear to deduce over last summer when prevalence was low but testing was increasing.

Well, that’s what the leadership at CEBM claimed, but as we know their outputs on covid are basically weapons grade nonsense.

I strongly dispute what you say.  Can you put forwards any hypothesis test to support your conclusion?  You have declined past suggestions on this.

https://www.covidfaq.co

https://www.covidfaq.co/Claim-PCR-tests-are-not-finding-real-cases-15a55602...

https://www.covidfaq.co/Carl-Heneghan-and-Tom-Jefferson-Oxford-CEBM-eb9a2ce...

We'd expect to see vaccinated people get covid. 

We have a vaccine with 90-95% efficacy. We've vaccinated 90 million in the US therefore we expect 5-10% of them to be susceptible to getting it again. However, it seems it's 100% protective against serious covid.

I'm saying the FPR would appear to be very fairly low if the rates over the summer are anything to go by and we can factor in some pre test probability into the mix.

I agree with that - last summer can put an absolute ceiling on the FPR (assuming it's a constant and not a multiplicative factor), and it shows that to be very low.  However, I still disagree strongly with your earlier statement:

IMO the FPR can not be deduced from the data last summer.  All we can do is use the positivity to define an absolute ceiling for the FPR, but not to deduce the actual rate.

Yes quite right, sloppy language.

Post lock down screening in Wuhan turned up some impressive results for PCR. Nearly 10 million people tested and only 300 positives (200 of which had no antibodies so likely false positives).

They were only testing two genes using their test too, though maybe that impacts FNR more than FPR?

https://www.nature.com/articles/s41467-020-19802-w#citeas

Thank you Jon. Interesting links. 

Thanks also to everyone else who responded to my post with analytical and anecdotal contributions. I take your point that it's ultimately a matter of probability but i suppose I was curious about the influential factors. Clearly we expect proximity to infectious people to be significant although in my son's case it runs somewhat counter to expectations. 

I was hoping perhaps for some comments from those with expert knowledge about what might be thought of as natural immunity. From what we understand of our body's response is it just that those who don't get it (e.g. Kids) simply have much more effective killer mechanisms ( so they do get infected much as an adult but they kill it off quickly) or is there something else more along the lines that their cells are resistant to infection in the first place. 

So for example if you did a challenge test would there be some who simply didn't get the infection. I'm pretty sure I've read about such relating to other diseases but I've not managed to find good references. So is there a distinction of merit between getting an infection and killing it quickly and simply not getting it in spite of a deliberate challenge. 

I am a scientist by qualification and training but this is not my field. Nevertheless the more I look into it the more fascinating and curious it seems. I suppose I should sign up for a course in molecular biology or something but I'm being lazy and trying to pick the brains of those who've spent years studying this stuff 🙂

Absolutely possible. One thing that's different about Covid compared to say.. flu is the variability of spread. Some people with Covid end up infecting no other people, some people with Covid end up infecting loads of other people. The level of that individual variability is way higher, to the point it's quite unlike otherwise comparable infectious diseases. At the end of the day much public health study is based on statistically comparing one population versus another population, not individuals, so this all averages out. Interesting though...

Yeah, she sort of proves it, she's fine, but had it twice now, and not needed hospital treatment, so all good. Just very strange and not something I'd heard of before. These are intelligent and honest people so would expect them to make stuff up or exaggerate.

You can work out the false positive rate by working backwards from detected cases and tests performed if you know the sensitivity and selectivity values. I did it with Excel and the UK never got low enough for false positives to be a problem.  I need to write the excel to do it again as I lost it .

We're introducing LFTs here for surveillance testing and our director of public health says the selectivity is 76%, however that also depends on viral load, and vaccinated people often don't have enough viral load to test positive with an LFT.  As such, their use is being phased out as our vaccination programme churns on.

Problem is what do you take as the values for sensitivity and specificity?   There's two different factors at work really - the values for the particular RT-qPCR test being performed, and those for the whole testing system of which the expensive ThermoFisher box is just one part.  If you use the values for any sort of PCR test you're going to get an insubstantial level of false positives.  If there are false positives, I'd imagine it's most would be related to cross-contamination (see the recent Panorama) and so they're not a small baseline rate but a small multiplier applied to test positivity in their absence.  Likewise the false negative rate of the ThermoFisher box will be much lower than of the wider testing system which includes factors like how well a test is administered and sample handling.

They just don't concern me at any point in this process to date. 

LFDs are a separate matter, but so long as they're confirmed by PCR, it's not a problem.  If we continue mass testing to the point most LFD positives are false positives, it does raise one question - is it better to quarantine people until their PCR confirmation, or to rely on them exhibiting informed caution until the confirmation comes back?  Otherwise you end up quarantining far more people than get positives which risks undermining the entirely voluntary commitment to the process; either way fast PCR turnaround and fast contact tracing on PCR confirmation are important.  It's great to see the significant reductions in PCR latency that have been made in the UK continue.

YES!! Found my excel.  Just emailed it to you

Interesting your director says that because my figures were from here https://www.gov.uk/government/publications/evidence-on-the-accuracy-of-late... however I was basing it on the sensitivity for self trained members of the public as it was in response to school kids 

It depends who is using the LFT and in what conditions. 76% seems optimistic for real world

"...PHE Porton Down and University of Oxford SARS-CoV-2 test development and validation cell found the sensitivity of the ‘Innova SARS-CoV-2 Antigen Rapid Qualitative Test’ dropped from 79% when used by laboratory scientists compared to 73% when used by trained healthcare staff compared to 58% when used by self-trained members of the public..."

We should avoid quibbling about the percentages though, as performing regular LFTs is way better than the alternative of not doing any!

I think the people using them here (government employees) are being properly trained how to use them - they're not dishing them out to the public. We have ~5k government employees out of a population of ~65k so they make a great surveillance cohort.  Teachers are doing two tests a week.