Pandemic blog 25: version

I’ve always thought of myself as an extravert, but am I? I read lots of articles about the almost unendurable pain of being cut off from physical contact with friends, relatives, and just random people out in the world. I’m lucky — I don’t experience that as pain. Partly, I guess, it’s because I haven’t really been contactless. I go for walks, I talk at a distance to friends I see; or I work on the porch and I talk to people I know who come by.

There are individual differences. I took CJ to the middle school to pick up the contents of his locker; it was the first time in two and a half months he’d been 100 feet from our house. He really doesn’t need variety. Me, I take my walks, and I go for bike rides with AB. I could really do things this way for a long time, forever if I had to.

I don’t have to. The restrictions on gatherings and business are starting to lift now; cases aren’t really declining, are maybe even going up a little, but there seems to be some sense that with testing protocols in place we can afford to experiment with a gradual, carefully monitored relaxation of restrictions.

It’s aggregates that matter. Not everybody has to be perfectly sealed off, which is good, because not everybody can be. But the easier it is for you to not see people, the less you should see people. From each according to, etc.

7 thoughts on “Pandemic blog 25: version

  1. Dear Jordan, the same for me here in italy. Finally we are “unlocked” now, and the unlocking here started a month ago, but most of the time I am still in the so called phase 1 (we are now in phase 4, you can move everywhere by keeping social distances, at least in principle). I stay with my family, I do math, a lot of videochat, many streaming events, and so… I’m fine this way (*). Is it bad? r

    (*) maybe is it the same for other mathematicians?

  2. Richard Séguin says:

    I always think of extroversion as referring to the tendency to be outgoing. The tendency to be outgoing should not be tied to the inability to be alone; these are two completely different things. Real life is complicated, messy, and multi-dimensional.

    Walking does wonders for ones mood. My late dog taught me the delight of awareness and actually stopping to look at things.

    Yesterday I went to the UW Hospital outpatient lab to get a blood draw in order to test for antibodies to the COVID-19 virus. The woman in the cubicle next to mine was telling her tech that she was really sick with some kind of respiratory infection back in March, that her husband also got it, and now her doctor agreed that she should be tested for the antibodies. She asserted that she would almost certainly test positive. When I was at the ER in very early March with an unusual respiratory infection and a collapsed lung, they could not test for COVID because (as per CDC directives) I had not been out of the country nor could I claim that I had been in direct contact with someone who had actually tested positive. (It was nearly impossible to claim the latter at that time). They only tested for strep and for influenza. My lab tech said that that was the story of most people coming in for the test: they had been sick with a nasty or weird respiratory infection back in February or March and couldn’t get tested for the virus at that time.

  3. Richard Séguin says:

    My test result came back negative for COVID-19 IgG. I actually feel a little deflated by the result because it fails to explain a mystery, which is what I was hoping for. Also, I’m a little irritated because now I have to ponder exactly what this negative result actually means in my case. Antibody tests have far more problems with interpretation than, say, PCR tests, and my case is complicated further by the fact that my B cells aren’t optimally producing antibodies, either in number or by function, and as a consequence I need regular IVIG infusions (exogenous IgG antibodies). The test was done by ARUP Laboratories, and this particular test was the “Qualitative by CIA” version. Qualitative means that they give a yes/no answer. (Can they really reliably detect a single COVID IgG molecule in the vial of blood?) They have another version called “COVID-19 IgG by ELISA.” The CIA version “detects IgG antibodies specific to the SARS-CoV-2 nucleocapsid protein in serum and plasma to evaluate exposure” and the ELISA version “detects IgG antibodies specific to the S1 domain of the spike protein of SARS-CoV-2 in serum and plasma to evaluate exposure.” These two tests appear to be testing for two different antibodies to the same organism. Is it possible to make other types of antibodies for this organism? Does the presence or absence of one type of antibody always imply the presence or absence of the others? If the answer to the latter question is no, then I think we have a problem.

  4. Tom S. says:

    Hmmm, good questions. I will try some answers based on general principles of immunology and liteterally my own current work to produce these CoV-2 antigens for immunoassays.
    – “Is it possible to make other types of antibodies for this organism?” Yes. In principle every protein of the virus, which is “foreign” to the human body, can be a target for the body mmune response and can lead to cellular responses of T lymphocytes (not trivial to measure) or the production of antibodies by B lymphocytes (easily sampled by drawing a blod sample). Some viral proteins could be more immunogenic than others. And confusingly similarity or dfferences between related proteins of related viruses become an issue. You as anybody else are likely to have suffered from a common cold after infection by coronaviruses loosely related to SARS-CoV-2. The echo of that old immune response may be present as blood antibodies and now needs to be distinguished from a suspected anti-CoV-2 immune response = fresh antibodies. Antibody reactions to viral proteins, which are similar between common cold and CoV-2 coronaviruses, are useless. Current thinking is that the receptor-binding domain of the spike protein (itself roughly half of the S1 domain) and the nucleocapsid are the most specific CoV-2 antigens. It may be possible that other CoV-2 proteins can be found to be specific antigens as well, but this is subject of current research. Interestingly spike is on the virus surface, and anti-spike antibodies in part will be those neutralising the virus. The nucleocapsid is hidden inside the virus, but is “seen” by the immune system during virus production and assembly. Anti-nucleocapsid antibodies won’t be capable of virus neutralization.

    – “Can they really reliably detect a single COVID IgG molecule in the vial of blood?” No, single-molecule analytic sensitivity is neither really possible nor required. The blood sample will contain antibodies to different parts of the antigen surface, so-called epitopes, and more than just a single antibody molecule of each type. Assay techniques vary and may be suited to qualitative versus quantitative results, respectively.

    – “presence or absence of types” Anti- nucleocapsid and anti-spike antibodies will in most cases appear together, but presence of one type in absence of the other currently cannot and should not be excluded. Over the coming months harder figures on these proportions will come from current epidemic research. In the meantime, particularly in your case, a test for spike antibodies is advisable to cross-check the first result. A quantitative test seems the way to go, particularly because you have to establish a baseline for these antibody titers as oer today, since your exogenous IgG therapy might cause therapy-related fluctuations in that background level.

    Oh, and the false-negative rate of PCR testing (often by imperfections of sample taking) should rightfully worry everybody involved as much as complicated interpretation of antibody tests…

    Anyhow, best wishes!

  5. Richard Séguin says:

    Tom — thanks for the detailed response! That was better information than I hoped for!

    I’ll pursue the idea of the “Qualitative by CIA” test for anti-nucleocapsid antibodies with my doctor(s), but I’m not optimistic that they will buy into the idea. What does “CIA” stand for? I know what “ELISA” stands for.

    I’m glad we’ve advanced to the point where we are thinking about and researching the problem of multiple antibody types. Hopefully sometime soon I’ll start hearing about some research results.

    IVIG at the moment shouldn’t be a complicating factor in interpreting positive antibody results. It’s made from the pooled blood of at least 1000 people and it takes at least 9 months of manufacturing and distribution time before patients get antibodies from any of that blood. I’m guessing that unless the virus has been here undetected for longer than we currently think, antibodies won’t be showing up in tests at all due to IVIG for a little while yet. It will probably be a year or more before IVIG starts becoming protective for the virus in the patients that get IVIG, if ever.

    I concede that there is probably a false negative problem with PCR tests. I was in the hospital about 11 years ago as the mystery patient being tested for a huge number of possible pathogens, but the young doctors did not recognize the rash I had as a possible measles rash, even though I told them it looked like something I had when I was a kid. (They had probably never seen one.) The skin sample report from dermatology finally prompted them to test for measles after I was discharged, the fever was gone, the rash was fading, and after I had been rinsing my nasal and sinus spaces for several days with saline rinse. I was finally swabbed. The result was negative. I complained to the state lab that measles is supposed to be tested for promptly after symptoms appear, and that I had been rinsing those surfaces for days anyway. Apparently IgM antibodies were detected, at least at low level, and the lab recommended in their report that I be retested in several weeks. The doctors didn’t even tell me about that recommendation and did not follow up on it. I had to discover this by requesting records. (I have a very long report on all this.)

  6. Tom S. says:

    CIA = as per ARUP website Chemoluminescent Immunoassay. Nucleocasid antigen probably coupled to a bead carrier and then bound anti-nucleocapsid antibodies are measured by a chemoluminescent readout.

    I agree that IVIG for the time being won’t present a problem with a content of some diluted anti CoV-2 antibodies. The point is rather that any normal blood contains a large antibody concentration with a wild wild wild mix of different binding specificities and, importantly, different binding strengths. There will be a surprising amount of immunoglobulin molecules which won’t have the high binding strengs/affinities of antibodies after immunization, but which still will show some weakish binding. This is exactly the protective role for your IVIG treatment (apart from making sure that te protein level of your Ig stays within reasonable bounds). Now any laboratory immunoassay for detection of specific high affinity antibodies needs to be developed and tweaked so that this normal “background” immunoglobulin does not give a specific signal, but only a background signal; signals are considered specific if e.g. 3 standard deviations over background. Due to the IVIG doses your “background” antibody composition is going to vary more over time than it would in a normal person, and any immunoassay results in the gray zone (not quite negative, not quite positive) should be looked at and possibly corrobated with additional tests and, if feasible, orthogonal methods.

    Swabbing for a coronavirus PCR sample probably has to be deeply unpleasant with a risk of throwing up in order to be done right…. ( as they say for cardiac reanimation, broken ribs are an acceptable sign for the right physical effort).

    To return to the thread topic: while we didn’t have strong lockdown in Germany, the restrictions are beginning to lift. My self-isolation was beavering away in the lab, not really a restriction at all. Family happiness was much more affected by shutdown of the currently “most dangerous hobby in the world”, choir singing (fully expeced to be one of the last activities to cone back). Nobody really knows why Germany has so far come out as golden as it did, but still every responsible person nervously eyes case numbers. I fully expect some increases due to rampant carelessness. Unfortunately the cynical viewpoint is right: loosening the restrictions doesn’t mean that the virus is s gone, but only that the ICUs have space for you….

  7. I generally put you on the scale somewhere between Pollyanna and Pangloss as far as your general levels of outwards positivity. To the extent that this accurately reflects your inner self, it probably is an attitude that comes in useful during a quarantine, extrovert or not.

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