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More Antibody Data

Unfortunately, we’re getting a dose these days of “That’s why you run clinical trials”. Word came Monday evening (Peter Loftus in the WSJ, and a Lilly statement) that the ACTIV-3 trial being run by the NIH has shown lack of efficacy for the combination of the Eli Lilly/AbCellera anti-coronavirus antibody (bamlanivimab, LY-CoV555) when combined with remdesivir in hospitalized patients. This is the trial that had been paused earlier this month for safety concerns, but now no more patients will be enrolled at all. A thorough review of the data showed that there were, in fact, no differences in safety between the arms of the trial with and without the antibody – but there was also no difference in efficacy.

Lilly’s own statement notes that their own BLAZE-1 trial continues. That one is studying patients who are not hospitalized, with this antibody as a monotherapy and in combination with another anti-coronavirus antibody candidate (etesevimab, LY-CoV016). The company provided some data earlier this month on this trial, and indeed has said that they’re asking for an Emergency Use Authorization for high-risk patients on the basis of the numbers so far. There’s also the NIH ACTIV-2 trial, which continues to study the antibody in mild-to-moderate disease, and Lilly’s BLAZE-2, which is looking at using it for prophylaxis in patients and staff at long-term care facilities. It would be a coherent story if these trials show positive data – that way we could say that this therapy needs to be given early, and is of little use after someone has already been hospitalized. That makes a lot of sense, too – but you know what? A lot of things make sense that still aren’t real. We have to get the clinical data to be sure.

As if to underline this point, we’ve also recently had a controlled trial of convalescent plasma report its results (Damian Garde at Stat, and the article in the BMJ). Recall that the earlier Mayo Clinic data on this had no control group, making it frankly impossible to say how much benefit the plasma treatment might have had. But the new PLACID trial was a study of 464 patients across India, randomized versus a control arm, and it found no benefit to the plasma treatment at all. One objection is that many of these patients may have been dosed too late as well – many of these patients, it seems, were already developing their own antibodies, and it’s possible that if there is a benefit, that it will only show up with earlier treatment. But we don’t know that yet. Right now, convalescent plasma treatment is, at the very least, not looking spectacular, and could even be more or less useless, which would be quite disappointing.

You’ll notice a theme here, to which we can add the recent remdesivir data from the SOLIDARITY trial. Earlier data had suggested that the drug has some positive effects (although not dramatic ones) but the larger data set didn’t bear that out. What these things do is set bounds for what you can expect for a given therapy: the level of response in these cases means that even if there is some benefit, it’s going to be limited (or, at the most optimistic, limited in these particular populations of patients). A Wonder Drug would have given a stronger signal, and none of these are wonder drugs. The question is whether there’s any signal left after more waves of well-controlled data come in – and if so, what patients can get what benefits there are.

A month ago, for example, Regeneron said that their own monoclonal antibody therapy showed some signs of benefit, particularly in patients who had not mounted their own immune response. But if that’s not going to be the best-responding group, who is? Perhaps this study ran into the same problem as the PLACID trial above, and that could mean that monoclonals won’t add that much to people who are already producing their own antibodies. But if the Regeneron antibody cocktail worked wonders, we would have seen something more impressive. It might be that prophylaxis is where these therapies will show their worth (can’t dose much earlier than before a person has the disease at all!) I very much hope so. I will admit to having expected better from the mAbs in general, though, and even from convalescent plasma.

Prophylaxis frankly might be an easier public health decision than one that relies on very early treatment. After all, most cases of coronavirus resolve, and most people don’t end up in the hospital. When do you make the call for an expensive bolus of monocolonal antibodies? Your best shot is probably to catch the highest-risk patients as early as you can, and hope that it’s still early enough. But if such treatment can protect high-risk workers (sort of like a temporary vaccine), then you can far more easily pick out the people who could benefit.

Of course, right now we’re heading back into high case loads in many parts of the country, with some (like Utah) already beginning to hit the wall of hospital capacity. Deploying mAbs under these conditions is going to be more complex than ever. Let’s hope that we get some more clinical data soon to guide these decisions. There really does look to be a gap before any vaccine rollout where the antibodies could help. The key word being “could”. Might. Maybe. Clarity has been in short supply in 2020, and here we are calling for more of it.

214 comments on “More Antibody Data”

  1. Matthew says:

    It’s amazing that this far into the pandemic that some people still don’t understand that antivirals must be used in the early, viral phase of the disease. Or even prophylacticly.

    1. Andy II says:

      I think that a part of the problem is the availability of timely diagnosis testing. Most patients do not know when they got infected (test positive) unless you are a part of WH, professional or college football players where COVID-19 testing is mandated everyday. If a doctor know when a patient was negative the last time, the doctor may be able to treat the patient more effectively.

    2. David E. Young, MD says:

      I agree. Early is better. Must start treatment within a day or two of symptoms, or test contacts of a case and start treatment when nasal / oral swabs are first positive, even before symptoms. Treatments may costly, and this argues against early treatment in younger people.

      And intravenous drugs (Remdesivir, monoclonal antibodies) might be resisted by healthy but positive individuals.

      I regret that studies of drugs were not started earlier. An outpatient study of Remdesivir could have been started in late April or sometime in May. Instead, it has just started in early October. Despite concerns of teratogenicity, Favipiravir could have been started in trials in mid April or early May. It is an oral drug that is easy to manufacture and had some reason to believe it would be helpful. Researchers in the US pretty much ignored this Japanese drug, an at this time, Favi is just being studied in a few puny studies. If limited to those over the age of 50, then the risks of teratogenicity would be considerably less.

      Regeneron, at least, has several studies going on for their monoclonal antibody combination, including a study on ambulatory patients and a study on contacts. I wish them luck.

      1. theasdgamer says:

        Are the safety studies on Remdesevir complete? How is outpatient treatment safe? Do you perhaps admit patients for monitoring and administration of Remdesevir within a few days of symptom onset?

        Should public health officials instruct people to monitor their O2 levels with a pulse ox so that they catch this “invisible” symptom of hypoxemia without dyspnea if it’s the first thing to manifest?

        1. David E. Young, MD says:

          Well, our president got admitted to get Remdesivir and ended up get the Regeneron antibodies as well. Her recovered rather rapidly, but that is just one person. You can’t generalize from that! I really can’t answer the rest of your questions. But safety monitoring is never complete. Only time will tell… I think… if they keep on doing studies.

          1. RightHandDrive says:

            That is strange: At least 2 serious risk factors, and yet he bounced out of it faster than people 20 years younger and 5 BMI points leaner.
            How did he do that?

          2. HappyTrials says:

            @RightHandDrive n=1

          3. confused says:

            Yeah. Trump was high-risk, but *most* high-risk people still survive. IIRC asymptomatic cases have been found even in nursing homes – it’s not like at a particular age it becomes certain death or even certain ICU.

            And (highly speculatively) maybe being the President, he got taken to hospital super-early, so remdesivir was “unusually” effective.

            Or – alternatively – maybe his case wasn’t actually all that serious and someone other than the President wouldn’t have been hospitalized at all (do we actually know how sick he was? Being given dexamethasone and remdesivir simultaneously sounds rather like they were just throwing stuff at the wall…)

          4. theasdgamer says:

            Early treatment with antivirals can be done–especially for the powerful–but is the system set up to do early treatment, especially in hospitals?

            There should already be PSAs from health depts. yelling at people to seek treatment early. And EDs shouldn’t be sending high risk patients to recover at home.

            Instead we have a lot of nonsense about masking and social distancing.

          5. theasdgamer says:

            Safety comparisons between Rem and HC are clear. Rem has to be given under inpatient management, while HC can be given outpatient. HC has a long and wide track record of safety with a wide therapeutic margin. Rem is novel.

          6. Irene says:

            Strictly speaking, we don’t yet know whether Trump is out of the woods. It’s only been about four weeks.

          7. Jim O'Hara says:

            @RightHand – The reason Trump bounced back so quickly is that he prophylactically takes hydroxychloroquine, zinc, and vitamin D. Once he started showing symptoms he went on a modified version of the MATH+ protocol. Dr. Zelenko all but admitted to Trump taking hydroxychloriquine on a Dr. Drew webcast, but because HCQ is so politically charged it’s not discussed and he wasn’t willing to go into details.

          8. theasdgamer says:

            Mr. O’Hara,

            I heard that Trump stopped HC prophylaxis back in May.

    3. James Millar says:

      Convalescent plasma will never be given as a prophylactic measure, and I highly doubt any mAb will either. Scale.

      1. TallDave says:

        yep and delivery in an effective time frame is a problem

        MIPs or nanobodies, otoh…
        Aashish Manglik, M.D., Ph.D., an assistant professor of pharmaceutical chemistry at UCSF, added that the AeroNabs should be easy and inexpensive to make “in industrial quantities” in bacteria or yeast. “It’s so robust that we can dry it down into a powder that enables us to ship it across the world,” he said.

        1. Hopeful Layman says:

          What’s the current status of AeroNabs? Have they begun animal trials yet? Are primate trials and/or human trials in the near future? Does anyone know what their projected timeline might be?

          1. Hopeful Layman says:

            ACH! Sorry –m you already answered this question, and I didn’t see it. My apologies.

  2. Barry says:

    mAbs may work for prophylaxis. But no insurer will remunerate the price of mAb therapy where there’s nothing to fix.

  3. frustrated says:

    There’s no good technological reason we don’t have a dipstick RDT costing under $1 (IIRC a malaria dipstick RDT costs about $0.33 to make, for example) that every person in the country who needs to be out in public could take every morning before leaving the house. Yes, sorting out the false positives would take some effort and cost and some false negatives would slip through, but this could get you both the earliest possible treatment for the majority of cases and dramatically slow disease spread.

  4. Mister B. says:

    This last post raised one provocative question.

    What treatment (with a potential chance of success) haven’t we tried yet ?

    Various repurposed drugs, mAbs, plasma treatment etc. Nothing gave us solid positive results.

    On a personal point of view, despite being a very positive person, I start to feel less optimistic about the course of this pandemic and potential protection / treatment. The current situation is terrible and despite huge hopes in vaccines, nothing will be really certain until… Who knows when.

    1. Nesprin says:

      I’d argue that masking is the great success story of this pandemic- there’s solid data for masks reducing viral spread.
      Whereas treating patients with complex medical conditions, and assisting the immune system to clear virus faster without inducing a cytokine storm is an endlessly difficult balancing act complicated endlessly by our limited understanding of biology.

      1. theasdgamer says:

        In my county, the mask mandate went in and our cases have plateaued higher than ever…for months. So I don’t have a lot of faith in masking.

        Then there’s this surgeon’s mask study from 1981 which seems quite compelling…

        1. Irene says:

          From 1981 and published on a site for a presidential candidate I’ve never heard of? Okay, player.

          1. theasdgamer says:

            Your logical fallacies are noted.

            Pro tip: The published evidence for gravitation comes from centuries ago from a guy named Newton.

            And you should work on your observation skills. The original article was photocopied on the intermediary site.

        2. Kaleberg says:

          In Tennessee, at least, counties with mask mandates have fewer COVID cases. This is particularly noticeable with the recent rise in cases in non-mandate counties.

          1. theasdgamer says:

            In my county, even with a mask mandate, cases are rising.

    2. cancer_man says:

      In a 100 person trial, NR (NIcotinamie RIboside) sold as NIagen taken for five days at 2,000 mg sped up the recovery time for those with mild to moderate symptoms by 30%. A 300 person trial has now started.

  5. Jim Hartley says:

    Speaking of Utah: for a nuanced and alarming view of the choices they will soon be making in their ICUs, see this excellent article in the Salt Lake Tribune:

    1. Keep on doomin says:

      This sounds like the same garbage that came from New York in March/April. “We’re running out of ventilators” even though only 16.5% of our ventilators are currently in use. “We’re at ICU capacity… well actually 75% capacity, though that really like 100%.” “If trends continue like this, we’ll be overwhelmed” when trends never continue “like this” for more than a month or so. New York barely used any of it’s field hospitals, and the Navy medical ship barely took any patients.

      1. Anonymous says:

        Trying not to be snarky here, but I believe they are trying to use something called “planning”. Critical care facilities are something you need in overcapacity, especially if your risk analysis indicates a rapid increase in cases in the near future. It’s like, it sure does take a lot of firefighters to run to the store to buy stuff for dinner, but if a call comes in, they all have to be where the truck is.

        Granted, planning beyond the next investor meeting (or news cycle) seems to be a foreign concept these days, but I’m kind of glad some of our public assets still do it.

        1. confused says:

          Yeah, the hospitals are doing exactly the right thing.

          I think there is some room for criticism of the *media reporting* as somewhat irresponsible though.

          Here in TX we were told that hospitals were about to start turning people away in June/early July, and that didn’t happen. (ICUs went over “100%” normal capacity, but remained within surge capacity.) I think the same is true for AZ and other “summer surge” states.

          Now maybe in the case of UT it will happen, but the reporting of it as basically-inevitable IMO ends up feeding the whole “COVID is overstated for political/social control purposes” conspiracy theory if it *doesn’t* happen.

          1. theasdgamer says:

            Hospitals will hire locums as needed and pay more when in surge.

      2. Chris Phoenix says:

        Don’t know what you were reading, but the Navy hospital ship for a long time would take no COVID patients. It was just there to get pressure off the hospitals.

        And there was plenty of reporting of horrific overcrowding and scrambling in NYC hospitals.

  6. Alfonzo Barbarossa says:

    It seems rather obvious/intuitive that supplemental antibodies would only provide benefit to those in the early stages of the disease, who have not yet developed their own — or those who are incapable of producing their own in sufficient quantities.

    One question I have, is if these much touted treatments wind up being not very effective at all, what accounts for the marked and significant decline in death rate we’ve witnessed over the course of the year? Surely it’s not only down to Steroids and putting patients in prone position?

    1. Simon AuclairtheGreatandTerrible says:

      Perhaps the virus is evolving to a lower mortality rate as often happens after a breakout into another species.

    2. Mister B. says:

      I’ve found a partial explanation in a french journal.
      Basically, the “standard of care” has evolved. Now, doctors know how to treat, in the best of their knowledge, the covid-positive patients.
      Remember, at first, it was said that patients should be on the belly, which has been proved counterproductive.

      As mentionned, steroids help also.

      IMHO (I’m just a chemist), like during any war, first victims are less well treated (if this makes sense) and the quality of treatment improve as the doctors have a better understanding of the disease.

      1. theasdgamer says:

        ICU docs have improved standard of care. Family med docs’ treatment is still heterogeneous.

    3. Moses says:

      @Alfonzo Barbarossa:
      Standards of care and treatments have evolved over the last few months. There’s much less intubation of patients, and non-invasive oxygen os being given much earlier.

    4. Nesprin says:

      And not overwhelming hospital ICUs, like what happened in the poorer parts of NYC, and nursing homes going on lockdown so now only younger folks without comorbidities are getting the bug, and improved understanding of when and why to intubate, and steroids when appropriate.

      1. Dark Day says:

        Well, not so fast — Hospitalizations are on the rise, and some hospitals are already considering whether to triage their patients to give priority to COVID cases at the expense of others who need (presumably less urgent) care. Predictions are that very soon we’ll be hearing hospital horror stories even worse than the ones out of places like New York back in the bad old days of early Spring 2020.

        1. theasdgamer says:

          We are in flu season and it’s extremely difficult to distinguish flu from covid.

          1. confused says:

            Isn’t that what COVID tests are for?

          2. Tony M says:

            CDC monitors for influenza:

            week 42 Positive specimens (%) 0.3%



          3. theasdgamer says:

            Covid tests only say that you have viral RNA in your system. They say nothing about whether you have covid. The RNA could be dead remnants of an asymptomatic infection.

          4. theasdgamer says:


            CDC only samples flu.

        2. confused says:

          Hospitalizations are definitely on the rise again, but I think “worse than spring” is very much on the implausible end of the range of outcomes.

          I’m not saying there won’t be hospital overwhelming & worsened standard of care in some rural (South Dakota) or isolated (Utah) areas, which would certainly be “worse than spring” for those specific areas – but nationally? The population of those areas is pretty tiny compared to say NYC.

          And those huge per-capita hospitalization rates aren’t that huge in absolute numbers, so patients might be transferred elsewhere.

    5. theasdgamer says:

      Giving antibodies will reduce the host immune response and the host will produce fewer antibodies. That’s part of the price of giving antibodies. Not saying it’s not a good tradeoff. If a patient is reinfected, odds are better for a mild progression.

  7. Philip says:

    Just another WHAT (Worthless Hopeless Antiviral Trial). Please stop the antiviral trials that wait until a patient is hospitalized. As frustrated said above we need a good cheap antigen test. HEARTs (Home Everyday Antigen Rapid Tests) need to be used by two groups ASAP. The first group are those that have a high chance of being hospitalized with COVID-19 that are part of trials for antiviral therapies that start before symptoms. The second group are schools so that students, faculty and staff can get tested daily. With daily testing we could open up schools safely.

    Go back to In The Pipeline Interferon and the Coronavirus post to see how we may be able to pick out those with a high probability of being hospitalized with COVID-19. Add HEARTs and the knowledge of which if any antiviral therapies work, and we have a workable plan B.

    1. theasdgamer says:

      We don’t need tests to open schools. The science is settled. Only bureaucrats are making it controversial.

      1. Philip says:

        Tell that to the kids sent home from my local school, UNC.

        1. Oudeis says:

          I think there’s a distinction here. I’m not on top of everything, but it’s my impression that elementary schools have been demonstrated not to spread the virus significantly and should probably all be opened with reasonable precautions.

          The same can’t be said about colleges.

      2. Dark Day says:

        Still plenty of reasons to be cautious . . .

        . . . and, of course, there remains the risk of children being asymptomatic carriers and infecting the adults back home.

        1. theasdgamer says:

          I’m very skeptical about the whole asymptomatic carrier thing. How does someone produce and shed trillions of viruses without corresponding tissue damage?

          It’s magic!

          1. TallDave says:

            would have agreed before I learned about CMV

            apparently you can be infected with all sorts of things that don’t damage you enough to notice

            who’s going to miss a few billion cells here and there?

          2. confused says:

            I think the difference is that some level of damage can happen without (subjective) symptoms. I’ve read in other contexts (air pollution) that in some cases temporary lung-capacity reductions may not be subjectively noticeable (no perceived symptoms) even if measurable.

          3. sort_of_knowledgeable says:

            Asymptomatic carriers may by shedding less than trillions of viruses but enough to be infectious in favorable conditions. And one infected cell could produce thousands of viruses

          4. Hap says:

            We carry an awful lot of bacteria (10 times human cell count) without much ill effects.

          5. Irene says:

            “How does someone produce and shed trillions of viruses without corresponding tissue damage?”

            You really don’t get how small a virus is, do you? You shed millions to billions from your gut every day. From

            “Viruses have been less studied than bacteria as components of the gut microbiota – the population of bacteria and viruses that live in our gut. It is estimated there are 100 million to 1 billion viruses per gram of wet faeces in most of us.

            “This number can change considerably when people become sick with viral gastroenteritis, such as in norovirus infections, where levels of more than a trillion viruses per gram of stool can be found.”

          6. chuck choi says:

            You don’t notice the spewing virus. You do notice your body’s immune response.

          7. theasdgamer says:


            Most of the viruses in our stool have bacteria as hosts.

            I’m still searching for a mechanism of egress for SARS-COV-2. Budding? Apoptosis? Exocytosis? Other?

          8. Wallace Grommet says:

            In fact, it has been estimated that N95 masks can filter approximately 99.8% of particles that have an average diameter of 100 nm. In this aspect, the size of a virus particle largely determines how individuals can protect themselves and those around them from acquiring SARS-CoV-2.

          9. theasdgamer says:


            Is there any science to back up the asymptomatic superspreader case?

  8. theasdgamer says:

    Lol @ using remdesevir in hospitalized patients.

    Only quacks would do such a thing.

  9. theasdgamer says:

    I wonder if Utah has started to crack down on doctors prescribing HC based on preliminary diagnosis.

    “The diagnosis has been confirmed by a positive test result which is documented on the prescription or medical order.”

    Maybe this bureaucratic red tape could end up costing some people of Utah their lives.

    Early treatment with antivirals is key.

  10. Hap says:

    Maybe putting all our eggs in the vaccine/treatment basket isn’t as good an idea as some people would like it to be.

    The issue seems to be similar to that of getting rid of impurities during synthesis – someone in Hudlicky’s book (The Art of Synthesis) was quoted as (roughly) “the best way to get rid of impurities is not to make them in the first place.” Maybe we need to find ways to make fewer cases of COVID, because we don’t know for sure that (any of) the pile of vaccines and interventions will actually work – some probably will, but that’s a thinner reed for society to stand on than seems reasonable. We seem to have a hard time being reasonable right now, however.

    1. John Wayne says:

      Three observations:

      1. I agree that the best way to not die in the ICU is to never get admitted.

      2. All of this highlights just how quickly we (as a society) get to the end of our medical knowledge. We have made huge strides over the last 100 years, but we don’t know 1 percent of what we would like to know to prevent the suffering of our fellow humans.

      3. I had reasonable expectations of how well the general population would understand things like aerosols and sterile technique, and use that knowledge to guide their behavior. What has surprised me is that scientists and medical workers appear to behave much more like the general population. It is shocking.

    2. No more lockdowns! says:

      The argument for lockdowns has been obliterated. Unless we morph into a small island nation and/or implement a totalitarian style lock-down that would make Stalin blush, the best we are going to do is delay the inevitable. Remember when Saint Fauci said that Italy handled the pandemic perfectly? Have you seen their case numbers recently? And now we also have to deal with the massive uptick in suicides, drug overdoses, other mental health issues, delayed childhood development, and deaths from delayed disease screenings and treatments. The lockdowns have been a disaster.

      1. Hap says:

        [citation needed]

      2. Anon says:

        We need this because people can’t behave. You open a store and 95% of customers will wear a mask and distance themselves, yet that remaining 5% is intentionally coughing on people (and filming themselves for some reason, as though it is a badge of honor/strength??).

        1. Lockdowns dont work says:

          Italy did everything you are asking for and more and are having a large new outbreak. You lockdowners are like Keynesian economists. Your ideas are unfalsifiable. It’s always “we didn’t restrict enough” or “we didn’t do a big enough stimulus.”

          1. Kaleberg says:

            Then the lockdowns ended. Apparently, news travels slowly from Italy.

      3. Pegacat says:

        Large Island Nation here – Australia had a second wave down south, implemented lockdowns, mandatory masks, contact tracing etc. Infections are back down to single digits, and occasionally we get zero in my state, which was worse hit. So it can work – the trick seems to be controlling external re-infection while getting the local reproduction rate down.

        It wasn’t easy, and there’s been an economic hit, but things are looking pretty good so far for a covid free rebound.

      4. Kaleberg says:

        How have the lockdowns been a disaster? I keep hearing this, but haven’t been given any examples.

  11. Ezra Abrams says:

    Am I wrong to say that the quote below implies that the mighty American Biomedical Research Establishment has done a *really* bad job with its Covid clinical trials ?

    Cause you write that Mayo Clinic ran a worthless trial, and people in India did it righty
    and this is not hte first time: we only have Dex from the Brits
    Something is really rotten in American Clinical Resarch

    As if to underline this point, we’ve also recently had a controlled trial of convalescent plasma report its results (Damian Garde at Stat, and the article in the BMJ). Recall that the earlier Mayo Clinic data on this had no control group, making it frankly impossible to say how much benefit the plasma treatment might have had. But the new PLACID trial was a study of 464 patients across India,

    1. Tony says:

      Getting results you don’t like is different from them doing a bad job. Sometimes, the data just isn’t with you. So you try something else. And maybe that Idea won’t work either, but you keep trying different things.

      The world doesn’t work like it does on Star Trek where one scientist in a lab with a computer can isolate and cure an unknown pathogen in a matter of hours and then inoculate the entire crew by spraying it through the air vents. Unfortunately, reality has no obligation to provide solutions.

  12. Victor says:

    Can it really be easier to roll out prophylactic mAbs than a vaccine? Is there a reason why phase 3 trials would be substantially shorter for mAbs? Or production/delivery easier?

    1. Jim Hartley says:

      Earlier in the pandemic Derek and commenters have discussed the enormous production scale required to treat large numbers of people with antibodies.

    2. CM says:

      Using Regeneron as an example, it’s 8g of mAb per dose, that’s more protein than in a large egg. I don’t see how they could sell that for less than $100K a dose just from a COGs perspective and protection only lasts for the half-life of the mAb so realistically I’d assume 30 days, maybe 45-60 given the huge dose. I don’t see insurers or the government lining up to take that deal, no way healthcare workers could afford it.

      1. Victor says:

        Yes, indeed

    3. sort_of_knowledgeable says:

      For treatments, effectiveness can be determined faster. If the infection is generally over in two week and the treatment group gets better in one week compared to two weeks for the control group then it is effective.

      For the vaccine that is not a challenge trial, you have to wait longer like maybe two or three months before a statistical difference if any appears.

  13. Marko says:

    “…When do you make the call for an expensive bolus of monoclonal antibodies?”

    When your rapid , point-of-care antibody test is negative in a high-risk patient. Or when a high-risk patient is picked up in a screening or contact-tracing program and their day 2 or 3 PCR shows a higher viral load ( lower Ct ) than their initial , day 1 PCR , indicating that they’re in the early , viral expansion stage of disease.

    The most sensible antibody study done to date was the one using convalescent plasma which was shut down prematurely when they discovered that virtually all of their patients were already making their own antibodies. Given the availability of rapid antibody tests , there’s no reason to continue making mistakes like this.

    1. theasdgamer says:

      …or when they have “invisible” hypoxemia, which is pre-ARDS

  14. Dark Day says:

    Disheartening news for the possibility of long- (or even intermediate)- term immunity? And what does this portend for vaccine efficacy?

    1. confused says:

      There have been articles going back and forth on “immunity lasts”/”immunity doesn’t last” for months. I’m not sure any one “moves the needle” on expectations very much, especially since people vary, and T-cells may be more important than antibodies for long term protection, etc etc.

      Does anyone with expertise in the field have an opinion on this one?

      1. Riah says:

        T-cells and the innate immune system are more important against a coronavirus.See and also the main article in the British Medical Journal that it is a response to.
        In any event it is confirmed that B and T memory cells against SARS-CoV-2 are retained – plenty of research over the summer confirms that. So the whole thing is being grossly (and probably deliberately) misrepresented in UK media as meaning people lose immunity to keep people scared but it means nothing of the sort – imagine if we retained masses of circulating antibodies against every one of the thousands (or more?) of pathogens we have encountered throughout life – we would just be a giant clump of antibodies!! Manipulation and gaslighting of the British public.

      2. Riah says:

        Re Confused’s “Does anyone with expertise in the field have an opinion on this one?”
        see also the video link further down as that contains a definitive answer on this question. Immunologists also agree 100% with this in private (ie. there is no doubt immunity is long lasting) but wont go public (because of their funding)except some that are retired like Prof Stadler, former Director of the Institute for Immunology at the University of Bern and a handful of others

  15. theasdgamer says:

    Someone in Salt Lake City should poll the docs/patients to see if they had been given hydroxychloroquine as outpatients and still ended up hospitalized.

    I haven’t heard that hospitals in Utah have started using surge beds yet. But their ICUs running at 70% capacity is like flu season. Are we in flu season now?

    Could people be getting the flu and being diagnosed as covid because they have positive tests even though there is no active virus in their bodies?

    1. Riah says:

      If like the UK you have already had a 1st wave in Spring, most people (estimate for UK over 70%) will now be immune or resistant (including priot T-cell immunity) and the so called 2nd wave is basically flu and other respiratory viruses as in any normal year, some of which have been classified incorrectly as Covid due to the false positives (true false positives plus “cold” RNA fragments). The extent of that would depend on the extent of testing (numbers) and aso the CT (amplificaltion cycles they use). The higher the CT the higher the false “cold” positives. There may also be some genuine Covid cases. But countries which did not really have a first wave like Poland and the Czech Republic are now seeing their 1st wave.

        1. Riah says:

          On what scientific basis? see the video link below

        2. Riah says:

          Marko, we actually do have a huge problem with false positives in the UK . CT cycles of up to 45 have apparently been used. And it has all got worse and worse as untrained lab workers have been brought in to meet the hugely increased throughput and tents are put up to cope with sample collection – all not very stringent conditions. Who knows what the increased chance of contamination are. Some scientists here are saying, with proof that the majority of positives are false and that in the summer it was even over 90%.
          The Centre for Evidence based Medicine, Oxford University, Professor Carl Heneghan as well as Dr Mike Yeadon (ex Pfizer) is where the info came from that you say is rubbish (as well as the above) so you can go argue with them.
          That we are just seeing a normal uptick in respiratory viruses that we see every year – Carl Heneghan was on mainstream TV tonight saying precisely that! And that deaths are only slightly above the last 5 years average but that’s to be expected as they havent been treating people for conditions what with general closure of hospitals and hospital staff not working for 6 months.
          So as it happens, someone has just sent me this excellent critical analysis by a consultant pathologist published today which comes at it from a very different angle to the scientists quoted above but arrives at the same conclusion : the pandemic is all but over in the UK. See if you can fault Dr Clare Craig’s logic:

          Just a PCR example I can personally verify -out of dozens that regularly come through every day – a major rugby team here tested all their players as they are required to do every week to be allowed to practice and play matches. 7 were positive so they tested them again within a day and they all came back negative. This is not an isolated example.

          A big problem for hospitals – they could really do with reliable tests. I have been contacted by someone senior who works in one today despairing of the situation and looking for alternative tests.

          Is whole genomic sequencing way too expensive? How does it compare cost wise? It might be preferable to do far fewer tests but of better quality that actually provides useful information. Any solutions?

          1. Marko says:

            “…the pandemic is all but over in the UK.”

            The spring peak in the UK resulted in daily deaths at ~900 per day. If you assume that the the fatality rate for patients in the UK has fallen by ~50% as it has in the US and many other countries ( due to better treatment , self-quarantine of the elderly , whatever ) then , for a fall infection peak of similar size to the spring peak , you’d expect to see ~450 deaths per day at peak. The UK is currently at over 200 deaths per day. Within a month , absent new treatment innovations , the UK will pass that 450 per day mark. It’s pretty much already baked in. If that indeed happens , it will prove conclusively that as of today , the pandemic is far from “all but over in the UK.”

            Revisit this post in a month. If I’m wrong , maybe then I’ll entertain some of the other junk your charlatan gurus vomit up. If I’m right , you should find some new gurus. Don’t worry , they’ll be plenty of new ones to choose from.

          2. theasdgamer says:


            So you think there’s not much confounding of flu and covid in UK?

          3. Marko says:

            No. There’s a well-established flu surveillance program operating globally. Watch the numbers. There will be no major flu season in the northern hemisphere this winter , just like the southern hemisphere was almost completely spared of one in recent months. The NPIs in place , while insufficient to completely stop the spread of Covid , are doing quite a number on the spread of flu.

            People with flu are diagnosed in the hospital by means of specific assays , just as for Covid. There is no meaningful cross-reaction. I know you don’t believe any of it , but that doesn’t make it any less true.

          4. theasdgamer says:

            Here’s a link that contains info on flu from the CDC. I suspect that a lot of flu cases aren’t even being tested and that they are assumed to be covid. A minimal number of flu test kits are available for sampling, right?


          5. theasdgamer says:


            40% of covid cases are asymptomatic. These cases will test positive, likely for months. Meanwhile, if one of them gets the flu, then gets tested for covid….

            Or people could get tested for flu, but have covid. That might account for high negative flu tests.

  16. Dark Day says:

    Latest prediction: Even with vaccine, we may be living this way until at least 2023:

    1. confused says:

      I don’t know why people even bother to make these predictions – there’s no way to know, and making them is probably actually counterproductive (a lot of younger people are likely to prefer getting COVID to living like this for 3 more years).

      1. Dark Day says:

        Well, if that’s the case, they should get vaxx’d so they might not have to do either of those things.

        1. confused says:

          Sure. But unfortunately a vaccine isn’t available yet.

          All I’m saying is that dire predictions may be actually counterproductive *in the time period between now and widespread availability of a vaccine*, since if people interpret them as meaning that *mandates* will be in place for that long, that may increase rejection of anti-COVID measures (“we’d be better off just getting it and getting it over with”).

          1. Dark Day says:

            Not only do I agree with that — I think that the messaging about personal behavior has been well-meaning but misguided in a lot of ways. Every time I hear that phrase, “New Normal,” I cringe — it’s basically saying, “We’re stuck with this, so you might as well give up on things getting better.”

            It would be much better to be honest and just say, “Hey — things are going to be pretty unpleasant for a while; you’re doing to miss a lot of ‘normal’ things in life that mean the world to you (e.g., socializing, singing in the church choir, smiling at people and having them smile back, shaking hands and hugging your friends, etc.), and it’s probably going to get pretty bleak and lonely. But if we all hunker down and grind this out together, we can get through it and eventually get a lot of those things back.”

            We’d probably still have a lot of “deniers” and “resisters” out there, but I’m guessing that blunt honesty would still have been the best policy from the beginning.

          2. Stop Lockdowns! says:

            But if we all hunker down and grind this out together, we can get through it and eventually get a lot of those things back.”

            Italy did this and Covid came roaring back. Lockdowns only delay the inevitable! Stop destroying people’s lives for a policy that the WHO now says is a terrible idea. Italy did everything you would have asked of them and they are still in this mess.

          3. confused says:

            “Not only do I agree with that — I think that the messaging about personal behavior has been well-meaning but misguided in a lot of ways.”

            Yes – but not *only* on personal behavior. The messaging in general has IMO caused a lot of problems.

            First there was that “2.2 million deaths” thing, which I think primed people to think public health types were panic-mongers (and now we have Trump claiming that 2.2 million might have died if Biden had been president – alongside the claim that it’s basically the flu and he got over it fine so nobody needs to fear it, apparently without caring about the self-contradiction).

            OK, the actual model didn’t show that, but I think they ought to have realized how the media would spin it.

            And then the early discouraging of masks because of limited availability – that made a lot of already-skeptical-of-government people more prone to reject the later promotion of masks.

            >> Every time I hear that phrase, “New Normal,” I cringe — it’s basically saying, “We’re stuck with this, so you might as well give up on things getting better.”

            Yes. And I think lots of public-health-type people are missing the *entirely plausible* possibility that a majority of the population will just say ‘forget it, I’d rather take the risk of getting COVID than live like this’. “Forget it” seems to be the current strategy out of the White House after all!

          4. Dark Day says:

            Well, this is probably a discussion for another time and place (this is supposed to be a science blog, not a public policy forum), but I do believe that a lot of the messaging about personal behavior has been misguided, leaving people feeling “shamed” for what is, in fact, natural (and emotionally / psychologically essential) behavior, especially in times of fear and uncertainty. Human beings are social animals; we are bred for “social gathering,” not “social distancing” — and yes, touch and physical contact are part of that, too. For some reason, a lot of well-meaning scientists and medical people seem not to understand the cognitive dissonance that arises when, all of a sudden, things like “empathy,” “caring,” and “loving our neighbor” are redefined as avoiding our fellow human beings, quite literally like the plague (i.e., “shunning our neighbor”) — when behavior that under normal circumstances would be considered mentally unhealthy, if not downright sociopathic, is redefined as good, compassionate, and socially well-adjusted. How do we expect people to react when the very things that we need most in times of crisis, the things that reflect the “better angel of our nature” — gathering together, showing our empathy through facial expressions, hugging one another and being physically close — suddenly become cast as vectors of death and pestilence?

            During a pandemic, in other words, “healthy” behavior is actually behavior that goes against our instincts, even our very being, in order to survive. It’s not just a matter of accepting a “new normal” — it’s a matter of adopting ways of living that are, in fact, abnormal, and which disrupt and violate the very essence of what it means to be human.

            This disconnect between two necessities — what it takes to stay alive, and what it takes to sustain a life worth living — is a tragic paradox for which there may be no resolution. It’s tantamount to telling a sick person: “You’ll need to take this drug to stay alive, but the side effects will be so severe that you’ll probably wish you weren’t.”

            There is no easy solution (possibly, no solution at all) to this paradox, but name-calling and “virtue signalling,” as we too often hear it done, only make things worse. Our public health spokespeople need to find other, more effective and proactive, approaches that acknowledge the genuine reasons why many people fear the alienation, isolation, and emotional emptiness that result from “distancing” and masking over protracted periods of time, and which leave room for optimism that if we can just hang on and do it this way for as long as necessary, a return to true “normal” may well still be in our future. Otherwise, we’re just playing into the anti-science/anti vax reactionaries’ hands.

          5. confused says:


            But I think that even the “what it takes to stay alive vs make life worth living” framing misses a point. For the majority of the population, COVID is very unlikely to be fatal (median age of the US population is 38). This makes it much easier for people to just give up on caring about it (in a way they wouldn’t for something deadlier, or something permanent like HIV).

          6. Dark Day says:

            Think that’ll affect vaccine uptake? I could see a lot of people, especially younger people, deciding that they didn’t want to go through the bother of waiting in line, filling out paperwork, getting jabbed, and possibly suffering some pretty unpleasant side effects (probably twice), to stave off something they’re not all that afraid of in the first place. I [shamefacedly] admit that for years I didn’t take the flu shot for basically that reason.

            This might depend to an extent on the kinds of restrictions that are put in place between now and when a vaccine gets rolled out. (People weren’t compelled to wear masks, stay out of public places, and avoid human contact during flu season.) Here in Illinois, it’s pretty clear that we won’t be living anything approaching a “normal” life until a vaccine is widely available, a significant number of us take it, and the incidence / morbidity / mortality numbers get down to a vanishingly low level and stay there. I’m betting New York will be the same. Other parts of the country? Probably not so much, and that might not bode well for vaccine uptake.

          7. confused says:

            That’s why I think the messaging should be “as soon as most people get vaccinated, we can forget all this social distancing and masks stuff” not “we’ll need to be distancing into 2023 or whatever”.

          8. Dark Day says:

            That would be my approach. I could see a p.r./education campaign showing vignettes of people doing things like having birthday parties, being at ballgames or concerts, singing in choirs in church, hugging their grandkids, raising a toast at a tavern, having a kid’s birthday party or a Quinceañera celebration (for Latino viewers), etc. . . . then delivering the message you just suggested, ending with the tag: “Let’s get our life back.” I think that could be really effective. A lot better than moralistic finger-wagging.

          9. Michael says:

            Strong messaging of hopelessness or permanence around these public health measures will, without a doubt, (a) prompt premature abandonment of compliance, (b) reduce vaccine uptake, and (c) prompt a mental health cascade of crises/overdoses/suicides.

            Often, public health types defend their messaging about enduring post-vaccine restrictions by saying “people need to understand that the virus doesn’t disappear on the day Moderna (or whoever) has its press conference.” The public needs to be given more credit than that. Everybody understands that they and many others need to take the vaccine for it to have an effect. But it has to be presented as a bridge to close human contact in the foreseeable future.

          10. Dark Day says:

            I also think journalists (and their editors) need to take some responsibility here. A lot of times the actual information in an article or an interview is a lot more nuanced (and a lot less hopeless and depressing) than the headline or the lead paragraph might indicate. Many readers simply scan headlines or read a couple of paragraphs, so they get conflicting messages. That’s all the more the case today, with the social media onslaught of “fake” news, conspiracy theories, “gotcha!”-game personal attacks, etc. (to say nothing of the disinformation and self-serving falsehoods emanating from the highest levels of government right now). Responsible journalism needs to be more responsible than ever in the face of all this, but too often even reputable sources fall into the “click-bait” trap.

          11. Dark Day says:

            . . . anyway, the current data themselves and the way they are trending are enough to induce “hopelessness” — they don’t need any extra help.

          12. DataWatcher says:

            Actually, the scenario that troubles me the most is the logistical chaos that could easy mar the actual vaccine rollout. I’m not aware of any coordinated national plan, and the different states don’t seem to have any available funding for the distribution plans they have submitted.

            In addition, more and more states are planning to have their own independent review boards assess any approved vaccines, before distributing them. That will add to the confusion, further public distrust, and in the even that a state actually refuses to accept a vaccine that the FDA has signed off on, it could easily torpedo public confidence entirely.

          13. Dark Day says:

            If it’s not kosher to post a link like this, please delete — but I’d have to add to the above comment that the tone and ignorance of the comments on stes like this is beyond discouraging. Can a vaccine (or anything else) possibly have a chance to be effective against this level of ignorance and anger?


          14. confused says:

            @ Michael

            >>The public needs to be given more credit than that. Everybody understands that they and many others need to take the vaccine for it to have an effect.

            Yes, exactly!!!

            @Dark Day
            >>I also think journalists (and their editors) need to take some responsibility here.

            Indeed, there’s been a lot of pretty terrible reporting through this whole thing. I tend to think that if the media hadn’t run with some of the crazy early stuff like “2.2 million deaths in the US!” the more accurate warnings would have been more widely accepted.

            When I saw the 2.2 million thing I was like “are they crazy, that’s the same % of the population as the 1918-19 flu, something’s seriously off here” (and then I saw the actual paper didn’t actually say that was likely. But those who only read the news articles wouldn’t have seen that.)

            @DataWatcher: the state review thing is definitely troubling, in that it raises the possibility of split messaging. I’m hoping that the data will be clear enough that there really is no reason not to approve.

          15. DataWatcher says:

            Unfortuntely, it’s not just about the “data” — it’s about distrust of Trump and the [alleged] politicizing of the FDA and the approval process. I distrust Trump, as well, and I agree 100% that his policizing of this entire issue has caused egregious (and fatal) harm. Nonetheless (and more or less as you are suggesting), I wish the state governors would wait until AFTER the results are in. Why fuel further distrust before we have any actual indication that there might be a problem?

          16. confused says:

            Well, I was talking about the state public health departments looking at the data, not the general public.

            But yeah, it’s definitely premature. The election is next week; if Biden wins, it’ll be a nonissue (while an EUA could still be issued while Trump is President, I don’t see mass public distribution happening before Jan 20th).

          17. Riah says:

            We seem to be missing the important science about immunity which does have a huge impact on what we predict. This following is from an ex very senior Pfizer/Glaxo scientist, starts off very fluffy but then gets vv serious, Very long but well worth sticking it out -very revelatory!!

            Two papers of 16th(updated 21) October, and 20 Sep referred to are also well worth reading.

        2. Dark Day says:

          Here’s an example of what I’d call misguided, if not downright irrresponsible, journalism.

          I think it’s GOOD news that Pfizer isn’t trying to “rush” things and request EUA approval before all the data are in. But an article like this, with the headline “HISTORIC VACCINE RACE MEETS HARSH REALITY,” and lead paragraphs that claim “Pfizer’s admission Tuesday that it still doesn’t know whether its coronavirus vaccine works . . .” represents “[t]he company’s failure to meet its self-imposed goal” will only result in readers going away from it less confident than ever in the vaccine developmenet and vetting process.

          The writers/editors could just as easily have “spun” this story into something like, “Pfizer releases reassuring news that science will take its course to ensure that their vaccine will be effective and safe.”

          1. confused says:

            Yeah, that’s pretty awful!

          2. Michael says:

            I’m with you, Dark Day. That was an appalling take.

            Professional investors had been speculating that the Pfizer Phase III must have had 60+ events by now, so there must be a problem with the vaccine if no results had been disclosed. Instead, there haven’t been 32. That fact is not only out of Pfizer’s control, but provides no negative information whatsoever about the vaccine’s safety or efficacy. And at least the disease hasn’t been ripping through the vaccinated cohort.

  17. Ajay says:

    Is there a resource that updates that status of all antibody clinical trials and their results?

  18. theasdgamer says:

    Does anyone else think that we should have viral culture testing to make sure that people have live coronavirus in their systems as opposed to say, dead coronavirus and influenza?

    Maybe some nursing homes aren’t using pulse oximeters to check residents for invisible hypoxemia?

    1. Philip says:

      Do you have any idea what it takes to do viable viral culture testing? Start with a BSL3. In other words it is not going to happen outside of a trial. Now we may be able to get to the same result with a combination of tests. RT-PCR stays positive long after active virus is cleared. Antigen tests used after a positive RT-PCR test may give you the viable virus test you are looking for.

      For more information about testing:

      1. Marko says:

        It appears to be possible to design a PCR test that only detects the RNA from intact virions , rather than also reacting with all of the RNA debris that shows up as the infection is resolved. Why development and rollout of this sort of test has not been been a priority since day one is a mystery to me. There’s been a distinct pattern of such mysteries.

        1. theasdgamer says:

          Keep going down that path if you want to be labeled a Great Reset Conspiracy Theorist. Great way to get cancelled. If you have the cojones, though, you won’t care.

        2. sort_of_knowledgeable says:

          The qPCR tests that are currently used amplify about 100bp and give results when finished because the label the product fluorescently as the reaction runs. non qPCR tests usually amply 500bp to 1000bp and you run a gel after reaction runs to determine if product was generated. You are still not going to determine if the virus is intact that way.

          Long read sequencing technology like Pacbio or Oxford nanopore will tell 10,000-50,000 and up bases and would be able to tell you if the RNA is intact although they are lot more expensive and still won’t tell you if the virus was infectious or rendered harmless with antibodies hanging all over it.

          1. Marko says:

            I’ve read that some researchers are already attempting home-brew intact RNA PCRs by first digesting all the junk RNA with an RNase , then inactivating said RNase ( w/protease? ) then lysing the intact virions using phage. The subsequent PCR then detects only intact RNA , at least theoretically.

      2. theasdgamer says:

        Why would you expect antigen tests to add more info?

        1. Philip says:

          I suspect that the antigen binding sites are destroyed much faster then the small segments of RNA that the RT-PCR tests are looking for. So after a RT-PCR positive test, give an antigen test 48 hours and later to find out when the person is no longer contagious.

          In other words the RT-PCR tests have a long false positive tail, if you define positive as active virus. The RT-PCR tests have a shorter false negative head.

      3. theasdgamer says:

        How do you test whether someone is currently infected with a virus without being able to detect a live virus?

        I don’t see any way out of culturing viruses in mammalian tissue if we really want to rely on lab tests, BSL3 requirements notwithstanding.

        Else we come up with a plan that doesn’t rely on lab tests.

        A PCR lab test, of course, is useful for determining if someone, at some point, had a virus in their system.

  19. Job says:

    Many commenters make sapient points about the importance of timing of administration of antiviral strategies whether immune globulins or directly antiviral drugs. Timeliness has been elusive in clinical trials. I think in real life, with real human being patients not confined to a test-tube, a treatment that is timeliness dependent will be of very little value. People routinely blow off symptoms, miss appointments, forget to take their meds, take a double dose of their meds because they forgot taking the first dose, etc. If the treatment only works if taken within 31.5 minutes of encountering the first virion, the treatment is of extremely limited value in real life. A good vaccine is inject and forget by letting the immune system do the remembering.

    1. theasdgamer says:

      Some family med docs have an excellent record of treating outpatients with Zelenko’s protocol (treatment within first 5 days post symptom onset).

      People may forget to dose or decide not to dose and that’s on them. It’s imperfect but it seems to work well in the vast majority of cases. Else you wouldn’t see 80% reduction in hospitalization of high risk patients in both Scholz and Heras (median age 85).

      If you want to accuse Risch of cherry picking his data, please show some retrospective studies of high risk patients who took hydroxychloroquine within the first five days of symptom onset and the results varied from Scholz and from Heras. I’d even accept a single family med doc who tried Zelenko’s protocol with his patients for two weeks as outpatients and found the treatment ineffective.

      What is the evidence supporting Zelenko’s protocol?

      We have positive retrospective studies of early treatment of high risk patients treated with Zelenko’s protocol. We have family med docs who say that they have tried it in thousands of patients and found benefit.

      Where is the evidence against Zelenko’s protocol? Late treatment studies are irrelevant. Small studies with low risk patients are irrelevant. So where is the cherry picking?

    2. Philip says:

      The timing issue is why some of the commenters go on and on about rapid antigen tests. For this post I will go on and on about TEsting, TRacing and ISolation (TETRIS).

      Our current testing is inadequate. Not even close to what we need to get SARS-CoV-2 under control. The insistence by the FDA to only have diagnostic quality tests is a real impediment to getting adequate surveillance testing. As many, including Anthony Fauci, have said, we should not let the prefect be the enemy of the good. I think the Rapid Antigen Tests (RATs) and Home Everyday Antigen Rapid Tests (HEARTs) are the way to go. Abbott has one on the market, a $5 RAT that would work great for point of care work. Once we have testing for at least the most vulnerable that can detect SARS-CoV-2 and have results within three days of infection, we will have adequate testing (I hope).

      Once testing is up to speed, tracing needs to be addressed. When testing is running way behind, tracing is almost impossible. Going back 10 days or so to contact those who may have been exposed is just too many people to be doable. With test result within 3 days of exposure, tracing becomes possible. I wish we had a national open source contact tracing phone application, but that does not seem to be happening.

      When/if we get testing and tracing working as they should, antiviral therapies should be about to be given in time to work.

      Isolation and quarantine will only work if we know who to isolate and quarantine. Without testing and tracing, that is going to be very difficult. With proper testing and tracing to find those needing isolation and quarantine, we need a place to put them. That needs to be a problem on somebody’s screen.

      1. theasdgamer says:


        Timeliness of results isn’t the only issue. You also need to know if any viable virus is present. I know of no way to check for that except to see if a source can cause an infection in mammalian tissue.

      2. Dark Day says:

        My prediction is that widespread contact tracing will be met with resistance, if not outright violence, in many parts of the U.S. We have store owners and security guards getting stabbed for requiring that customers wear masks; we have self-styled militiamen plotting to kidnap a governor over her efforts to control the virus (and a president who shouts “Liberate Michigan!” in a not-so-subtle attempt to egg them on); we have conspiracy theorists spreading the “theory” that COVID is a “plandemic” designed to take away our liberties and freedoms via manadory testing and (eventually) vaccination. Does anyone believe that in this atmosphere, people will willingly submit to a mandate to “name names” and tell “the authorities” whom they’ve been associating with over the past few days? I anticipate things getting really, REALLY ugly if this is attempted.

        1. theasdgamer says:

          Don’t know if covid is a “Plandemic” or not (not convinced it is), but I’m certain that globalists are attempting to use it to push The Great Reset. They kind of said as much. World Economic Forum.

        2. Some idiot says:

          That is a very interesting point… I hadn’t thought of that, but you are absolutely correct in that there is/will be a significant difference in the public acceptance of different measures, purely due to cultural differences.

          One example is possibly US vs Australia and New Zealand. In the latter to, track and trace has been considered by the residents to be a public good, and therefore they have been very effective. If, as you suggest, track and trace is considered to be a violation of private freedoms (or similar) in the US, then that would certainly hinder efforts a lot…

          Europe is probably somewhere between the two, but with a lot of heterogeneity mixed in for good measure.

  20. Daren Austin says:

    mAb prophylaxis is really passive vaccination. Palivizumab set the precedent for RSV. I doubt that anti-SARS-CoV2 antibodies will be different. Welcome to the wonderful world of drug development. It’s a hell of a ride.

    “If you thought the science was certain, well that’s just an error on your part”. R Feynman

    1. Barry says:

      Effective vaccination will elicit IgG and IgA and killer T-cells. mAb therapy floods the plasma compartment with IgG only. That’s not what is needed

      1. Daren Austin says:

        Indeed, but it might be all you have. So some comfort that is is a possibility.

  21. confused says:

    A stupid question… if monoclonal antibodies are actual human anti-COVID antibodies, how *can* they have no effect? Did they pick the wrong antibody to clone?

    1. Barry says:

      The primary covid infection is on respiratory mucosa. Putting antibodies into the plasma compartment doesn’t get there unless those antibodies can ride a Secretory component to the work-site

  22. exGlaxoid says:

    If the antibodies are given after the virus has already multiplies and spread and caused massive damage, then it is too late to stop its growth. Much like putting a bullet proof vest on a gunshot victim or closing the barn door once the horse is gone. If the antibodies are given within a few days of exposure, the virus can be prevented from taking hold. This works best if you are being tested daily or so, like the president or many athletes. Sadly, most doctors and nursing home staff are not tested daily yet. I agree that a cheap and rapid test should have been the priority from the beginning. We need a test that we can produce billions of at a time.

  23. TallDave says:

    yep quite disappointing, though there’s still a dozen or so arrows left in the mAb quiver

    vaccines now more important again

    and tis’ an ill wind indeed that blows no one any good, latecomers like nanobodies may be gaining relevance

    1. Hopeful Layman says:

      Any word on AeroNabs? There were some very encouraging preliminary reports a few months ago — haven’t heard anything since. Have animal trials begun? Are primate and/or human trials in the near future?

      1. TallDave says:

        heard nothing since the August report

        supposedly they are working on approval for human trials

        1. TallDave says:

          Exevir in the same link appears to be another nanobody, trials to begin in 2020

          likely much cheaper to scale up than mAbs but of course there’s still the open question of whether they will do any good 🙂

  24. Calvin says:

    Interesting comments here. This closest comparison is indeed probably RSV. The mAbs in that space are also fusion antibodies and also clearly only work pre-infection or very very early in the infection. We also know that small molecule F inhibitors have a slightly longer window of activity (in vitro with some evidence this is also the case in vivo/clinically) which has always suggested that the antibodies don’t penetrate the tissue/compartments in the way you need. So it’s not a huge surprise, I think, that this antibody did nothing in patients who are past peak viral load most likely. What is interesting, is that the cocktails look much much better. The preclinical data supports virtual sterilizing immunity and the clinical data also seems to support decent therapeutic use. They are all still fusion antibodies. This does raise the suggestion that the lack of efficacy for the mono-therapy is escape mutant driven (which is one rumor I’d heard).

    Such negative data has made me a little more nervous about the vaccines also, if only because it suggests the the antibody response will have to be spectacular to see any level of sterilizing immunity. We’re going to be relying on those T-cells I suspect!

    1. DataWatcher says:

      Are we really shooting for sterelizing immunity? My understanding is that we aren’t — preventing actual clinically recognizable disease, not eliminating the infection entirely, seems to be the primary endpoint. (That’s where the worries about still having asymptomatic carriers after vaccination have come in.) As for T-Cells — correct me if I’m wrong (it’s been a lont time since I’ve read the reports), but my memory tells me that one of the encoraging things about the original Oxford/AZ trials was that their vaccine appeared to stimulate an especially strong T-Cell response. Does anyone know whether that still seems to be the case?

      1. sort_of_knowledgeable says:

        I’m sure we are shooting for sterilizing immunity, but we’ll take a 50% reduction in symptomatic cases. It’s not like the drug companies could increase the chances for sterilizing immunity by adding vibranium but it would cost too much.

        It’s a lot of extra work to determine if there is sterilizing immunity. They’d have to track every contact of everybody in 30,000 person trial and see if they have covid-19 and determine if the person in the trial is the most likely source and its not going to affect the vaccine approval process anyway.

        If it turns out that two vaccines are 99+% effective in preventing illness then maybe follow up investigations might be made to see if one of them is better because it provides sterilizing immunity.

      2. Calvin says:

        Normally I would’t worry about not having sterilizing immunity; it’s a nice to have not a must have. The problem with SARS CoV2, is that it is contagious at a level that is highly problematic. Without sterilizing immunity it’s going to infect the entire planet. Every single human being on earth, and then every single new birth. And because it’s so infectious and it has a reasonable level of mortality and morbidity that’s a huge problem. And it will keep going round and round and round so without a vaccine with long term immunity we’re talking about immunizing the planet every year or two. It’s an extraordinary situation.

  25. Hopeful Layman says:

    Here’s another “Layman’s” question, RE:

    “. . . Don’t necessarily abandon wearing masks in public and maintaining social distancing just because you got the vaccine unless you also get an antibody test that confirms you have been protected by the vaccine.” (Here’s the source:

    According to this, after a person is vaccinated, he or she will be able to take an “antibody test” to ensure that the vaccine has truly taken effect. I did not know of such a thing — will this be a standard (even require) part of the vaccination process? In other words, if the vaccine requires two doses, will an additional visit be necessary to complete the additional antibody test? It doesn’t really bother me if that’s the case, but if it is, this needs to be explained to the public very clearly before any vaccine is rolled out.

    1. Todd says:

      The short answer is yes. The longer answer is that this is standard practice for many other vaccines. That’s why it’s not tragic if you somehow lose your childhood vaccination records. These sorts of tests are folded in common blood tests panels for physicals. There’s already a test for this for SARS-CoV-2 in the marketplace. You’d get checked to ensure that you’re producing antibodies, and the vast majority of people would get sent on their way. For the few that don’t, I suspect that some flow cytometry tests to check for sensitive T-cells will come down the pipe and clean those folks up from concerns.

  26. Joey Ortiz says:

    It’s abundantly clear that no antiviral is going to work in late-stage disease. Severe, late-stage COVID-19 is fundamentally an autoimmune disease, not a viral disease. The efficacy of antivirals lies in stopping massive cellular death that leads to the immune system attacking human cells – that means earlier administration. Waiting for Day 9 of symptom onset to trial an antiviral is a useless waste of clinical resources; it’s a miracle ACTT-1 found a benefit of remdesivir that far out. Conducting antiviral trials like SOLIDARITY without recording time from symptom onset is massive waste of clinical resources. Getting antivirals into COVID-19-infected individuals earlier in the disease, starting antiviral therapies before hospitalization, in outpatient settings is the way forward for monoclonal antibodies and RdRp inhibitors like remdesivir and favipiravir.

    1. Michael Bell says:

      Indeed, it’s in essence identical to influenza. If Tamiflu is not administered within about 48 hours of symptom onset, it will not work to control the virus. Administering Veklury(Remdesivir) once you are severe enough to get to the hospital is far, far to late to have any meaningful effect. The sars-cov2 virus is already dead, or nearly dead by that point and what you’re dealing with then is a severe autoimmune overreaction to the immune response to the virus. No, the time to administer Veklury is within 48 hours of infection, which would be very useful for the at risk population.

      1. Phil says:

        It’s definitely in line with the appalling, and now completely normalized, waste of medical resources–both material and human–that almost the entire US has come to loathe. Most people are aware only that something is profoundly broken. Those who know what’s wrong generally choose to profit from their knowledge, as there is no greater source of profit than a helpless, ignorant, desperate counter-party. Thus American health care has achieved, at last, a parity of evil with the American legal system. A whited sepulcher doesn’t begin to describe it.

  27. Marko says:

    ” Needed: a national coalition to coordinate Covid-19 clinical trials”

    Coordinate ? This is America. We do our own thing. Resist this assault on our freedom !

    MagaMorons Unite !

    1. Thomas says:

      The UK has trials that work. Other countries? I mostly see retrospective results.
      Oh well, a tiny one on calcifediol in Spain.
      But where is the systematic research? I mean, doctors have theories and proposed treatments. Sounds smart to fold these into proper trials, but one needs the (permanent?) structure for that.

    2. theasdgamer says:

      Actually, it’s the media leftists that have been pushing RCTs of late treatment with antivirals as evidence that antivirals don’t work. We magamorons are on the other side.

  28. Kiss the Chemist says:

    The dramatic upsurge in cases across Europe is in large part down to the young people who will not follow the guidelines strictly enough. Japan, South Korea and Germany have much lower infection rates for (amongst other reasons) the simple fact that the population abides by the rules. Here in France we are entering lockdown again….good, it WILL slow down infections. But the crux comes when we are we relax the restrictions again, because its down to the people to carry it through and some people refuse to do so. So we will be back here agian in a few months.

    1. Dark Day says:

      Do you think that when a vaccine is available, the combination of getting vaccinated and following the restrictions for as long as it’s still necessary might make an appreciable difference?

      1. Some idiot says:

        Absolutely. It will be a while before we get there though (my rough guess is probably 10-12 months time, realistically). But we will get there…

        1. Dark Day says:

          . . . but, as K.T.C.’s point indicates, we’ll probably get there faster (and with less tragedy along the way) if people do the right thing and still practice protective measures as we move toward that goal.

          1. Some idiot says:

            And Amen to that!!! Yep… Agree 100%…

    2. theasdgamer says:

      Idk, maybe flu cases are masquerading as covid?

  29. Bill says:

    The public is fixated on when a vaccine will be available. But has anyone done the math as to how long it’s likely to take to actually put needles in 200 to 300 million arms — X2?

    I don’t see standing in long lines while trying to not get infected is something I’ll be looking forward to.

    1. Some idiot says:

      The answer is “X months”, where X is a fairly large number… Which is a point I always make to people when we are talking about how long it is likely to take to achieve a reasonable level of vaccination.

      I would expect that things will be organised such that there will not be large groups gathered together at one time. Having said that of course, there will probably be very significant country to country variations…

    2. Dark Day says:

      Having just spent about two hours this morning shivering in sub-freezing temperatures waiting in line outside the Illinois Secretary of State’s office to get my driver’s license renewed, I think you have a very good point!

      Uptake will depend a lot, I think, on accessibility. We can’t rely solely on pharmacies and clinics to administer the vaccines — there simply aren’t enough of them, and quite a few people live in areas where there isn’t a good one available nearby. It will take creative thinking and aggressive outreach to ensure as much uptake as possible.

      Non-traditional community venues such as church facilities, schools, fraternal organizations’ lodge halls, and other community-based locations should be repurposed as temporary vaccination centers whenever and wherever possible. (I seem to remember the gymnasium of my elementary school being used this way for either polio or measles vaccines when I was in second or third grade in the early 1960s, so this kind of thing is not entirely unprecedented.) This can also help reduce vaccine skepticism in communities where local institutions and venues are trusted more than “official,” often geographically remote, points of service. Also, we need to remember that it will take aggressive outreach and networking with local people to ensure that the most at-risk communities and individuals are identified and included.

      Might I suggest that traveling mobile health clinics could also be a valuable part of the solution? They have been shown to be effective in other contexts, such as delivering health care to the homeless, and helping to provide medical and social services to at-risk mothers and children. In fact, if Bill Gates, Jack Dorsey, and other well-meaning billionaires are sincere in their protestations that they want to do all they can to assist in this crisis, they might do well to partner with the government in investing in, and equipping, a fleet of buses to serve as mobile health clinics to deliver vaccinations to poor rural communities in the U.S. They could also spur investments in clinics in underserved urban settings. The benefits could be immeasurable.

      Again — creative thinking and coordinated efforts.

      1. Kaleberg says:

        It will be tough in Texas when the governor only allows one vaccination site per county. There are a lot of people who want COVID to succeed.

        1. confused says:

          TX actually has a COVID vaccine distribution plan, and I think it is a pretty reasonable one. I don’t think vaccine distribution will be politicized in the way masks and such have been (and TX does in fact have a mask mandate…) since it will be seen as a way to get back to normal.

    3. Dark Day says:

      Dr. Fauci seems to be a bit more pessimistic about the “normalcy” timeline than he was a few weeks ago — now he’s suggesting that it won’t be until 2022. He’s also suggesting that the U.S. and most of the rest of the world will probably have “normalized” mask-wearing by then to the extent that it will become an everyday cultural constant, just as it’s become in many Asian countries.

      1. confused says:

        As much as I respect Dr. Fauci, I still think saying things like that is a bit irresponsible & possibly counterproductive at this point — young adults don’t necessarily have a ton of patience, especially given how low their risk is. (I mean, it’s not *low* low like flu or something, but compared to a lot of risks taken by young adults, the numbers at say the 18-30 age group don’t sound all that alarming.)

        Normalized mask-wearing… eh maybe in NYC or somewhere. I see zero chance of that in the central US.

        1. Metaphysician says:

          so, should he just lie to them instead? “Well, since you aren’t going to take precautions anyway, fine, it’ll be alright! You totally won’t kill a ton of people with your reckless indifference!”

          1. confused says:

            No! I’m suggesting simply to not make statements like that at all. Focus on the process of developing and rolling out a vaccine, don’t say “we won’t be back to normal until year X”.

        2. Dark Day says:

          Well, again this may be a discussion for a different thread, and I know this idea is very controversial, but more and more people whom I talk with (incl. professional musicians and other entertainers, as well as nurses and healthcare proviers) are starting to agree. If private venues and gathering places — maybe restaurants, nightclubs, theaters — mandated a “proof of vaccination required for entry” rule, it could probably both encourage vaccine uptake and make the people who attended feel more safe, thus more likely to feel comfortable unmasked. I’m also guessing that many venues will have “partial” masking requirements — e.g., in elevators but not necessarily in more spacious areas — to walk the line between safety and hospitality.

        3. David says:

          confused: “young adults don’t necessarily have a ton of patience, especially given how low their risk is”

          Their risk of spreading the disease to elderly, or to people with pre-existing conditions, is still high.

          We don’t allow people to scatter poison in the community drinking water, nor to drive drunk. Mask wearing has very low cost, and clear benefits. This should not be something to be confused about.

          1. Dark Day says:

            Well, to be fair, I don’t think Confused is making excuses for anyone not wearing a mask — the original discussion was the exhaustion and depression a lof of people feel when they keep getting these messages that masking and “distancing” are going to be the “new normal” and we’ll be stuck living this way forever. And I agree — that’s a horrible, soul-killing thing to contemplate. What’s benig discussed, I think, is how to advocate good, responsible behavior without implying that kind of hopeless “get over it, it’s never going to change” fatalism. And in fact, Dr. Fauci has more or less made the same point — defeatism leads to “who cares?”, which can lead to more nihilistic, selfish behavior.

          2. Dark Day says:

            . . . on the other hand, overly optimistic predictions that have to be walked back can also have deleterious effects. Until recently, many experts (incl. Fauci) were suggesting that the first actual vaccinations could begin sometime in December, and be well underway by January. Fauci is now saying that approval MIGHT happen by January, if not later. I think most of us here understand that that’s how science works — we go with our best estimate based on the current data, and then modify/adapt as the data change or as we understand them more clearly — but to the general public, it can easily morph into “Oh, here he goes again — just like what he originally said about masks!” and further erode credibility. So it’s a difficult tightrope to walk.

          3. Michael says:

            Dark Day, a more sensitive assay (and a paper on this very website) should give you more confidence about duration of antibodies:


          4. Dark Day says:

            Good article, Michael — and just to be clear, I’m not necessarily saying that the actual research data are depressing or hopeless; I’m referring to the messaging (whether intentional or otherwise). It’s difficult, if not impossible, to accurately convey the reality of a situation that’s so volatile and even amorphous (let alone pretty arcane for laypeople to keep up with and understand). That’s the problem that’s so difficult to address.

          5. confused says:

            Yeah, it’s the “defeatism leads to ‘who cares'” part I was talking about.

            Also, if you’re making public statements you need to consider what people probably *will* do, not just what they *should* do. And there is a very high degree of distrust in scientific authority in the US (even pre-existing the current administration).

          6. Dark Day says:

            Well, of course, if people “won’t” do what they “should,” then the pessimists are probably right — we’re stuck in the “new normal” for the long, long haul.

          7. confused says:

            >>Well, of course, if people “won’t” do what they “should,” then the pessimists are probably right — we’re stuck in the “new normal” for the long, long haul.

            I’m not sure – it would make it *worse*, but why would it make it *take longer*?

            COVID isn’t going to go extinct anytime soon; the “end” will be when there isn’t a significant immunologically-naive portion of the population, surely?

            So I’d think people being infected before they can be vaccinated would change the severity of the pandemic, but not its duration.

            Unless reinfection becomes really common, but that doesn’t seem to be the evidence so far.

          8. theasdgamer says:

            The science about mask wearing is still unclear and is unlikely to be made clear anytime soon. Forming public policy based on unclear science muddies the water and science loses.

          9. Kaleberg says:

            Actually, the science on mask wearing is pretty good and keeps getting better. There’s a reason that more and more serious cases and deaths are in younger people. (e.g. In Washington State, half of all new cases have been people under 40.) Older people are wearing masks and not getting COVID as often.

            Tennessee, where some counties mandate masks and others don’t, shows that people in mask mandate counties are less likely to require hospital admission.

  30. Marko says:

    New Regeneron data , this time with early usage :

    “Regeneron Pharmaceuticals Inc. said data from a late-stage clinical trial suggest that its antibody cocktail therapy for Covid-19 significantly reduces virus levels and the need for further medical care.

    The results offer another encouraging signal in the race to find treatments for the deadly virus. Patients outside the hospital who got the therapy were 57% less likely to need medical care later, with 2.8% of those given the antibody and 6.5% of those on placebo seeing a health-care worker within 29 days….”

      1. Hopeful Layman says:

        Encouraging! A 57 – 72% reduction in medical visits (not the same as “hospital admissions,” right?) isn’t quite a “magic bullet,” but it would definitely be a significant step in the right direction. And, of course, if it were available alongside a good vaccine, we could see something close to a “game-changer” situation.

        1. confused says:

          Hmm, yeah, this would be very good if it holds up. I hope Derek does a post on this one.

    1. Marko says:

      Similarly , on the Lilly Mab :

      I suspect this paper prompted the Regeneron press release.

      1. confused says:

        OK, now I’m doubly confused — how is this different from the trial that this post said didn’t show efficacy? Earlier administration/less sick patients?

        1. Marko says:

          Yes. Outpatients instead of hospitalized.

          1. confused says:

            Hmm, so would early treatment be critical here like for antivirals?

            Seems like it would take an impractical/implausible number of doses if you wanted to give it to everyone who had COVID, not just the serious cases… though I guess it could be given to specifically elderly/high-risk outpatients?

  31. Erik Dienemann says:

    My bet since March was that Regeneron’s antibody cocktail was going to be our best hope for seriously improving patient response to being infected and that seems like what we’re seeing with today’s additional results from the ongoing phase II/III trial in mild to moderately ill COVID patients (prior to hospitalization, when an antiviral is likely to have the biggest benefit).

    Certainly can’t say it’s a “cure” yet, but it’s looking much better than any other drug out there, so far and could be a bridge to vaccines, especially as it’s also being looked at as a prophylactic to prevent infection in high risk workers/possible patients. Regeneron intends to apply for an Emergency Use Authorization soon, which I think makes sense. With ~1MM doses supposedly available soon, this could be enough for at least moderately symptomatic patients right now.

  32. Dark Day says:

    More confusing reportage. It seems clear that neither Pfizer nor anyone else will be in a position to even request an EUA before late December at the earliest. Nonetheless, the people of Indiana are being given false hopes. . .

    1. confused says:

      That does look wrong, but where do you get late December? I was reading the earliest possibility was in mid-late November, based on safety data — with efficacy data being dependent on how many people get COVID in the study population.

      I thought the Pfizer announcement was just that they hadn’t hit that number *yet*,

      1. Dark Day says:

        I was going by Facui’s latest estimate —
        which does seem as if he’s walked his predictions back by a couple of months.

        1. confused says:

          Oh I mean late December could easily be a more likely *estimate*, especially if people in trials aren’t being infected at a rate comparable to the overall population; I just don’t think it’s earliest-possible.

          Whereas I think the “third week of November” thing was a ‘hard’ limit based on having to wait a specific amount of time for safety data.

  33. theasdgamer says:

    Does anyone here actually treat patients for covid?

    Check out the Dr. Peter McCullough webinar. Dr. Tyson joins him at 46:40. Dr. Tyson says that he has treated over 2,000 patients at his clinic in El Centro, CA, with 1 hospitalization and 0 deaths. His clinic was designated the premier California clinic by the state health authority.

  34. Dark Day says:

    RE: Our ongoing discussion about how “scare” headlines and less-than-prescient journalism can create unnecessary pessimism and panic — here’s a good article from the New York Times that brings some perspective to the recent “dimnishing COVID antibodies” scares:

    1. Dark Day says:

      On the other hand, looking at the comments on this YouTube segment of an interview Dr. Fauci recently did with Rolling Stone, the level of ignorance and paranoia is so high that it makes one despair . . . will “we” ever be able to get out of this, if these comments are really representative of what’s going on “out there”?

      1. Duncan says:

        A valuable life lesson reinforced by this pandemic. Whatever you do, don’t take the internet too seriously.

  35. Dark Day says:

    Sorry to keep citing these examples, but — compare the headline of this article (“Merck CEO . . . predicts mask use for the foreseeable future”) with what Frazier actually says in the article (he does use the phrase “foreseeable future,” but then he clarifies it to “well into 2021,” which is pretty much what Facui and most others have suggested).

    1. Michael says:

      For you and me both, Dark Day, the media has not helped with the mental health aspects of enduring the crisis.

    2. theasdgamer says:

      Otoh, the absolute risk to an 85 y.o. of dying from covid is 1%. Much less for the rest of us.

      Pro tip: Don’t live in fear.

    3. confused says:

      Yeah, that is also incredibly awful. “Well into 2021” could mean 6 months from now…

  36. Kaleberg says:

    It’s like World War II. We’re all in it for the duration. Some people just want that second marshmallow now.

  37. anonymous says:


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