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Clinical Trials

Dexamethasone for Coronavirus Infection

News came yesterday from the Recovery trial effort in the UK that they had seen positive results from dexamethasone treatment in severely ill COVID-19 patients (news article from Science here). This set off a number of headlines that everyone has since been trying to deal with, unfortunately, so I thought I should try to do my part, too.

Let me start off by echoing journalist Kai Kupferschmidt here, and pointing out that – as has been too damn often the case in the last few months – we don’t have the real data on this yet. What we have is basically a press release, with the most impressive top-line numbers in it, and that makes interpretation and context a lot harder. We saw this with the initial remdesivir numbers, with Moderna’s human data on their vaccine, and all over the place during the hydroxychloroquine story. Under normal conditions this wouldn’t be acceptable – and this “new normal” shouldn’t be different. Make your headlines when you release your data, folks.

So here’s what we have: 2104 patients, either on ventilation or receiving supplemental oxygen, were given 6mg dexamethasone (oral or i.v.) daily for ten days. Comparing them with 4321 patients on standard-of-care, the death rates definitely decreased with dexamethasone: the 28-day mortality for patients on ventilation with standard of care was 41%, and dex treatment decreased that to 27%. For patients receiving supplemental oxygen, the 28-day mortality was 25%, which decreased to 20%. And the 28-day mortality for patients who needed no respiratory intervention, the 28-day mortality was 13%, and dexamethasone had no effect on that whatsoever. p-values for these numbers and confidence intervals were very good indeed, as one would hope from the large number of patients – these look like very solid results, from what we can see so far.

Now, the headlines have all been about “first drug to show reduction in deaths”, but while that’s true for intentional RCT data, it ignores the recent observational study on tocilizumab, which showed similar effects. There are a lot of key similarities in these results – you’ll note that such treatment really only seems to have an effect on the sickest patients, and that is almost surely because those patients are in trouble because of the “cytokine storm” immune response. That, in fact, is where I think we can expect the real improvements in clinical outcome, because we have far more options to modulate something like that than we do to treat the viral infection itself. The good news here is that dexamethasone is far, far cheaper and more widely available than the anti IL-6-receptor antibody.

Are they doing the same thing? There’s probably a great deal of overlap. Dexamethasone itself is of course a steroid derivative, a corticosteroid that is used to damp down inflammation and immune response.Such compounds have a huge number of downstream effects in cells and in organ systems (among them a decrease in IL-6 signaling). It’s administered in a wide variety of situations, everything from severe poison ivy through arthritis, Crohn’s disease, asthma, lymphoma, Addison’s disease, multiple sclerosis, and many more. It’s an extremely useful drug, but has to be used with care and generally for a short period, because it’s so powerful – the number of potential side effects with high or prolonged dosing is impressive indeed. The dosage in this study was not particularly high, which is a good thing to see.

A point that I think should be made with all of these therapies is that they’re not actually “drug repurposing” per se. What they are is a new use for a drug’s intended mechanism. Dexamethasone is given to lower inflammation and immune response, and that’s exactly what it’s doing here (and exactly why it was put into the Recovery trial in the first place – it’s clearly something that you would want to investigate). I’m very glad that it’s worked out, because there are never any guarantees – this sort of thing was tried, for example, during SARS and in the H1N1 epidemic, with unclear results.

Another key point, which others have emphasized as well during the pandemic, is that it’s become increasingly obvious that therapy for coronavirus patients needs to be biphasic. In the early part of the infection, you would want to have something with antiviral activity – slow or shut down viral entry and replication. Now, we don’t have much in that line – remdesivir is about it at the moment, possibly favipiravir (another broadly acting RNA polymerase inhibitor) – their effects are real, but not as big as one would like. If a patient later goes on to severe respiratory problems, that usually seems to be caused or exacerbated by the overactive immune response, which has to be treated as a separate issue. And the drugs used to treat that would be a bad idea earlier in the infection, since you need all the immune function you can get at that stage. Note that dexamethasone did nothing in this study for patients who weren’t in respiratory distress – that’s exactly what you’d expect. This also means, of course, that such compounds are completely useless as prophylactics, and would likely be outright harmful. It’s a good thing that dexamethasone is a prescription drug, because that last thing you want is a bunch of people running out and taking it in hopes that it will protect them from the coronavirus. It’ll probably do the opposite, and cause all sorts of side effects besides if people aren’t careful.

The other thing to emphasize, as Kai Kupferschmidt did yesterday, is that none of these drugs directly alter the pandemic itself. They will save more lives when people get infected, but we really need to try to keep more people from getting infected in the first place, especially now that it’s become more apparent that social distancing and as trivial a thing as public use of face masks can help. We could be mitigating this pandemic with such measures in this country, but in too many regions we don’t seem to be doing that. Eventually, though, what makes this disease go away will be a vaccine.

The people (a minority, but a loud one) ranting about how such masks are an infringement on their liberties can go to hell, in my considered view of the situation, and I only wish that they could do that without taking other innocent people with them. Of course, some of those same never-wearing-a-mask people are also publicly swearing never to take a vaccine. Idiots. Loud, dangerous idiots who are endangering all our lives and our livelihoods.


193 comments on “Dexamethasone for Coronavirus Infection”

  1. Adrian says:

    Wouldn’t the “first drug to show reduction in deaths” be heparin?

    1. Marees says:

      Heparin is an injection to be administered in hospital setting.

      For non-hospital settings dipyridamole can be explored. But as yet no study on that, I guess.

      1. David Young MD says:

        Or Enoxaparin, or Apixaban. But I would consider these to be supportive care and not actual treatment.

        1. Ted says:


          When I saw the headlines, and then saw that they were just talking about dexamethasone, I thought “why isn’t this just considered standard of care?”

          Next thing you know, IV fluids are going to have their day in the corona…


          1. HFM says:

            Corticosteroids were a very obvious thing to try. But they were tried in SARS 1.0 (back in 2003) and didn’t help. My understanding is they could help keep the patients breathing in the short term, but the resulting immune suppression meant that they were in the hospital longer and were at least as likely to die. That’s why this was not standard of care. But it’s so obvious that I guess someone couldn’t help but try it again…with what I understand are similar results.


        2. base651 says:

          Thrombolytics and subsequently anticoagulants have been postulated as possible therapies as many patients are hypercoaguable and present with VTE (and IIRC DIC). disclaimer, I work for a company vested in both of the above areas.

        3. Mark Antony LaPorta MD FACP says:

          Define “treatment.”

  2. rhodium says:

    Regarding vaccination, I think people who refuse to be vaccinated are engaged in germ warfare against the rest of us.

    1. Catherine C Wilson says:

      So then will you be one of the first to line up to receive the vaccination?

      1. metacelsus says:

        I definitely would be!

      2. Harvey 6'3.5" says:

        Are you kidding? I volunteered for a Covid-19 study, but apparently because I am normally a full-time teleworker, I don’t fit the study design. I suspect they are looking for people at greater risk of getting the virus, which is probably a good thing.

      3. loupgarous says:

        Show me a vaccine with science-based safety and efficacy data (not one pushed on people for political reasons), and yes, I’ll be the first guy in my neighborhood to take it. What I’m afraid of is NIH and FDA being pliable enough to “command guidance” from SECDHHS to sign off on the first thing that is likely to show only slight efficacy, and downplay adverse events.

        1. Somhairle MacCormick says:

          Like every vaccine approved for human use?

          1. Timothy Chase says:

            … as with smallpox and polio?

            Normally there is extensive testing, with animals, humans for possible side-effects, humans for efficacy, and it takes ten years to develop and test before mass production and distribution. However, there is the worry that in the hurry to achieve a vaccine this will be rushed and insufficiently tested, and judging by recent actions on the part of the US administration involving the acquisition of nearly 30 million tablets of hydroxychloroquine tablets for rapid distribution on the US Cast coast, this may not be entirely unfounded.

  3. Marees says:

    Small correction

    It is Favipiravir & not faviparivir !

    1. David Young MD says:

      Correct, and Derek, please give us an update on Favipiravir. There is more to say.

      1. A Nonny Mouse says:

        I was contacted by the owner a major Indian generic company last week about trying to shorten the synthesis for them. I asked if there was any evidence that Favipiravir actually worked and his response was that that wasn’t important so long as people were buying it.

        Don’t think that I can be bothered (although I did have a brief look at supposedly improved Chinese routes a few months ago, which just produced dark matter).

      2. Mike Owens says:

        Actually, it is favipiravir.

        1. Derek Lowe says:

          Yeah, swapped my vowels there. Thanks!

          1. Jeff says:

            Hmmm… a vowel movement?

  4. Matt Gruner says:

    There is evidence from the tenOever lab that a strong early immune response (as measured by type I interferon) is required for an appropriate late immune response ( This begs the question if an injection of IFN early on would prevent severe signs and symptoms of the disease? Ongoing clinical trial to test efficacy of interferon lambda to prevent severe covid-19 (Not as familiar with these type III IFNs). Now with the Dexamethasone results an obvious combo would be early IFN and Dex to treat if symptoms get out of hand. It would be great to get a differential diagnosis (as they say in medicine) on the various IFN based therapeutics that might be useful against SarsCoV2. Thanks Derek!

  5. Adrian says:

    As an evidence-based person, I begin to wonder how large the actual benefits of masks really are.

    The reason why I am wondering is that I am living in Finland.
    The Finnish government does not and never did recommend wearing face masks, and people who wear a mask are extremely rare (less than 1% of the people on the streets). This also applies to office/shops/bus/metro/train/restaurants/bars/…
    During the past 2 months R has always been < 1, usually around 0.8.

    While the proposed mechanism of masks sounds plausible to me, I am seeing first-hand that social distancing without masks can be enough for getting a fast reduction of new COVID-19 infections.

    Is there any scientific evidence that face masks are necessary for R < 1 in the US?

    1. Anonymous says:

      Masks aren’t a substitute for social distancing. So if, as you claim, there’s already sufficient adequate social distancing, then there wouldn’t be as much of an effect to observe. Masks are most important for where adequate social distancing isn’t possible. I’m also curious how you determined that your estimate of one percent is accurate?

      1. Adrian says:

        When I look out of the window and count the next 100 people passing, chances are I am not seeing any face mask.
        Masks are so rarely used in Finland that the few people with them really stand out when you see them.
        Noone is making a culture war around that and would treat people bad who wear a mask, it is just rare.

        Do you have any evidence for your “Masks are most important for” claim?
        Most of the research about mask benefits remind me of all the reports that something helps against COVID-19 in vitro.
        My subjective feeling is that I am in the control group of a trial, and our R is not significantly higher than the R of the groups with a mask treatment.

        As far as I can see vitamin D and face masks are both in the same “it cannot harm but actual benefits are unclear” category, but people who are demanding to see randomized studies with a control group for believing in vitamin D benefits are not requiring the same for judging whether or not a scarf in front of your face brings any benefits.

          1. emba says:

            Derek, that first link is the Molina paper.

            You may want to read the critical commentary around it.


          2. Derek Lowe says:

            Thanks, will do! Just added another one to the list as well.

          3. Adrian says:

            I wanted to ask why the first one is not mentioning that Maryland had higher daily increases for weeks after face masks became mandatory, but I see that I am not the first one to find problems in this one.

            Regarding the 2nd and 4th, it is worth emphasizing that these are Asian countries where everyone is wearing a surgical mask designed to protect others.
            Based on what I’ve seen on data a surgical mask lets 10% of the virus through, a scarf or cotton tshirt 50%.

            Taiwan increased mask production so that every one of their 23 million citizens could buy 2 surgical masks per week in February and now 4.5 surgical masks per week.

            In the US people are calling other people dangerous idiots for not using a scarf as mask.
            Why is Taiwan able to produce 0.65 surgical masks per citizen per day, but California is not?
            20% of the population wearing a surgical mask should have an effect (how big or small it might be) comparable to 100% of the population wearing a scarf.
            Trying to force 100% of the US population to use a scarf as mask is very effective for starting yet another culture war, but not effective for containing COVID-19.

          4. Harald says:

            FWIW, here is another study from a German university about mask use. It’s kind of unique, as there was one city (Jena) in Germany making them mandatory about 3 weeks before the rest of the country. They try to compare the cases in Jena feel that day on to a „virtual second Jena“ comprised from several other German cities. The effect at least in this study is quite substantial…


          5. eub says:

            “20% of the population wearing a surgical mask should have an effect (how big or small it might be) comparable to 100% of the population wearing a scarf.”

            Nah, the math doesn’t go like that (because you’re increasing the dispersion there). The other 80% with unimpeded transmission will continue with uncontrolled exponential growth.

            I agree it seems ridiculous that the U.S. doesn’t have the willpower and logistics to crank out paper procedure masks that with ordinary supply cost twenty cents.

          6. emba says:

            (earlier comment seems to be stuck in moderation with links…feel free to delete either this one or the previous)

            Derek, I believe the added health affairs link is already in your list (pubmed vs publisher).

          7. Lynne says:

            I wear a mask indoors, but not outdoors. I don’t think the data support outdoor mask wearing as beneficial. The problem is that many of the scientific articles that show, at best, a modest effect used medical or surgical masks in the tests. They didn’t use a fabric bandana or an old tshirt wrapped around your face or a dish rag held over your face, all of which I’ve seen as face coverings. I wouldn’t trust any of those face coverings to stop the size of droplets carrying CV19. Your outrage is noted. However, I would direct more of that towards the wholly inconsistent advice from Dr Fauci himself and other experts. I couldn’t care less about Trump, it’s the scientists many actually did listen to. The inconsistency from the experts has led to the average person believing they have no idea what they are talking about. Dr Fauci went on 60 minutes in early March and laughed derisively about the worthlessness of a face covering – only serves to make one feel better. He knew at that recording that there was community transmission and asymptomatic spread. Within weeks, he changed his tune. When asked for data leading to the change, there was nothing new. Now, it’s that the CDC only said “no masks” because the USA didn’t have enough medical masks. Unlike Taiwan, which was well prepared w mask stockpiles. So they told us masks won’t help, when in fact they only said that because they didn’t want us using them and keeping them from caregivers. Not to mention other scientifically ignorant directives, such as swimming in the ocean was safe, but lying on a beach more than 6ft from someone else wasn’t. Or shooting basketball alone at a park or paddleboarding alone on a lake was dangerous. Or believing that, today, it’s too dangerous for your children to play outside with the neighbor kids or at a playground. Just teach them to cover their faces for sneezes and coughs (and not with their palms) and have them wash their damn hands.

        1. Omar Stradella says:

          If you are looking out the window, you are looking outside. People tend not to wear masks outside where the air movement would dissipate any “floating” virus-laden particles. You should provide a statistic of their use inside public places like a supermarket.

          1. emba says:

            Wearing masks outside has become law in a number of cities. I see a great deal of anger being directed towards those who are not wearing masks outside.

          2. Adrian says:

            Same situation as outdoors.
            The rare people who are wearing face masks seem to wear them always when they are outside their apartment.
            I have never seen supermarket staff wearing a face mask.

            Black muslim women with a niqāb might be the largest group of people wearing a face mask in Finland, some ethnically Asian people and very few pensioners.

        2. Darby says:

          I remember reading this a while ago – no idea how accurate it is, but it suggests that social distancing has been the default approach in Finnish culture.

          I feel weird posting a non-journal link, but what the hey –

          1. WST says:

            Vietnam has a boarder and lots of exchange with China, so, it is at high risk of imported infections. The mask became mandatory few days before the first positive case, today, Vietnam (50M) has had 350 cases and no deaths. In any case, the infection did not spread.
            But they had SARS and were apparently prepared for a next one.

            I’ve observed an interesting difference is the attitude towards “doubt” or “uncertainty” between developed countries and the rest of the world. Lots of people question masks because they doubt it’s useful, even if common sense says that it can limit arenosol exposure (to unknown degree at this level of reflection), while in the less advanced countries, people tend like masks because they hope it somewhat limits risks.

    2. emba says:

      I’ve found the religiosity around masks (i..e the required wearing of masks in public) to be really odd. It’s more the pro-mask camp that starts to get shouty when you ask for evidence.

      Take a look at every interview in early march, every epidemiologist was pretty equivocal around masks. Most pro-mask reviews and opinion articles (forget the recent Molina PNAS paper) are sensible but they all admit that there isn’t much direct evidence for cloth mask wearing in the public. A few important observations:

      1) I haven’t found any evidence anywhere that ‘mask wearing countries’ enjoy lower rates of influenza or any other seasonal illness.

      2) I haven’t see good evidence that ‘mask law’ interventions have had effects in covid cases (or any other illnesses like influenza which can result in hospitalization).

      3) Why do we see the infection demographics we do? No one has suggested that it is a result of mask compliance.

      There are also public appeals to symbolism (wearing a mask shows you care etc.). Some of the laws are absurd (San Francisco is requiring mask wearing outside within *30ft* of someone….it’s quite easy to see that vey few people are complying with this impossible to enforce rule).

      I’m have very little tolerance for the type of person that likes to go on about ‘liberty’ etc. and I’d be happy to wear a mask if I found good evidence, they mostly don’t bother me. The only thing that I can surmise from the evidence is that the mask protection effect is small if it exists and is difficult to see amongst the background of noise and confounding.

      1. emba says:

        ‘She said face masks are only “potentially beneficial” when worn properly and incorrect use can lead to an increased risk in infection.’

        So says Dr. Michelle *Science* in the Toronto Star’s June 17 covid update.

      2. Hap says:

        My assumption early on was that it probably doesn’t help me but may lower spread (so if I’m asymptomatic, I don’t spread it as much). If wearing a mask is useless, then it doesn’t cost me much, but if it’s useful, then it’s easy to do and cheap and could help a lot (it would basically a cheap vaccine with not many effects on me but benefits to society as a whole). Scott Gottlieb had tweeted that there was evidence that masks helped, but I don’t know.

        I think when it comes down to it that mask people are getting cranky about a segment of the population asserting that they should be able to do as they wish with disregard for the consequences to others (opening businesses without a plan, don’t wear masks, don’t take vaccines). Essentially, people in a society (by which their rights are secured) are asserting that they don’t have to play by the rules that others do, and that they should not be responsible, a position inconsistent with the existence of a society in which people have those rights. Society is people in a treehouse safe while hungry wolves lurk below, and those people are busy sawing away at the branches the treehouse sits on.

        1. Adrian says:

          Society does not work the way that you can just invent arbitrary rules that everyone else will then follow.

          Being forced to wear a mask is pretty invasive.

          If you want to wear a mask, that is fine.
          If you want to force other people to wear a mask, you should be able to provide good evidence that it is really necessary.

          1. eub says:

            “Being forced to wear a mask is pretty invasive.”

            ^ this right here is current U.S. society in a sentence, and why we’re in such a nasty situation.

          2. TallDave says:

            We’re in this situation because the Chinese Communist Party is so dysfunctional that it could not admit — even to itself — that a pandemic was underway in Wuhan until the infection was already global, and also just happened to have installed a friendly WHO head who naturally ignored the dire warnings from across the Strait because the concept of Chinese people actually voting for their leaders is so problematic.

            De-recognizing Taiwan was a devil’s bargain and he’s been collecting bits of the world’s soul ever since.

          3. confused says:

            It’s not “current” US society, we’ve always been like that. More in some eras and less in others, and it varies widely between states, but the US in general is a highly individualistic society and has been since the colonial era.

            There were political movements against masks in 1918-19 pandemic too.

          4. Hap says:

            More invasive than expecting people who don’t want to/can’t get sick to not go out of their houses or to be with people who have been? That’s an interesting definition of invasive, I think.

          5. confused says:

            Yeah, wearing a mask is not that much of an imposition.

            The thing is though that its being *mandated* by government is a big deal in US culture/politics. It’s clearly within the government’s powers (US states have pretty broad public health authority) but there is a major cultural difference between doing something ‘voluntarily’ (even if there are strong e.g. risk of disease, loss of income)

            I mean, how much of politics is based on any kind of rational assessment of costs/risks vs. benefits? I’d say very little.

            However, I also think that most of the anti-mask-mandate people think that COVID is low-risk enough (for people healthy enough to go out and do stuff in the first place) that staying strictly at home is an irrational over-reaction. I think that’s quite wrong, especially in the middle-aged and independent/healthy elderly.

      3. Anonymous says:

        Public health officials: “Please wear a mask if you might get close to strangers.”
        Some random guy: “I don’t listen to experts, I do my own research!”

        This is the issue, ignoring advice from good sources by default. You basically said that you were only going to follow your own research, and would otherwise ignore advice from anyone whose job it is to do this research and make judgement calls in the public interest.

        Unless you have good reason to think that the advice is harmful, or that the officials are not acting in the public interest, the logical thing to do is to follow the advice, even as you question whether it is actually helpful, because the odds are that someone who looks at this research as a full-time job knows something you don’t.

        1. emba says:

          There are examples in the above threads of public health officials providing guidance that *does not* recommend the use of masks in public settings. WHO, Finland, Denmark, Sweden, Toronto Sick Kids Hospital among them.

          Why are you trying to frame this as “public health officials” vs “some guy”. It’s quite clear that not all public health officials agree.

          1. Anonymous says:

            Different countries have different circumstances in transportation, gatherings, prevalence of virus, etc. The WHO certainly isn’t telling people to ignore their own country’s or state’s guidelines and health officials.

          2. fajensen says:

            Being Danish, I wouldn’t exactly trust Denmark and Sweden 100% on this:

            We are bored to tears for years already with the “Danish Values” discussion, but, Denmark still reliably goes into a collective hissy-fit + “value discussion” over ANY non-Danish cultural manifestations in public such as the Muslim headscarfs, shaking hands, and (I.M.O.) of course “Asian” masking in public will also be Unacceptable!

            And Sweden has a special form of experts. In Sweden, experts, are people who with little actual knowledge or experience in a subject can draw very detailed conclusions on the matter and then never change their positions, instead fitting everything that happens downstream to “The Model” so it supports their rather unique intellect!

            Thus, In Feb-2020 the “Swedish Experts” declared Covid-19 to be “a kind of flu” and they are 100% committed to going down upon that ship, with all hands busy and with all of their guns blazing (especially fierce when someone compares them with Italy, which the “Swedish Experts” themselves brings up all the time as “the worst example” in the belief that it makes them look better. Another sign that they can’t change The Model, fwiw).

            So, yeah, “different countries, different circumstances”, but, I know *two* of those circumstance are what I would call irrational!

      4. loupgarous says:

        Since San Francisco reportedly has issues with keeping members of the populace from emptying their bowels outside, and Los Angeles is once again plagued with typhus, good luck to them with enforcing that mask ordinance.

    3. gippgig says:

      1. emba says:

        Representative quote from the SBM article:

        “Although direct evidence is limited, the optimum use of face masks, in particular N95 or similar respirators in health-care settings and 12–16-layer cotton or surgical masks in the community, could depend on contextual factors; action is needed at all levels to address the paucity of better evidence. Eye protection might provide additional benefits. Globally collaborative and well conducted studies, including randomised trials, of different personal protective strategies are needed regardless of the challenges, but this systematic appraisal of currently best available evidence could be considered to inform interim guidance.”

        “I’d agree that this is the best evidence we currently have, but I’d also caution that there is still a lot of uncertainty.”

        Not exactly a ringing endorsement of public mask wearing.

    4. anon says:

      Let’s say wearing masks can reduce R0 from 1 to 0.9. Wouldn’t that be worth it? Or is that level of reduction not worth the inconvenience?

      1. Ted says:


        The difference in those particular two numbers is huge. Any Ro/Re that is at or below 1.00 means that the virus is persisting in the population. Like the bad guy in the slasher flicks, he may be slow, but he IS going to catch you.

        Any number below 1.00 (even 0.99) means that the virus is going away. Even if it’s slow, it will eventually go away (largely…).

        As for masks, you don’t need to be an aerosol scientist, a genius, a rocket surgeon, a mass transport engineer to figure this out. We teach CHILDREN to cough into their elbow crooks for precisely the same reasons – to limit the atmospheric spread of disease. A mask does the same thing, but better.


        1. Ted says:

          sorry, typo – I meant any number ABOVE 1.0 means the virus persists…

          1. Adrian says:

            This kind of evidence-free “you don’t need to be an” arguing is dangerous since this kind of knowledge often turns out to not be true.
            It is not obvious how good or bad non-surgical masks are.
            It is not obvious that masks are not making things worse, by collecting high virus concentrations in one place.
            It is not obvious that masks are not making things worse, by giving people a false sense of security resulting in fewer social distancing.
            The last one would be my biggest worry.

            As for “We teach CHILDREN to cough into their elbow crooks for precisely the same reasons – to limit the atmospheric spread of disease.”, you are definitely wrong on that.

            Coughing into the elbow is not for limiting the atmospheric spread, I could imagine it might be similar or even worse for that.
            Coughing into the elbow is to avoid coughing into your hands, and spreading the virus then from your hands to surfaces.

          2. Hap says:

            It’s a matter of cost-benefit (just like drugs). If the cost is low (like for masks) then you can afford either a low (but significant) benefit or a low (but nonzero) probability of significant benefit (but not both, probably). If the benefit or the probability of benefit is likely to be zero from an intervention, then any cost will make much less sense; if the costs are high enough, then there has to be stronger evidence of effect and effect size.

            Prior experience (the covering your mouth when you cough thing) suggests that the probability is greater than zero and the likely benefit is significant (though to others, not to oneself). So it makes sense to do it unless there’s significant evidence that it doesn’t do anything for disease spread, because the cost is low and the probability of benefit is significantly greater than zero.

          3. Adrian says:

            If your arguing would also be applied to drugs as you claim, there would be a strong push for everyone to take vitamin D.

          4. emba says:

            “Prior experience (the covering your mouth when you cough thing) suggests that the probability is greater than zero and the likely benefit is significant (though to others, not to oneself). ”

            This is the crux of the matter. It isn’t clear to many, and indeed a number of sincere authors and policy makers that it is true that the likely benefit of public mask wearing is significant ,

          5. Hap says:

            Vitamin D’s got some side effects – it’s lipophilic so it builds up over time in fat. What’s the side effects of the mask (that can’t be mitigated with mask material or construction)?

        2. emba says:

          Look at the sickkids report:

          Guidance statement(s):
          • Non-medical and medical face masks are not required or recommended for children returning to school.

          Most of the reasons they enumerate for children not wearing masks are quite applicable to adults. The evidence is weak here, it may be worth it since the cost is low but there are plenty of sensible reasons to think it may not be.

    5. RA says:

      I don’t think one country’s needs are the same as another’s. If a country has less coronavirus circulating because they are more effective with other measures, then there is less need for control measures like masks. Compared to the US, Finland has far lower income inequality, a system of universal health care, higher levels of trust and social cohesion, favorable geography, greater effectiveness in border/flight control, and better political leadership.

      1. emba says:

        Maybe. Or maybe the small effect of masks is independent of those differences or is largely drowned out by those differences.

        1. RA says:

          No, the effectiveness of masks is related to how much virus you have around you. If there isn’t much virus circulating, masks obviously don’t do anything. If it is, they do a lot. In hospitals where there is COVID everywhere, everyone is wearing masks, even the administrative staff who are far away from the patients. It’s called universal masking…and it works. Very few health care workers are infecting others in the hospital environment. If there come to be high levels of circulating COVID in your community, then your community comes closer to mimicking the risk of being in a hospital…and thus you have to do more of what we do effectively to control spread among personnel in hospitals. I want all the mask skeptics to come to hang out unmasked in a hospital…even in the lobby far away from the units. I suspect a high percentage of “brave” anti-maskers would wet their pants in that scenario.

          1. Olandese Volante says:

            The reason for the use of face masks by the general public is *not* to protect the wearer, but to limit the spreading of virions in the environment in case the wearer is infective.

    6. Jim Hartley says:

      A recent paper on the effect of mandatory masking in some US states:

    7. Gorge Gregory says:

      It is not enough to be without a mask and social distancing if you are shouting, sneezing or coughing

  6. A Nonny Mouse says:

    Tocilizumab is one of the drugs under investigation in the RECOVERY trials, so there ought to be some definitive data soon

    1. Baldrick says:

      We got this positive topline announcement for dexamethasone. Could that be an indication that the results in the other arms are not so interesting?

      1. Alan Goldhammer says:

        The monitoring board stopped the dexamethasone trial as the number of patients and statistics were robust enough to show efficacy. I’ve not seen any other trial stopped in this manner thus far.

      2. Baldrick says:

        I’ve just noticed that tocilizumab was added to the trial a month later, so it may still need some time.

  7. TallDave says:

    meh, 25% to 20%… there are lots of HCQ studies claiming larger effects… too marginal, synthetic antibodies will have far better efficacy

    on the plus side UK was among first to take seriously the rather astonishing Vitamin D correlations from the Philippines study, particularly thanks to Rose Kenny’s work… naturally there is a lot of skepticism due to the many, many unwarranted claims made for supplements generally but the knee-jerk response in the US is still disappointing, given the low risk and strong correlations

    1. David Young MD says:

      Taking extra vitamin D has almost no risk. But you will have to show me a prospective study before I get really excited. If that is being done, fine, but make sure it is randomized to a control am. Otherwise you are just adding fuel to the debate fire.

      1. TallDave says:

        True, supplementation of Vit D might turn out to be completely useless, and we can’t really know for sure without a lot more study. OTOH…

        “Moreover, controlling for other effects known to influence COVID-19 mortality rates such as age, gender, and preexisting conditions, the researchers find that vitamin D-deficient patients are still 10 times more likely to die from the disease.”

        If there’s a reasonable chance a single factor may be responsible for a tenfold increase in death rates after controlling for all other factors, most deaths will occur before rigorous testing of the factor’s efficacy is possible, the factor might very well have *already* saved tens of thousands of lives among the infected, and the factor poses very little risk, the cost/benefit of immediate action is (as Kenny says) a bit of a “no-brainer.” And yet…

        1. Ron Schnell says:

          Has anyone tested for causation w.r.t. the vitamin D stuff? I mean couldn’t be that since people are not going outside they become vitamin D deficient? So the population in general has a higher percentage of vitamin D deficiency, so therefore people who go to the hospital are more likely vitamin D deficient?

          1. kismet says:

            Yes, this has been a problem with vitamin D for a long time. The level of confounding is so gigantic (via exercise, frailty, etc), that there is always the risk of residual confounding. By and large, vitamin D, while it used to be promising, was a complete disaster when it was tested in large randomized, controlled trials like the VITAL study. This was for primary prevention, mind you — but nonetheless a cautionary tale.

          2. TallDave says:

            again, we won’t truly know whether there’s any Vit D causation re COVID until it’s too much late for that information to save most COVID victims

            re Vit D supplementation generally, the literature is broad… the VITAL study is interesting but perhaps not definitive, e.g. the control group was also allowed to take the supplements at lower levels

      2. Charles H. says:

        Even if vitamin D doesn’t work against COVID, there are lots of studies saying that many people are deficient in vitamin D, and could benefit with a higher level. If you’re living far from the equator, that probably means supplements.

        That said, there ARE racial differences in average vitamin D metabolism. It’s not clear that these are properly accounted for in the studies claiming that many people are deficient in vitamin D. But the costs are small, the downside (unless you go overboard) is minimal, and the potential benefits are major. So *I* take a vitamin D3 supplement. I hope it will help if I get exposed to COVID, but I was doing this before COVID appeared on the scene. (Still, better information would be nice. But there’s LOTS of variables, and we’ll always want better data.)

    2. nat says:

      That 25% to 20% was for the supplemental oxygen, not intubated group. For the intubated group it was 41% 28 day mortality down to 27%.

    3. PV=nRT says:

      Vit D levels decrease with age and a number of other diseases. So these correlations are highly likely to be just be a complicated way to say “Covid19 is more lethal in the aged and those with pre-existing conditions”. Useless without an interventional study, and my money is on ‘no effect’ as an outcome.

      1. Adrian says:

        How can you be so confident?
        Vitamin D deficiency might impair the ability of the immune system to fight infections.
        Black people living in North America or Europe are prone to vitamin D deficiency for literally obvious reasons.
        Vitamin D deficiency is a plausible biological factor why minorities are hit harder by COVID-19.

        1. PV=nRT says:

          I’m confident because I’ve seen a number of correlative studies that looked way better than this one that turned out to be not causative.

          We just don’t know for sure until we do a randomized, double blind interventional trial. That’s a major theme of this blog, BTW.

  8. Student Driver says:

    The parting shot about masks detracts from the rest of the excellent writing. Wish it was left out or saved for a twitter feed.

    1. Brian R says:

      I don’t think it detracts from a well-written piece. Just like an article about automobile safety regulations and technology leading to safer roads/driving might end with a wear seatbelts disclaimer and don’t drive drunk, if there were, say, a mass movement led by a particular political party who nominally claimed to be for safer automobile driving on the roads but were inspiring 5-75% of the population, depending on zipcode, to be adamently convinced that seatbelts and DUI laws were anticonstitutional and an impingement on rights.

    2. Derek Lowe says:

      Oh, it’s not just a shot at mask behavior – it’s a shot at vaccine attitudes as well. I wouldn’t want to minimize how pissed-off I am at those people, for sure.

      1. David Young MD says:

        I agree!!! Wear masks everyone! Look at the Shibuya Crossing live webcam. Everyone in Tokyo wears a mask!

        My daughter and I have our eyes glued to the web trying to find where we can get a vaccine.

      2. TallDave says:

        So, you oppose the protests as well?

        Sort of amusing watching everyone twist their tails around.

        1. Hap says:

          Everyone at the protest I was at were wearing masks (anecdote =! data) – more, for the most part, than people in other places (which would be consistent with politics, alas). At Walmart where I live (OH) maybe half the people wear masks on a regular basis.

          1. TallDave says:

            yes rationalizations are fun

            my favorite part of the farce was when governments actually gave different requirements for outdoor group sizes based on whether they were protesting… and then ignored those too

            “funeral service? oh sorry no can do”
            “massive gatherings of the ethnic group most likely to die of COVID in areas with high infection rates? sure why not”

        2. dumbass says:

          Protesting for justice is worth the extra risk. Riding the bus without a mask is not. Not everything has the same risk reward ratio.

          1. TallDave says:

            Yes, we all want justice (and liberty). I only wish that they could do that without taking other innocent people with them, as someone once said.

          2. emba says:

            Not everything has the same risk reward ratio.


            Everyone has different risk reward ratios for the same things.

          3. Hap says:

            It matters what the benefits are and (to some degree) whether the people accept those risks voluntarily. People showing up at a protest chose to do so (though their families and friends may not have), and there are ways to protest that minimize the risks to themselves and others.

            On the other hand, the barrier seems lower for daily activities that people have to engage in – in that case, I am imposing costs on others who didn’t choose to accept those costs. If you should have the freedom to go out, so should others, and they shouldn’t have to accept significant risks to themselves and others to exercise their freedoms. It seems less reasonable to expect others to stay home because I won’t wear a mask than to expect both of us to wear masks since the costs of both of us wearing masks are far lower than the costs of expecting everyone else (or just everyone who doesn’t want to play COVID roulette) to not be around me because I won’t.

      3. Student Driver says:

        At the start I was thinking about dexamethasone, inflammatory response and biphasic treatment, based on the studies cited. Then, at the end, face masks, anti-vaccination and who is hell-bound shows up. It just seemed like a sudden jump into totally different topics with a different style and purpose, like two different posts fused together.

        It is your blog, maybe you are in two streams of thought and we’re getting both. I’ve been a long time reader and appreciate your work writing it.

        1. Derek Lowe says:

          Oh, it was a switch there at the end, no doubt. I think looking at the Texas, Arizona, and Florida numbers before writing the post may have been a factor.

          1. Surfactrant says:

            I found it quite cathartic, and appreciated the sentiment, thanks Derek!

            For too many years now it seems that ‘good people on both sides’ has trumped reason
            to the point of inflicting harm to us all.

            “One day someone will explain to me why it is that, at a time when science has never been wiser, or the truth more stark, or human knowledge more available, populists and liars are in such pressing demand.”
            -John le Carre

        2. I. P. Freely says:

          I totally agree that prevention remains the key to getting out of this mess, until there’s (hopefully) a vaccine. There’s no easy outs. I have no problem with people exercising their rights to disregard basic sanitation and prevention, if only they would do it among themselves, but that’s not how covid19 in an open society works. Effectively, they’re claiming the right to urinate in a public swimming pool – “don’t mind me over here; just peeing in my side of the pool.” Regarding the conspiracy theory anti-covid19-vaccine sorts, if only there was a vaccine for this kind of anti-social stupidity!

          American exceptionalism and covid19 – we’re Number 1

          1. David says:

            I’m reminded of the 2015 Onion article, “I Don’t Vaccinate My Child Because It’s My Right To Decide What Eliminated Diseases Come Roaring Back.”

      4. Alan Goldhammer says:

        A “proof” that masks work is in the papers today. Two weeks ago at a Springfield MO salon, two workers who were infected with SARS-CoV-2 worked on a lot of women customers. Everyone was wearing masks and contact as you might expect was close. None of the customers were infected as judged by follow up studies: this may be as good a study as one can get.

        The converse was shown also in the paper today of a group of young women going out to a bar in Florida and everyone of them contracted COVID-19. A good time was had but at a cost.

        1. emba says:

          Those stories are consistent with the pro mask idea, but masks certainly aren’t the only plausible factor.

          In the case of the hair stylists, there were 140 customers, 46 were tested and returned negative results. The remainder (I presume some fraction of) were followed up with questions about symptoms. If one considers the great deal of difficult to integrate observations (e.g., some large number of people are asymptomatic:

          That between 5% and 80% of people testing positive for SARS-CoV-2 may be asymptomatic
          That symptom-based screening will miss cases, perhaps a lot of them

          and the fact that the stylists seemed to be taking other precautions (I imagine, not speaking to the customers etc.), there are other sensible explanations to what happened. I’m happy to agree that this is consistent with a protective mask effect, but it isn’t very strong evidence.

          Consider what the demographics of the hair salon customers were, what about at the bar where the people *did* get infected. I have not heard anything about the involvement of the most recent outbreak in ‘mask-wearing’ Beijing.

          All this to say that there seem to be a lot of hidden variables that make the the transmission of this virus difficult to understand.

          1. Kaleberg says:

            It’s like welding masks. Welders wear them because they believe they prevent serious injuries when working with a welding torch. There are NO double blind controlled studies to show that they have any beneficial effect at all.

          2. emba says:

            I doubt there are double blind controls for oven mitts as well; no one doubts that the benefit of wearing them outweighs any cosmically improbable harm.

            Public mask use doesn’t quite work the same way unfortunately.

        2. Charles H. says:

          The two cases you site aren’t really equivalent. This isn’t surprising as they weren’t set up to test the idea that masks are/aren’t significant, but the result is that it counts as a supportive anecdote, not as a real test.

          That said, if the transmission is via air borne particles, any mask that slows down the air stream or absorbs damp particles is going to have a positive effect. (It may also have negative effects, but those need to be specified. And it may have other positive effects as well.) How much of an effect, however, is harder to determine. The gross statement can be seen to be true by inspection, but details require an explicit study.

        3. Chris Phoenix says:

          I’m in favor of masks. But I don’t think this is proof, because superspreaders are probably a thing. Viral load (RNA per swab) can vary between people by a factor of 10,000. There are cases of one person giving it to dozens in a single evening (bar, choir rehearsal). With an R of 2-ish, that strongly implies that the median transmission-per-case is 0. I’ve also read that it’s often _not_ transmitted in homes where a person is infected, which is consistent with superspreading.

          (Viral load reference (I’ve seen others too): b and c of Fig. 1 of )

  9. RA says:

    Thanks for an interesting post. I think these data raise some important questions about how chronic use of inhaled corticosteroids (i.e. among those with asthma) affects the likelihood to get severe COVID disease, if at all.

    The biphasic nature of COVID would suggest that chronic inhaled steroid use would be harmful in the 1st phase, but possibly helpful in the second phase. However, there have been some data to suggest that those with asthma are underrepresented in those hospitalized…are the inhaled steroids they may be on protective? I don’t know of any good data looking at inhaled steroid use and association with risk for severe COVID disease.

    Given that there are a lot of patients who should be on inhaled steroids, but aren’t or only take them sporadically, I think there could be real clinical utility to figuring this out. Even if there were a small benefit to inhaled steroids for COVID, the effect of motivating more patients who should be taking their inhaled steroids to actually do so might produce a helpful secondary benefit in terms of improved asthma control in more of the population!

  10. Barry says:

    Secondary bacterial infections are common with viral pneumonias. Dexamethasone could actually make those worse. Ultimately, it’s the impact on mortality (“delta-Death”) that must guide us, and that has to be mortality from all causes, not only the deaths attributed directly to the novel Coronavirus.

    1. Dingo says:

      The thing is that those deaths from pneumonia are already considered covid deaths, as covid is the underlying cause of death (covid caused the infection which lead to death).

      So that should be accounted for already.

  11. Rob says:

    Anything more on using an interferon in early stage disease? There was a tiny trial in Hong Kong with good results, then radio silence. Is it effective? If effective, is it practical?

    1. Barry says:

      In the mouse models, Interferon-lambda makes viral infections of the lung worse, not better:

      1. Rahul says:

        True but the mouse models in the Science article were not infected with covid-19. There seems to be something unique about covid-19 that it suppresses interferon production while increasing cytoines. Tis may be why initial treatment with interferon could help as a few RCTs have shown.

      1. Rob says:

        Small, fairly obscure trials, but they look pretty good. I’m surprised this isn’t getting more attention. If we could just slow the early stage infection down and give time for adaptive immunity to kick in, it might have a big impact. Especially with anticoagulants, steroids, anti-il-6 and better vent management chipping away at the late stages.

  12. Anthony Burnetti says:

    Indomethacin should really be looked at clinically for antiviral effects.

    Strong in vitro results for both SARS and SARS-2, and in vivo results in dogs for canine coronaviruses with viral loads going down by a factor of a hundred after twenty four hours of treatment. Anecdotal reports from doctors in New York about massive improvement in symptoms during early disease.

    1. Robert Clark says:

      You mean there have been doctors in the U.S. looking at early treatment with antivirals with COVID-19? As soon as an antiviral is seen effective in vitro, the first thing doctors in the U.S. do is try to see if it works under severe disease cases, forgetting about the early disease case.
      Why not ALSO try it for EARLY treatment where theory and prior results show they’re much more effective?

      Robert Clark

  13. Farmer John says:

    Did not the Broggi et al paper (above) observe bacterial superinfection, rather than worsening viral infection?

    Anyway, the interferon in this case was endogenous. I believe I saw that SARS-CoV-2 is able to down-regulate the host’s interferon, so adding it may help prevent viral replication and spread. It is not clear to me where exogenous interferon would interact with the host’s immune system and if it would accumulate at high enough levels in the lower respiratory system to induce barrier damage.

    Hopefully, the Stanford study will soon shed some light early interferon-lambda treatments.

  14. Marko says:

    Multiple incremental improvements in the treatment regimen , combining things like steroids , anticoagulants , Remdesivir , convalescent plasma , etc. , may eventually drive the IFR down to a low level , comparable to that of the flu. The “COVID is a hoax” cult will then proudly proclaim : “You see ? It’s just like the flu , and we don’t do shutdowns for the flu. It’s all a big hoax. We were right all along!”

    The MAGAmorons are nothing if not predictable……

  15. dearieme says:

    Thank you for a clear and fascinating post, Derek.

    My problem with masks is not the mild discomfort of my wearing one, but the near-impossibility of my understanding what another mask-wearer is saying to me.

    In this I am probably in a minority: much of the opposition gives a distinct impression of being mere infantile feet-stamping. Won’t, won’t, won’t, won’t! Are many Americans really so unmanly that they are embarrassed to wear a mask?

    1. Hap says:

      Deaf people are likely having problems, and I have had some problems being understood with a mask. Someone had an electronic mask that showed mouth forms, but not enough to read lips (and it can’t be cheap). A whiteboard might work, but asking for you to carry a whiteboard for common conversations seems OTT.

    2. Thomas says:

      It may be difficult, but in many situations there may not be a reason to speak.
      But indeed, even for non-deaf people, masks change the voice by closing off the vocal tract.
      Note that masks do exist which do not have this effect as much; these do not sit flat on the face, but are of thinner material than FFP2/KN95 filtration masks.

    3. Charles H. says:

      Well, FWIW, I have lots of trouble wearing a mask with glasses. It needs to be on just right, or they fog up. And right now I’m on my backup pair of glasses, because last time I took off my mask it got tangled in the glasses and they ended up on the floor…in two pieces. (Fortunately it’s just that a lens popped out, but I haven’t been able to get it back in, so that’s going to mean a visit to an optometrist…and I’m in lockdown.)

      That said, I still wear a mask. But until I get my glasses repaired I’m probably going to refrain from wearing glasses at the same time.

      1. Hap says:

        I get some fogging of my glasses but it’s not too bad, but I’m not yet at work (with air conditioning) and the summer hasn’t gotten hot and humid.

        Can’t be worse than the full plastic lab goggles with (alleged) ventilation from undergrad; it was like trying to read in a car wash.

  16. StanleyIpkiss says:

    Dear Derek,

    as someone who started wearing masks at the beginning of February, please reconsider your vitriol for non-mask wearers. I am sad to see this issue becoming a culture-war topic in the US, and your words are probably not helping in that regard. Protesters right now are also plain ignoring social distancing guidelines, and people against mandatory mask usage similarly have their reasons for going against public health guidelines. Yes, one reason is not like the other in your eyes, but everybody always thinks that unlike other people’s causes their own cause is obviously much more important.

    Otherwise, thank you for the very informative post.

    1. Derek Lowe says:

      You have a good point; yelling at these people isn’t going to make any of them wear a mask. And I don’t think the protests are going to do us any coronavirus favors, either, obviously. But then again, neither is the upcoming Tulsa rally, is it?

      1. Adrian says:

        There is anecdotal evidence that calling 47% of the population deplorable is not good a recipe for winning the hearts and votes of the people in the US.

        From outside it always feels as if the media and politics in the US are dominated by 1% extremists on each side, and most of the rest of the population is not that extreme.

        Even in conservative places like Texas > 95% of schoolchildren have all recommended vaccinations, this shows how many people can be convinced of a vaccine.

        If the first COVID-19 vaccines are not effective and safe many people will not trust COVID-19 vaccines, and you cannot blame them for it.

        If the first COVID-19 vaccines are effective and safe, the bottleneck will not be people willing to get a shot.

        1. Derek Lowe says:

          I should emphasize that not all the vaccine skepticism here is on the Right – many of the “I’ll never take the Gates vaccine!” types are on the right-hand fringe, but there’s a lot of anti-vax sentiment over on the all-natural no-chemicals-please left as well, often associated with very high income and education levels (see certain zip codes in California, among others).

          1. Adrian says:

            The data says that < 5% of the people in the US are refusing vaccinations for their children, all political beliefs included.
            There is no point in trying to convince or attack them, and they are few enough that they don't matter.

            What will matter is that all approved COVID-19 vaccines have to be effective and safe.
            Emergency approval of a vaccine with 100 million doses already produced that later turns out to not be safe is my huge worry.
            If something like that proves that the approval process fails to ensure that all approved vaccines are safe, then trust in vaccine safety is permanently damaged for good reason.

          2. TallDave says:

            agree, vaccine skeptics are a bipartisan curse… amusing to see “protest skepticism” on the right and left completely reverse over a week or two… imho everyone possible should stay home, wear masks, and possibly also spray Windex on each other every few minutes until the synthetic antibodies get here, but ymmv (e.g. my wife is in the complete opposite camp, we have several small children and she wants to take them out as much as legally possible)

            of course some of those people changing their minds with the political winds (on both sides mind you) were public health officials which is still amusing if they’re far away but less so if they’re responsible for your own personal health

      2. anon says:

        Are you going to tell protestors to go to hell to? Or is that just for people who aren’t wearing face-masks?

    2. x says:

      Are you kidding?

      Yes, culture war is a problem in the US. But I didn’t see the right complaining about protesters not wearing masks or social distancing during the astroturfed right-wing protests demanding that we end lockdowns and open all the businesses back up and go back to normal. I didn’t see them lambasting the “masks are enforced cowardice” people. Yet now that liberals are protesting police brutality, suddenly the right is deeply concerned and offended by all these people not wearing masks, while at the same time making facile excuses for not wearing them?

      Pleas for tolerance and civility don’t go over so well when they are nakedly self-serving and hypocritical.

      Common sense says that masks have some benefit to others (and therefore to everyone), if only by containing coughs, sneezes, and heavy sighs, and the cost and inconvenience is small. If you want to claim that what is obvious is actually wrong, your standard of evidence had better be a little higher than arguments to ignorance… particularly if you want all the people around you, who will otherwise believe you are endangering the public, not to think you’re a dumb asshole throwing a tantrum.

      As for culture war, crying victim over trivial offenses like a precious snowflake and speaking in bad faith is unlikely to lead to detente any time soon.

  17. Stewart says:

    “The dosage in this study was not particularly high, which is a good thing to see.”

    Does that mean that it would be sensible to do a RCT comparing the effects of that dosage with a higher dosage (in the hope that a higher dosage would be more effective)?

    1. Derek Lowe says:

      IMO that’s asking for trouble, although I’d be interested in hearing how the Recovery folks decided on their dose.

      1. The reported risk reductions with dexamethasone were so substantial that I’d be surprised if meaningfully better results could have been achieved with higher doses. That said, dose-exploration might not be all that technically or ethically difficult.

        First of all, the reported patients who got dexamethasone all got the same dose (6 mg qd), and that means that the mg/kg or mg/m^2 dosing probably varied by at least a factor of 2. It might be possible to reexamine the existing data, divide the population into quartiles by weight or body-surface area, and see if the risk reduction associated with dexamethasone varied monotonically in one direction or the other, suggesting that a higher dose (or a lower dose) might have been better.

        Suppose for definiteness that the existing data suggest that optimal efficacy was achieved with doses of about 3 mg/m^2, but that neither heavy patients who got only 2 mg/m^2 nor small patients who got 4 or 5 mg/m^2 seemed to do very badly. With these hypotheses, I find it hard to see how anyone could say that there are data that present ethical obstacles to a new trial that randomized patients among 2, 3, and 5 mg/m^2.

        1. eub says:

          It’s a side point, but I’m curious why they used an unscaled dose given the setting, IV admin I assume. The DEXA-ARDS trial (linked from name) did too — that dose was IV 15 mg averaged — so they’re not alone in it. Anyone know why this is?

          The low dose may have been following the SARS experience, where high-dose steroids caused harm and (as I understood it) didn’t help much. But it’s interesting to see critical patients getting a lower dose than I’ll see people taking as prophylaxis for altitude sickness.

          1. Now that a preprint is available on line (, the dosing the RECOVERY trial used is easier to understand.

            According to the protocol, the dose could be administered IV or PO. Also, an otherwise-eligible patient could be excluded if dexamethasone was not available at that hospital.

            I remember dexamethasone as being universally available in US hospitals, but prednisone is much cheaper, and it is sometimes used instead. Dexamethasone is more purely anti-inflammatory, and prednisone has more mineralocorticoid action, but for short courses the difference is usually harmless.

            I surmise from the RECOVERY protocol that dexamethasone is not all that widely used in the UK, especially IV. The investigators could have randomized patients to the caregiver’s choice of equi-anti-inflammatory doses of prednisone/prednisolone/dexamethasone, but then one can imagine a variety of difficult-to-interpret results. In the event, they probably decided that the least-common-denominator strategy was built around the most widely available dosage form of PO dexamethasone.

  18. JasonP says:

    Can someone please tell me how I can join a clinical trial for one of the vaccines? Seems like if they need 30,000 enrollees for one trial and there are a half dozen trials or so, I ought to be able to find one within a 50 mile radius?

    Good Post Derek and kudos to those who provided discussion! I learn from both sources.

    1. Ian Malone says:

      If you’re in the UK then you may be near a site for the Oxford vaccine study,
      The Imperial study might only have the one London site

      Most of these studies will be trying to recruit from the public, so if you’re in a different part of the world just find out what trials are going on in your country and google for the institution and covid vaccine (or coronavirus vaccine). Obviously make sure the site you’re looking at is actually associated with the institution or pharma company you think.

      I’ve been tempted to apply, but I suspect I’m not a good candidate as my routine is not bringing me into contact with many people, meaning I’d probably be part of the noise.

  19. RA says:

    Interesting and depressing to read the comments on masking. But I think it’s worth noting that the anti-maskers are hurting themselves too, even if they never get sick.
    A lot of people who are informed and have discretionary income to spend are not going to resume normal economic activity in the US because they are justifiably afraid of the unmasked people roaming around everywhere. You can “open” but you can’t force us to come out and spend money when you only care about your liberties and not our safety. So, enjoy the economy you have wrought! You “win.”

  20. Yancey Ward says:

    The press release seemed to omit one piece of data that would have been useful for assessing this: 28 day mortality was reduced for the dexamethasone treated intubate patients, but this doesn’t tell us if those saved actually got off the ventilators- it one thing to still be alive and awake, it is another thing to still be in an induced coma and ventilated. Will it be the case that 56 or 84 day mortality is unchanged.

  21. Tom Davies says:

    What do you die from if you die without needing respiratory intervention?

    1. emba says:

      I think dysfunction of any vital organ.

      “Now that more scientific data are available on COVID-19, the Global Sepsis Alliance can more definitively state that COVID-19 does indeed cause sepsis. Sepsis is “a life-threatening organ dysfunction caused by a dysregulated host response to infection.” In the case of COVID-19, the effects on the respiratory system are well-known, with most people requiring hospital admission developing pneumonia of varying severity; however, virtually all other organ systems can be affected.”

  22. monty says:

    First I’d like to see conclusive proof that this study was not financed by Big Dexamethasone.
    (just kidding)

  23. johnnyboy says:

    Meanwhile, my 70 year old neighbour just told me she’s so happy about this news, because she’s been taking dexamethasone for years for her rhumatoid arthritis, so this means she’s protected and won’t catch the coronavirus… Can’t really blame her after the breathless news headlines we’ve had about this. I still persist in thinking that it would be better for people if there were no news at all about medical treatments, rather than the type of coverage we have now.

  24. Luis says:

    I am waiting on the results of the Bemcentinib trial,for what i been reading about it we could be in for really good news,fingers and toes crossed….

  25. Xa says:

    blood coagulation complications such as DIC, Lung Embolism, MI and stroke may cause high % of death among COVID 19 patients. Curious to know if the anti-coagulation scheme in the the Dexamethasone group was similar to that in the control group.

  26. Robert J Spiegel says:

    Has anyone seen statistics tracking mortality rates over time for patients admitted to ICU or placed on ventilator. Obviously remdesivir is not widely available and the dexamethasone data is brand new, but it would be interesting to see how best practices in ICUs are changing outcomes since the pandemic appeared. Has anyone seen data tracked?

  27. NotanAttorney says:

    I, for one, would really appreciate a post analyzing the data we have on the effects from wearing masks (differentiating between N95, surgical, and cloth) on interference with COVID or other airborne disease transmission. Unlike for vaccinations, there seems to be little data on these issues without conflating the different types of masks as well as social distancing.

    My concern is that people seem to be more willing to invade the 6 ft space when another person is wearing a mask (only my observations), which may cause more harm than good (particularly if some of the masks aren’t doing any good in the first place).

    I respect Derek’s analysis on all things COVID, and I would appreciate a post addressing this evidence (or directed to a post where it was addressed). There is obviously a (bizarre) political angle to all of this that I think may be interfering with scientific thoughtfulness on this issue as well as others.

  28. TallDave says:

    did not know plastic antibodies were a thing, apologies if everyone saw this already but might be worth sharing, will have to learn more about MIPs

    perhaps this will be our last pandemic… COVID research splurge might even spawn cheap, widely available one-day cures for cold/flu with high efficacy

  29. dave margolis says:

    Your last paragraph was very disappointing… You couldn’t resist, you had to show your smug pomposity.

    Many of us more clear thinking individuals are capable of behaving responsibly and are inoculated, thank God, from the hysterical media…and types like you. Sadly, I think you actually believe yourself.

    I work in a hospital where, at one point, we had over 50 cases and 8 deaths (early on…now it has been eradicated with proper procedures). I have remained virus free because, like hundreds of thousands of responsible people, I know when to wear a mask and when I don’t have to wear a mask. I also know how to wash my hands…mom taught me that one. I have not sequestered myself and I have enjoyed the company of responsible like-minded friends throughout this insanity. I am a psychologist and I treat people with depression and anxiety disorders. The toll this lock down has had on my patients has been very severe for many of them. They have been truly traumatized by this process and the impact will be life long. Well-intended but narrow-minded physicians and capitalistic media are to blame. As soon as adequate PPE and ventilators were made available, the lock down could have ended.

    The simple fact is…wear a mask when you have to be less than 6 feet from someone or inside a poorly ventilated room for more than a half an hour…and wash your hands. If you are outside and 6 feet apart, take your mask off and RELAX. The odds of catching the virus in this way and then the odds of dying from it are so ridiculously low that it becomes laughable seeing masked people jumping away from each other as they pass on the street…calm down everyone and enjoy your lives.

    1. Derek Lowe says:

      “If you can’t annoy someone, there seems little point in writing” – Kingsley Amis. In other words, no guarantees on the timing of eruptions of smug pomposity, I guess.

    2. Anon says:

      Speaking of “smug pomposity”, the claims you make in your last paragraph are of course backed up by solid evidence based on your research? Or are we supposed to just take your word on it, Mr. Psychologist? (being the renowned biomedical researcher that you are??)

      1. Derek Lowe says:

        Nullius in verba – on no one’s authority. I provided some references, though, earlier in the comment thread.

        1. Anon says:

          My comment was directed at “dave margolis”.

    3. RA says:

      It is the anti-maskers that display smug pomposity. Their actions and the messages they send to the public are responsible for the deaths of many essential workers, health care workers, and others who couldn’t go into hiding and were not given enough protective equipment and had to be breathed on bareback by mask refusers.

      And yet, it is the anti-masker who is offended when someone calls them out on their irresponsible messaging. They don’t value other’s lives but are snowflakes themselves when called out. Cry me a river!

      1. emba says:

        “Their actions and the messages they send to the public are responsible for the deaths of many essential workers, health care workers, and others who couldn’t go into hiding and were not given enough protective equipment and had to be breathed on bareback by mask refusers.”

        This is an absolute lie. We barely have come to understand the demographics, we know little about the actual routes of transmission. We don’t have any good evidence that links infection to non mask wearers.

        All of this is quite an insult to the one specific context that has been extremely susceptible: elderly care holmes.

        1. RA says:

          Not an insult, it’s the truth. Your ilk have (clotted) blood on their hands. Why on earth do you think the within-facility spread has been so bad in “elderly care homes” compared to hospitals? Hospitals had relatively more access and utilization of masks and other protective equipment than did nursing homes in the midst of an overall shortage.

          Oh….and unlike masks, there is no evidence that wearing pants provides any health benefit for anything, so perhaps we should exercise our constitutional duty to go pantsless. Many people find pants uncomfortable, and I would think that if you don’t think people should be required to wear masks, then we can throw out the requirement for pants as well!

    4. Just saying..... says:

      Well, Dave, let’s talk about smug pomposity. You state that you are a psychologist working in a hospital and “I have not sequestered myself and I have enjoyed the company of responsible like-minded friends throughout this insanity”. So you work in a hospital that was treating over 50 cases of COVID-19 with 8 deaths and then you risked being an asymptomatic carrier and infecting these like-minded friends of yours. Great, we have established that you are both a selfish psychologist and a moron. Let’s move on.

      Guess you never met anyone in your line of work who appeared to be a “responsible like-minded” type of person but who was actually banging the person down the street who just happened to give them an infectious disease like herpes or HIV, right? Guess you never met the upstanding citizen who happened to be a child molester or beats their spouse, leads a double life or is shooting up heroin at night? I’m sure that you can stake your life on those responsible like-minded friends of yours as well. Where they’ve been, who they’ve been hanging out with, who they were sharing a joint with behind their house, etc. Guess you have them all figured out because, after all,…………you…….are………a……..psychologist.

      Here’s the thing: I worked for 30 years as a medicinal chemist (mostly in infectious diseases) and now I help run a mental health counseling center with my wife (she’s the LCSW-R). Let’s just say that I have to deal with people like you every single day of my life. Thirteen of them, currently. (Trust me, dealing with people like you all day makes you depressed and anxious.) And all of our counselors are working remotely and are not allowed on-site. And, by the way, they are all responsible like-minded people. Regardless, I keep them away from me and each other to protect me and them from their own stupidity.

      I don’t take infectious disease advice from a psychologist and I don’t take my car to my proctologist either. Your credentials mean jack to me. And the way I do enjoy life is to keep stupid people like you very far away from me because I can tell from what you wrote that you are a smug, pompous, arrogant wanker who thinks that they have all the answers and is most likely to infect me. I would even guess that you somehow think you are smart.

      Now that was therapeutic………..and I already feel less depressed. Thanks for the 90834! (I actually didn’t spend 30 minutes on you.) I’d wager that you probably don’t know how to submit a HCFA form or the handful of CPT codes for your services, do you? I think you can add on “interactive complexity” (90785) for this session, Dave. That’s because you are such a douchebag.

  30. Paul says:

    “The people (a minority, but a loud one) ranting about how such masks are an infringement on their liberties can go to hell, in my considered view of the situation.” Very bold, Derek, and so de rigueur; but show me the data that masks are of any use on anyone but the obviously ill.

    1. Lane Simonian says:

      To add to the list of studies Derek provided above is this latest one:

      As is almost always the case, the evidence is not air-tight (no pun intended). However, I do not really understand the anti-mask sentiment. For vaccines at least there is the fear that the vaccine may be neither effective nor safe (whether this be a rational fear or not), but unless you are asthmatic or suffer from some other respiratory condition, there is no argument to be made that masks are unsafe and there is substantial evidence that they help slow the spread of the virus. The idea that they somehow impinge upon people’s freedom and liberty also seems overwrought.

      When I see someone wearing a mask, I smile underneath mine. When someone is not wearing a mask my thought is you selfish bastard.

      1. emba says:

        If that study is the study that definitively show the effect of mask interventions at population scale, so be it.

        It *just came out* and hasn’t yet been reviewed (just like the dex trial above). Uou can see from the comments in that very article that such a study has been “what we’ve been begging for for months,” ….many people in this thread suggested we already knew masks works and it is obvious, why then have we been “begging for for months” when the evidence was already so clear?

  31. Jim says:

    Wearing a mask is simply an expression of your belief that thoughtful behavior on your part may help society as a whole as well as protect yourself and other people from infection with a dangerous virus. Just like getting vaccinated or even voting. America the selfish (led by our President) believes that it is all about me and any inconvenience, like a mask or washing your hands or attending mass gatherings is simply intolerable. Derek’s sentiments are right on.

  32. MMDN says:

    Anyone who thinks that masks and other physical barriers are useless to slow down the spread of the pandemic should put their health where their mouth is and spend time with Covid-19 patients “au naturel”.

    I haven’t seen much footage or heard witnessing of such people in the icu recently. Coincidence?

    1. emba says:

      The balance of evidence does indeed suggest that surgical masks are effective in the hospital setting. It isn’t as obvious as many people here may think.

      1. MN says:

        Some people are not surprised that physical barriers offer more protection against droplet infections that no barrier at all.

        1. emba says:

          That makes a lot of sense, but Nature doesn’t owe your intuition anything.

          1. MN says:

            And with that I’m going to move on with my day. Have a great weekend!

  33. emba says:

    This is the standard appeal to virtue we see on the pro mask side. Wearing a mask “may help society as a whole as well as protect yourself and other people from infection with a dangerous virus”, it may not. You can find a number of scientists and policy makers above and their sound reasoning as to why it may be and why it may not be.

    It’s much more thoughtful to think critically about reason and evidence so the most effective actions can be made instead of base appeals to virtue.

    1. Anon says:

      “This is an absolute lie. We barely have come to understand the demographics, we know little about the actual routes of transmission. We don’t have any good evidence that links infection to non mask wearers.”

      Wait, both the demographics and “routes of transmission” have been understood very well by even the most dimwitted. This is an airborne transmitted contagion. Certain demographic groups (quite obvious from the hospitalization/mortality data) are more susceptible.

      “It’s much more thoughtful to think critically about reason and evidence so the most effective actions can be made instead of base appeals to virtue.”

      This isn’t about virtue, it’s about common sense at this point. And before you lecture us about “inalienable individual rights”, recall that the Constitution starts with the words “We The People”…wearing a mask to reduce an airborne/aerosol transmissible disease is hardly a burden given the human and economic cost of letting this pandemic drag on due to the idiocy of the deluded few. Enough already.

    2. Anonymous says:

      Portraying everyone who says “you should follow advice from your own public health officials” as an irrational cultist says a lot about you. It isn’t “thoughtful” at all for people to ignore their public health guidelines until they are personally convinced of the evidence.

      Critical thinking is a good skill for exploring ideas in low-risk, not-time-critical circumstances. It is not a substitute for consideration of others or a timely response to new threats. Please stop pushing this “let’s stop and think, and meanwhile not listen to our experts” garbage.

      And before you say “but Finland, and WHO, and kids, and…” again, different locations/ages have different circumstances, and the public health officials in your own location are taking these factors into account, so the advice SHOULD be different in different circumstances, for good reason.

      1. emba says:

        You’re trying to portray as advice from other authorities responsible for large populations as specifically tailored to those populations. That’s just not true.

        You can ignore the sensible reasoning coming from other places, but the ostrich algorithm has never been a particularly good solution to problems.

  34. Robert Clark says:

    So now it’s apparent that antivirals should be given EARLY to prevent progression to severe disease? Drs. Raoult and Zelenko have been saying this for months about HCQ and nobody tried it. (Except for those who DID and found it worked.)

    Robert Clark

    1. Tom says:

      Dr Zelenko in his own words, ” I’m a clinician, not a researcher, I don’t understand fully the language of clinical research”, yet he ‘claimed that the clinical trial he was helping organize, sponsored by St. Francis Hospital in New York, had been approved by the F.D.A.’ (

      Dr Raoult meanwhile has had his work heavily criticized.

      While the debate will continue on HCQ, I’m with Derek that it is not something to keep touting as a treatment (as he has said in his previous blog posts), especially when others are currently being investigated with less apparent safety concerns (at least at the moment).

      1. I would take care in criticizing the approach of HCQ proponents when one trial by HCQ opponents used faked data, another didn’t even test the majority of their subjects, and another, RECOVERY, used toxic levels of HCQ in their treatment.

        Robert Clark

        1. Covidiot19 says:

          Donald? ….That you?

        2. Some idiot says:

          Oh dear. The trolls are back. Btw, again, there is no indication that side effects due to toxicity were seen in the RECOVERY trial; instead, a dosing strategy based on getting the pharmacological parameters up and running quickly, to give the drug a chance.

          And, again, lower doses would not have been expected to give better results, as is obvious from dose-effect principles.

          And despite these obvious points, you keep repeating this misinformation.

          1. Robert Clark says:

            You can’t say there were no bad side effects until the RECOVERY trial actually releases their data. Those who have doubts about the effectiveness of dexamethasone just because of a press release absent of the actual data, should also have doubts about the claim of no bad side effects at the toxic levels of HCQ used in the RECOVERY trial absent the actual data being released.

            Keep in mind the Brazil trial that was terminated because of excessive deaths at the high dosage level of HCQ, used 1,200 mg, only half that of the RECOVERY trial.

            Robert Clark

          2. Some idiot says:

            Side effects of the HCQ arm were at the same or lower than that of the control arm. So it’s pretty tough to say there were toxic effects!

            I don’t know the dosing regimen in Brazil, but it is important to not just look at the size of the dose in isolation, but how it was taken. The pharmacokinetics are extremely important!

            And, again, there is no data or rationale to indicate that a lower dose would have had a better effect. So your point is scientifically irrelevant.

            Therefore more misinformation.

    2. Daren Austin says:

      Always treat a patient early and when they are deteriorating. If treatment fails then It must be because it wasn’t early enough 😉 . There is some truth in this. Antiviral activity can help with viral replication, and anti-inflammatory activity can help with an inflammatory cascade. It’s unlikely that the reverse is true. Hence tocilizumab/sarilumab won’t reduce early symptoms and Remdesivir won’t stop ARDS-like end-stage disease. But if you have nothing else to give, then on the principle of do no harm, you test. Other mechanisms will be tested in due course and outcomes will improve further. Recovery is a solid first step

  35. Robert Clark says:

    Using antivirals to treat viral infections EARLY on is Infectious Disease 101. This is well known in regards to influenza and HIV, for example. Yet only now is this starting to be accepted in regards to COVID-19???

    Rethinking antiviral effects for COVID-19 in clinical studies: early initiation is key to successful treatment.

    Even if skeptical of HCQ, several antivirals shown effective against coronaviruses in vitro, but then shown ineffective in patients under severe disease. But should be tested instead for EARLY cases.

    Robert Clark

    1. Edward R says:


      A group of researchers and doctors have been recommending a methylprednisolone based treatment protocol for months now.

      They are claiming an 80%+ decrease in the death rate of mechanically ventilated patients. They have a new June 18th update on why methylprednisolone is far superior to dexamethasone. Could you give their stats a look at and tell us what you think?


      1. Robert Clark says:

        I hadn’t heard about methylprednisolone. I’ll read that web page and let you know what I think about it.

        Robert Clark

      2. Robert Clark says:

        Here is another report that it shows definite benefits:

        Prolonged low-dose methylprednisolone in patients with severe COVID-19 pneumonia

        Robert Clark

  36. J N says:

    Here in the US we’re conducting an uncontrolled trial on 330 million people. I figure that by October around 1 million of us per day will be catching COVID-19.


    1. Edward R says:

      If you are depressed now just wait another month or two J N

      The same bankers that just got a $4.5T bailout from .gov and the Fed courtesy of the Dems and Repubs CARES Act, are now busy prepping the next round of residential foreclosures. In 2008-2009 a staggering 5 million homes were foreclosed uoon. This time around it will likely be 3 to 4 times that number and those people will now be unceremoniously thrown out onto the streets in the middle of a pandemic.

      The entire system is corrupt.

      1. Marla Garcia says:

        Correct! Someone who knows what they are talking about, finally.

  37. PDINV says:

    Sorry but I have to disagree about remdesivir acting as an antiviral in humans. Not once has it demonstrated reduction ov viral loads or titers in clinical trials, not for sarscov2 and not for any other virus.

    1. Daren Austin says:

      Hint of a signal in their preclinical cyno study. That’s about it. The Ebola trials, against a virus it was screened for, were particularly dissapointing.

      1. PDINV says:

        In vitro and in animals under very controlled conditions (eg treatment 12h after infection) they have shown some reductions in viral loads but never in humans even though they have tried.

  38. Ryan says:

    I think it’s time to run an article on the histories of Zostavax and Shingrix, which both target the same disease. I’ll be first in line for a COVID-19 vaccine right after the results of a large-scale, double-blind, placebo-controlled safety study are released. Oh, and after being tested for COVID-19 antibodies.

    1. Marla Garcia says:

      A voice of Reason.

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