Yes, but the recommendation that healthcare workers take 40mg/day? Do you *really* want me making life-and-death decisions about your kid when I've taken that much melatonin?
There is also evidence that regular antihistamines (2nd generation, loratadine, fexofenadine, and especially cetirizine) may be helpful in averting the cytokine storm, and in more believable doses.
Then, someone is looking into the histamine H2-blocker famotidine, but don't go out and buy a bunch. This is given IV and in doses about 10x the usual.
It appears like the journey into a cytokine storm is a mathematically chaotic
process in which there are at least three attractors
. One of these is for critical severity with ventilator dependence, one of these is for moderate-to-severe severity without need for ventilator support, and one is for mild/asymptomatic cases. If my little model is true, then some small initial changes in the starting point (optimizing vitamin D levels, some cetirizine, maybe some melatonin) might be enough to tip the trajectory to one of the latter two attractors.
All of us have hope that somehow a viable vaccine will be available quickly but have many concerns about them.
Will it work. Will it give lasting immunity. Could it have have deadly or crippling side affects. Can it made quickly, on a large scale and safely.
All very valid questions. The leading candidates take an approach that is somewhat different from most existing vaccines. They use viral genetic sequences to force the patient's cells to start expressing SARS-CoV-2 S protein. This has some significant advantages over just injecting S protein. In other posts, I have spoken about the "two arms" of adaptive immunity, the cell-mediated arm (T cells) and the humoral arm (antibodies). When you just inject a protein, you get humoral immunity, but not fantastic cell-mediated immunity. But when you force cells in the patient to express viral proteins, you get both cell-mediated and humoral immunity.
In the past, live-attenuated vaccines have been used to this end, but those vaccines do contain the actual proteins against which these immune responses will be directed. These newer approaches only contain the genetic code, which is interesting, and at least in the Moderna version, might lead to better effect from a booster dose because existing antibodies will not inactivate the second dose of the vaccine before it can reach its target. The Oxford vaccine uses an adenovirus, and it's likely that the patient will develop anti-adenovirus antibodies that make boosting more challenging.
It's not likely to have worse side-effects than getting the actual illness. I'd say that my big worry is setting off this inflammatory cascade with the vaccine, but I'm going to guess that the risk will be much lower with the vaccines because the vaccines cannot replicate, so the inflammatory response that they trigger will be brief and mild. However, some people may react badly to it, but those people would also probably react badly to getting COVID-19.
Certainly, the scaling is also a valid concern, and I sincerely hope that manufacturers who produce syringes and needles are ramping up production. Consider this: if you can make one million doses a day, you will need about three years to make one billion doses.
But here is my take on the vaccine and what it will and will not do: from the Oxford data, it appears that the vaccine does not provide complete sterilizing immunity against infection with the virus. Sterilizing immunity is akin to what you get from a measles vaccine. If you get two doses of measles vaccine and then I have someone with measles cough in your face, the virus might get as far as infecting a couple of cells in your nose and then be completely wiped out before it can complete even one round of replication.
But with these vaccines, they found that the monkeys that they challenged with the virus did get infected with it. However, those animals did not get pneumonia. They had viral replication in their noses and that's all. That's consistent with prior studies of endemic human coronaviruses, where antibody titers fall after some time, but repeat infection results in mild or subclinical (asymptomatic, or inapparent) infection. And this is not completely unprecedented. Flu shots are not very good at preventing infection with influenza, but they are very effective at preventing severe influenza pneumonia.
So that means that this vaccine will probably stop you from getting severe COVID-19. It may reduce the amount of viral replication in the nose and by that route reduce shedding, but I don't think that it will completely stop infection and shedding.
That means that the vaccine will likely protect those who get it, but it won't protect those who don't get it, like the measles vaccine does. The entire concept of "herd immunity" might not work with this vaccine very well.
The other thing is that we aren't going to have a good idea of how long this protection lasts when the first doses of vaccine are given to the general public (which I predict will be sometime between Christmas and Valentine's Day).
So all of this raises some public policy issues. Do we require people to get the vaccine before they can get on an airplane? Before they can go to the barber? Before they can go to the gym? How do we enforce that? Or do we just say: "Don't get the vaccine at your own risk"? As pro-vaccine as I am, I'm not comfortable with using heavy-handed tactics to require people to take such a new vaccine with so little clinical data behind it. I probably will take either the Oxford or Moderna (I'd prefer the Moderna) but I'm a physician and a former molecular virologist and I have a very sophisticated understanding of these matters.