Now that we seem to be getting the Covid-19 situation under control, not that life will return to true normal for a long time, discussion about a second wave this fall is getting much more attention. Let’s just accept, or at least assume, that there will be a second wave 6 months from now. Things are going to be very different. I’ll go further, and at the risk of sounding overoptimistic, argue that it will be a quite manageable situation.

The biggest problem with Wave 1, which is only now starting to abate, is that it had a high amount of what Donald Rumsfeld famously called the unknown unknowns:

…there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns—the ones we don’t know we don’t know. And if one looks throughout the history of our country and other free countries, it is the latter category that tend to be the difficult ones.

Every few years there is a pandemic, or at least an epidemic, from some new novel virus. And while occasionally they cause significant harm, outside the medical community,  here in the U.S. we tend to ignore them. So when word of a new virus in Wuhan China started making the rounds in January 2020 (the WHO was alerted on 12/31/2019, which explains the SAR-CoV-2019/Covid-19 naming) there was somewhat of a Chicken Little effect. Been there, done that, have some t-shirts, there are no hand sanitizer dispensers out at the airport so it can’t be a big deal, etc. By the way that last one was me for a while. In previous major outbreaks like H1N1 hand sanitizer stations was everywhere even if people weren’t paying attention to why. But even for my final airplane flight to shelter at home on March 13th, neither SeaTac nor Denver airports had deployed hand sanitizer. Yes I know a shortage developed, but the airports must have had stockpiles they never deployed. By the end of February we were in WTF mode, which transitioned a couple of weeks later to “we are F…..” mode.

Think about all the known unknowns and unknown unknowns from just 60 days ago. How does it spread, how long does it live on surfaces, how deadly is it, why people die from it, etc. We had no idea what supportive treatment protocols worked. We knew we had no therapeutic, prophylactic, or vaccine solutions but didn’t know how long it would take to find and prove what worked. Yes we’ve barely scratched the surface on all this, but we do have some scratches now.

So we panicked, and shut down as much human interaction as possible. I’m not going to discuss that here,  but maybe in a future blog post. The point is the extreme social distancing was a response to the level of known unknowns and unknown unknowns. And my premise is that by September 1st the number of unknowns, of both varieties, will be so greatly reduced that Wave 2 will be manageable without shutting down the world.

Even though it has only been a bit over two months since Covid-19 went from stories out of Wuhan China to deaths in a nursing home in Kirkland Washington, treatment protocols for the disease have already changed dramatically. In March a huge part of the panic was that we had insufficient ventilators for the most serious patients. Lots of companies have stepped into fray and by September we will have a lot more ventilators, but more importantly perhaps, we’ve learned that we were putting people on invasive ventilators prematurely and that for many alternate approaches were called for. More recently the need to aggressively confront blood clots has emerged as a front in the battle.  Even ignoring theraputics, by September supportive treatment protocols will be far more mature and likely (hopefully) lead to improved survival rates and a reduction in lasting damage for serious cases. We also learned how to quickly increase the number of intensive care rooms to handle serious Covid-19 cases.  The protocols healthcare professionals are following keep evolving to better protect themselves and their patients. At one point an acquaintance who works in a hospital told me they were getting protocol updates multiple times per day. By September these protocols should be much more mature.

Another huge change when comparing September to March is Personal Protective Equipment (PPE) availability. We went into this crisis with an inexcusable lack of supply of PPE for both healthcare professionals and individuals. Again there is a huge ramp-up in both manufacturing of PPE underway, and rollout of technology to sterilize what are traditionally disposable PPE to alleviate shortages. Between massively increased supply and some demand slowdown over the summer months, in September there will likely be adequate PPE. It is even likely that there will be adequate supply for non-healthcare professionals , for example Chinese KN-95 masks are increasingly available outside the healthcare environment (where U.S. N-95 respirator masks are the standard).

Now let’s talk about theraputics. Last week we got the initial results from the first large scale high quality study on the use of an antiviral, Remdesivir, for treating Covid-19. It showed a 1/3 reduction in time to recovery for patients with severe Covid-19. Is this a silver bullet? No. The problem with Remdesivir is that it is administered by IV for 5 days in a hospital setting. Because of that, it is only likely to be used on patients who have severe enough illness to require hospitalization. But what we know about antivirals is that they work best when administered very early, like in the first few days after infection. So it isn’t a silver bullet, but cutting the time someone needs to be hospitalized by 1/3 means a significant reduction in the number of hospital beds required.

Taken together, the improvements in treatment protocol, the increase in ventilators, the ability to rapidly scale up intensive care rooms, the abundance of PPE, and at least one drug that reduces the length of hospital stays suggests we will go into September without the same pressure to “flatten the curve” to avoid overwhelming the healthcare system that we had in March.

Of course these developments also suggest we will start to reduce the so-called Case Fatality Rate from Covid-19 as well. So let’s explore that some more. I’ve already mentioned Remdesivir, and now investigation into use of blood thinners, but is that all we’ll have in September? I certainly hope not. There are a lot of trials of medications to address the cytokine storm that is believed responsible for Covid-19’s high fatality rate. There is even a blood filter that is being tested for this. Is it possible that all attempts to mitigate the cytokine storm will fail, or require more extended development? Yes. Is it likely? My gut says lots of people wouldn’t be pouring immense amount of energy and money into this if they didn’t have pretty high confidence of success. While I can’t say what precisely will work and what won’t, it is very clear that by September doctors will have additional tools at their disposal for combatting the effects of Covid-19.

So what about “silver bullets”? I’ll distinguish silver bullets from nuclear weapons, where that latter are vaccines. Let’s split this into two different categories. First there are other antivirals beyond Remdesivir that might look silvery if not actually be silver bullets. Favipiravir is an antiviral approved in Japan for fighting influenza and currently undergoing trials in multiple countries for use against SARS-Cov-19. In Japan they are already ramping up production in anticipation of successful trials. EIDD-2801 is a promising antiviral just entering trials here in the U.S. Both are taken orally, so can be administered early on. For example, you test positive even if asymptomatic and are given one of these drugs to cut the disease short. Or perhaps you were exposed to someone who was infected, and one of these are given to you prophylactically. By stopping the virus early you both prevent progressive into more serious disease state and reduce its transmission. There is a decent chance that one of these will be available (possibly favipiravir as an approved drug, or EIDD-2801 under an emergency use authorization), though perhaps in very limited quantities, by September.

The area that excites me the most are antibody treatments. Not only could they cut short the disease for those infected, they have the potential to provide immunity for several weeks after dosing so are ideal prophylactics until vaccines are ready. Trials of convalescent plasma antibodies are already under way and, if successful, would have the clearest path to being available in September. But that approach has limitations (e.g., you need plasma donations from recovered Covid-19 patients with high concentrations of antibodies in their bloodstream). Many companies are pursuing non-plasma antibody theraputics for battling Covid-19, and Regeneron’s is about to enter trials. They are going to ramp up manufacturing in parallel with the trials so that if the trials are successful they will have a large number of doses available by September. If this approach works out then we will have a real way to stop the virus in its tracks, at least in hospital settings, and possibly provide 8-10 weeks of prophylactic protection. BTW, if you want to participate in development of another antibody treatment it turns out distributed bio is accepting crowdfunding to boost its efforts.

Vaccines are the real nuclear weapons in the fight against Covid-19. They also take time to develop and test, and so most estimates don’t have them available (and certainly not in quantity) until late 2021. But there are a couple of approaches that might provide vaccines by September. One is a repurposing of the BCG tuberculosis vaccine, which appears to have some broad protective ability. Although I’m not a doctor, and don’t even play one on TV, if the BCG vaccine helps at all I’m not getting the feeling it is preventative so much as something that leads to milder disease. More promising is a vaccine developed at Oxford University that could be ready in 6 months, but even if successful it is unlikely to be available in large quantity in time to make a big difference in a fall outbreak. What it could be used for is to protect healthcare workers, and perhaps some very vulnerable segments of the population, while manufacturing ramps up and other vaccines are developed. Bottom line is that we may have help from vaccines by this fall, but I’d put a lot more on antibody treatments being available and highly successful.

At this point what I think I’ve established is that by September our ability to treat patients who come down with Covid-19 will be tremendously improved. Survival rates should be higher. Concerns about running out of resource should be greatly reduced. We may even be able to protect healthcare workers and vulnerable populations from becoming infected. But what about the non-medical response to managing the fall outbreak?

Lack of testing has been the bogeyman of the entire coronavirus outbreak. I was a skeptic about the value of having more testing when we (a) had no treatments and (b) the tests took days to yield a result. But you can see in the news pretty much every day a massive expansion in test availability, and in particular rapid point of care testing.  By September we should expect wide availability of testing that allows us to to discover within a few minutes if someone is currently sick or if they have antibodies. Tools will also be available for contact tracing, though I suspect there will be significant resistance to using the more automated mechanisms like cell phones, for this. In any case, this will allow the use of narrowly targeted measures to stem the disease (i.e., isolating only specific individuals, or temporary closures of specific business locations).

Combine all this with what is sure to be continuing voluntary social distancing, ongoing efforts to reduce the density of human gatherings, and generally heightened use of infection control tools, and the fall outbreak should be far less scary or impactful than the winter/spring one has been.

Could I be totally completely wrong? Of course. Not only is this not my area of expertise, which adds more uncertainty to everything I’ve said, but its actually possible that every drug and treatment currently being tested will ultimately fail. And we are already so fatigued of “stay-at-home” that by September “authorities” won’t be able to convince enough of us to go back into it, nor will they be able to sufficiently enforce a stay-at-home order, sending us right back into March madness. But I’m going to stay positive and keep to my message, Fall Covid-19 will be nothing like Winter/Spring Covid-19.