• Josh Schiffer

Lower the death rate

Tomorrow, I will return to posting key new articles and trying to provide context. Today I am doing something different and posting a position piece. I have been thinking about the pandemic non-stop for the last 6 weeks, and am increasingly focused on what should be done, right now, to lessen our burden, and to get things somewhat back to quasi-normal within 3-6 months. I was once told by a mentor to learn the viruses’ rules and play by them. Below is my idea.

I really want this to end up on an opinion page and to have some influence because as I describe below, I am increasingly convinced that we are missing a golden opportunity. So if you find this compelling, then please share broadly.

Again, thanks for reading. I would really value any commentary, critical or supportive.

Lower the death rate

The SARS CoV-2 epidemic represents the greatest public health emergency of the last century. While still in its infancy, it has killed over 8800 people, brought several major countries to the brink of collapse, completely shut down global cultural and athletic events, and disrupted the daily routine of a majority of people on the planet. Left unchecked, COVID-19 will destroy health care systems, kill millions and potentially unravel societies.

The virus is a cunning foe. It is often transmitted during the pre-symptomatic phase which allows it to silently navigate its way through the population before ultimately inflicting its most lethal effects on the elderly and chronically ill. Experience throughout Asia demonstrates that massive physical distancing can temporarily stop local spread. Mathematical models suggest that the slightly less draconian mitigation efforts currently being implemented in the US and Europe may partially save hospitals from unmanageable surges in critically ill patients. This approach has led to the first great slogan of the pandemic: flatten the curve.

Unfortunately, this solution is not sustainable. Too many jobs rely on leaving home and connecting with other people. The global supply chain is too interconnected to maintain our current level of isolation for more than a few months. Yet, modeling from the Imperial College of London suggests that relaxation of physical distancing will inevitably result in renewed, rapid, deadly outbreaks. The only long-term solution is a vaccine which could take 18 months or longer to develop, test and manufacture. Thus, we are left to navigate an impossible tight-rope between two untenable options, with no end in sight.

Thankfully, there is another strategy at our disposal: lower the death rate. While multiple vaccines are being developed and tested, there is currently no known effective vaccine. Yet, as I write, there are several known compounds which have the capability to make the virus stop replicating in cells and in animals. It is imperative that these drugs are tested and compared in humans as quickly as possible, but also that they are targeted towards the right population.

COVID-19 has an Achilles heel. The duration between time of first symptoms and severe illness is almost a week, as opposed to influenza or bacterial sepsis which are sometimes fatal less than a day or two after symptoms develop. The optimal time to cripple SARS CoV-2 is early during this first week. To nobody’s surprise, a majority of studies that have been conducted on other acute, life-threatening infections, demonstrate that early treatment is more effective. Much like managing an epidemic is more challenging when a city has 10000 cases rather than 10, managing a lung infection is far more difficult when the entire tissue is overrun with virus, rather than just a small portion.

Yet, we are missing this opportunity. A majority of current trials testing antiviral medications are only enrolling people sick enough to require hospitalization. Most participants in these studies have been ill for a week and already developed pneumonia. Some are critically ill. While it is noble to target research towards our sickest patients, it would be highly regrettable to not also conduct trials that have the highest likelihood of success, and of saving the most people.

Another benefit of treating infected people as soon as they develop symptoms is that they may subsequently shed less virus and therefore transmit less efficiently. The concept of decreasing transmission probability with antiviral medicines is proven for several viruses, most notably HIV. For COVID-19, this may not be enough to quell a local epidemic but could still indirectly save many lives. For those who were not destined to develop severe illness, antiviral therapy also has the potential to limit duration of symptoms and missed days of work.

The first priority to establish an early treatment approach is properly done clinical trials. Had we been using our time valuably during the first two months of the Wuhan epidemic, multiple outpatient trials of various promising agents would already be enrolling in the US with results pending in a few weeks. At present, to my knowledge, none exist. Funders, manufacturers and researchers should rapidly prioritize studies that target outpatients infected with SARS CoV-2 who may later develop significant illness or transmit to others.

Structural barriers to early treatment studies must be rapidly addressed. One urgent need is rapid and widely available testing. The Bill and Melinda Gates foundation is funding home testing for SARS CoV-2 with kits delivered by mail. Home testing and at local pharmacies, should rapidly become the national standard for diagnosis, particularly in the elderly who may be less mobile overall. Both in test of concept clinical trials, and in real world scenarios, treatment should be available within hours of diagnosis, again preferably with delivery by mail.

When I mention this idea to colleagues, they list many reasons that these plans cannot be easily implemented in our country. The inefficiencies are too great, the arcane rules too many. Today, I spoke with a friend who spent 5 hours consenting a single infected patient into a treatment study! In this time of national emergency, artificial and cumbersome bureaucratic hurdles and inefficiencies must be eliminated. We must take a wartime approach. These crucial studies must be rapidly drafted, approved and executed, and then converted into a new paradigm of routine practice.

The early stages of the HIV epidemic offer a clear precedent for bypassing traditional barriers to rapid study and licensure of promising agents. In the face of an unimaginable crisis, the gay community lobbied for a faster and leaner drug development process, thereby saving thousands of lives. Now is the time for a similar plan for COVID-19.

The current case mortality rate of COVID-19 in persons over the age of 70 is approximately 15%. The effects of decreasing this rate by half or perhaps much more would be transformative. Such an outcome is plausible with widespread implementation of an early and aggressive treatment strategy. SARS CoV-2 would still be more deadly than yearly influenza, but perhaps not so lethal that we are forced to suspend all travel, social events and schooling.

To survive this brutal first wave of the US epidemic, we must flatten the curve. To return to our regular lives over the next two years, we must diagnose early. We must treat early. Let us lower the hospitalization rate. Let us lower the death rate.

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