COVID-19: Reasons for Optimism

First, like many of you, I’m flooded with information and news about COVID-19 and for the record, I’m worried, very worried. There’s a myriad of reasons to be concerned, ranging from the pathogenicity and transmissibility of SARS-CoV-2 - the R0 (R "naught") is estimated to be in the range of 1.4-5.5 and the case fatality rate (CFR) rate in the range of 0.25%–3.0% - to hospitals potentially being overrun and needing to triage and prioritize who among the sick will get ventilators, not to mention the socio-economic impact of the disease which is getting worse by the day (and will have far reaching and long lasting consequences).

Just this morning, California Governor Gavin Newsom ordered all Californians to stay home and indicated the state is projecting 25.5 million people in California will be infected over an eight-week period (currently 19 people have died and at least 1,000 have tested positive for the disease). As of this writing, there have been 247,400 total confirmed cases, 10,067 deaths, and 86,037 recoveries globally.

All of that said, I’d like to pause for a minute and acknowledge the incredible pace, urgency, and collaborative efforts that are happening on a global basis to combat the pandemic. For example, just 60 days after the genetic sequence of COVID-19 was shared by China, the first vaccine trials began, a truly “incredible achievement” according to the UN World Health Organization (WHO) Director-General Tedros Adhanom Ghebreyesus.

China is already conducting over 200 trials for new agents to treat COVID-19 and there are another 90 in the U.S, with a combined 50+ drugs and vaccines now being tested (some drugs have multiple ongoing trials). Furthermore, the WHO recently announced a large, international study designed to "generate the robust data we need to show which treatments are the most effective,” what they are calling the SOLIDARITY trial.”

The speed at which drugs have moved into clinical trials - in some cases in as little as 3 months - is frankly astonishing. This type of rapid advancement into first-in-human trials has never happened before. Companies such as Gilead, Moderna, CureVac, BioNTech, Inovio, Janssen, and dozens of others have mobilized their resources and R&D efforts to prioritize finding a vaccine and treatments.

Chloroquine - which is currently approved to treat malaria, lupus, and rheumatoid arthritis - and Gilead’s remdesivir - which was originally developed to treat Ebola - are both being used under emergency authorization to treat people infected with SARS-CoV-2 (under what’s known as compassionate use). There are multiple ongoing studies to determine if chloroquine can reduce the duration of symptoms in mild-to-moderate infections as well as cut down on viral shedding. Remdesivir is now being repurposed and is being tested in a Phase 3 clinical trial.

Regeneron initiated a randomized, controlled trial of sarilumab, which is an interleukin-6 (IL-6) receptor inhibitor that has the potential to reduce lung inflammation and slow progression of the infection. Earlier this week the NIH announced the launch of a Phase 1 clinical trial in Seattle, studying 45 healthy adults with the investigational vaccine candidate mRNA-1273 from Moderna. mRNA-1273 uses a segment of the virus' genetic code rather than a piece of the virus, which may make it faster to develop.

As a quick aside, there are two critical pieces to understand with respect to the potential impact of many of the treatments being developed: vaccines vs. anti-virals. Vaccines are for prevention while anti-virals are for treating patients who already have the virus. Anti-virals (a) will be much faster to market since the required trial sizes will be much smaller (you’re testing the treatment in patients looking for a big effect rather than in healthy individuals looking for a small effect); (b) you'll know in days whether or not an anti-viral drug is working rather than having to wait for months to determine if a vaccine is working; (c) the endpoint of anti-viral trials is easier to measure since you're looking at viral load rather than immunity or safety; and (d) many of the anti-viral trials are repurposing existing drugs, so safety has already been established (Source: Safi Bachall On COVID-19).

There’s no question we collectively have a long, long way to go and significant personal and societal pain lies ahead (both from a health and economic standpoint), but among the chaos I find a myriad of reasons to be, dare I say, optimistic that we'll find a way to conquer this devastating pandemic (History in a Crisis — Lessons for Covid-19).

-NL