By Edward Hu, MD

As physicians, we were all pretty good test-takers in school. As this country prepares for its COVID-19 future, the health and economic future of our country will depend on the same concept – preparing for the test – or in this case, preparing to test large numbers of people for COVID-19.

Until an effective vaccine is developed, SARS-CoV-2 (the virus that causes COVID-19) will continue to circulate around the world. The best estimates are that sufficient quantities of an effective vaccine are still 12-18 months away. Until that (hopefully) happens, what are our best hopes for living with the virus among us?

Personally, I’m not holding out for any wonder drug to be found to treat those with COVID-19. If a drug -such as hydroxychloroquine, remdesivir, or favipirarir – could decrease deaths or mechanical ventilation by 50% compared with placebo, we’d already know about it. Trials would already be stopped at interim analyses and heralded across the world. Some drugs may end up showing benefit in randomized controlled studies, but they are unlikely to demonstrate miraculous efficacy. Two therapies whose trials are understandably delayed – convalescent plasma from COVID-19 survivors and monoclonal antibodies to SARS-CoV-2 – may hold more promise than the other drug trials, but scalability (and cost) will prevent these therapies from being available for the foreseeable future to all but the sickest COVID-19 patients.

As I write this, states such as New York and Washington are either at or just past their inflection points in terms of COVID-19 cases and deaths. Most other states will reach their inflection in the next week or two. The widely publicized IHME models from the University of Washington are predicting COVID-19 to largely dissipate with continued social distancing through the end of May. It is worth noting that many other models exist, and not all portray as desirable a scenario for the next few months. However, if we assume that IHME is correct, hospitalizations and deaths from COVID-19 will largely dissipate by June 1. IHME is predicting approximately 60,000 cumulative deaths in the US by June 1. How many Americans will have been exposed to COVID-19 by then? We know the number is far greater than the number of confirmed cases, due to asymptomatic infection and the abandonment of testing, isolation, and contact tracing strategies once community spread occurs. Simply put, most people with symptoms are no longer being tested for COVID-19 unless management would change based on the result.

So, to estimate the number of exposed Americans by June 1, if we figure a mortality rate of 1-2% as has been widely reported, that means that 3-6 million Americans will have been exposed and presumably have immunity from COVID-19, for a least some period of time. That’s only 1-2% of the US population. Not even close to the minimum threshold of about 40% needed to even think about herd immunity. Though identifying this 1-2% of the population is valuable, as these individuals are essentially immunized absent significant mutation of the virus, the fact that 98% of Americans will not have been exposed essentially gives us only a mulligan once community spread ends, if it ends, in a few months.

So where does that leave us? Looking at the successes of South Korea, Taiwan, and China in slowing community transition, it is clear that our ability to test large, even massive numbers of people for SARS-CoV-2, will have to be the cornerstone to the US strategy to combat COVID-19 until a vaccine is available. This is not the time to dwell on the early failures of US testing for COVID-19, but it is absolutely the time to determine how to ramp up our ability to test massive numbers of people. Without widespread testing, the only workable strategy of testing, isolation, and contact tracing will fail, and we will be in another repeat wave of March and April all over again. Our communities still have a dearth of testing swabs and reagents for SARS-CoV-2 today, and this is a problem must be solved before social distancing policies can be relaxed. Nobel prize winning economist Paul Romer has estimated that 20-30 million COVID-19 tests a day will be needed to prevent a resurgence of COVID later this year. I don’t know if that is the right number or not, but considering that only about 2 million tests have been performed to date in the US, it is clear that our testing infrastructure needs to get a whole lot better, and fast.

Another consideration with testing is that our tests are not perfect. One manufacturer, Abbott Labs, has estimated a sensitivity of 95% and a specificity of near 100% for its polymerase chain reaction (PCR) test. However, real world sampling and transportation difficulties undoubtedly decrease the sensitivity of our testing. Dr. Harlan Krumholz, a noted Yale epidemiologist and clinical researcher, has estimated that the “false negative” rate in patients truly infected may actually be 30% or higher.

All this leads back to being able to perform massive numbers of COVID-19 tests, if we are to be successful in the US. It also means that we need to have a healthy suspicion to retest, or even retest again, when clinical suspicion of COVID-19 is high. As physicians, we need to understand the value as well as the limitations of COVID-19 testing, because no longer are we preparing for our own MCAT or USMLE tests, but rather a much more important one with national and worldwide consequences should we fail.