As the United States ramps up rapid testing for the coronavirus, the results will surely show a sharp uptick in the number of cases of coronavirus-caused COVID-19. Those tested will learn whether they are infected, but, paradoxically, the public – and public health officials – will not know whether the overall results are encouraging or discouraging, because the rates of the coronavirus infectivity and mortality will remain poorly understood. The existing tests will not identify the potentially large numbers of people who were infected but didn’t seek medical attention, were never tested, and then recovered.
We also need to know how the coronavirus statistics are changing as governments take various actions to mitigate the spread of infections. Washington Post reporter Harry Stevens has created graphics that show clearly how assumptions about the disease and various public health interventions can “flatten the curve” to slow the spread of the disease.
But we need a deeper dive for more comprehensive information, such as what the curves look like for the asymptomatic, mildly ill, critically ill, and the fatalities. The differences among the rates for these groups would offer public health officials important guidance on the benefits of specific mitigation efforts.
Using crude estimates of infectivity and mortality available at the time, in February the Centers for Disease Control and Prevention considered various possible scenarios for how the outbreak would progress, based on characteristics of the virus, including estimates of its infectiousness and the severity of the illness it caused. The “worst case” was chilling, indeed, with the possibility of more than 200 million Americans infected, 2.4 million to 21 million possibly requiring hospitalization, and as many as 200,000 to 1.7 million dying. This scenario was worse than the 1918 Spanish flu pandemic, which killed at least 50 million people worldwide and 675,000 in the United States alone. Some 500 million people, or one-third of the world’s population, became infected with the virus.
The CDC’s worst-case scenario would crush the nation’s medical system, which has only about 925,000 staffed hospital beds, with less than a 10th of those for the critically ill. But worst-case scenarios are, by definition, intended to depict the extreme, not taking into consideration mitigation strategies.
Patient testing alone with the available tests will not provide the answers the public and the government need to calm anxiety and provide direction for informed government action. As University of Southern California professor Neeraj Sood explained, if we test only those who needed to be hospitalized with the coronavirus, the result will be an overestimate of infectivity, virulence, and mortality rates. In contrast, broad testing of the population, in addition to offering diagnosis of an individual’s disease, can provide the kinds of answers that can quell fear and anxiety.
First, it can provide accurate information on the coronavirus’ infectivity and mortality rates, which require an accurate denominator. Second, population testing can avert spread by allowing isolation of those who are infected but asymptomatic.
Population testing will reveal other information essential to the management of the pandemic. For example, how many people of different ages, sex, ethnicities, and other demographic characteristics in a particular population become infected with the coronavirus? How many remain asymptomatic, and how many have symptoms? And of those with symptoms, how many cases are mild, flu-like, require hospitalization, or are fatal?
Analysis of those test results will also offer critical information about important characteristics of this particular virus: how readily it is transmitted from person to person, and how many people an infected person will subsequently infect, the length of the incubation period, the usual course of the disease, and how long post-infection immunity to infection persists.
Only with that granular level of detail can public health experts most effectively advise on the appropriate methods to control and predict the spread of the epidemic and manage the available health care resources.
However, the coronavirus test kits currently available in the U.S. can provide only part of the puzzle. They detect only viral genomic RNA, either intact or fragmented. Thus, in ascertaining the proportion of the population that has had any degree of infection (asymptomatic, mild, or more serious), post-recovery testing will yield “false negatives” because the body clears the RNA soon after recovery.
Additional essential information about the coronavirus and the COVID-19 disease profiles will need to come from different “serological tests” that measure anti-coronavirus antibodies in the blood. These will reveal whether a person has been infected with the coronavirus and recovered. Serological tests (which become and remain positive approximately 10-14 days after exposure) are currently being used in Singapore and China, and two, which are apparently at an advanced stage of development, are being developed by the U.S. CDC.
The percentage of the population that has been infected – and, therefore, has developed antibodies to the virus – is a critical factor in determining the likely course of the epidemic and the best approaches to managing it.
The U.S. government was slow and inept at developing and distributing coronavirus tests, which wasted valuable time and delayed effective disease prevention and treatment. Federal agencies should avoid another missed opportunity by aggressively conducting population studies with both testing for viral RNA and serological testing for antibodies. That will enable us to better understand the epidemiological characteristics of COVID-19, slow its spread, and flatten the curve. And to figure out when we can safely roll back restrictions on Americans’ movements and activities.
Cohrssen, an attorney and statistician, served in senior positions for White House agencies, including the office of the vice president. He also was minority staff director of the Aging Subcommittee of the Senate Committee on Health, Education, Labor, and Pensions, and counsel for the House Committee on Energy and Commerce. Miller, a physician and molecular biologist, is a senior fellow at the Pacific Research Institute. He was the founding director of the FDA’s Office of Biotechnology.
Thank you for this excellent piece, particularly the explanations of differences between testing for viral material versus human antibodies. If someone was infected during the holiday travel season and didn’t realize it, for example, then the body has by now eliminated all viral remnants. This person will test negative for viral RNA but would likely test positive for serum antibodies. So many January-early February mild infections may go undetected using the RNA test kits. The epidemiology is more complicated that most of us appreciate. I’m glad we have detectives like these authors on the case.