Issues & Insights

We’re Accumulating More Critical Information About The Coronavirus Every Day

With cases of the new coronavirus (officially SARS-CoV-2, and the illness it causes designated COVID-19) spreading, there is intense interest in what we know and what we can expect. Here’s a primer.

There are several factors that determine how damaging and worrisome outbreaks will be. The first is the degree of infectiousness, or ability to spread. Examples of the extremes are noroviruses, which can sweep rapidly through an institution or cruise ship, and the rabies virus, which is almost always transmitted to humans through the bite of a warm-blooded animal.

The second is virulence — the severity or degree of pathogenicity of the infection. Using the same two examples as above, norovirus infections cause severe nausea, vomiting, and diarrhea, but the symptoms are short-lived and almost never cause significant morbidity if treated symptomatically. Thus, although high in infectivity, they are low in virulence. By contrast, by affecting the brain, rabies gives rise to central nervous system symptoms and is almost always fatal once symptoms occur.

Not surprisingly, the most worrying events are a combination of high levels of both infectiousness and virulence. An example of that would be flu in a bad year — one in which the vaccines aren’t a good match for the viruses circulating in the population, which gives rise to high numbers of illnesses, hospitalizations, and deaths. This flu season in the Northern Hemisphere is looking like a pretty average one; the Centers for Disease Control and Prevention estimates that so far this season there have been at least 32 million flu illnesses, 310,000 hospitalizations and 18,000 deaths from flu. And those figures are in spite of pretty effective vaccines — again, about average, at 45%.

That brings us to the new virus, a member of the coronavirus group (seven of which are known to infect humans, and four of which cause common colds), that originated in Wuhan, China. What we would like to know, of course, is where on the spectrums of infectiousness and virulence this virus falls.

The short answer is that we don’t yet know definitively — but the situation is rapidly evolving, as more kits to test for the presence of the virus in body fluids become available and more testing is done.

We should expect that more testing will lead to more confirmed cases. Dr. Anthony Fauci, the articulate, veteran director of the National Institute of Allergy and Infectious Diseases, described at a press conference on Saturday how the efforts to prevent the spread — or “contain” the virus — would continue, but warned that we should expect the number of coronavirus cases in the U.S. to increase.

Fauci emphasized that the chance of becoming infected remains low and that the majority of those who contract the virus — 75% to 80% — will experience symptoms like a “bad flu or a cold.” The other 15% to 20%, he said, may need “advanced medical care.”

“For the most part, the people who get in trouble and ultimately tragically would die from this are people who are elderly and or have underlying conditions … heart disease, chronic lung disease, diabetes, obesity,” Fauci said.

Some of the “if it bleeds, it leads” media immediately jumped on the 15%-to-20% figure, multiplied it by the entire U.S. population of about 330 million, and concluded that we might need 50-60 million hospital beds, for which we are unprepared.

Not so fast.  

What Fauci didn’t explain, and the pundits didn’t know or didn’t care about, is that the 15%-to-20% figure is based on the official number of confirmed cases of COVID-19 in China, as reported by the country’s public health officials.

And that’s where an understanding of simple fractions comes in.

The 15%-to-20% figure is derived by taking the number of “serious” illnesses requiring advanced medical care, such as the administration of oxygen or hospitalization, and dividing it by the number of confirmed cases of infection. But here’s the rub: In China and elsewhere, there have undoubtedly been many — possibly very many — illnesses that were never confirmed, both because of a shortage of test kits and because people with asymptomatic or mild infections didn’t seek medical attention at all.

In other words, the true denominator of the fraction is higher than the official number of cases and, therefore, the 15%-to-20% figure is unquestionably an overestimate of how many people need “advanced medical care.”

A similar distortion occurs in estimates of the case fatality rate, the fraction of people who are infected and die. Estimates of the coronavirus death rate from Wuhan, China, the epicenter of the outbreak, have been around 2%. But again, we have the problem of the uncertain denominator, which includes only confirmed cases. The true denominator is unquestionably much larger, which would make the actual case fatality rate lower.

As Fauci and two colleagues put it in a just-published editorial in the New England Journal of Medicine:

If one assumes that the number of asymptomatic or minimally symptomatic cases is several times as high as the number of reported cases, the case fatality rate may be considerably less than 1%. This suggests that the overall clinical consequences of COVID-19 may ultimately be more akin to those of a severe seasonal influenza (which has a case fatality rate of approximately 0.1%) or a pandemic influenza (similar to those in 1957 and 1968) rather than a disease similar to SARS or MERS, which have had case fatality rates of 9% to 10% and 36%, respectively.

There’s yet another important angle in this saga. The test kits in use until now detect viral genetic material (RNA, in the case of coronaviruses), so once the patient has recovered and the virus has been cleared, the tests will be negative — in other words, another factor making the denominator appear lower than it actually is.

Additional, important critical information will come from tests for antibodies in blood — “serological tests” — which will tell us whether a person has been recently infected with SARS-CoV-2 and recovered. (Note that antibodies take about 10-14 days from exposure to the virus to appear.) An experimental serological test is already being used in Singapore, and research groups elsewhere are hurriedly developing them.

The purpose of this somewhat pedantic discussion is not to minimize the significance of the new coronavirus, but rather to put into perspective some of the media’s misinterpretation of data and warnings of apocalypse. 

In the face of limited information, U.S. public health officials are currently taking appropriate actions to prevent outbreaks from expanding, including isolation of patients and contacts, in order to prevent cascades of infections. However, community spread could require a shift from containment to mitigation. Social distancing strategies in order to reduce transmission could include isolating ill persons (including voluntary isolation at home), school closures, and telecommuting where possible.

None of us likes uncertainty, but we are becoming more knowledgeable every day.

Miller, a physician and molecular biologist, a senior fellow at the Pacific Research Institute. He was the founding director of the FDA’s Office of Biotechnology and formerly did research on the influenza virus.

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1 comment

  • A very level headed description of Covid-19, however, the author neglected to mention that the estimated mortality rate could be lower than actual if institutions have not properly diagnosed those who have died and instead reported cause of death as “viral pneumonia” or other.

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