Getting a handle on asymptomatic SARS-CoV-2 infection

By Daniel P. Oran and Eric J. Topol, MD | September 22, 2020

Since human-to-human transmission of the SARS-CoV-2 virus was first confirmed in January 2020, the early identification and testing of individuals with symptoms of COVID-19 has been the primary focus of public health measures in virtually all locales affected by the pandemic. But over the last two months [1], it has become increasingly clear that a sizable proportion of individuals infected with SARS-CoV-2 do not, in fact, have any symptoms of COVID-19. This new knowledge has significant implications for the targeting and scale of our testing efforts.

For reasons that are not yet known, SARS-CoV-2 infection in certain individuals appears to cause no detectable illness. Presumably, though, because these individuals shed enough virus particles to trigger positive results in PCR testing, they may be capable of transmitting SARS-CoV-2 to others, an uncertain number of whom will develop COVID-19. Such cryptic transmission might explain the rapid spread of SARS-CoV-2 around the globe—and the grave challenge involved in containing the virus.

In the studies that we have summarized in the table, the range of infection rates is wide: from 0.76% for residents of Iceland to 36% for residents of a Boston homeless shelter. It is striking, however, that the proportion of individuals who test positive for SARS-CoV-2, but who have no symptoms of COVID-19, remains consistently high: from approximately 31% to 88%, with a mean of 56%. Because of various limitations in the summarized studies, this likely overstates the overall population mean, which some observers have suggested is around 40%.

It should be noted that the summarized studies are essentially convenience samples. They do not purport to depict anything more than the circumscribed populations from which data were collected. Large, well-designed studies with representative samples are desperately needed to accurately assess the prevalence of those who are infected with SARS-CoV-2, yet are asymptomatic for COVID-19—and to determine their impact on the pandemic.

The pressing need for far more SARS-CoV-2 testing has been apparent for quite some time. This new and accreting knowledge about the potential role of cryptic transmission in the pandemic, though, should lead us to broaden the target of testing. Instead of seeking to identify only those who are already ill, we may need to test a vast number of individuals in order to identify—and quarantine—the silent spreaders of SARS-CoV-2, who themselves will never develop COVID-19.

In the absence of a national SARS-CoV-2 testing enterprise of truly unprecedented scale, we risk proceeding blindly without crucial data, at our own peril.

Postscript. In the five months since we published this blog post on April 20 — and our subsequent review in the Annals of Internal Medicine on June 4 — a considerable amount of additional data has appeared on this topic, shedding more light on what had been only dimly illuminated last spring.

We have updated the table here, increasing the number of datasets to 33. Three of the new datasets include longitudinal data, allowing researchers to distinguish between individuals who are presymptomatic, i.e., go on to develop symptoms, and those who are truly asymptomatic, i.e., never develop symptoms.

We have also included fascinating new data from eight serosurveys. In contrast to the other listed studies, in which a current active SARS-CoV-2 infection is detected by a PCR test (typically from a nasopharyngeal swab), serological testing looks for SARS-CoV-2 antibodies in a blood sample. In this manner, researchers can determine who has previously been infected with SARS-CoV-2.

Notably, two of the serosurveys are large, nationwide, representative samples from England and Spain, including more than 170,000 people in total. It is remarkable that the proportion of asymptomatic infection was nearly identical in both countries: 32% in England and 33% in Spain.

REFERENCE [1] Bai Y, Yao L, Wei T, et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020;323(14):1406–1407. doi:10.1001/jama.2020.2565.

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