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Ja. 24 marks the first anniversary of a momentous but largely unnoticed event in the history of the Covid-19 pandemic: the first published report of an individual infected with the novel coronavirus who has never developed symptoms. This early confirmation of asymptomatic infection should have triggered the alarm bells and profoundly altered our response to the growing storm. But it was not. A year later, we are still paying the price for this catastrophic mistake.
At least one of three people infected with SARS-CoV-2, the virus that causes Covid-19, does not develop symptoms. This is the conclusion of a review that we have just published in the Annals of Internal Medicine. It summarizes the results of 61 studies involving more than 1.8 million people.
But during much of the pandemic, fierce resistance – and even outright denial – to recognizing this not-so-typical disease pattern led to ineffective testing practices that allowed the pandemic to spiral out of control.
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On January 28, 2020, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said: “In the history of respiratory viruses of all types, asymptomatic transmission has never been the cause of epidemics. … Even if there is a rare asymptomatic person who could transmit, an outbreak is not caused by asymptomatic carriers.
It was a widely held opinion. On June 8, 2020, a senior official at the World Health Organization called asymptomatic transmission “very rare.”
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To his credit, Fauci was among those who immediately criticized the remark. Based on epidemiological data that had become available since his previous comments, he said it was “not correct” to characterize asymptomatic transmission as rare.
In June, when we published a report of 16 cohorts with significant proportions of asymptomatic infection and suggested that it could play a role in the progression of the pandemic, several researchers wrote letters to the editor requesting that our article be withdrawn.
Today, the best evidence suggests that about half of Covid-19 cases are caused by infected people who do not show symptoms when transmitting the virus. These symptomless spreaders are roughly split between those who later develop symptoms, called pre-symptomatic individuals, and those who never develop symptoms.
While the importance of asymptomatic infection in understanding Covid-19 has been surprising to some, infectious disease experts have long known that infection without symptoms is common in many diseases. More than 90% of people infected with poliovirus have no symptoms. And about 75% of influenza infections were estimated to be asymptomatic. Yet these important precedents have been largely ignored.
An asymptomatic coronavirus infection does not have to be mild. Several studies have reported abnormal lung scans in infected people without symptoms, as well as myocarditis, a type of inflammation of the heart. The long-term health implications of asymptomatic infection are not known.
Although knowledge about asymptomatic infection has evolved a lot, the tactics to fight the pandemic have not. It is now evident that testing only people with symptoms, as was common at the start of the pandemic, is a mistake because it ignores the invisible legions of infected people who do not have any symptoms. But it is not enough to simply increase the number of tests. The problem is that current screening practices are ill-suited to detect and contain asymptomatic infection.
Virtually all coronavirus tests done in the United States look for the genetic material of the virus using the polymerase chain reaction (PCR). It requires expensive equipment and skilled technicians. Results are usually returned days – sometimes even weeks – after the test. This means that people find out they have been infected with SARS-CoV-2 long after they have passed the virus on to others. Testing becomes more about bookkeeping – counting the number of infections found – than containing the spread of the virus.
What is needed is a pivot to another type of test. Antigen tests, which look for a bit of coronavirus protein, cost just a few dollars each and can give results within minutes. Like home pregnancy tests, they require minimal instruction. Antigen tests are ideal for detecting infectious people, rather than those who are long past the infectious phase of Covid-19, or who harbor levels of the virus so low that they are unlikely to infect others.
Inexpensive rapid home tests would help those infected to isolate themselves before they can spread the virus. Frequent testing – at least several times a week – is essential, as demonstrated by successful testing efforts at some universities, which have allowed students to return to campus. A new emphasis on self-testing, in combination with financial assistance and perhaps even temporary accommodation for isolation, would directly address the problem of asymptomatic infections.
The deployment of Covid-19 vaccines carries the risk of a new wave of asymptomatic infections. The two vaccines approved by the Food and Drug Administration have been shown to prevent disease, but not asymptomatic infection. Even after vaccination, the coronavirus can still temporarily settle in the lining of the airways, allowing others to be infected. Preliminary results from a vaccine trial appear encouraging, with an apparent two-thirds reduction in asymptomatic infection after the first dose. But many other studies are underway.
There is no time machine that would allow us to go back to January 24, 2020 and make the plans we should have made, which would have recognized the importance of asymptomatic infection. But it’s not too late to recognize the blunder and aggressively move on to testing practices that will help end the pandemic.
Daniel P. Oran is a member of the digital medicine group of the Scripps Research Translational Institute, of which Eric J. Topol is the founder and director.
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