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Jan. 24 marks the one-year 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 never developed symptoms. This early confirmation of asymptomatic infection should have set off alarm bells and profoundly altered our response to the gathering storm. But it did not. One year later we are still paying the price for this catastrophic blunder.

At least one of three people infected with SARS-CoV-2, the virus that causes Covid-19, do not develop symptoms. That’s the conclusion of a review we just published in the Annals of Internal Medicine. It summarizes the results of 61 studies with more than 1.8 million people.

But during much of the pandemic, fierce resistance — and even outright denialism — in acknowledging this not-so-typical disease pattern led to ineffective testing practices that allowed the pandemic to spin out of control.

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On Jan. 28, 2020, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said, “In all the history of respiratory-borne viruses of any type, asymptomatic transmission has never been the driver of outbreaks. … Even if there’s a rare asymptomatic person that might transmit, an epidemic is not driven by asymptomatic carriers.”

This was a widely held view. On June 8, 2020, a senior official of the World Health Organization called asymptomatic transmission “very rare.”

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To his credit, Fauci was among those who immediately criticized this remark. Based on epidemiological data that had become available since his earlier comments, he said it was “not correct” to characterize asymptomatic transmission as rare.

In June, when we published a report of 16 cohorts with sizable proportions of asymptomatic infection and suggested that it might play a role in the progression of the pandemic, several researchers wrote letters to the editor demanding that our paper be retracted.

Today, the best evidence suggests that about half of Covid-19 cases are caused by infected people who do not have symptoms when they pass on the virus. These symptom-free spreaders are roughly divided between those who later develop symptoms, known as 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 illnesses. More than 90% of people infected with poliovirus have no symptoms. And about 75% of influenza infections have been estimated to be asymptomatic. Yet these important precedents have largely been ignored.

Asymptomatic coronavirus infection is not necessarily benign. Several studies have reported abnormal lung scans in those infected without symptoms, as well as myocarditis, a type of heart inflammation. The long-term health implications of asymptomatic infection aren’t known.

Even though knowledge about asymptomatic infection has greatly evolved, tactics for combating the pandemic have not. It is now obvious that testing only those with symptoms, as was common early in the pandemic, is a mistake because it ignores the invisible legions of infected people who have no symptoms. But it is not enough to merely increase the number of tests. The problem is that current testing practices are ill-suited to detecting and containing asymptomatic infection.

Virtually all of the coronavirus testing performed in the U.S. looks for the genetic material of the virus using the polymerase chain reaction (PCR). It requires expensive equipment and trained technicians. Results are typically returned days — sometimes even weeks — after the test. That means people learn they have been infected with SARS-CoV-2 long after they may have passed the virus to others. Testing becomes more about accounting — tallying the number of detected infections — than about containing the spread of the virus.

What’s needed is a pivot to a different type of testing. Antigen tests, which look for a bit of coronavirus protein, cost just a few dollars each and can yield results in minutes. Like home pregnancy tests, they require minimal instruction. Antigen tests are ideal for spotting people who are infectious, rather than those who may be long past the infectious phase of Covid-19, or who harbor such low levels of the virus that they are unlikely to infect others.

Inexpensive rapid home tests would help infected people isolate themselves before they could spread the virus. Frequent testing — at least several times per week — is essential, as demonstrated by successful testing efforts at some universities, which have enabled students to return to campus. A new focus on self testing, in combination with financial assistance and perhaps even temporary housing for isolation, would directly address the problem of asymptomatic infection.

The rollout of Covid-19 vaccines brings with it the risk of a new wave of asymptomatic infections. The two vaccines authorized by the Food and Drug Administration have been proven to prevent illness, but not asymptomatic infection. Even after vaccination, the coronavirus may still temporarily take up residence in the lining of the respiratory tract, making it possible to infect others. Preliminary results from one vaccine trial seem 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 return to Jan. 24, 2020, and make the plans we should have made, which would have acknowledged the importance of asymptomatic infection. But it is not too late to recognize the blunder and move aggressively toward testing practices that will help end the pandemic.

Daniel P. Oran is a member of the digital medicine group at Scripps Research Translational Institute, of which Eric J. Topol is founder and director.

  • The ignorant media blamed Trump for the virus in the beginning like when Biden is inaugurated the virus will disappear , their ignorance is glaring for sure

    • Trump isn’t responsible for the virus. He is responsible for public acceptance of misinformation (“99.9% harmless … affects virtually no one”), discrediting disease experts, and encouraging millions of Americans to follow his example of ignoring mitigation measures – especially mask wearing. Whatever one’s opinion of Trump, his legacy is one of disease and death. The man has much blood on hs hands.

  • The study used in this story was an analytic study based on assumptions not facts. You can come to any conclusion you want by manipulating the baseline assumptions. In my opinion this study and this article is useless. Actual case tracking has shown that asymptomatic transmission is rare. In fact, the majority of infected people never infect another person. The vast majority of infections come from “super spreaders.” I don’t have sources to quote at my fingertips so you’ll have to Google it yourself and you’ll see that I am correct. The conclusion to the real studies is: avoid extended time indoors with multiple persons.

    • While it is true that most people spread the virus to no one, it is also misleading. Most “super spreaders” are asymptomatic at the time of spread.

      And the virus will never go away. Once the vaccines are made and distributed to everyone, serious illness and death from COVID will drop to much lower levels, but the virus will become another common cold.

  • As scientists both my wife and myself have advocated the need for a most aggressive testing regime to be implemented. It is so long overdue. Testing at home for the presence of antibodies would provide the Government with an actual read on the prevalence of the disease with little strain on professionals and front line workers. Testing at home for Antigens would similarly take away the need to rush to professionals when an infection that might only be a common cold sets in. As yet MRHA has acted slowly to approve home testing kits. It is critical we now put this in place. Thanks for the article a very good read!

  • The problem with current tests also stems from the fact that depending upon the initial viral load, it may take a variable time before the variable number of PCR cycles is necessary to yield a positive test. Thus it seems that depending upon viral load the number of days that might elapse after iinfection before abecame positive could theoretically be from 1 to 14 days. I believe that I read that the 5th cay after symptoms appear may be the date on which an infected person is most likely to have a positive test. This article does not talk about the specificity and sensitivity of rapid Covid-19 antigen tests. Very sensitive tests tend to have higher numbers of false positives and lower numbers of false negative such that a NEGATIVE test tends to rule the disease OUT. In contrast highly specific tests tend to have lower numbers of false positives and higher numbers of false negatives such that a POSITIVE test result tend to rule the disease in. And then one needs to know the estimated pretest possibility that persons in a tested population has the disease. Tests that are highly sensitive tend to be less specific and vice versa. A perfect test would be 100% sensitive and 100% specific. And if the pre-test probability that a person has the disease is very high or very low, the utility of testing strategies is diminished in the ability to increase substantially the post test likelihood as compared with the pretest likelyhood that a person has or does not have the disease. So what are the sensitivities and specificities of the rapid antigen test that the authors suggest?

  • Sorry but the experiences of country’s who have had widespread and effective testing alongside contact tracing and isolation of positive symptomatic cases argues against this.

    Australia, NZ, Taiwan, Thailand, Vietnam, China, Singapore etc have all managed to keep COVID-19 either near eradicated or extremely low in the community by testing symptomatic cases aggressively, isolating them, then contact tracing them and testing these people.

    If asymptomatic as opposed to pre-symptomatic spread was as widespread as suggested these approaches would not be effective enough to rapidly being outbreaks under control.

  • This is speculative. Your study link that half of infections(johannson) are asymptotic is garbage and should be retracted. This study used other studies for its conclusion. The fundamental data from these studies did not agree with what (Johannson) study concluded. You should retract this article.

  • I see that asymptomatic and presymptomatic spread is taken as a given in this article. Can someone point me to studies that prove this? I’ve only seen one, a presymptomatic that likely turned symptomatic on a 16 hour plane flight. Others I’ve read simply are models and don’t prove anything. With all the contact tracing there has to be some real hard scientific data right? Something that has overwhelming indisputable evidence?

    • Honestly, it is hard to know at this point… it seems like one can find support in the literature for most claims these days. Acknowledging my personal bias, which is that asymptomatic spread is unlikely to be a major source of transmission, here are two recent papers from reputable peer-reviewed journals that, in my reading, support my bias:

      https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2774102
      (large meta-analysis showing only about 0.7% of cases of secondary spread within households are attributable to asymptomatic spread)

      https://www.nature.com/articles/s41467-020-19802-w
      (pcr and contact-tracing study on 10M people in Wuhan, claiming that not a single asymptomatic patient produced positive virus cultures, and that contact tracing of over 1,100 close contacts of asymptomatic/re-positive cases showed zero positive cases)

  • It was easily deduced that the rate of spread was too rapid to be wholly by intentional transmission by those who were sick and inconsiderate. The human race is not so unempathetic.

    • Pre-2020 the assuming and deducing by nearly all scientists was that viruses were not spread by non-symptomatics. I have yet to see compelling evidence to the contrary. Not saying it doesn’t exist but genuinely want to see the evidence if it does exist.

  • Claiming that the results from a simulation study (https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2774707) prove asymptomatic spread as a major source of infections from SARS-COV2 is not only disingenuous, it is ignoring a sizable body of literature to the contrary. For two of the more recent examples, please see:

    (1) https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2774102 a meta-analysis of 54 studies comprising >77K people, in which it was found that only 0.7% of secondary infections in households resulted from asymptomatic spread

    (2) https://www.nature.com/articles/s41467-020-19802-w the massive Wuhan PCR study on millions of people, in which they failed to obtained cultured virus from even a single asymptomatic positive case, and found that 0 out of more than 1,100 close contacts of those 330 asymptomatic positive cases tested positive.

    Perhaps your perspective has been biased by something else?

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