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A systematic review suggests that at least a third of SARS-CoV-2 infections occur in people who never develop symptoms, providing strong evidence for the prevalence of asymptomatic infections.
The finding that nearly one in three infected people remains symptom-free suggests that the tests should be changed, the researchers note.
“To reduce the transmission of people who are pre-symptomatic or asymptomatic, we need to shift our focus from testing to screening at home,” said lead author Daniel Oran, AM, Medscape Medical News. “Cheap rapid antigen tests, provided to millions of people for frequent use, can help us to significantly reduce the spread of the virus.”
The systematic review was published online on January 22 in Annals of Internal Medicine.
The findings come at a terrible time, when the official number of COVID-19 cases in the United States exceeds 25 million for the first time. Public health officials have raised concerns about more transmissible and possibly more deadly variants of SARS-CoV-2, while a new presidential administration is trying to meet the challenge of improving vaccine distribution and acceptance rates.
The results are also based on previous findings by the same research team – Oran and senior author Eric Topol, MD – who published a review article examining asymptomatic COVID-19 cases. Even though initial data was more limited, they also suggested that a broader scope of testing is warranted, pointing out that asymptomatic individuals can transmit SARS-CoV-2 for up to 14 days. Topol is also editor-in-chief of Medscape.
In the current systematic review, high-quality evidence comes from large studies in England and Spain. Nationally representative evidence included serological surveys of more than 365,000 people in England and more than 61,000 in Spain. When analyzed separately, approximately the same proportion of asymptomatic cases emerged: 32.4% in England and 33% in Spain.
“It was really remarkable to find that antibody testing studies across the country in England and Spain – including hundreds of thousands of people – produced almost identical results: about a third of SARS-CoV-2 infections were completely asymptomatic,” said Oran, a researcher at the Scripps Research Translational Institute in La Jolla, California.
The systematic review included 43 studies with PCR testing for active SARS-CoV-2 infection and another 18 with antibody results that indicated present or previous infection. The studies were published until November 17, 2020.
An appreciation for the asymptomatic transmission of SARS-CoV-2 infection has come a long way since initial rejections of its importance, Topol noted via Twitter. “When Dr. @Camilla_rothe reported an asymptomatic transmission a year ago, the @NEJM report was refuted and discredited. Later, she was named TIME 100 Person of the Year.”
8. When Dr @camilla_rothe reported an asymptomatic transmission a year ago, the @NEJM report was refuted and disparaged. She was later named a TIME 100 Person of the Yearhttps://t.co/vSgQsx1qj8 pic.twitter.com/keNVF2misD
— Eric Topol (@EricTopol) January 24, 2021
Not symptomatic vs never symptomatic
The term “asymptomatic” can be misleading because some people in this group progress to develop signs of infection. This “pre-symptomatic” group of patients is probably a minority, the authors note. Longitudinal studies indicate that about three quarters of people who are asymptomatic with SARS-CoV-2 remain that way.
Topol anticipated that a third of asymptomatic findings could generate some feedback on the distinction between asymptomatic and pre-symptomatic individuals. He tweeted: “Some will argue that there is a mixture with pre-symptomatic cases, but the review of all data supports this estimate as being conservative.”
5. Based on the totality of the data, we conclude that asymptomatic covid occurs in at least one-third of infections.
Some will argue that there is admixture with presymptomatic cases, but review of all the data supports this estimate as being a conservative one.— Eric Topol (@EricTopol) January 23, 2021
The heterogeneity of configurations, populations and other characteristics of the studies prevented the authors from performing a meta-analysis of the results.
Home is where the test is?
Based on their findings, Oran and Topol believe that “COVID-19’s control strategies should be changed, taking into account the prevalence and risk of transmission of asymptomatic SARS-CoV-2 infection,” they write. They suggest the frequent use of quick and inexpensive home tests to identify people who are asymptomatic or pre-symptomatic, along with government-provided programs and housing to offer financial assistance and allow this group of people to isolate themselves.
Further research is needed to determine whether and how well SARS-CoV-2 vaccines prevent asymptomatic infection.
Topol and Oran created a short video to highlight the findings of their systematic review.
The study was funded by a grant from the National Institutes of Health.
Ann Intern Med. Published online January 22, 2021. Full text
Damian McNamara it’s a staff Miami-based journalist. It covers a wide range of medical specialties, including infectious diseases, gastroenterology and intensive care. Follow Damian on Twitter: @MedReporter.
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