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A systematic review suggests that at least one 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 people infected remains symptom-free suggests that testing needs to be changed, the researchers note.
“To reduce transmission of presymptomatic or asymptomatic people, we need to shift our testing focus to at-home screening,” lead author Daniel Oran, AM, told me. Medscape Medical News. “Low-cost rapid antigen tests, offered to millions of people for frequent use, can help us significantly reduce the spread of the virus.”
The systematic review was published online January 22 Annals of Internal Medicine.
The findings come at a dire time when the official number of COVID-19 cases in the United States first exceeds 25 million. Public health officials have raised concerns about more transmissible and potentially deadly variants of SARS-CoV-2 as a new presidential government seeks to address the challenge of improving vaccine distribution and acceptance.
The results also build on previous findings from the same research team – Oran and senior author Eric Topol, MD – who published a review article on asymptomatic COVID-19 cases. While the initial data were more limited, they also suggested that a broader test scope is warranted, noting 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, the highest quality evidence comes from large studies in England and Spain. The nationally representative evidence included serological examinations of more than 365,000 people in England and more than 61,000 in Spain. Separate analysis revealed about the same percentage of asymptomatic cases: 32.4% in England and 33% in Spain.
“It was really remarkable to find that nationwide antibody testing studies in England and Spain – including hundreds of thousands of people – yielded almost identical results: about a third of SARS-CoV-2 infections were completely asymptomatic,” said Oran, a researcher. at Scripps Research Translational Institute in La Jolla, California.
The systematic review included 43 studies with PCR assays for active SARS-CoV-2 infection and an additional 18 with antibody results indicating current or previous infection. The studies are published until November 17, 2020.
An appreciation for asymptomatic transmission of SARS-CoV-2 infection has come a long way since the first layoffs over its importance, Topol noted via Twitter. When Dr. @Camilla_rothe reported an asymptomatic transmission a year ago, the @ NEJM report was refuted and discredited. She was later 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 versus never symptomatic
The term “asymptomatic” can be misleading because some people in this group do develop signs of infection. This “presymptomatic” group of patients is likely to be a minority, the authors note. Longitudinal studies indicate that about three-quarters of people who are asymptomatic with SARS-CoV-2 still do.
Topol expected that the one-third asymptomatic finding could provide some feedback on how to distinguish between asymptomatic and presymptomatic individuals. He tweeted, “Some will argue there is admixture with presymptomatic cases, but review of all data supports this estimate as 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 the settings, populations, and other characteristics of the studies prevented the authors from conducting a meta-analysis of the findings.
Home is where the test is?
Based on their findings, Oran and Topol believe “that COVID-19 control strategies should be changed to take into account the prevalence and transmission risk of asymptomatic SARS-CoV-2 infection,” they write. They propose frequent use of low-cost, rapid home tests to identify asymptomatic or pre-symptomatic people, along with programs and housing provided by the government to provide financial assistance and allow this group of people to isolate themselves.
Further research is warranted to determine whether and how well vaccines for SARS-CoV-2 prevent asymptomatic infection.
Topol and Oran made a short video to highlight the findings of their systematic review.
The study was supported by a grant from the National Institutes of Health.
Ann Intern Med. Published online January 22, 2021. Full text
Damian McNamara is a staff journalist based in Miami. It covers a wide variety of medical specialties, including infectious diseases, gastroenterology and intensive care. Follow Damian on Twitter: @MedReporter.
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