Does Omicron Cause “Mild” COVID-19?

New evidence suggests the threat of severe infections.

William Hanage

William HanagePhotograph courtesy of Harvard T.H. Chan School of Public Health

Within a few weeks of the Omicron variant’s first appearance in Botswana and South Africa late last November, reports began to appear that it caused a milder infection than prior coronavirus variants. But that is probably not an intrinsic property of Omicron, argue assistant professor of medicine Roby Bhattacharyya and associate professor of epidemiology William Hanage in a Perspective article published February 2 in the New England Journal of Medicine. Instead, they say, the apparent mildness of Omicron-caused infections is a function of three factors: prior population-level immunity, the ability of the virus to infect people with some level of immunity (gained from vaccination or previous infection), and statistical distortions caused by Omicron’s greater transmissibility.

South Africa’s demographics played a role, too, the authors say. Because that country’s population is relatively young, cases are skewed toward a higher frequency of mild infections (since age is one of the primary risk factors for severe outcomes). Moreover, high rates of prior infection, combined with South Africa’s vaccination program that targeted the elderly, meant that much of the populace already had some type of immunity when Omicron struck.

Understanding these distinctive factors in the lessons learned from South Africa’s early, pervasive Omicron surge matter in inferring what the real risks are in different contexts—like the still-high level of new cases in much of the United States and Europe.

Prior Immunity Dilutes Perceived Severity

Crude measures of the severity of a particular coronavirus variant involve comparing the number of hospitalizations or deaths it causes to the total number of cases of infection. 

But because Omicron frequently infects both the unvaccinated and the large number of people who are vaccinated or were previously infected by a prior variant (critically, without subsequently leading to hospitalization or death), those latter cases swell the number of infections, but not the tallies of severe illnesses or deaths. This is one way in which prior immunity has distorted the picture of Omicron’s severity, say Bhattacharyya and Hanage, who is co-director of Harvard’s Center for Communicable Disease Dynamics.

Two studies that controlled for this distortion by estimating the extent of prior undocumented infection in a population determined that Omicron was about 75 percent as likely as the severe Delta variant to cause hospitalization in someone unvaccinated and without a history of prior infection. “This meaningful but fairly small difference,” Bhattacharyya and Hanage write, “implies that Omicron, Alpha, and wildtype SARS-CoV-2 have similar intrinsic severity.”

Rapid Spread Swells Case Counts Faster than Hospitalizations and Deaths

The speed of Omicron’s spread has only added to perception that it is less severe. Because there is a long lag time between infection with SARS CoV-2 and severe outcomes, more transmissible variants such as Omicron will rapidly lead to large numbers of infections long before they cause a commensurate number of hospitalizations and deaths. This distorts the apparent ratio between the number of infections and the number of severe outcomes, at least until sometime after the outbreak has peaked. 

“Extrapolating population-level effects from one setting to another,” such as from South Africa to the United States, “requires extreme caution,” Hanage and Bhattacharyya warn. Omicron’s “immune-evasion capability has enabled it to infect many people who wouldn’t have been infected by previous variants, which has fueled its rapid spread and allowed it to more quickly infect nonimmune people, thereby offsetting what appears to be a moderately lower intrinsic severity and exacerbating overcrowding of hospital systems and demands on caregivers.”

Calculating Omicron’s true virulence, they say, will require more time and carefully controlled data. In the meantime, they and other public health experts emphasize, the importance of vaccination and boosting cannot be overstated.

Read more articles by: Jonathan Shaw

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