Did the WHO upgrade Omicron prematurely?
The new coronavirus variant does not actually meet WHO official “variant of concern” criteria. Maybe the definitions should change.
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All viruses mutate while replicating. The more infections, the more mutations. That’s why in just two years since the first known human case, there are already many notable variants of SARS-CoV-2, the virus that causes Covid-19. Omicron is but the most recent to grab our attention.
Most mutations—which are changes to a genetic code—are “silent.” They don’t cause detectable differences in a virus’s behavior. Some can actually be good for us, such as when a mutation makes a virus easier for neutralizing antibodies to cling to. Some can be bad, such as when a mutation makes it harder for neutralizing antibodies to attach to them.
Whether or not a mutated version of a virus is a threat does not actually depend on the number of mutations. One single change in a virus’s genetic code could be a calamity for us while 100 others could add up to no meaningful difference. What matters is the behavior of each resulting virus.
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Late last week, the World Health Organization declared the B.1.1.529 a “variant of concern,” and therefore designated it with a Greek letter, Omicron. Did the WHO jump the gun by bypassing other variant classifications which by definition are less, well, “concerning” than those that rise to the level of “variants of concern”?
I think so.
To know that, let’s explore how the WHO classifies variants. There are four categories: variants under monitoring (VUM), variants of interest (VOI), variants of concern (VOC), and variants of high consequence (VOHC). (Emphasis added in the descriptions below.)
Variants under monitoring (VUM) contain genetic changes which are “suspected to affect virus characteristics with some indication that it may pose a future risk.” However, the virus’s actual behavior or epidemiological impact is not clear. This classification is based on biological/laboratory information, not clinical observations.
Variants of interest (VOI) must meet two separate criteria: 1. There must be genetic changes which are “predicted or known to affect virus characteristics such as transmissibility, disease severity, immune escape, diagnostic or therapeutic escape,” and; 2. The variant must have been identified to cause “significant community transmission or multiple COVID-19 clusters, in multiple countries with increasing relative prevalence alongside increasing number of cases over time…[to] suggest an emerging risk to global public health.” This classification is based on a combination of biological (laboratory) and clinical (patient) data.
Variants of concern (VOC) must meet one of three criteria, in addition to those that would qualify it as a VOI. There must be: 1. a documented “increase in transmissibility or detrimental change in COVID-19 epidemiology,” or; 2. a documented “increase in virulence or change in clinical disease presentation,” or; 3. a documented “decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.” This classification is supposedly determined on clinical data only (more on this in a moment). The biological criteria for a VOC do not differ from those in the VOI category.
Variants of high consequence (VOHC) can be designated when there is “clear evidence that prevention measures or medical countermeasures have significantly reduced effectiveness relative to previously circulating variants” or when there is evidence that the variant causes “more severe clinical disease and increased hospitalizations.” In other words, a VOHC is a worse disease that renders our diagnostic tests, vaccines, and effective drugs measurably and substantially less effective. Like VOC, VOHC is determined based on clinical information. (Any alterations in vaccine and drug effectiveness must be determined from “real-world” clinical data, not merely changes detected in laboratories, such as lower antibody affinities to the variant.)
So far, there have been 21 VUM, 7 active, and 14 “retired.” Currently, there are two VOI, five VOC (including Omicron), and (officially) zero VOHC. (Of note, no Covid-19 variant has ever been designated as a VOHC. But in my view, Delta clearly met the definition months ago, because it has been shown to decrease vaccine effectiveness for severe disease and hospitalization among older adults.)
To my knowledge, and from private conversations with officials at the WHO and the Centers for Disease Control and Prevention, Omicron has not actually met the definition of a true “variant of concern.”
Just about everything we know about Omicron is based on genetic information that has emerged in just the last 5 days. That implies that Omicron technically belongs in the “variant of interest” category, not the elevated “variant of concern” category. However, Omicron remains worrying and, in my view, it warrants intense investigation. Let’s be safe and assume the worst for the next week or two before we de-escalate.
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The WHO devised its variant classifications for a specific purpose: to propel action when needed and not to overreact to every new version of SARS-CoV-2 that jumps onto the scene. When the WHO designates a new “variant of concern,” that triggers important steps, such as coordination among nations, ramping up testing, and even updating previous guidance and guidelines. And these classification standards are working definitions which can and should be amended to suit our needs. Definitions should serve us, not the other way around.
So while a series of resource-intense actions are being taken for Omicron before it has met the actual definition of a “variant of concern,” perhaps in the end the WHO will have been justified in sounding the alarm. But they should not do this too often, or else people will start tuning out these alerts.
The “variant of concern” classification results in immediate international cooperation which will generate answers much sooner than we would otherwise have had them. But investigations can begin too early and often or too late and infrequently. Bearing all of that in mind, maybe it is time for the WHO to update its definitions.
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