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Is 'breakthrough infection' a misleading term?

People queue, wearing masks against the coronavirus, outside a theatre for a performance of Les Miserables in London, Tuesday, Dec. 28, 2021. Many Eur...

People queue, wearing masks against the coronavirus, outside a theatre for a performance of Les Miserables in London, Tuesday, Dec. 28, 2021. Many Eur...

What is a “breakthrough infection?” It is being described during the COVID-19 pandemic as an infection with the virus after being fully vaccinated. What does the virus “break through?” The term implies that the immune response produced by a vaccine was insufficient to prevent infection.

Is this how vaccines really work? Some published articles have used influenza as an example of how COVID-19 will affect our lives. We design influenza vaccines to try to minimize the damage caused by the strains that emerge every year.

Similar to what happens when a pathogen invades, inoculation with a vaccine that mimics the pathogen structurally, and the immune system is triggered to produce B- and T-cell immunity specific to the structure of the vaccine. In the case of many people, the response produces the right amount of immunity; others have a weak immune response or none at all. Some experience too much of a response, and their immune system starts to attack normal cells.

When the immune response is still active and the pathogen gets into our body, the immune system is ready to neutralize the pathogen to limit its effect. However, when the body receives no challenge from the pathogen for a period of time, the immunity against it becomes dormant and is only triggered by said pathogen or another dose of the vaccine. The duration of immunity depends on the immune response to the vaccine. In the case of some viruses, it lasts a lifetime; in other cases, another dose is eventually needed to maintain immunity. This is what is called a “booster” shot. The tetanus vaccine is a good example. Adults are recommended to get a tetanus vaccine booster every 10 years, as our defenses against that pathogen are nearly gone after a decade.

Another factor in the effectiveness of the vaccine is how similar it is in structure to the pathogen. The vaccine is relatively fixed unless the manufacturer changes it. Meanwhile, a pathogen might never change its structure, or it might mutate frequently to adapt to its environment. When the structure of a pathogen can no longer be recognized by the immune system, immunity is lost. As mentioned above, influenza viruses mutate often, so we have to change the vaccine each year to keep up. This is what happens when we are dealing with RNA viruses.

COVID-19 is an RNA virus, so it also mutates frequently. Each “variant” has some structural differences. Although all variants are called COVID-19, mutations are making the original vaccines less effective.

However, even when the structure of a vaccine is a good match for the pathogen and the immune response that is triggered would be adequate under ordinary circumstances, immunity can still be overwhelmed by a vast quantity of the pathogen.

With these scenarios in mind — the strength of the immune response, the duration of action, vaccines' structural resemblance to their targets, and the viral load — it should not be a surprise that someone develops side effects to a vaccine or is infected by COVID-19 after being "fully vaccinated." Of these four factors, perhaps only the fourth scenario can truly be labeled a “breakthrough infection.”

When a fully vaccinated person encounters the COVID-19 virus, they can still be infected, and at that point it is just a matter of how severe the symptoms are. We may never know the actual case numbers because quite a few infected people are asymptomatic. Rarely will a vaccinated person become severely ill or die.

Recently, the media has begun reflecting on this. “We Need to Start Thinking Differently About Breakthrough Infections” is the title of a recent article from Time Magazine. The experts stress the usual measures: individual hygiene, social distancing, vaccination, and strengthening of the health care system to “flatten the curve.” Interestingly, the article concludes with the statement that after 10-12 weeks, people may be able to “move into a normalized response,” meaning that “eventually, COVID-19 breakthrough infections may be treated like any other respiratory viral infection.” Basically, there is no need to panic or treat the Omicron variant like an omnipotent monster.

If Omicron causes milder symptoms, especially in fully vaccinated people, in order for the world to prepare to return to normalcy we should stop viewing breakthrough infections as the product of bad pathology. The media should recognize that this is the response we have against pathogens after vaccination, not that the pathogens are "breaking through" a barrier set by vaccines.

The Time article emphasizes the importance of vaccination, including booster shots, as the antibodies triggered by each dose can reduce the risk of a severe outcome. This allows us to be less afraid of a “breakthrough infection.” Prime Minister Boris Johnson has urged the U.K. to get the booster vaccine to protect themselves. What are we protecting? Do we gain more from a booster shot after being “fully vaccinated?” Granted, the antibody count does increase after a third dose, but does this further reduce symptoms beyond “full vaccination” without any additional side effects? Where does this end?

In response to a media inquiry on whether the White House had been invaded by COVID-19, Press Secretary Jen Psaki said: “I would just note that we do expect there to be breakthrough cases, as there will be across government.” Several staffers, including herself, were diagnosed with COVID-19 despite the fact that more than 90% of White House workers were “fully vaccinated,” with many having received a booster. The comments from the White House followed announcements by Senators Elizabeth Warren and Cory Booker and Representative Jason Crow that they had tested positive. All three credited their mild symptoms to being vaccinated and boosted.

However, booster shots started being rolled out in the U.S. in late August. Based on the information provided by the industry, antibodies should still be abundant four months after the third dose; therefore, the booster shot does not prevent infection, and it may make symptoms milder. The question is, are the symptoms really that much milder than full vaccination without the booster?

Many media outlets report the daily number of COVID-19 cases and deaths but not the ratios. To understand the impact of the Omicron variant, we can review the daily numbers over time. On Nov. 22, 2021, for example, there were 93,878 new cases (14-day change +27%) in the U.S. and 1,092 new deaths (14-day change -9%). These were virtually all caused by the Delta variant. On Dec. 11, 2021, there were 119,325 new cases (14-day change +40%), 64,614 hospitalizations (14 day change +22%), and 1,288 deaths (14-day change +31%). These numbers were a mixture of Delta and Omicron. On Dec. 25, there were 201,330 new cases (14-day change +69%) and 71,000 hospitalizations (14-day change +9%) but only 1,345 deaths (14-day change +4%). By then, about 73% of U.S. cases were being caused by the Omicron variant. Indeed, Omicron has infected more people, but the number of hospitalizations and deaths has not increased proportionally, indicating that the majority of Omicron patients experience mild illness.

Looking at the big picture, the cumulative number of COVID-19 cases in the U.S. as of Dec. 11, 2021, was 49,845,209 (15.1% of the population), with cumulative deaths numbering 795,727 (1.6%). By Dec. 25, 2021, cumulative cases had reached 52,054,982 (15.8%), and cumulative deaths and mortality 814,891 (1.56%).

The surge of positive cases has not been accompanied by a corresponding surge in mortality among the infected but instead trended down. The Omicron variant is not as scary as we thought. The way COVID-19 has morphed into this version is in line with the theory of the “attenuation of virulence” of microbes. They want to survive alongside us.

CNBC cited experts as predicting that "Omicron could burn through the U.S. and expedite the end of the pandemic. Again, when it comes to breakthrough infections we should understand this is an overemphasized term. The immune response from the vaccines is based on simulation of the virus. We do believe that the vaccines sufficiently reduce the severity of illness and death when the actual virus attacks us, but there will be a delayed reaction when there has been no challenge from a real enemy.

On the other hand, too many or too frequent booster shots may cause more side effects. There is a balance that we have to choose. If Omicron has been attenuated, the majority of the healthy and fully vaccinated individuals should not be afraid to face the real virus. Such exposure may allow a healthy, vaccinated individual to achieve even stronger, longer-lasting immunity.

A "breakthrough infection" of the Omicron variant may actually be considered a "naturally live-attenuated booster vaccine." The availability of oral antiviral drugs makes this approach even more feasible.

Certainly, minimizing the viral load, distancing, hygiene, and early treatment with effective drugs are still important. It is still reasonable to administer booster shots to high-risk and elderly people as recommended by the U.S. FDA. But countries where the majority of the population has been fully vaccinated should choose to open their societies to end the pandemic once and for all.

In recent days, several new local cases were identified in Taiwan. They were eventually determined to be old cases due to their high PCR cycle threshold (CT) and negative results on subsequent PCR tests, and COVID antibodies were found in their blood. In fact, if the criterion for PCR positivity is set at < 30, many "cases" will not register as positive at all.

Taiwan has vaccinated enough people to face the pandemic. Over-restriction is no longer necessary. In particular, "fully vaccinated" and PCR-negative travelers should be allowed to enter the country without having to quarantine. The government should seriously consider this approach instead of promoting the third booster shot, and getting it should be optional.

On Dec. 18, all four questions in Taiwan's recent referendum were defeated. In the public debate leading up to the votes, the ruling party expressed it wanted the people to believe in science when deciding on public policies. It was able to convince the people that the party runs the government based on science. If this is true, the policies on epidemic control should also be rooted in science.

Opening the border and connecting with the world is the science. Is the Omicron variant a “breakthrough infection” or a "naturally live-attenuated" booster vaccine? It is time to let vaccinated individuals direct the government toward the right track.

Yang Sen-Hong earned his MPH at UC Berkeley. Shih Hue-Teh earned his MPH at Harvard School of Public Health.

Updated : 2022-05-18 06:05 GMT+08:00