Omicron outbreaking in China: Chinese COVID-19 vaccines still effective?

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Omicron outbreaking in China: Chinese COVID-19 vaccines still effective?

Most people in China are vaccinated with two or three inactivated vaccines, most are vaccines developed by SINOPHARM or SINOVAC . After the two vaccines were put into use, they have been asked whether they are useful.

At the beginning, the questions about Chinese inactivated vaccines were asked because the results of the Phase III clinical trial did not come out. Later, questions continued because the results were not so good as the mRNA vaccines. Later, still questioned about the effect of various mutant strains on the effectiveness of the vaccine.

There are many ways to ask questions: after the shot, there is no reaction at all, is it because the vaccine is too weak? SINOVAC is only 50% effective when it is made in Brazil, is it relatively tasteless? Neutralizing antibodies are much lower than mRNA vaccines.

Is it not much use to fight? we went to test the antibody and it didn’t come out. Is it a waste of time? XX study said that after a few months, no antibody can be detected / no neutralizing ability to Omicron, is it useless?

With the recent outbreak of Omicron in many places in China, many people are even more worried about whether the inactivated vaccine they have been vaccinated has enough protection. Let’s analyze whether our inactivated vaccine will work in the face of Omicron.

1. The focus should be on severe illness and death

First of all, it should be clear that the protective effect of the COVID-19 vaccine should be focused on protecting severe diseases and greatly reducing the risk of death .

In the face of Omicron with severe immune escape (including BA.1 and BA.2), it is still not uncommon for breakthrough infections to occur even after three doses of the most effective mRNA vaccine.

According to the tracking data of the British public health department, after the completion of the mRNA vaccine booster injection, the effectiveness of preventing Omicron infection in a short period of time is only about 70%, and it drops to 30%-40% after three or four months [1] .

Combined with the rapid spread of Omicron and the shortened incubation period to a median of 2-3 days, breakthrough infections have become very common. On March 13, former U.S. President Obama, who had been vaccinated with a booster shot, disclosed that he was infected.

Although it is difficult to prevent infection, it is also obvious that foreign studies on tracking breakthrough infection and mRNA vaccination have shown that these vaccines still have very good protection against severe disease and death.

In countries with high vaccination rates, the case fatality rate of the COVID-19 is very low – there are still many infected people, but the number of deaths and severe cases has been greatly reduced, such as the United Kingdom:

Omicron outbreaking in China: Chinese COVID-19 vaccines still effective?

The fatality rate is still the entire population. In fact , after the mRNA vaccine booster injection, the risk of severe death is very low , which mainly occurs in the unvaccinated population.

Faced with Omicron now, our focus on inactivated vaccines should also focus on its role in preventing severe illness and preventing death.

2. The assessment of critical illness prevention is more complicated

However, the assessment of effectiveness in preventing severe illness and death is more difficult.

The real effectiveness must be compared between vaccinated and unvaccinated infection, severe disease, and death differences in outbreak areas. Previously, we could see the results of tracking inactivated vaccines in places like Chile and Brazil.

However, these countries have now used mRNA vaccines and adenoviruses in Europe and the United States to enhance inactivated vaccines on a large scale, and it is difficult to obtain data on the effectiveness of only inactivated vaccines against Omicron.

Many people have begun to pay attention to the neutralizing antibody data of inactivated vaccines. It is often seen on the Internet that the antibody levels of different vaccines are compared, and inactivated vaccines undoubtedly induce relatively low neutralizing antibodies – especially for Omicron, it is not uncommon for two doses of inactivated vaccines to fail to detect corresponding neutralizing antibodies. As a result, many people believe that inactivated vaccines are ineffective against Omicron.

But this judgment is one-sided, and neutralizing antibodies do have a good correlation with vaccine effectiveness. But the correlation is more direct in the effectiveness of preventing infection, and much more complicated in preventing severe illness and death.

Whether it is from the principle of viral infection or the current follow-up observation, the existing antibody titer in the body is more closely related to the COVID-19 infection. It can play an important role in severe protection, including immune memory and T cell immunity [1]:

Even in mRNA vaccines that induce excellent antibodies, the effectiveness of preventing symptomatic infection, according to the modeling of clinical trial results, the contribution of antibodies is 68%, and the remaining 32% is memory that cannot be reflected from antibody titers. B cell and T cell immunity [1]:

Therefore, the protective effect of the vaccine cannot be fully assessed from the antibody titer alone . Especially for the prevention of severe illness, we have to fully consider the immune response stimulated by a vaccine.

3. Inactivated vaccines still lay a good foundation

If we carefully analyze the results of some immunological studies, we will find that the immune foundation of the inactivated vaccine is not bad.

In the face of Omicron, it is theoretically possible to prevent severe death.

One piece of evidence is the result of boosting with mRNA vaccines following inactivated vaccines.

A number of studies have now shown that on the basis of two inactivated vaccines, the mRNA vaccine is used as a booster, and the neutralizing antibody titer will be very high, reaching a level similar to that of mRNA vaccination .

For example, this study from the cooperation between the United States and Nicaragua [3]:

Whether it is total antibody, RBD antibody, or neutralizing antibody against the original strain (c) or Delta (d), two doses of SINOVAC and one dose of Pfizer are no worse than two doses of Pfizer .

Many people have read this type of research. The main point of view is that the mRNA vaccine has a good effect of enhancement, and inactivated vaccine recipients need to consider using mRNA vaccine enhancement. There is absolutely no problem with this angle, and I agree with the conclusion.

But considering that so many people in China have only been vaccinated with inactivated vaccines and have no chance of being boosted with well-validated mRNA vaccines for the time being, I would like to point out another aspect of this type of research.

That is, the inactivated vaccine has established a good basic immunity to the COVID-19, and the vaccinated body has formed an immune memory .

We can imagine this: If the first two doses of inactivated vaccine did not form an immune memory and were hit for nothing, what would happen to an additional dose of mRNA vaccine? It should be similar to a person receiving the first mRNA vaccine. In this case, it is impossible to form such a high antibody titer [4]:

It can be seen from the above figure that the neutralizing antibody titer of the same mRNA vaccine is very low after the first injection and before the second injection (three weeks interval), which is basically lower than the detection limit.

After two shots of inactivation and one shot of mRNA, the antibody can rise so rapidly.

The only possibility is that the inactivated vaccine establishes an immune memory, and the additional mRNA vaccine quickly activates the immune memory and produces a large number of antibodies.

Imagine again, what would happen if you encounter a new coronavirus instead of an mRNA vaccine after two shots of inactivation? Viruses also rapidly activate the immune memory established by vaccines—after all, vaccines are designed for viruses.

Some might argue that the vaccine is designed from the original virus strain, unlike Omicron.

However , Omicron’s immune escape is serious but incomplete , which is why the third dose of the vaccine based on the original virus strain can still increase neutralizing antibodies to Omicron. Therefore, even Omicron activates immune memory.

What follows is rapid antibody production—not necessarily to prevent infection, but it should be useful to prevent the virus from rapidly expanding in the body and causing severe illness.

In addition to such mRNA booster results, other new studies are also pointing to the fact that inactivated vaccines are not completely at a loss for Omicron on an immune basis. A paper from the Chinese Academy of Sciences published in “Nature” at the end of January showed that memory B cells corresponding to antibodies that efficiently neutralize the Omicron mutant can be isolated after three injections of inactivation [5].

From a pharmaceutical point of view, these antibodies that efficiently neutralize Omicron may become the next monoclonal antibody drug. From the perspective of immune memory, this means that the immune foundation laid by the inactivated vaccine is still useful to Omicron – the absolute antibody titer is not high, but the establishment of immune memory is a good sign for severe disease prevention.

4. Inspiration from Hong Kong Statistics

In addition to immunological evidence pointing to the foundation laid by inactivated vaccines to prevent Omicron from causing severe disease, the statistics of the current epidemic in Hong Kong can also be corroborated.

Analysis of the vaccination status of 3,231 people who died of the COVID-19 as of March 12 in this wave of Omicron BA.2-based epidemics in Hong Kong, 90% of the deaths did not complete the two-shot vaccination [6]. Take a look at this graph of the crude case fatality rate (deaths/confirmed cases) by age group:

Among the elderly over 80 years old, the fatality rate of those who did not complete two doses of the vaccine reached 12.15%, while that of those who received two doses of the vaccine was 3.01%.

There are two vaccines in Hong Kong: mRNA vaccine Fubitai (ie Pfizer/BioNTech in Europe and America) and Sinovac. However, among the elderly, SINOVAC’s vaccination accounts for the absolute majority:

As of March 12, the vaccination rate of elderly people over 80 was only 35%, but Sinovac accounted for nearly 80%. The market share is so high that it can suppress the fatality rate in this age group from 12% to 3%. It is impossible for inactivated vaccines to fail.

Today the same virus strain, Omicron BA.2, is also present in several parts of the continent. I hope that the long-term dynamic clearing can still be successful, but this mutant strain is spreading too fast and the future is unpredictable.

At this stage, our primary concern is not whether the inactivated vaccine will be useful to Omicron if the reset fails, but what will happen to those who have not been vaccinated, especially the elderly .

5. It is imperative to optimize vaccines

Compared with those who have not been vaccinated, whether from the principle of immunology or the rough data of Hong Kong, the inactivated vaccine should still have a certain preventive effect on Omicron.

Even so, it is urgent to optimize and strengthen immune protection for inactivated vaccine recipients, especially high-risk groups .

It is still the crude case fatality rate in Hong Kong. The case fatality rate of people over 80 years old after receiving two injections of the vaccine is still 3%, which is much lower than that of those who have not been vaccinated, but the absolute value is still very high.

This is only the data of death, and the proportion of severe cases that need to be admitted to the ICU for treatment and need to be hospitalized is definitely higher.

If the mainland cannot be cleared this time and Omicron expands as rapidly as Hong Kong, can we afford such a fatality rate and hospitalization rate?

Both Chile and Brazil showed a marked decline in the effectiveness of inactivated vaccines in preventing severe illness over time—especially among the elderly.

These results are not surprising, there is a concept in immunology called “immunosenescence” ( immunological aging ). Even the most efficient COVID-19 mRNA vaccine, the immune response in the elderly will be weaker [1]:

Omicron outbreaking in China: Chinese COVID-19 vaccines still effective?

From Brazil’s tracking data during the Delta period, for the elderly over 80 years old, the effectiveness of two doses of inactivated vaccines to prevent hospitalization or death dropped from a peak of 68% to 41% after 6 months, and 60-79 years old. From 81% to 72% [7]:

Omicron outbreaking in China: Chinese COVID-19 vaccines still effective?

The decline in protection against severe disease with inactivated vaccines declined over time in all age groups.

But the underlying risk is different for different age groups. Healthy young people have a low risk of severe illness.

On this basis, even if the prevention of severe illness is no longer 80-90%, but reduced to 50-60%, the final absolute risk may still be low enough.

The elderly and high-risk groups with underlying diseases are different. The COVID-19 severe risk base is very high.

In the face of Omicron, which spreads very quickly, the protective effect of the vaccine must be maintained at a high level in this group.

Inactivated vaccines can bring protection to the elderly, but the effectiveness still needs to be strengthened, especially with the increasing urgency of strengthening over time .

Another peculiarity of vaccination in China also makes us now have the urgency to switch to a more efficient vaccine.

Different from the vaccination sequence of most countries, in mainland China, the vaccination sequence of the elderly is relatively low.

To date, there are still a large number of elderly people who have not been vaccinated [8].

One data is that the vaccination rate of people over the age of 80 is less than 50%.

From the results of clinical trials and real-world tracking of inactivated vaccines, the protective effect is very limited after the first injection and before the second injection [9].

For the elderly who have not received a single shot of the vaccine, it may be a month and a half after the two shots are fully effective (4 weeks plus two weeks for the formation of an immune response). With the speed of Omicron’s transmission, it may not give us such a waiting time.

In contrast, the more effective mRNA vaccine showed a certain protective effect about 10 days after the first injection [10]:

Omicron outbreaking in China: Chinese COVID-19 vaccines still effective?

Today, the mainland is a rapidly spreading Omicron, and a large number of elderly people have not yet been vaccinated. Of course, we hope to stop Omicron through strict physical epidemic prevention measures, but such a life-and-death matter must have multiple measures and preparations, not just hanging on the tree of physical epidemic prevention.

Compare Hong Kong, which has a low vaccination rate in the elderly, with New Zealand, which has a very high vaccination rate (enhanced with high-efficiency vaccines in the elderly) [11]:

Omicron outbreaking in China: Chinese COVID-19 vaccines still effective?

There are a large number of Omicron infections in both places (Hong Kong wants to prevent it, New Zealand knows it can’t prevent it and choose to coexist), one has the highest fatality rate in the world, and the other has a very low fatality rate.

We have to think clearly, if Omicron still breaks out, whether we are going to be Hong Kong or New Zealand.

Individuals, especially the elderly and other high-risk groups, must now be vaccinated as soon as possible.

Based on some studies, inactivated vaccines should still have a certain ability to protect against severe diseases.

For individuals, the vaccines that can be vaccinated today are good vaccines.

However, as an overall epidemic prevention method, it is urgent to promote more efficient vaccines with clear evidence .

References:
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050236/technical-briefing-34-14-january-2022.pdf
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-09-22/03-COVID-Thornburg-508.pdf
https://www.nature.com/articles/s41591-022-01705-6
https://www.nature.com/articles/s41591-021-01330-9#Tab2
https://www.nature.com/articles/s41586-022-04466-x
https://www.covidvaccine.gov.hk/en/dashboard
https://www.nature.com/articles/s41591-022-01701-w
http://czt.gxzf.gov.cn/zt/yqfkgz/yqfkzs/t10885375.shtml
https://cdn.who.int/media/docs/default-source/immunization/sage/2021/april/5_sage29apr2021_critical-evidence_sinovac.pdf
https://www.nejm.org/doi/full/10.1056/nejmoa2034577
https://www.science.org/content/article/news-glance-hong-kong-s-high-covid-19-death-rate-biden-s-test-and-treat-and