How useful is it to prevent the next infection after being infected with the new coronavirus? Recently, heavy research from the three top journals suggests that the effect may be limited.
Writing | Jun Ling
Source | “Medical Community” Official Account
On March 23, the New England Journal of Medicine published an article by an Austrian scholar showing that people who are only infected with the Omicron variant but not vaccinated may not be adequately protected against infection other mutants.
Coincidentally, two studies published March 17 and March 18 in The Lancet Infectious Diseases and Cell reached similar conclusions. The latter researchers found that the rise in antibody titers from a breakthrough infection in Omicron was only one-third that of receiving a booster shot. This may reveal that the breakthrough infection of Omicron is less immunogenic, reducing protection against reinfection or against future mutant infection.
Unvaccinated infected individuals
Neutralizing antibodies are barely detectable
Start with an article by an Austrian scholar in the New England Journal of Medicine.
The study consisted of four groups (Figure 1):
A: Vaccines (15 people) who have not been previously infected with the new coronavirus;
B: Not previously infected with the new coronavirus and not vaccinated (18 people);
C: vaccinated patients (11 people) who have been infected with the new coronavirus;
D: Unvaccinated patients (15 people) who have been infected with the new coronavirus.
After the group B was infected with Omicron, the serum mainly only had antibodies against Omicron, and only a small amount against other mutants. Two of them had no neutralizing antibodies at all against other mutants, suggesting that infection with Omicron alone could not provide adequate protection against other mutants.
At the same time, after infection with Omicron, the serum neutralizing antibody titers of subjects in group A were significantly higher than those in group D, suggesting that vaccination may be more “effective” than previous infection.
Figure 1 Study grouping and results
In The Lancet, Infectious Diseases, Swedish researchers came to a similar conclusion.
The researchers collected serum samples from 26 health care workers who were diagnosed with COVID-19 in April or May 2020. Of these, 9 medical staff had serum samples taken two months later (before vaccination), and the other 17 were vaccinated thereafter.
In sera of 9 infected but unvaccinated medical staff, some neutralizing activity against wild-type SARS-CoV-2 was maintained, but neutralizing activity against Omicron almost undetectable.
Figure 2 Neutralizing antibodies in 9 infected but unvaccinated individuals
Health care workers who were vaccinated fared much better. Both the wild-type SARS-CoV-2 and the Omicron variant showed high neutralizing antibody activity.
The average ID50 titers of the 17 medical staff were 495 for wild-type SARS-CoV-2 and 105 for the Omicron strain, with 2 of them targeting both strains There was no difference in neutralizing antibody activity (Figure 3).
Figure 3 Neutralizing antibodies in 17 vaccinated individuals
“Although other components of the immune system also help prevent serious disease, neutralization sensitivity is significantly reduced, which may translate into vaccine-mediated protection against infectiondrop. ” said the Swedish researchers.
At the same time, the researchers believe that vaccination after infection can significantly increase the activity of neutralizing antibodies against mutant strains, again suggesting that simple acquired immunity after infection is limited, and the effect of vaccination Irreplaceable.
Antibody titers after infection are only 1/3 that of boosters
Compared with the research of Swedish scholars, the research published by American scholars in “Cell” is much more complicated, analyzing the breakthrough infection of Delta and the breakthrough infection of Omicron respectively. , and the control group inoculated with the booster needle was separately included.
These people were all vaccinated, either mRNA vaccine or adenovirus vaccine, in 4 groups:
a: 48 people who received two doses of the vaccine but were not infected;
b: 15 people who received a booster but were not infected;
c: 39 vaccinated (no booster or not) vaccinated patients with breakthrough delta infection;
d: 14 vaccinated (no booster or not) vaccinated patients with breakthrough infection by Omicron.
In the pseudovirus experiment, the comparison of two groups a and b showed that after two doses of vaccine, the neutralizing antibody activity against Omicron decreased to a very low level over time. level (17), and was significantly increased (635) after booster vaccination (Fig. 4).
Figure 4 Results of group a (n=48 on the left) and group b (n=15 on the right)
Looking at the data of group d, after the breakthrough infection by Omicron, the neutralizing antibody titers against wild-type, Delta, and Omicron were 1524 and 467, respectively. , 387.
This shows that after the breakthrough infection by Omicron, although the activity of neutralizing antibodies against different mutants has increased, it is still far from the effect of booster needles. For the progenitor wild-type strain, the titer of neutralizing antibody after infection was only 1/3 of the booster dose(1524 vs. 4272). Even against the Omicron strain itself, it was only 3/5 (387 vs. 635).
Delta breakthrough infections are different. The comparison of b and c in the true virus test shows:
The rise in antibody titers following breakthrough infection with the delta strain is similar to receiving a booster;
However, in the face of the improvement of Omicron’s immune escape ability, it is suggested that the broad-spectrum neutralization effect is not strong, and the effect is not as good as receiving a booster needle.
Conversely, the cross-neutralizing ability of the Ormicon strain against delta after infection is limited. In the true virus test, the efficacy against the original wild-type strain and the delta strain was The difference is 2.2 times.
In group a, the difference was 3-fold among those who had not been infected with Omicron.
The article thus concludes:
For Delta and Omicron breakthrough infections, the degree of cross-neutralizing immunity that patients receive is limited, in addition to increased neutralizing activity against the ancestral wild-type strain.
Omicron does not represent “the end of the pandemic”
U.S. researchers also specifically compared “face-to-face” differences in breakthrough infections between Delta and Omicron strains.
55 breakthrough infections, 35 delta, 20 Omicron.
In all patients, Delta breakthrough infection resulted in a 3.5-fold increase in neutralizing antibody titers against wild-type compared with Omicron (19806 vs. 5682). The researchers believe that this difference is not significant, and it is estimated that the strengthening needle played a large role in it.
However, when only patients who did not receive a booster shot were analyzed, breakthrough delta infection had 10.8 higher neutralizing antibody titers against progenitor wild-type compared to Omicron times (20481 vs 1905, P=0.037, Figure 5).
Figure 5 Comparison of neutralizing antibody titers for breakthrough infection of different strains
Further analysis found that no matter what kind of viral infection, without receiving the booster injection, the antibody titers of moderate and severe patients were 12.3 times higher than those of mild patients. 5 times.
This nicely explains part of the reason for the higher antibody titers after Delta’s breakthrough infection:
Because Omicron infection is mostly mild (28.6%) and asymptomatic (55%), and the more severe the symptoms, the more neutralizing antibodies may be produced.
At this time of the pandemic, the Omicron strain, which has been shown to cause less severe disease, is seen by many as a sign of the end of the pandemic, researchers believe , but Omicron’s breakthrough infection produced very limited levels of neutralizing antibodies.
“So if in the future another more pathogenicSexual mutant strains, in terms of infection prevention, may not be as durable as other mutant strains (such as Delta) from the immunity that comes from a breakthrough infection in Omicron. “
The researchers also re-emphasized the importance of vaccination boosters.
“There is no way to enter ‘herd immunity’ through infection”
In response to the findings, virologist Chang Rongshan responded to a request from the “medical community” for comment.
“Compared with various viruses in history, the mutation rate of the new coronavirus itself is not so fast, but the mutant strains are frequently found at present. The reason is that the infection base is too large, causing the virus to constantly evolve. ‘, while the transmissibility is significantly enhanced, the immune evasion ability is also increasing day by day.”
“In the face of these new coronavirus variants with strong immune evasion ability, natural infection cannot form ‘herd immunity’, as the above Swedish study can prove.”
“After being infected with the progenitor new coronavirus, the neutralizing antibody titer in the body was initially high, but almost all decreased significantly after 4 months. When the new variant came, the previous generation Neutralizing antibodies and cellular immunity produced by natural infection are not enough to prevent a new round of infection, which has happened three times, with alpha mutants, delta mutants and Omicron mutants.”
“The root cause of the current appearance of ‘herd immunity’ abroad is the high vaccination rate and booster shots. Although protection from natural infection cannot be ruled out, the effect is very limited. “
“In the final analysis, the domestic epidemic has entered the second half, and the most important strategy is to further increase the vaccination rate of booster needles, and at the same time accelerate the improvement and in-depth research of existing vaccines.”
References:
[1]Neutralization Profile after Recovery from SARS-CoV-2 Omicron Infection,
https:https://www.nejm.org/doi/full/10.1056/NEJMc2201607?query=featured_home
[2]Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants, https://www.sciencedirect.com/science/article/pii/S0092867422003294
[3]Neutralisation sensitivity of the SARS-CoV-2 omicron (B.1.1.529) variant:a cross-sectional study, https:https://www.thelancet.com/ journals/laninf/article/PIIS1473-3099(22)00129-3/fulltext#fig3
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