How effective is infection with COVID-19 in preventing the next infection? Recently, heavy research in the three top journals suggests that the effect may be limited.
Written by | Ling Jun
Source | "Medical Community" public account
On March 23, the New England Journal of Medicine published an article by Austrian scholars showing that people infected with only the Omiljunn variant but not vaccinated may not be able to adequately prevent infection with other variants.
Coincidentally, two studies published by The Lancet Infectious Disease and Cell on March 17 and March 18, respectively, came to similar conclusions. The latter researchers found that the antibody titers caused by the Opichron breakthrough infection increased to only 1/3 of the recipient of the booster needle. This may reveal that Omilon breakthrough infections are less immunogenic, reducing their protective effect against reinfection or future variants.
Infected people who have not been vaccinated
Neutralizing antibodies are almost undetectable
Let's take a look at an article published by Austrian scholars in the New England Journal of Medicine.
There were four groups of studies (Figure 1):
A: Vaccinated people who have not been infected with the new crown virus before (15 people);
B: Have not been infected with the new crown virus before and have not been vaccinated (18 people);
C: Patients who have been vaccinated and have been infected with the new crown virus (11 people);
D: Unvaccinated patients who have been infected with the new crown virus (15 people).
After Group B was infected with Omikejong, only antibodies against Omikejong were mainly found in the serum, and only a small amount was available to other variant strains. Two of them had no neutralizing antibodies against other variants, suggesting that infection alone with Omi kerong did not adequately provide protection against the other variants.
At the same time, after infection with Omiqueron, the serum neutralizing antibody titers of the subjects in group A were significantly higher than those in group D, suggesting that vaccination may be more "effective" than previous infections.
Figure 1 Study groups and results
In The Lancet Infectious Disease, Swedish researchers came to a similar conclusion.
The researchers collected serum samples from 26 health workers who were all diagnosed with COVID-19 infection in April or May 2020. Of these, 9 medical staff were given serum sampling two months later (before vaccination) and another 17 were vaccinated thereafter.
In the serum of 9 infected but unvaccinated healthcare workers, some neutralizing activity against wild-type SARS-CoV-2 remained, but the neutralizing activity against Omi kerong was almost undetectable.
Figure 2 Neutralizing antibodies in 9 infected but unvaccinated patients
Health workers who are vaccinated are much better off. Whether it is for wild-type SARS-CoV-2 or The Semikeron variant, it exhibits high neutralizing antibody activity.
The 17 medical staff had an average ID50 titer of 495 for wild-type SARS-CoV-2 and 105 for the Omiljung strain, with 2 of them having no difference in neutralizing antibody activity against the two strains (Figure 3).
Figure 3 Neutralizing antibodies in 17 vaccinated people
"Although other components of the immune system also help prevent serious disease, the sensitivity of the neutralizing effect is significantly reduced, which may translate into a decreased vaccine-mediated anti-infection protection." Swedish researchers said.
At the same time, researchers believe that vaccination after infection can significantly improve the neutralizing antibody activity against the mutant strain, once again suggesting that the acquired immune effect of simple post-infection is limited, and the effect of vaccination is irreplaceable.
The post-infection antibody titer is only 1/3 of that of the booster needle
Compared with the swedish scholar's study, the study published in Cell by American scholars is much more complex, analyzing Delta breakthrough infection and Omilon breakthrough infection, respectively, and separately including a control group with booster needles.
These people were all vaccinated, in the form of mRNA vaccine or adenovirus vaccine, in 4 groups:
a: 48 people who received two shots of the vaccine but were not infected;
b: 15 people who were given a booster needle but were not infected;
c: 39 patients who were vaccinated (without distinction between vaccination and booster injections) who were infected by Delta Breakthrough;
d: 14 patients who were vaccinated (without distinction between vaccination and booster injection) who were infected by the Aomi Kerong breakthrough infection.
In the pseudoviral experiment, comparisons between groups a and b showed that after receiving two doses of the vaccine, the activity of neutralizing antibodies to Omilon decreased to a very low level over time (17), and after receiving the booster needle (635) (Figure 4).
Figure 4 Results of group a (figure left n=48) and group b (figure right n=15).
Looking at the data of group d, after being infected by the breakthrough infection of Omikeron, the neutralizing antibody titers for wild type, Delta and Omilon were 1524, 467 and 387, respectively.
This suggests that after being infected by Aomi Kerong breakthrough, the neutralizing antibody activity against different variant strains has increased, but it is still far less effective than the strengthening needle. For ancestral wild-type strains, the post-infection neutralizing antibody titer was only 1/3 of the booster needle (1524 vs. 4272). Even against the Omiljung strain itself, it is only 3/5 (387 vs. 635).
Delta Breakthrough Infection is different. True virus test comparison with b and c showed:
The titer of antibodies acquired after breakthrough infection of the Delta strain rises, similar to receiving a booster needle;
However, in the face of the increase in the immune escape ability of Omi kerong, it is suggested that this neutralizing effect is not broad-spectrum, and the effect is not as good as receiving a reinforcing needle.
Conversely, the cross-neutralization ability of the Omikeron strain to Delta after infection was limited, and the difference in efficacy between the original wild-type strain and the Delta strain in the true virus test was 2.2 times.
Among those in group A who had not been infected with Omikeron, the difference was 3 times.
The article thus concludes:
For Delta and Omilon breakthrough infections, in addition to increased neutralization activity against ancestral wild-type strains, the degree of cross-neutralization immunity obtained by patients is limited.
Omi kerong does not represent the "end of the pandemic"
U.S. researchers also specifically compared the differences in breakthrough infections of Delta and Omicron strains "face to face."
There were 55 breakthrough infections, 35 deltas and 20 Omikron.
For all patients, Delta Breakthrough Infection resulted in a 3.5-fold increase in neutralizing antibody titers against the wild type compared to Omilon (19806 vs. 5682). The researchers believe that this difference is not significant, and it is estimated that the strengthening needle plays a large role in it.
However, when only patients who did not receive booster needles were analyzed, breakthrough Delta infection had 10.8-fold higher titers of neutralizing antibodies to the ancestral wild type compared to Omikeron (20481 vs. 1905, P=0.037, Figure 5).
Fig. 5 Comparison of neutralizing antibody titers of different strains breaking through infection
Further analysis found that regardless of the virus infection, the antibody titer of moderately and severe patients was 12.3 times that of patients with mild disease, and 5 times that of receiving booster needles.
This explains part of the reason for delta's higher antibody titers after breakthrough infection:
Because Omiljung infection is mostly mild (28.6%) and asymptomatic (55%), and the more severe the symptoms, the more neutralizing antibodies may be produced.
Researchers believe that at the moment of the Omiljung virus pandemic, although it has been shown to cause a mild degree of disease, and many people still believe that it is a sign of the end of the pandemic, the level of neutralizing antibodies produced by the Omiljung breakthrough infection is very limited.
"Therefore, if another, more pathogenic variant emerges in the future, immunity from the Aomi Kerong breakthrough infection may not be as persistent as from other variants (such as Delta) in preventing infection."
The researchers also re-emphasized the importance of vaccinations to boost the needle.
"There is no way to get into 'herd immunity' by infection"
In response to the above research results, virology expert Chang Rongshan responded to the "medical community" request for comment.
"Compared with various viruses in history, the mutation rate of the new crown virus itself is not so fast, but the current frequent discovery of mutant strains is that the infection base is too large, resulting in the continuous 'evolution' of the virus, while the spread of significantly increased, the immune escape ability is also increasing day by day."
"In the face of these new coronavirus variants with strong immune escape ability, it is impossible to form 'herd immunity' by natural infection, as evidenced by the above Swedish study."
"After infection with the ancestral new crown virus, the neutralizing antibody titer in the body is initially higher, but almost all of them drop significantly after 4 months, when the new variant strain strikes, the neutralizing antibodies and cellular immunity produced by the previous generation of natural infection are not enough to prevent a new round of infection, the above has occurred three times, namely the Alpha variant, the Delta variant and the Omiljung variant."
"The fundamental reason for the current appearance of 'herd immunity' abroad is to rely on high vaccination rates and booster needles. Although the protection obtained by natural infection cannot be excluded, the effect is very limited. ”
"At the end of the day, as the domestic epidemic enters the second half, the most important strategy is to further increase the vaccination rate and accelerate the improvement and in-depth study of existing vaccines."
Resources:
[1] Neutralization Profile after Recovery from SARS-CoV-2 Omicron Infection，
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://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00129-3/fulltext#fig3
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