Multiple studies have confirmed that the body still has COVID-19 antibodies one year after infection!

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Recently, Sinopharm Group and Shanghai Jiaotong University have collaborated to reveal the changes in the levels of COVID-19 antibodies in patients who recovered from COVID-19 infection in Wuhan for up to 12 months. The study included 869 patients who recovered from natural infection in Wuhan, and a total of 1,782 plasma samples were collected and analyzed. The results showed that more than 70% of patients who recovered from COVID-19 infection remained positive for COVID-19 antibodies within 12 months after infection; according to the analysis of plasma samples, the antibody titer levels in patients who recovered from COVID-19 infection stabilized in the 9th month.

Written by Yang Xinzhou

As the COVID-19 vaccination rate increases, many people are concerned about how long the vaccine can provide immune protection. Because the vaccination time is not long enough, the academic community cannot yet provide direct evidence to show how long the vaccine is effective. However, we can find some data from the side to indicate the time dimension of individuals retaining COVID-19 antibodies.

This method was tried during the SARS period. Although there was no SARS vaccine on the market, the persistence of relevant antibodies can be understood by tracking patients over a long period of time and collecting blood samples. According to existing data, SARS patients can maintain a certain amount of specific antibodies within two years of infection on average, but in the third year, the antibody level will drop sharply.

Immune memory persists one year after infection

Is this the same for COVID-19 patients? Some studies have found that COVID-19 patients produce large amounts of IgM (the earliest antibody to appear after antigen stimulation) and IgG (accounting for 70%-75% of the total immunoglobulin in the blood, which disappears slowly) within a few days of infection, with the IgM titer reaching its peak around 10 to 12 days.

The difference is that IgG levels will continue to rise three weeks after the onset of symptoms. A study published in Science in February this year suggested that the receptor binding domain (RBD) of the coronavirus spike protein will decrease eight months after infection. However, the number of memory B cells targeting the spike protein will increase from the first to the eighth month, among which IgG memory B cells still occupy the main position. According to the conclusion of Science, 95% of infected people can still maintain the main immune memory for at least half a year.

Six months after infection, the human body can maintain a variety of immune memories, including IgG, memory B cells, and specific T cells against RBD. (Image source: DOI: 10.1126/science.abf4063) So can the human body maintain this immune memory for a longer period of time? Recently, a number of studies have investigated the changes in antibodies in COVID-19 patients within 12 months. One of them was jointly completed by Sinopharm Group and Shanghai Jiaotong University. Their collaborative study published in Nature Communications showed that even 12 months after infection, the recovered patients still had a certain titer of IgG antibodies (RBD IgG) against the new coronavirus RBD in their bodies, and in the virus neutralization test, these antibodies can have a neutralizing effect.

Image source: Nat Commun 12, 4144 (2021). The study collected 1,782 plasma samples from 869 recovered COVID-19 patients in Wuhan, which were collected 12 months after infection. The study first tested the IgG levels of samples in different time periods. In the first two months after diagnosis (early stage), the RBD IgG (1:80) positive rate was 94.6%; and in the 6th to 7th month (mid-term), 89.4% of the samples could still detect RBD IgG; this data will drop to 81.2% in the 11th to 12th month (late stage).

The study used gradient dilution to set 1:320-1:640 as medium titer antibodies, and 1:1280 and greater than 1:2560 as high titer antibodies. According to the test results, the proportions of medium and high titer antibodies in the early, middle and late samples were 72.6%, 41.3% and 27.2%, respectively. It is worth mentioning that in the early samples, 5.4% of them still had almost no RBD IgG detected, which indicates that a small number of people cannot produce effective antibodies after infection.

From the timeline, the patient's RBD IgG antibody level will continue to decline within 9 months of diagnosis and stabilize after 9 months. Compared with the antibody titer in the first month, the antibody titer in the 12th month decreased by 69.9%. In addition, those who recovered and produced a large amount of antibodies at the beginning of the infection also had higher RBD IgG titers in the 12th month.

Image source: Nat Commun 12, 4144 (2021).

In addition, there are gender differences in RBD IgG levels. Within 12 months of diagnosis, the RBD IgG titer of men is always higher than that of women, especially in the early stage, the difference in IgG titer is more obvious. In the early stage of the epidemic, there were studies reporting that people with type A blood are more susceptible to infection with the new coronavirus, but in this study, no significant difference in RBD IgG titers was found between people with different blood types.

Multiple studies support

Coincidentally, the Uniformed Services University of the Health Sciences in the United States conducted an analysis on this. In short, the results are almost the same as the above study, except that there is a special group of people in the United States (people who were infected but not hospitalized) who can be analyzed in additional groups. One year after infection, 100% of the recovered patients in the hospitalized group had COVID-19 antibodies; in the non-hospitalized group, 95% and 80% still had COVID-19 antibodies 6 months and 1 year after infection. The relevant research is currently published on the preprint website medRxiv.

Similarly, at the beginning of the infection, the antibody levels of hospitalized people were significantly higher than those of non-hospitalized people. In subsequent tests, the half-life of antibodies in the two groups was 88 days and 77 days, respectively.

Among non-hospitalized people, antibody levels are positively correlated with age, with people aged 65 and above having the highest levels of antibodies. This can also be confirmed in studies of the Wuhan population, and the Nature Communications study also found that the older the age, the higher the RBD IgG titer.

In June this year, Tongji University and Huazhong University of Science and Technology analyzed a small number of samples from recovered COVID-19 patients. According to a study published in Frontiers in Immunology, a total of 76 patients provided a total of 162 samples. It is certain that 90% of patients still have RBD IgG after one year.

In this study, we can also see that IgM will reach its peak within 1 to 2 months, but it is basically undetectable after one year. The IgG antibody is still able to exist stably, and the IgG antibody of different individuals is basically the same at 9 to 10 months after infection.

However, only 42.5% of recovered patients showed neutralizing antibody activity, suggesting that even if they have been infected with the new coronavirus, they may still be infected again. People under the age of 65 who have experienced mild symptoms are most likely to have high levels of neutralizing antibody activity.

In addition, the sensitivity of the immune response of recovered patients to the new coronavirus mutant strain is also low. The researchers used serum samples from 53 recovered patients in the sixth month to conduct neutralization tests on the "Beta" mutant strain (the B.1.351 mutant strain found in South Africa). As a result, only 12 samples (22.6%) showed neutralizing activity, and only 3 samples (5.7%) showed high neutralizing antibody titers. This means that the initial recovered patients of the new coronavirus may have almost no resistance to the mutant strain and can still be infected again.

The figure on the left shows that the neutralizing activity of recovered patients' serum against mutant strains will be significantly reduced. (Image source: DOI=10.3389/fimmu.2021.708523)
These studies suggest that our immune system can maintain memory of the new coronavirus for a long time.

Vaccination in the form of active immunization can also activate the immune system and provide long-term protection. In June, researchers from the Chinese Center for Disease Control and Prevention said that existing studies have shown that several domestic vaccines can neutralize multiple mutant strains. As time goes by, there will definitely be studies in the future that show longer-term changes in human COVID-19 antibodies. At this moment, vaccination is definitely the best way to obtain immune protection (it is always better than getting immune protection through a wave of infection).

References:

https://www.nature.com/articles/s41467-021-24230-5#citeas

https://science.sciencemag.org/content/371/6529/eabf4063

https://www.frontiersin.org/articles/10.3389/fimmu.2021.708523/full

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