In the global effort to overcome COVID-19, much scientific and medical attention has focused on our immune system’s ability to make antibodies. Antibodies are one of our body’s main weapons against viruses, designed to recognize specific proteins on the surface of a virus and initiate processes that eventually neutralize and eliminate the virus.
We know that for other human coronaviruses, when the body makes antibodies against them, these then provide immunity. Teams developing vaccines against SARS-CoV-2 are therefore convinced that their vaccines can produce equally effective responses against COVID-19. But there is still a lot to understand – not least how long these vaccines will protect us. Fortunately, science is gradually catching up with the virus, and we’re starting to understand more about the antibody responses to it.
An unexpected finding was recently discovered by one French study. The study (which is not yet to be peer-reviewed) examined SARS-CoV-2 antibodies in the blood of hospital personnel who tested positive for the virus and showed mild symptoms. By analyzing two samples from each person taken a few months apart, the researchers were able to determine how quickly antibody levels fade after infection and which factors were associated with this decrease.
The study found that antibodies that recognized the SARS-CoV-2 spike protein, one of the main proteins on the surface of the virus, decreased faster in men than women. As these levels dropped, so did the body’s ability to neutralize the virus. Although the study also looked at the effect of age and body mass index (BMI), none of these variables were associated with a faster decrease in antibodies or were linked to the effect in men.
Antibodies specific for another target, the SARS-CoV-2 nucleocapsid protein, were also examined. These antibodies also disappeared from the blood over time, but unlike the spike protein antibodies, there was no difference in this decrease between men and women.
Do these findings mean that immunity to re-infection in men disappears faster and that women are protected from the virus longer?
Not necessary. A closer look at the data shows that there was no difference between the antibody levels in men and women at the end of the study. The faster decline in men occurred because their antibody levels started at a higher starting point. Since antibody levels in men were not lower than those in women after six months, there is no evidence that they are less protected.
However, the research poses some intriguing questions. We know that elderly people, people with a higher BMI and men are at greater risk of severe COVID-19 and all higher antibody responses are seen in patients with more severe disease. In fact, the French study reported that each of these clinical or biological features was associated with higher antibody levels shortly after infection, suggesting that these patients were likely to suffer from more serious infections. But unlike men in general, antibody levels in those with a higher BMI or those older afterward remained high.
If higher antibody levels are maintained longer in those who have had a more severe infection, why didn’t it seem to be happening in men?
The Puzzle of Sex Differences in Immunity
The question of how the level of antibodies in the blood is maintained has interested immunologists for years. Antibodies are produced by immune cells called plasma cells, which in turn develop from cells known as B lymphocytes. We know that in order for antibody responses to last, it is crucial that plasma cells can also survive a long time, in a special form known as long-lived plasma cellsor LLPCs.
We still do not fully understand the critical factors that affect the lifespan of LLPC. However, it is likely that the characteristics of the LLPCs themselves, as well as factors from their environment or “niche” within the body, are involved. These factors may very well differ between men and women – there are gender-related differences in immune responses well described earlier.
For example, women have more B lymphocytes that produce antibodies and generally make more antibodies. Thus, it may be that as a result, women make a more effective ‘measured’ response to SARS-CoV-2, while the male response is more erratic: ineffective at first, then extremely during severe acute infection, but disappear more quickly once the infection is cleared.
Antibody-producing LLPCs are also not the only components of the immune response important for long-term protection against viruses. Another type of immune cell – memory T lymphocytes – that persist long after the virus is cleared and orchestrates a stronger, faster immune response upon reinfection is also crucial.
Promising, data will now appear to show that these cells, which can kill virus-infected cells and also aid in the production of antibodies, also persist for up to six months after the initial infection with SARS-CoV-2 in both men and women.
It is hoped that several effective vaccines against SARS-CoV-2 will be available soon. While it is too early to say whether these will result in long-term protection, it is safe to say that they will require sustained antibody responses for them in both women and men. From what we’re starting to see, the trajectory of these responses can be different with each gender.