Abstract
As we navigate through the third year of the coronavirus disease 2019 (COVID-19) pandemic, and face the sixth or seventh wave of infections, which now includes multiple subspecies of the Omicron variant, it is starting to feel like the pandemic might soon be over. Unfortunately, such a statement must always be qualified because many people around the world do not yet have the luxury of living normally while severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still circulating at high levels in most places.
When SARS-CoV-2 first emerged, no one had virus-specific immunity against it, although we now know that some individuals already possessed low-level cross-reactive immunity acquired from seasonal coronavirus infection, but clearly this was not sufficient to prevent the high rates of morbidity and mortality that was originally observed. This meant that for millions of people, the first time their immune system saw the virus was during natural infection. Thankfully, most countries did not choose to try to establish herd immunity through unchecked natural infection. Other countries, unfortunately, may have had no other option.
For developed countries, vaccines became available in record time, meaning that for millions of other people, the first time their immune system saw any part of the virus was through COVID-19 vaccination. So for some time, and even now at the time this article is being written, we have the luxury of comparing the immune response elicited by natural infection of SARS-CoV-2 versus immunity generated through COVID-19 vaccination. In this issue, Moore et al. have done just that, and report the presence of SARS-CoV-2-specific memory B cell responses in both naturally infected and vaccinated groups. Interestingly, they also found that memory B cell responses directed against spike protein showed less waning over time in vaccinated versus naturally infected donors. By now, we have seen other similar reports and we will continue to learn more on this topic in the near future.
As the pandemic progressed and vaccines were rolled out at different times and rates in various parts of the world, we began to see additional groups emerge with differently acquired SARS-CoV-2 immunity. With the rapid rise in cases due to the emergence of Omicron, and its stealthy ability to evade the immune system, we saw a sharp increase in breakthrough infection of vaccinated individuals. What this means is we now have two groups of previously infected people who were either infected and subsequently vaccinated, or vaccinated and subsequently infected. This “hybrid immunity” refers to the combination of virus- and vaccine-derived immunity. These two forms of hybrid immunity will be interesting to compare with respect to the magnitude and breadth of the immune response acquired in the presence of two reciprocal timings of immune exposures. It will also be interesting to know whether one or the other form of hybrid immunity results in a more durable memory B or T cell response.
In the bigger picture, many parts of the world are now administering, or about to administer, second boosters. The presence of two different forms of hybrid immunity with a spectrum of different intervals between infection and vaccination ranging from weeks to years will need to be considered when recommending the timing of first and second boosters. For example, thousands of children under 5 years of age have by now been infected before they will be vaccinated. It will be interesting to compare immune responses in children who were vaccinated before they were infected with that of children who were infected before they were vaccinated.
At this point in time, we are all very tired of the pandemic and longing for the day when we can stop worrying about this virus altogether, but from the viral immunology perspective, the pandemic remains to be a fascinating time when we are learning in real time about a virus that we are living with every day.
Finally, I want to sincerely thank all of the authors for their outstanding submissions to Viral Immunology, as well as the many reviewers for their commitment to maintaining a high standard of scientific assessment.