Immunity Debt, a Gap in Learning, or Immune Dysfunction?

Viral ImmunologyVol. 36, No. 1 EditorialFree AccessImmunity Debt, a Gap in Learning, or Immune Dysfunction?Robert F. Needle and Rodney S. RussellRobert F. Needlehttps://orcid.org/0000-0001-8844-4981Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St. John's, Canada.Public Health and Microbiology Laboratory, Eastern Health, St. John's, Canada.Search for more papers by this author and Rodney S. RussellAddress correspondence to: Dr. Rodney Russell, Division of BioMedical Sciences, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's A1C 5S7, Canada E-mail Address: [email protected]E-mail Address: [email protected]Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St. John's, Canada.Search for more papers by this authorPublished Online:16 Jan 2023https://doi.org/10.1089/vim.2022.0204AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail As we bring in the new year of 2023, and say farewell to the year when many of us got acquainted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the first time, the “new normal” is looking much as predicted. Many people have been vaccinated against coronavirus disease 2019 (COVID-19), and many now have hybrid immunity. Anyone watching the pandemic closely would have expected the new normal to include most people living much as they did before the pandemic, but others still having to be extra careful. We expected things to settle down and for most of society to function as it always did, but once everyone accepted that this virus was here to stay, there came the realization that many individuals would not get back to normal as quickly as others would.Unfortunately, the immunologically vulnerable still have to be very careful, especially if they do not yet know how they will fare with COVID-19. Anyone with any kind of immunocompromised state may struggle with clearing a SARS-CoV-2 infection, and more importantly, might not realize that they may not have responded well to the COVID-19 vaccines they received. These immunologically vulnerable individuals were probably already being extra careful about influenza and other infections, but now they have another virus to worry about, one that is still very prevalent and highly contagious within our communities.On the topic of community prevalence, at the beginning of the pandemic, there was much debate over the potential effectiveness of masks and physical distancing with respect to containing SARS-CoV-2, but it became very clear very early that these public health measures indeed helped to reduce transmission rates. One of the more obvious impacts of such measures was evident when the usual respiratory viruses failed to arrive in their normal numbers during 2020 and 2021 when extensive public health guidelines and encouragement of masking were still in place in much of the world. It is not surprising now to see respiratory viruses, such as influenza virus, respiratory syncytial virus, adenoviruses, rhinoviruses, among others, returning with what feels like a vengeance.Collecting data on prevalence and severity also comes with new and interesting challenges. Substantial investment into respiratory testing during the pandemic has led to increased testing of all respiratory pathogens, including testing of different patient populations and different viruses. So while epidemiology confirms that influenza virus and respiratory syncytial virus were prevalent earlier than usual this year, the percent positive remains within historical ranges. This begs the question, would the current higher percentage positive numbers still differ had a similar more targeted patient population been tested prepandemic? Or, are the laboratory data revealing that respiratory viruses are just more common this year, and it is this larger number of cases that is causing the influx seen in many hospitals? In the end, this is another topic for research to increase our understanding around the many impacts of the COVID-19 pandemic.What may not have been so predictable was the severity of these common respiratory infections. When “flu season” began in 2022, signals were emerging that indicated pediatric hospitals were experiencing more traffic than usual. As the data began to emerge, we saw the usual respiratory viruses arriving earlier and in higher numbers than usual. This increase in children needing medical attention and even hospitalization, unfortunately, has led to some dangerous theories. For example, the term “immunity debt” has emerged, and basically proposes that children's immune systems are now weaker because they have not been exposed to as many pathogens as they would have been in the absence of the public health response to the pandemic.However, the term immunity debt is misleading, and we see this situation as more of a slight “gap in education” that will be made up in short time. Of course children's immune systems are not weaker, but if they have not been exposed to certain viruses on the usual schedule, then they are missing the memory response they would have made had they been infected with some of these viruses for the first time over the past couple of years.On one hand, what is being perceived and immunity debt may just be a delay in education of the immune system that will disappear over the next year as children's immune systems make up for lost time by finally seeing the viruses that have been less prevalent than usual over the past 2 years. However, we cannot dismiss this situation so easily because there are some things we still cannot explain. We know that many viruses actively cause immune dysfunction, although this is more commonly observed in the context of chronic viral infections, and often includes documented T cell exhaustion as well as epigenetic and immunological scarring.Long-term immune dysfunction is not typically caused by acute infections that resolve relatively quickly. With most SARS-CoV-2-infected children experiencing mild COVID-19 symptoms, it is unlikely that their subsequent exaggerated responses to other viruses are linked to SARS-CoV-2-induced immune dysfunction, but some scientists are beginning to ask whether this might be the case.Another theory that might explain the increased severity of current respiratory viral infections could be the simple timing of these infections. In many cases now, we are seeing 5- and 6-year-old children getting introduced to certain viruses for the first time, when in the past, they would have encountered these viruses at the age of 2 or 3 years. So are they experiencing heightened inflammatory responses now at later ages because their immune systems are more developed and, therefore, respond in a more vigorous manner that can include a cytokine storm and extensive inflammation?The other very important immune aspect that needs more attention in this discussion is that of maternal antibodies. At least for very young children, they may have also missed the important benefit normally provided by maternal antibodies acquired during breastfeeding. Then, with females of child-bearing age also experiencing comparably less respiratory infections in the past few years, and many pregnant women potentially trying harder than usual not to get infected with viruses, there had to be a gap in maternal antibody coverage compared with nonpandemic years.And then there is long COVID-19, which is still very much a mystery with respect to how we define it, why some get it and others do not, and what impact it has on the immune system. In individuals with long COVID-19, it would not be surprising to see a detrimental effect on how well the immune system can subsequently deal with other viral infections, but it will take time to determine whether this is the case.Many people would now argue that the pandemic is over, and perhaps the urgency of it is, but we are still very much living within the impacts and the fallout of the pandemic. The topic of viral immunology continues to be in the forefront of our minds because, for example, the resurgence of respiratory viruses is affecting the daily lives of anyone with, or interacting with, children. It will be interesting going forward to know the answers to these questions around immunity gaps and immune dysfunction. Despite all the torment and tragedy that came with the pandemic, it has been, and will continue to be, an intense period of learning for the field of viral immunology.FiguresReferencesRelatedDetailsCited byNo signs of “tripledemic” in Finnish children6 March 2023 | Journal of Medical Virology, Vol. 95, No. 3 Volume 36Issue 1Jan 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Robert F. Needle and Rodney S. Russell.Immunity Debt, a Gap in Learning, or Immune Dysfunction?.Viral Immunology.Jan 2023.1-2.http://doi.org/10.1089/vim.2022.0204Published in Volume: 36 Issue 1: January 16, 2023PDF download