Are we really done with Covid? The general perception now seems to be that Covid is like getting a cold or the flu—you get it, you get over it, and life goes on. No big deal. We are certainly not in the 5-alarm-fire mode that we were in four years ago, but that doesn’t mean the fire is out. The pandemic may not have been an extinction-level event for humanity, in that we survived it, but Covid appears to have permanently altered our ability to resist infections at a “herd immunity” level.
I don’t know how many of you saw (or read) the excellent article by Examined: Covid. It’s On. Again. There are three resources linked in that story, which I would encourage you to read. There is an amazing amount of research that has been done and is still being done. The good news is that we know a lot more now about how Covid affects the immune system. The bad news is that it really, really does a number on our immune system.
From the linked Memorial Sloan Kettering website, we have this [emphases added]:
CD4+ helper T cells and CD8+ cytotoxic T cells have been identified as crucial in the immunologic response to SARS-CoV-2 infection. CD4+ T cells are responsive to the virus's spike protein, and the presence of CD8+ T cell expansion in bronchoalveolar lavage is correlated with illness moderation. However, one of the most remarkable characteristics of immune dysregulation in COVID-19 is an immense depletion of CD4+ and CD8+ T cells associated with disease severity.
While lymphopenia is observed in other respiratory viral illnesses such as influenza A H3N2 viral infection, COVID-19 induced lymphocytic depletion is distinctive for its magnitude and longevity. Additionally, CD8+ T cells, crucial for their cytotoxic activity against virally infected cells, may experience the more stark reduction. <snip>
Now, three years into the pandemic, with millions of infections and immunizations behind us, severe acute COVID-1 infections are becoming significantly less common -- though COVID-19 is still causing significant hospitalizations and mortality across the globe. But generally speaking most individuals are no longer concerned with the acute infection stage of COVID-19. To the point that getting the virus may seem unremarkable and not a cause for concern.
However, a new idea about how COVID can affect immunity has emerged: that even mild infections routinely cause consequential damage to our bodies’ defenses. This degradation was referred to as “immunity theft” by T. Ryan Gregory, an evolutionary biologist, as a counterargument to "immunity debt" being the reason why respiratory infections were more severe than usual this past fall. <snip>
A March 2023 study published in the journal Immunity looked at how the immune system responded to both COVID-19 infection and COVID-19 vaccination. What the researchers found was that the magnitude and quality of CD8+ T cell activation and expansion after two COVID-19 vaccine doses were considerably lower in people with prior SARS-CoV-2 infection compared to people without prior infection, suggesting that previous infection can influence the T cell response to vaccination.
Taken together, the researchers write, "these findings suggest that SARS-CoV-2 infection damages the CD8+ T cell response, an effect akin to that observed in earlier studies showing long-term damage to the immune system after infection with viruses such as hepatitis C or HIV. The new findings highlight the need to develop vaccination strategies to specifically boost antiviral CD8+ T cell responses in people previously infected with SARS-CoV-2, the researchers conclude."
And from the linked World Health Network article, we have this [emphases added]:
We know that reinfections occur, and they seem to be increasing. With our present high levels of transmission, many individuals will likely be experiencing two or more infections per year going forward. The immune system is damaged for more than half a year after infection, with dendritic cell deficiencies at least 7 months and both innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune cells (T helper, T follicular helper, and regulatory T cells) shown to be involved in immune dysfunction which had not ended at 8 months after infection. Reinfection has been shown to increase the cumulative risk of death, hospitalization, and sequelae in multiple organ systems in both the acute and postacute phase. This shows the immune system is not protective enough to limit damage by further COVID-19 infections or other infections, even after vaccination. This is a serious issue if we are continually reinfected before the immune system recovers each time. It is also important to remember that although children can still produce naive T cells, adults have a limited number. A very serious concern is that multiple COVID-19 infections early in life might age the immune system leading to immune systems similar to those of elderly in considerably younger individuals.
Our immunological protection against infection is also showing signs of decline with the omicron variant, and especially its new subvariants. Immune responses are not effectively induced against the omicron variant by previous infections with earlier variants, even in triply vaccinated individuals, and omicron infection itself is not an effective natural immune booster against itself. Furthermore, this study indicates a decline in the positive aspects of the immune response by some means. Hence, we can expect the negative aspects of infection to increase in severity because the antibody responses are not as effective. Combined with the increased SARS-COV-2 binding affinity, and reduced ability to clear the virus, it appears we should anticipate more chronic infections.
COVID-19 infection has several very concerning effects on the immune system that might easily lead to advantages for other pathogens as well as worse outcomes in COVID-19 reinfections. This immune dysfunction or aging is at least one of the most likely scenarios explaining the recent surges in diseases like RSV, influenza, Strep A, and other infections. By contrast, immunity debt is not considered a viable explanation as the surges of these diseases continue in countries that had surges last season and immunity wanes for many of these diseases. Another serious concern at this point is that repeated infections by COVID-19 might lead to depletion or exhaustion of cytotoxic CD8+ T cells which could have downstream effects on other diseases like cancers, as these T cells are instrumental in limiting tumor proliferation and have been shown to differentiate to become dysfunctional.
The World Health Network article has a list of research articles at the end. The author has kindly quoted the researchers’ conclusions or summarized their articles, and in several cases, has included a figure from an article that helps explain how the immune system works and how Covid damages it. Reading through these summaries makes it clear how devastating Covid is. It is not “just like a cold.”
The bottom line is that, even if you had a mild case and fully recovered from the initial Covid infection without getting long Covid, your immune system has been compromised. This makes it more difficult for your body to resist other pathogens, like RSV and influenza viruses, which would account for the increased rates and severity of those infections that are now being seen. There is also evidence that Covid causes permanent, long-term changes in the immune system that are similar to AIDS.
The full effects of Covid will not be seen for years, but it is not hard to predict that we will have far more people who are disabled in the future. Our (inadequate) social safety nets for people with disabilities were already maxed out and now we have millions more who have been disabled from Covid-associated events (e.g., stroke, heart attack, kidney failure) and from long Covid. We already have a shortage of doctors and nurses as well as a shortage of long-term care facilities, but we haven’t even begun to see the impacts from the increased incidence of autoimmune diseases and the increased susceptibility to other infectious diseases and cancers.
It is astonishing to me that there is not more concern about Covid and more effort to avoid infection. I understand that folks are just over it and want to move on with their lives. But Covid is not done with us. It’s just getting started. We really should be paying attention.