The COVID-19 pandemic has significantly elevated our familiarity with the immune system’s key players. While antibodies, B cells, and T cells are widely recognized as crucial components of the body’s defense against SARS-CoV-2 and similar viruses, they aren’t operating in isolation.
A recent study, published on August 18 in the journal Cell, reveals a fascinating discovery: innate immune cells, which play a pivotal role in combating COVID-19, undergo persistent changes for at least a year after infection. This finding raises intriguing possibilities regarding the connection between these altered cells and the enduring symptoms observed in Long COVID patients. However, further research is imperative to establish this potential correlation.
The innate immune system acts as the body’s primary line of defense, encompassing versatile pathogen-fighting cells designed to combat various threats, including viruses, bacteria, fungi, and parasites, in a broad manner. Unlike B cells and T cells that specifically target certain pathogens, innate immune cells respond more generically. Steven Josefowicz, an associate professor at Weill Cornell Medicine, and his research team discovered that even after a severe COVID-19 infection, innate immune cells retain a memory of their encounter with SARS-CoV-2. This retained memory leads to a sustained response that endures for at least a year after the initial infection.
This groundbreaking revelation holds implications for comprehending how infections shape the immune system, including the non-specific elements that don’t tailor responses to particular pathogens. Additionally, it may provide insights into the reasons some individuals continue to experience prolonged symptoms after encountering SARS-CoV-2. Josefowicz’s focus was on the precursor cells of innate immune cells—stem cells residing in the bone marrow responsible for continuously replenishing the immune cell reservoir. While most of these stem cells are located in the bone marrow and necessitate the invasive procedure of bone marrow aspiration, a subset of them circulate in the blood. Josefowicz managed to extract and amplify these circulating stem cells, enabling their study without resorting to intrusive bone marrow biopsies.
The study uncovered that these cells underwent genetic changes, altering their gene expression to favor increased production of inflammatory factors. This transformation persisted for at least a year following a severe COVID-19 infection. Since these stem cells generate new batches of innate immune cells, the genetic changes propagate to subsequent generations of cells. In laboratory tests, these altered cells demonstrated an enhanced capacity to produce inflammatory factors and exhibited an elevated likelihood of migration, which could potentially spread inflammatory effects to other tissues. In animal models, these hyperactive cells migrated predominantly to the lungs, brain, and heart—organs significantly affected by Long COVID.
The escalation of inflammatory factors could be a response to the severity of a SARS-CoV-2 infection. Josefowicz explained that the immune system might perceive severe COVID-19 as the onset of a chronic infection, prompting an intensified defensive response to bolster the odds of countering the virus.
While the relationship between this COVID-19 memory and Long COVID remains uncertain, this research may inspire additional investigations into how viruses like SARS-CoV-2 reshape the immune system, both in the short and long term. Dr. Lindsay Lief, a co-author of the study, suggests that this marks the initial stage of exploring distinctions between viral infections like COVID-19 and more common illnesses. Understanding how infections influence the immune system’s responses could influence not only symptomatology but also how individuals react to future infections or vaccinations.
The pandemic provided a unique opportunity to scrutinize how the immune system evolves in response to a virus, given the simultaneous infections and the absence of vaccine interference. The blood samples analyzed were obtained from ICU patients in the spring of 2020, predating the availability of vaccines. By examining health records during ICU stays, researchers identified a potential hint regarding an intervention that could temper the extent of immune system changes. Patients who received drugs to inhibit IL6—a molecule that triggers inflammation—displayed lower levels of innate immune cells prone to producing inflammatory factors. Although the drug’s impact on alleviating severe COVID-19 symptoms during ICU treatment was limited, the study suggests it might have curbed gene expression changes in innate immune stem cells. This, in turn, could reduce the likelihood of Long COVID-like symptoms, though additional research is necessary to confirm this hypothesis.
Josefowicz underscores that this discovery opens the door for further research to establish links between these changes and specific clinical outcomes and disease states. The adaptability of blood cells offers the potential to guide them toward a healthier state post-infection.
