The COVID-19 pandemic has presented a wide range of outcomes, from severe illness to no noticeable symptoms. This variability leads many to wonder why some individuals avoid infection or serious disease. Understanding these differences involves exploring factors such as an individual’s genetic makeup, their immune system responses, and the distinction between truly resisting the virus and having an asymptomatic infection.
Genetic Influences on Susceptibility
An individual’s genetic code can play a part in their likelihood of contracting SARS-CoV-2 or developing severe COVID-19. One area of focus is the ACE2 receptor, the primary entry point for the virus into cells. Variations in the ACE2 gene, located on the X chromosome, could influence how effectively the virus binds and enters cells. While some studies suggest ACE2 gene variants might impact susceptibility, others find no statistical significance between these variations and disease severity.
Human Leukocyte Antigen (HLA) genes are also being investigated for their role in COVID-19 susceptibility and severity. HLA genes are crucial for the immune system’s ability to recognize foreign invaders like viruses. Certain HLA alleles have been linked to increased susceptibility or protection against severe COVID-19, with some showing a higher capacity to bind to SARS-CoV-2 peptides and offer protection. For example, the HLA-DRB104:01 variant is more frequent in asymptomatic individuals compared to symptomatic individuals, suggesting a protective role against severe outcomes. Additionally, variations in genes related to inflammatory responses, like the macrophage migration inhibitory factor (MIF) gene, influence both susceptibility to infection and the risk of severe disease.
Immune System Responses and Protection
The body’s immune system mounts a multifaceted defense against SARS-CoV-2, influencing infection and symptom severity. The innate immune system is the first line of defense, recognizing viral patterns and initiating an immediate response to limit viral replication. An effective early innate immune response can reduce the viral load and allow the adaptive immune system to develop a specific defense.
Beyond this initial response, prior exposure to common cold coronaviruses (HCoVs) can contribute to cross-reactive immunity. Immune cells, particularly memory T-cells, from past HCoV infections might recognize and react to SARS-CoV-2, offering some protection or leading to milder disease. Studies show activation of these cross-reactive T-helper cells in exposed individuals, indicating their role in enhancing the immune response. While antibody responses against SARS-CoV-2 can wane quickly, memory T-cell responses persist longer, recognizing new viral variants.
Understanding Asymptomatic Cases and True Resistance
Many who believe they “didn’t get COVID” may have experienced an asymptomatic infection, meaning they contracted SARS-CoV-2 but developed no noticeable symptoms. Asymptomatic cases are common, with studies suggesting that at least one in five infected people remain asymptomatic. Factors contributing to asymptomatic infection can include a lower initial viral load or a robust and rapid early immune response that clears the virus before symptoms emerge. Asymptomatic individuals can still transmit the virus to others.
True resistance, in contrast to asymptomatic infection, means an individual is exposed but fails to establish infection. This phenomenon is less understood and is much rarer than asymptomatic infection. Research investigates the mechanisms that might confer true resistance, such as unique genetic predispositions or efficient initial immune responses that prevent viral entry or replication. While some genetic factors are associated with reduced susceptibility or milder disease, complete immunity to infection upon exposure remains an area of ongoing scientific exploration.