Immunity and resistance to infections: why you get sick more often than others

The frequency of colds, herpes reactivations and other viral episodes can differ even with a similar lifestyle, sleep and diet. This difference is related to how quickly the immune system can recognise a virus and how effectively it can contain its spread. This ability varies between people because of the combined contribution of many genetic variants, each of which has its own effect. So there is no point looking for a single “immunity gene”.

Population studies confirm a genetic component in susceptibility to respiratory tract infections and other viral infections (Tängdén et al., Sci Rep, 2022). For some viruses — in particular Epstein-Barr and varicella — specific mechanisms of immune control over the virus after primary infection have been documented (Wang et al., Front Microbiol, 2024; Lens et al., Cureus, 2025). These mechanisms are related to how the immune system responds to a virus — from recognising it to building lasting protection.

How the body responds to a viral infection

A virus entering the body comes into contact with cells of the innate immune system — macrophages, neutrophils, dendritic cells. On the surface of these cells there are pattern-recognition receptors that bind to characteristic molecular structures of the virus. This binding triggers two processes in the cell: the synthesis of interferons, which limit the multiplication of the virus in neighbouring cells, and the release of pro-inflammatory cytokines, which mobilise additional immune cells to the site of infection (Stergioti et al., Biomedicines, 2022). A raised temperature, swelling of the mucous membrane and general weakness during a cold are a physiological consequence of the action of these cytokines, not a separate process. Innate immune receptors recognise structures common to many viruses, so this reaction develops within minutes to hours, although it does not provide protection specific to this particular virus.

Dendritic cells that captured viral particles during this initial reaction carry fragments of viral proteins to the lymph nodes and present them to T lymphocytes (Marongiu et al., Clin Sci, 2021). This triggers the multiplication of T and B lymphocytes specific to this virus, which takes several days. Cytotoxic T lymphocytes destroy already infected cells, while B lymphocytes produce antibodies that bind to viral particles and neutralise them. Some of these T and B lymphocytes remain in the body as memory cells, so on repeated contact with the same virus the specific response develops faster (Hope & Bradley, Science, 2021).

The speed and strength of each of these processes — recognition of the virus by receptors, interferon production, the intensity of the inflammatory reaction, the speed of formation of specific T and B lymphocytes — differ between people even in the absence of chronic diseases. Some of these differences are inherited. So the consequences of contact with a virus depend on how quickly and actively these lines of defence are triggered. A strong receptor reaction and active interferon synthesis can contain the multiplication of the virus even before symptoms appear. If this early response is weaker, the virus has time to multiply more before the specific response of T and B lymphocytes is formed.

Which genetic features influence the antiviral response

A study based on UK Biobank data identified 57 unique regions of the genome associated with an increased risk of bacterial and viral infections of the respiratory tract, abdominal cavity and other sites (Tängdén et al., Sci Rep, 2022). This confirms that susceptibility to infections is not only a matter of lifestyle but also a measurable genetic factor, although a study of this scale does not yet break this susceptibility down into individual antiviral mechanisms.

A review of genetic studies of viral infections notes that for some viruses — in particular seasonal influenza — genome-wide studies remain insufficiently powered to identify significant loci because of the high variability of the virus and the difficulty of controlling for the real influence of the environment (Butković & Elena, Front Syst Biol, 2022). So for now one should not claim the existence of a specific, well-replicated genetic profile of susceptibility to influenza, and likewise one should not extend these isolated findings to other viral infections.

At the same time, there is more precise data for the antibody response to specific viruses: a study of the genetic determinants of the antibody response to 13 infectious agents based on UK Biobank data showed that the region of the human leukocyte antigen (HLA) genes — the same ones that present antigens to T lymphocytes — is associated with variability in the antibody response to different pathogens (Butler-Laporte et al., Open Forum Infect Dis, 2020). For the Epstein-Barr virus the same study identified additional loci outside the HLA region: RASA3 (RAS p21 protein activator 3), MED12L (mediator complex subunit 12L) and IRF4 (interferon regulatory factor 4).

Variability through the HLA region recurs as a significant factor for different pathogens, whereas genes outside this region are specific to a particular virus and require separate confirmation for each phenotype.

Why some viral infections can return after primary infection

Some viruses remain in the body even after the acute symptoms of the illness have passed. Herpesviruses — a family of DNA-containing viruses that includes the Epstein-Barr virus and the varicella-zoster virus — after primary infection go into a state of latency and remain in the body for life. More than 90% of the world’s adult population is infected with the Epstein-Barr virus (Wong et al., J Cancer Res Clin Oncol, 2022). In the latent state the virus usually causes no symptoms, but, unlike a completely eliminated infection, it retains the ability to reactivate periodically. For the Epstein-Barr virus the site of such latency is the B lymphocytes; for the varicella-zoster virus it is the neurons of the sensory ganglia (clusters of nerve cells).

In the case of the Epstein-Barr virus, latency is maintained directly by the activity of the immune system: cytotoxic T lymphocytes constantly detect and destroy the few B lymphocytes in which the virus enters an active phase, preventing the infection from developing again (Wang et al., Front Microbiol, 2024). When this control weakens — because of exhaustion of the immune system, stress or other temporary factors — the virus gets more opportunities to reactivate. Researchers have not yet carried out a direct genetic assessment of the variability of this particular cellular control. And the available genetic data for Epstein-Barr virus infection mostly concern the variability of the antibody response, which is associated with the HLA region — the same cluster of genes responsible for antigen presentation (Butler-Laporte et al., Open Forum Infect Dis, 2020).

A similar mechanism underlies herpes zoster infection — the reactivation of the varicella-zoster virus, which is stored for years in the nerve ganglia in a latent state. A review of the stimuli and deterrents of reactivation of this virus points to cellular immunity as the main barrier that keeps the virus in an inactive form, and the weakening of this particular barrier — through age, stress or other factors — increases the likelihood of the infection returning (Lens et al., Cureus, 2025). Age is one of the documented factors of such weakening, but not the only one. And not all people of the same age show the same decline in cellular control over the virus, which also leaves room for inherited differences.

Allergy and frequent infections: different immune mechanisms

Susceptibility to frequent viral infections and susceptibility to allergy are immune processes that are opposite in direction. In the first case it is a matter of an insufficiently effective or slowed response to a real pathogen: the immune system recognises the threat later or more weakly than is needed to suppress the infection quickly. In the second case, on the contrary, it is an excessive reaction to substances that in themselves pose no danger: pollen, pet allergens or food components.

These two processes involve different parts of the immune system and are regulated by different genetic factors, so frequent colds or herpes rashes should not automatically be explained by allergic hyperreactivity or, conversely, susceptibility to allergy should not be perceived as a sign of weak immunity in general.

What determines susceptibility to frequent infections

The frequency of infections does not depend on a single factor. It is influenced by the number of contacts with pathogens, age, state of health, sleep, chronic stress, diet, vaccination and other conditions in which the immune system works. Genetic differences can also influence how effectively the body recognises a virus and controls an infection. At the same time, genetic data do not explain why an infection occurred at a particular moment: they describe stable differences in the work of certain parts of the immune response, whereas a specific episode of illness also depends on which pathogen a person came into contact with, under what circumstances this happened and what state the body was in. A genetic predisposition to certain features of the antiviral response does not in itself indicate immunodeficiency.

As part of the Ultima genetic panel, which analyses more than 1000 indicators, Apixmed Prism assesses genetic markers associated with features of the antiviral response and susceptibility to reactivation of individual herpesviruses. Such information provides additional genetic context, but does not replace an assessment of symptoms, medical history and other medical data by a specialist if infections recur frequently or have an unusual course.

Answers to common questions

Does a genetic susceptibility to infections mean that my immunity is weakened?

No. A genetic susceptibility reflects individual features in the work of particular parts of the antiviral defence. So the results of a genetic test are not a diagnosis of immunodeficiency. Clinical immunodeficiency is determined by other medical criteria and requires assessment by a doctor.

Is there a gene that determines susceptibility to colds or herpes?

No, for such infections there is no single gene that determines whether a person will get sick or not. Genetic susceptibility is formed by the contribution of many genetic variants, and whether it manifests also depends on contact with the pathogen, the state of the immune system and other factors. So it is correct to speak of genetic variants associated with features of the antiviral response, rather than of a “cold gene” or a “herpes gene”.

Can a single test tell me why I got sick last time?

No. A genetic report describes inherited features that remain unchanged throughout life, not the cause of a specific episode of illness. Whether an infection occurs at a particular moment is influenced not only by genetic features but also by contact with the pathogen and its properties, the state of the body and other circumstances.

How does a frequent cold differ from an allergy with similar symptoms?

A cold occurs through infection with a virus, whereas an allergy occurs through an immune reaction to a normally harmless substance, for example pollen or components of house dust. The symptoms can be similar, but the mechanisms behind them are different: with a cold the body reacts to an infectious agent, and with an allergy — to an allergen. So the symptoms alone do not always allow the cause of these conditions to be reliably determined.

The results of a genetic test are not a diagnosis and not a substitute for a consultation with a doctor. The Apixmed Prism report provides genetic context that complements the results of examinations and helps make decisions together with a doctor.

Sources

1. Stergioti, E. M., Manolakou, T., Boumpas, D. T., Banos, A. (2022). Antiviral Innate Immune Responses in Autoimmunity: Receptors, Pathways, and Therapeutic Targeting. Biomedicines, 10(11), 2820. https://doi.org/10.3390/biomedicines10112820

2. Tängdén, T., Gustafsson, S., Rao, A. S., Ingelsson, E. (2022). A genome-wide association study in a large community-based cohort identifies multiple loci associated with susceptibility to bacterial and viral infections. Scientific Reports, 12, 2582. https://doi.org/10.1038/s41598-022-05838-z

3. Butković, A., Elena, S. F. (2022). Genome-wide association studies of viral infections — a short guide to a successful experimental and statistical analysis. Frontiers in Systems Biology, 2, 1005758. https://doi.org/10.3389/fsysb.2022.1005758

4. Butler-Laporte, G., Kreuzer, D., Nakanishi, T., Harroud, A., Forgetta, V., Richards, J. B. (2020). Genetic Determinants of Antibody-Mediated Immune Responses to Infectious Diseases Agents: A Genome-Wide and HLA Association Study. Open Forum Infectious Diseases, 7(11), ofaa450. https://doi.org/10.1093/ofid/ofaa450

5. Wang, Y., Yu, J., Pei, Y. (2024). Identifying the key regulators orchestrating Epstein-Barr virus reactivation. Frontiers in Microbiology, 15, 1505191. https://doi.org/10.3389/fmicb.2024.1505191

6. Lens, A., Smith, B., Landi, J., Sibaja, K., Pearl, K., Snytte, C., Prashar, S., Sobczak, A., McConnell, B., Muralidhar, R., Demory, M., Kesselman, M. (2025). Exploring the Potential Stimuli and Deterrents of Varicella-Zoster Viral Reactivation: A Scoping Review. Cureus, 17(3), e81491. https://doi.org/10.7759/cureus.81491

7. Wong, Y., Meehan, M. T., Burrows, S. R., Doolan, D. L., Miles, J. J. (2022). Estimating the global burden of Epstein-Barr virus-related cancers. Journal of Cancer Research and Clinical Oncology, 148(1), 31–46. https://doi.org/10.1007/s00432-021-03824-y

8. Hope, J. L., Bradley, L. M. (2021). Lessons in antiviral immunity. Science, 371(6528), 464–465. https://doi.org/10.1126/science.abf6446

9. Marongiu, L., Valache, M., Facchini, F. A., Granucci, F. (2021). How dendritic cells sense and respond to viral infections. Clinical Science, 135(19), 2217–2242. https://doi.org/10.1042/CS20210577