Why the flu returns every year: the mechanism of virus mutation

Influenza is not just a "cold with a fever." It is an acute viral respiratory disease that claims tens of thousands of lives worldwide each year and threatens the operation of schools, hospitals, and even entire sectors of the economy. Its characteristic feature is the ability to return every season, like clockwork, even in the presence of a vaccine. Why does this happen? The answer lies not in the laziness of the immune system or in "bad weather," but in the astonishing, almost cunning biology of the virus itself: its genetic structure constantly changes, "deceiving" the body's defense mechanisms. And if you think that last year's vaccination should protect you — you are mistaken. The virus has already changed. And it is this mutation mechanism that makes influenza one of the most difficult infectious agents to control on the planet.

Classification of the disease according to ICD

According to the International Classification of Diseases 11th Revision (ICD-11), influenza falls under the category "Respiratory infections," code J09–J11. Specifically:
— J09 — influenza caused by a new virus that has not previously been detected in humans (for example, a pandemic strain like H1N1 in 2009);
— J10 — influenza caused by an identified influenza virus (usually seasonal, for example, A/H3N2 or B/Victoria);
— J11 — influenza, unspecified (when laboratory confirmation is unavailable, but the clinical picture is typical).
It is important to understand: the diagnosis of "influenza" in medical documentation requires either laboratory confirmation (PCR, ELISA, rapid test) or a clear clinical picture during an epidemic rise. Simply "fever + cough" is not yet influenza — it could be ARVI, adenovirus, or even the initial stage of pneumonia. Therefore, when consulting a doctor, it is important not to call your condition "influenza" until confirmed — this affects the treatment and prevention strategy.

History of the disease and interesting historical facts

Influenza has been known to humanity since ancient times. The first reliable descriptions resemble the modern picture: a sudden rise in temperature, headache, body aches, cough. But a real breakthrough in understanding came only in the 20th century.
In 1918, the most terrible pandemic in history broke out — the "Spanish flu." Despite the name, it most likely started in the USA, not in Spain. Spain was a neutral country in World War I at the time, and its media freely reported on outbreaks, while other countries concealed the scale. Over two years, the pandemic claimed between 50 and 100 million lives — more than the entire war. It particularly affected young healthy people aged 20–40, which contradicted the usual picture of influenza. DNA studies from burials showed: the virus was a strain of A/H1N1, but with unique mutations that enhanced the inflammatory response of the immune system — the so-called "cytokine storm."
Another important point: in 1933, scientists first isolated the influenza virus — this was done by British researcher William Smith along with colleagues. Before that, influenza was considered a bacterial infection. The discovery of its viral nature became the starting point for the creation of the first vaccines in the 1940s.
An interesting fact: in 1976, panic arose in the USA due to a new strain A/New Jersey/76 (H1N1), allegedly as dangerous as the "Spanish flu." A mass vaccination campaign was launched, but an epidemic did not occur. However, some vaccinated individuals developed Guillain–Barré syndrome — a rare autoimmune nerve disorder. This case became a lesson: vaccination should be based not on fear, but on scientific data about real risk.

Epidemiology (statistics of disease occurrence)

According to WHO, annually, influenza affects between 51 million to 101 million adults worldwide and between 201 million to 301 million children. This amounts to about 1 billion cases per year. Of these, 3–5 million are severe forms requiring hospitalization, and 290,000–650,000 deaths. Most deaths occur in people over 65 years old, as well as in those with chronic diseases: cardiovascular, pulmonary, diabetes, immunodeficiencies.
In Russia, the flu season usually begins in November–December, peaks in January–February, and subsides by April. According to Rospotrebnadzor, in the 2023/2024 season, over 12 million cases of ARVI were registered, of which about 15–20% were confirmed as influenza (by PCR). The highest incidence is among children under 14 years old (up to 400 cases per 10,000 population), then it decreases for those aged 25–44 and rises again after 65 years.
Important: flu statistics heavily depend on the level of laboratory monitoring. In countries with a developed testing system (for example, Japan or Canada), more confirmed cases are recorded than in regions with limited access to diagnostics. Therefore, global figures are an estimate, not an exact count.

Genetic predisposition to the disease (involved genes and mutations)

There is no direct "flu gene." However, studies show that some people's immune systems recognize viral antigens less effectively due to the characteristics of genes coding for major histocompatibility complex (HLA) proteins. For example, carriers of the allele HLA-B*27 tend to experience milder flu, while holders of HLA-DRB1*15:01 have a higher risk of complications.
There are other genetic markers as well:
— Polymorphisms in the gene IFITM3 (interferon-induced transmembrane protein 3) affect the ability of cells to block virus entry. In people with the rs12252-C variant, the risk of severe influenza increases by 6 times.
— Mutations in the gene MBL2 (mannose-binding lectin) reduce innate immunity to viruses, including influenza.
— The gene CCR5, known from HIV, also plays a role: its delta-32 variant may partially protect against severe forms of influenza, although the data is still inconclusive.
But! Genetics is not destiny. Even with an "unfavorable" set of genes, the risk can be significantly reduced through vaccination, hygiene, and a healthy lifestyle. Genes set the potential, but the environment and behavior determine the outcome.

Risk factors for the development of this disease

Risk factors are divided into modifiable and non-modifiable. The latter are age, gender, genetics. The former are those we can influence.
**Non-modifiable factors:**
— Age: children under 5 years and people over 65 years;
— Chronic diseases: bronchial asthma, COPD, heart failure, type 1 and type 2 diabetes, kidney failure;
— Immunodeficiencies: HIV, oncological diseases, use of cytostatics or glucocorticoids;
— Pregnancy (especially the II–III trimester) — due to changes in the immune system and lung function.
**Modifiable factors:**
— Refusal of vaccination — the most significant. Even if the vaccine does not provide 100% protection, it reduces the risk of hospitalization by 40–60%;
— Smoking — damages the cilia in the airways, reducing mechanical protection;
— Lack of sleep and chronic stress — suppress the production of interferons;
— Poor ventilation of premises, overcrowding (schools, offices, public transport);
— Vitamin D deficiency is associated with increased susceptibility to respiratory viruses.
The special risk is "secondary exposure": when a person has had an acute respiratory viral infection, immunity is temporarily weakened, and the flu virus easily takes hold. This is why in autumn and winter, after the first colds, the number of flu cases sharply increases.

Diagnosis of this disease

The diagnosis of influenza is based on three pillars: clinical picture, epidemiological history, and laboratory confirmation.
**Main symptoms:**
— Sudden onset (within 1–2 hours);
— Temperature 38.5–40 °C;
— Severe headache, muscle and joint pain;
— Dry cough, sore throat;
— Weakness, adynamia ("I can't get out of bed");
— Sometimes — nausea, vomiting, especially in children.
Unlike ARVI, during influenza, runny nose and nasal congestion are often weakly expressed or absent in the first days.
**Laboratory studies:**
— Rapid antigen tests (nasal/throat swab): result in 15 minutes, sensitivity 50–70%. Suitable for quick decision-making — whether to prescribe oseltamivir or not.
— PCR (polymerase chain reaction): gold standard. Detects viral RNA, determines subtype (A/H1N1, A/H3N2, B). Sensitivity >95%.
— Serology (ELISA for IgM/IgG antibodies): used retrospectively, for example, to confirm the diagnosis in a patient who sought help on day 5–7 of the illness.
**Radiological examinations** are not needed in typical cases. But if there is suspicion of pneumonia (worsening cough, shortness of breath, confusion), a chest X-ray or CT is performed. Typical signs: focal or diffuse infiltrates, more often in the lower lobes of the lungs.
**Differential diagnosis** includes:
— ARVI (adenovirus, rhinovirus) — milder symptoms, without body aches;
— Coronavirus infection (SARS-CoV-2) — often with loss of smell, less pronounced fever;
— Bacterial pneumonia — progressive shortness of breath, purulent sputum;
— Mononucleosis (Epstein–Barr) — swollen lymph nodes, sore throat with plaque;
— Pulmonary tuberculosis — persistent cough, weight loss, night sweats.
If you need to quickly determine: "is it the flu or not?" — focus on the combination of acute fever + aches + epidemic season. In doubtful cases — do a rapid test.

Treatment

Treating the flu is not about "curing the virus," but helping the body cope with it and preventing complications. It is divided into etiological (antiviral), symptomatic, supportive, and preventive.
**Etiological treatment** is based on drugs that block key viral enzymes:
— Oseltamivir (Tamiflu) — neuraminidase inhibitor. Prevents new viral particles from exiting the cell;
— Zanamivir (Relenza) — an analogue of oseltamivir, but in the form of inhalations;
— Umifenovir (Arbidol) — blocks the fusion of the viral envelope with the cell membrane;
— Baloxavir marboxil (Chofitol) — inhibits the cap-dependent endonuclease of the virus, stopping viral RNA synthesis.
Important: antiviral drugs are effective **only in the first 48 hours** from the onset of symptoms. After that, their benefit sharply decreases. The exception is severe forms and at-risk groups: there, the course may start up to 5 days.
**Symptomatic treatment:**
— Antipyretics: paracetamol (up to 4 g/day) or ibuprofen. Aspirin is prohibited for children under 15 years old — risk of Reye's syndrome.
— Cough suppressants — only for dry, painful cough without phlegm (codeine, butamirate). For wet cough — expectorants (ambroxol, acetylcysteine).
— Abundant warm drinks — not for "detoxifying," but to compensate for fluid loss during fever and to keep mucous membranes moist.
**Supportive therapy:**
— Bed rest for the first 3–5 days — even with normal temperature. The heart and lungs are still under strain.
— Saturation monitoring (pulse oximetry) — if below 94%, hospitalization is needed.
— Oxygen therapy for hypoxia.
Surgical treatment for influenza is not used — except in extremely rare cases when a lung abscess or empyema of the pleura develops as a complication of bacterial superinfection.

List of medications used to treat this disease

Here is the current list of medications approved for use in the Russian Federation as of 2026, indicating the form of release and application features:

Note: self-treatment with antibiotics for influenza is a mistake. They do not act on viruses. Antibiotics are prescribed only in case of confirmed bacterial superinfection (for example, with radiological signs of pneumonia and leukocytosis).

Disease monitoring (control stages, prognosis, complications)

Monitoring of influenza is not only observation of the patient but also epidemiological surveillance at the national level. In the Russian Federation, this is handled by Rospotrebnadzor in conjunction with the Federal State Budgetary Institution "National Research Center for Epidemiology and Microbiology named after G. N. Gabrichevsky."
**Control stages for the patient:**
— Day 1–2: assessment of severity (temperature, saturation, respiratory rate);
— Day 3–4: if the temperature does not decrease, or shortness of breath appears — re-evaluation, possible hospitalization;
— Day 5–7: disappearance of fever, transition to recovery. If the cough worsens, purulent discharge appears — check for bacterial pneumonia;
— Day 10–14: monitoring for residual phenomena (asthenia, cough, fatigue). In 10–15% of patients, symptoms persist for up to 3 weeks.
**Prognosis:** in healthy adults — favorable, complete recovery in 7–10 days. In at-risk groups — complications may occur. Mortality with timely treatment — less than 0.1%. Without treatment — up to 1–2% in at-risk groups.
**Main complications:**
— Viral pneumonia (more common in the elderly);
— Bacterial pneumonia (Streptococcus pneumoniae, Staphylococcus aureus);
— Acute respiratory distress syndrome (ARDS);
— Myocarditis, pericarditis;
— Neurological complications: meningitis, encephalitis, Guillain–Barré syndrome;
— Exacerbation of chronic diseases (heart failure, asthma).
Special concern is raised by influenza in pregnant women: the risk of premature birth, low birth weight in newborns, and intrauterine hypoxia. Therefore, vaccination in the 2nd-3rd trimester is not a recommendation, but a mandatory measure.

Age-related features of the disease

Influenza in children, adults, and the elderly is three different clinical scenarios.
**In children under 5 years:**
— Often starts with vomiting and diarrhea — "stomach flu" (although this is an incorrect term);
— Temperature can reach 40.5 °C, febrile seizures are possible;
— High risk of otitis media (up to 30% cases) and bronchiolitis;
— Children under 2 years may not have a pronounced cough — instead, there may be apathy, refusal to eat, respiratory failure.
**In adults aged 18–65:**
— Classic picture: fever, body aches, cough;
— The risk of complications is lower, but not zero — especially with overexertion or chronic diseases;
— Often underestimate the severity and go to work — becoming a source of spread.
**In individuals over 65 years old:**
— Temperature may be subfebrile (37.2–38.0 °C) or even normal — "afebrile flu";
— Main symptoms — weakness, confusion, shortness of breath;
— Very high risk of pneumonia and decompensated heart failure;
— Mortality in this group — up to 90% of all fatal cases.
Important: in elderly people, the immune response is "blunter" — fewer interferons, slower antibody production. Therefore, vaccination should not just be done, but done correctly: it is better to use adjuvanted or high-dose vaccines (for example, Fluad® or Fluarix Tetra® with adjuvant MF59).

Questions and Answers

Question 1: Why does the flu vaccine not provide 100% protection?
Because the virus mutates in two ways: antigenic drift (small changes in hemagglutinin and neuraminidase) and antigenic shift (sharp change of subtype during recombination in pigs or birds). The vaccine is prepared 6–8 months before the season, based on WHO forecasts. If the virus is "guessed" inaccurately — effectiveness drops to 40–50%. But even in this case, the vaccine reduces the severity of the disease and the risk of hospitalization.
Question 2: Can you get the flu twice in one season?
Yes. First, there are two types of virus — A and B. Several subtypes circulate during the season (for example, A/H1N1 and A/H3N2, plus two lines of B). Having contracted flu A, you are not protected from B. Secondly, if you were ill at the beginning of the season, and then a new strain with antigenic drift appears — immunity may not recognize it. This is especially relevant for children and the elderly.
Question 3: How to distinguish flu from ARVI without tests?
Compare based on three points:
1. Onset: flu — acute (1–2 hours), ARVI — gradual (1–2 days);
Temperature: flu — 38.5–40 °C, ARVI — up to 38.5 °C;
Symptoms: flu is dominated by aches, headache, weakness; ARVI — runny nose, sneezing, scratchy throat.
If the symptoms correspond to the flu and it is currently the epidemic season — the probability is high. But a test is needed for an accurate diagnosis.
Question 4: Is it necessary to take antivirals if the temperature has already dropped?
If more than 48 hours have passed since the onset of symptoms — the benefit is minimal. Exception: a patient from a risk group (pregnant, elderly, with chronic diseases) and there are signs of deterioration (shortness of breath, decreased saturation). Then the doctor may prescribe a course even on days 3–5 — for the prevention of complications.
Question 5: Why is flu more common in winter?
Not directly because of the cold. It is due to three factors:
1. The virus is more stable at low temperatures and low humidity (the air in heated rooms — 20–30% humidity, ideal for the virus's survival in aerosol);
2. People spend more time in enclosed spaces, closely interacting;
3. Sunlight is weaker — less vitamin D, reduced production of interferons.

Typical mistakes in treating influenza and how to avoid them

1. Error: "I'll take aspirin - it will quickly reduce the temperature."
Consequences: in children - Reye's syndrome (acute liver failure + encephalopathy), in adults - gastrointestinal bleeding.
How to avoid: use paracetamol or ibuprofen. Aspirin - only as prescribed by a cardiologist for coronary artery disease.
2. Error: "I've had a fever for three days - I urgently need antibiotics."
Consequences: dysbiosis, resistance, allergy. Antibiotics do not work against viruses.
How to avoid: wait 5-7 days. If the cough has become wet, purulent sputum has appeared, the temperature has risen again - then see a doctor for assessment of bacterial infection.
3. Error: "I got vaccinated last year - so I don't need it this year."
Consequences: lack of protection against new strains, risk of severe course.
How to avoid: vaccination annually, ideally in September–October. Even if the season has already started — the vaccine is still beneficial.
4. Mistake: “I feel better — I’m going to work.”
Consequences: virus spread, relapse, complications (myocarditis against the background of physical exertion)
How to avoid: rest for at least 5 days after normalization of temperature. Even if “the strength has returned” — the heart and lungs are still recovering.

Conclusion

The flu returns every year not because of our laziness or bad weather — but because the virus can change faster than we can “remember” it. Its genetic plasticity is not a weakness, but an evolutionary survival strategy. But we are not helpless. Vaccination, timely antiviral treatment, hand hygiene, and airspace hygiene — all of this works. The main thing is not to wait until it gets bad, but to act in advance: get vaccinated in the fall, know the symptoms, be able to distinguish flu from ARVI, and not be afraid to see a doctor in the first days.
If you are a parent of a small child, an elderly person, or suffer from a chronic illness — your prevention should be more serious than that of others. Don’t skimp on the vaccine. Don’t ignore the first signs. And remember: the flu is not “just a cold.” It is a serious infection that can and should be controlled. And I, Dr. Korzhikov, hope that this article will help you not just learn more — but make the right decision at the right moment.