Navigating respiratory virus season

COVID-19, sometimes known as COVID or coronavirus, is caused by a coronavirus called SARS-CoV-2. Symptoms vary from person to person, with some people experiencing no or mild symptoms, while others experience life-threatening disease. COVID-19 symptoms can include fever or chills, cough, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, stuffy or runny nose, nausea or vomiting, diarrhea, and shortness of breath.

People with COVID-19 are most contagious within the first five days of symptoms but can infect others up to 14 days or longer. Note that people who are immunocompromised, including those with PI, can have prolonged infections that last for a month or more. People who are infected with COVID-19 but have no symptoms are also contagious and can still spread it to others.

Risk factors

There is no good data on whether those with PI are more likely to get COVID-19 than others. Certain risk factors make people more likely to have severe COVID-19, but anyone can develop severe disease, even individuals who have had mild COVID-19 in the past. Importantly, older age is the single greatest risk factor for developing severe COVID-19. An analysis of adults hospitalized in 2020 found that those 65 and older were more than six times more likely to die from COVID-19 than adults 18-39 years old.

PIs that disrupt the type I interferon response like TLR7 deficiency or autoimmune polyendocrinopathy syndrome type 1 (APS-1, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy or APECED) place individuals at very high risk for developing severe COVID-19. The interferon response is critical for controlling the virus early on and, without it, the virus spreads rapidly in the body.

The data for most other types of PI are less certain. However, a large CDC study looking at healthcare records found that adults with PI and COVID-19 who went to the emergency room were hospitalized, were admitted to the ICU, were put on ventilators, and died at higher rates than those without PI. The increased risk ranged from 1.4 (ventilation or death) to 2.4 (hospitalization) times those without PI.

In addition to PI, certain medical conditions, including some that tend to co-occur with or result from PI (bolded below), make it more likely that someone will develop severe COVID-19.

• Asthma.
• Cerebrovascular disease (e.g., stroke, aneurysm).
• Chronic kidney disease.
• Chronic lung diseases:
  • Bronchiectasis.
  • Chronic obstructive pulmonary disease (COPD).
  • Interstitial lung disease.
  • Pulmonary embolism.
  • Pulmonary hypertension.
• Chronic liver diseases:
  • Cirrhosis.
  • Non-alcoholic fatty liver disease.
  • Alcoholic liver disease.
  • Autoimmune hepatitis.
• Cystic fibrosis.
• Dementia.
• Diabetes.
• Disabilities, including Down syndrome.
• Heart conditions:
  • Heart failure.
  • Coronary artery disease.
  • Cardiomyopathies.
• HIV.
• Leukemia and lymphoma.
• Mental health conditions:
  • Mood disorders, including depression.
  • Schizophrenia.
• Obesity (BMI >30).
• Parkinson’s disease.
• Pregnancy and recent pregnancy.
• Tuberculosis.

Medical treatments and behaviors can also be risk factors for severe COVID-19, including:

• Being a current or former smoker.
• Being physically inactive.
• Being the recipient of hematopoeitic stem cell or solid organ transplant.
• Use of immunosuppressants like corticosteroids.

Risk factors are cumulative, which means that the risk of developing severe COVID-19 increases for every additional risk factor a person has. For example, a person who is 18 years old with an antibody deficiency (one risk factor) is less likely to become severely ill with COVID-19 than someone who is 65 years old with an antibody deficiency and bronchiectasis (three risk factors).

People who have had COVID-19 can also develop two very different complications after their initial infection—multisystem inflammatory syndrome (MIS-C (children)/MIS-A (adults)) or long COVID. Again, while there are factors that increase a person's risk, anyone, including children and those with mild COVID-19 symptoms, can develop these complications.

What is multisystem inflammatory syndrome (MIS-C/MIS-A)?

Multisystem inflammatory syndrome (MIS) is a life-threatening condition that develops up to eight weeks after a COVID-19 infection. MIS-C affects about 1 in 10,000 children who have had COVID-19, but there are also reports of MIS in adults (MIS-A). Those with MIS-C/MIS-A have a fever above 100° F (38°C) for more than 24 hours with evidence of inflammation throughout their bodies, including:

• Stomach pain, diarrhea, or vomiting.
• Bloodshot eyes.
• Dizziness or lightheadedness.
• Confusion or seizures.
• Skin rash.
• Swelling of the hands, feet, lips, or tongue.
• Signs of shock.

Seek medical attention immediately if you have MIS-C/MIS-A symptoms.

Certain types of PI that include immune dysregulation are associated with developing MIS-C. Genetic studies of children with MIS-C have identified variants in the following PI-related genes:

• AP3B1: Hermansky-Pudlak syndrome, type 2.
• C6, C9: Complement deficiency.
• CYBB: Chronic granulomatous disease (CGD).
• IFNAR1: IFNAR1 deficiency.
• LRBA: LBRA deficiency.
• LYST: Chédiak–Higashi syndrome.
• PRF1, STXBP2, UNC13D: Hemophagocytic lymphohistiocytosis (HLH).
• SOCS1: SOCS1 deficiency.
• TLR3: TLR3 deficiency.
• WAS: X-linked thrombocytopenia.
• XIAP: X-linked lymphoproliferative syndrome 2 (XLP-2).

There are no data on whether individuals with other types of PI, such as antibody deficiencies, are at increased risk for MIS-C/MIS-A.

What is long COVID?

The National Academies of Sciences, Engineering and Medicine defines long COVID as a chronic condition that lasts at least three months after the initial COVID-19 infection. Symptoms vary and can include shortness of breath, cough, persistent fatigue, fatigue after exercise or exertion, cognitive problems such as brain fog and memory changes, recurring headache, lightheadedness, rapid heartbeat, sleep problems, problems with taste or smell, bloating, constipation, and diarrhea.

Around 6% of adults and 1% of children develop long COVID according to estimates. There isn’t much research on long COVID and PI, but one study of healthcare claims within a nonprofit health system in New England found that those with PI were about three times more likely to have a long COVID diagnosis after infection compared to people without a PI diagnosis.

Influenza, commonly known as "the flu," is a respiratory disease that comes on suddenly. Symptoms that vary from person to person. These symptoms can include aching muscles, sore throat, a dry cough, a runny or stuffy nose, tiredness, headache, a burning sensation in the chest, eye pain, sensitivity to light, and fever and/or chills (note that people with primary immunodeficiency (PI) may not spike a fever).

Although many people think of the flu as harmless, from 2010-2024, the U.S. Centers for Disease Control and Prevention (CDC) estimates that between 6,300-52,000 people died of flu-related complications each year.

The flu is caused by influenza viruses. The two main types that infect people, influenza A and influenza B, are genetically different. Influenza A can cause moderate to severe illness in all age groups and infects many species, including pigs, birds, and horses. Influenza B usually causes milder disease and primarily affects children. Both influenza A and influenza B strains cause seasonal outbreaks, typically during the fall and winter months in the U.S. See recent flu activity in your state.

People with the flu are most contagious 1-2 days before symptoms appear and for 4-5 days after. It takes 1-4 days for symptoms to appear once you are infected. While most people recover in a few days, some experience severe illness.

Risk factors and complications

People with PI are equally at risk of contracting the flu as those without PI. Except for those with interferon pathway deficiencies like IRF7 deficiency, people with PI are not necessarily at higher risk of developing complications from the flu unless they meet other high-risk criteria:

• Are 5 years old or younger (especially younger than 2 years old).
• Are 65 years old or older.
• Have asthma, diabetes, or chronic lung, heart, kidney, liver, metabolic, neurologic, or blood conditions, including conditions that may be complications of PI.
• Have had a stroke.
• Have a secondary immunodeficiency caused by disease (e.g., HIV or blood cancer) or medication (e.g., immunosuppressive therapy).
• Are pregnant.

The flu's most common complication is bacterial lung infections (pneumonia). Other complications include viral pneumonia, myocarditis (inflammation of the heart muscle), and worsening of chronic lung conditions. See a healthcare provider right away if you have:

• Difficulty breathing, shortness of breath, or rapid, shallow breathing.
• Blue-ish lips or nail beds.
• Chest pain or pressure.
• Seizures.
• Signs of dehydration (not passing urine).
• Dizziness, confusion, or other signs of altered mental state.
• Severe muscle pain, weakness, or unsteadiness.

Reye's syndrome is another flu complication often related to using aspirin for fever that primarily affects children and causes severe vomiting and confusion. To decrease the chance of developing Reye’s syndrome, infants, children, and teenagers under 19 years old should not be given aspirin for fever reduction or pain relief.

In the U.S., RSV season typically lasts from October through April, with a peak in December or January. Symptoms include runny nose, coughing, sneezing, fever, and difficulty breathing. RSV has two subtypes, A and B, that differ genetically, but there is no difference in disease severity between them.

The U.S. Centers for Disease Control and Prevention (CDC) estimates that between 190,000-350,000 people were hospitalized with RSV in the 2024-2025 respiratory virus season, mainly for breathing difficulty and dehydration. While most people recover, 10,000-23,000 people ultimately die from the infection or its complications. Along with chronic heart and lung disease, being immunocompromised is a risk factor for developing severe RSV.

Research on RSV in those with primary immunodeficiency (PI) has primarily focused on infants and children. A 2012 paper found that children with PI are 3.8 times more likely to be hospitalized for an RSV infection than children without a chronic condition. Studies in Japan and Spain found that, in particular, children with PIs that affect T cells (for example, combined immunodeficiencies) are at the greatest risk of hospitalization for RSV.

The current 2025-2026 COVID-19 vaccines target the LP.8.1 strain and became available in September 2025. Because of their limited FDA approval and a recommendation for shared decision-making by the CDC, accessing the 2025-2026 COVID-19 vaccine differs by state. Talk to your healthcare provider and/or pharmacy to find out where you can get the shot.

The American Academy of Family Physicians (AAFP) and the American Academy of Pediatrics (AAP) recommend that the following groups receive at least one dose of the most current COVID-19 vaccine:

• Everyone aged 6-23 months old.
• People aged 2-18 years old who:
  • Are at high risk of severe COVID-19, including those with PI.
  • Reside in long-term care facilities or other group settings.
  • Have never been vaccinated against COVID-19.
  • Live with individuals that are at high risk of severe COVID-19, including those with PI.
• Everyone aged 19 years old or older.
• AAFP recommends that people 65+ years old get two doses at least two months apart.

Discuss AAFP’s recommendations for those who are moderately to severely immunocompromised with your immunologist to determine whether you should receive more than one dose. In general, booster doses should be spaced out by at least two months.

The COVID-19 vaccine is safe and cannot cause COVID-19 in anyone, no matter how weak their immune system, because it does not contain live virus. Although there is no data in patients with PI, receiving the most recent COVID vaccine booster may prevent or reduce long COVID complications.

For the 2025-2026 season, all flu vaccines are trivalent, which means they protect against three different influenza virus strains: two influenza A strains and one influenza B strain.

There are multiple types of flu vaccines available and selecting the right type is important. The inactivated or recombinant flu vaccine types are best for people with PI and their household members. People with PI and their household members should not receive the live attenuated flu vaccine (trade name Flu Mist).

Additional recommendations from the American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) include:

• People aged 65+ should receive the high-dose inactivated, adjuvanted inactivated, or recombinant vaccine because these formulations provide greater protection in older individuals.
• Solid organ transplant recipients aged 18-64 who are on immunosuppressants can also receive either high-dose inactivated or adjuvanted inactivated influenza vaccines.
• Children 8 years old or younger who have not received at least two flu vaccine doses previously should receive two doses of flu vaccine spaced four weeks apart.
• People with egg allergy may receive any vaccine (egg-based or non-egg-based) that is appropriate for their age and health status.

The flu vaccine is safe, and the inactivated and recombinant versions cannot cause the flu in anyone, no matter how weak their immune system. The vaccine is available from late summer, and AAP and AAFP recommend getting vaccinated by mid-October for the best protection through flu season.

The U.S. Food and Drug Administration (FDA) has approved five preventative products for RSV within the last couple of years: three vaccines and two long-lasting monoclonal antibodies. Unlike vaccines, monoclonal antibodies are a type of passive immunization that provide protection regardless of how well a person’s immune system works. Monoclonal antibodies work like immunoglobulin replacement therapy but only protect against one specific germ.

The American Academy of Family Physicians (AAFP) recommends that the following people get an RSV vaccine:

• Pregnant individuals who have not received an RSV vaccine previously. These individuals should get one dose of the Abrysvo vaccine when they are 32-36 weeks pregnant from September through January.
• People aged 50-74 who are at high risk of severe RSV infection (including those who are moderately or severely immunocompromised).
• People age 75+.

Unlike the flu and COVID-19, experts consider RSV vaccination protective for a long period of time. There are currently no recommendations for any group to receive more than one dose in their lifetime.

The RSV vaccine is safe and cannot cause RSV in anyone, no matter how weak their immune system, because it does not contain live virus.

The American Academy of Pediatrics (AAP) recommends one dose of either of the two long-lasting monoclonal antibodies for:

• Babies 7 months old or younger born to individuals who have never been vaccinated for RSV or were vaccinated for RSV during a previous pregnancy.
• Babies 8-19 months old who are at high risk of severe RSV infection either because of a medical condition (including severe immunocompromise) or because of American Indian/Native Alaskan heritage.