Respiratory health

Key points:

People with PI have a higher risk of severe respiratory tract infections such as pneumonia.
In certain PIs, chronic inflammation of the lung not due to infection (non-infectious lung disease) can lead to permanent lung damage (fibrosis) if it is not diagnosed early and treated.
Both respiratory infections and non-infectious lung disease can cause lung damage that gets worse over time, so it’s important to tell your healthcare provider about any breathing problems or other signs of lung disease so you can get properly diagnosed and treated.
Vaccination against germs that cause respiratory infections, like influenza and COVID-19, helps prevent severe infections in many types of PI.
The early diagnosis and treatment of influenza and COVID-19 can prevent severe infections, hospitalizations, and death.

The respiratory system, or respiratory tract, refers to all the passageways and organs involved in breathing. The upper respiratory tract includes the mouth, nose, throat (pharynx), sinuses, and the upper part of the voice box (larynx). The lower respiratory tract includes the lower part of the voice box, the windpipe (trachea), the breathing tubes leading from the trachea to the lungs (bronchi and bronchioles), and the lungs themselves.

Parts of the respiratory system. Source: OpenStax, Anatomy and Physiology. https://openstax.org/books/anatomy-and-physiology]

Your immune system works to prevent or clear an infection caused by germs such as bacteria or viruses. Inflammation is one way the immune response clears these infections. For example, when you get a cold, your immune response brings white blood cells and immune system proteins to the site of infection. When the infection is cleared, the extra white blood cells and inflammatory proteins go back to normal levels. Because you need a working immune response to prevent and clear infections, people with PI often have more respiratory tract infections and more severe respiratory tract infections than people without PI. These repeated infections can cause permanent damage to the airways.

Some lung disease caused by PI is not due to germs or the result of damage from infections (non-infectious lung disease). Instead, it is caused by an imbalance in the immune system known as immune dysregulation. One type of immune dysregulation is autoimmunity, where either T cells (autoreactive T cells) or antibodies from B cells (autoantibodies) target healthy tissue. Another type is chronic inflammation, where the immune system is not properly controlled. If it’s not treated, non-infectious lung disease gets worse over time and can cause scarring (fibrosis) that permanently reduces how well your lungs work.

Always let your healthcare provider know if you have symptoms of a respiratory infection or are having trouble breathing or catching your breath. Your provider may need to work with a lung specialist, called a pulmonologist, to properly diagnose and treat any lung conditions.

Respiratory tract conditions

Rhinitis

Rhinitis is inflammation of the mucous membranes in your nose. Common symptoms of rhinitis are runny nose (rhinorrhea), sneezing, cough, and congestion. Rhinitis can be acute (< four weeks) or chronic. The common cold is a frequent cause of acute rhinitis and usually gets better much sooner than four weeks.

On the other hand, chronic rhinitis has several different causes such as allergies, medications, irritants, chronic sinusitis, or structural problems in the nose. In addition to the symptoms of acute rhinitis, people with chronic rhinitis may have a decrease or loss of smell. If your rhinitis symptoms last longer than four weeks, you should see your healthcare provider to identify the cause of the problem.

Common cold

The common cold, also called coryza or an upper respiratory infection, is when the upper part of your respiratory tract (nose and throat) is inflamed because of a viral infection. Early signs are a scratchy or sore feeling in your throat, then sneezing, coughing, and a runny nose. You might also feel tired and have body aches.

There are many different viruses that can cause a cold but the most common is rhinovirus [1]. While testing for rhinovirus is available through healthcare providers, testing isn’t usually necessary unless the infection is severe. Over-the-counter medications can help you feel better, but there are no antiviral medications for rhinovirus or other cold-causing viruses. Antibiotics do not work for a cold because they kill bacteria, not viruses.

For people with most types of PI, a cold usually lasts about a week and will get better on its own. For people with untreated severe combined immune deficiency (SCID) or another PI that causes low T cells, a cold can become severe and needs immediate medical attention. If a cold lasts longer than a week and you have a fever, are coughing up mucus, or have trouble breathing, it could be something more serious, and you should see your healthcare provider.

Sinusitis

Sinusitis is inflammation of the mucous membranes lining your sinuses, which are small spaces in the facial bones around your nasal passages. Because mucous membranes in the nose can also be involved, healthcare providers sometimes use the term rhinosinusitis.

Your sinuses warm, humidify, and filter air before it goes into your lungs, help to reduce the weight of your skull, and affect the sound of your voice. The mucous membrane lining clears the sinuses by using tiny, hair-like structures called cilia to sweep mucus, particles, allergens, and germs out of the sinus cavities.

Acute sinusitis

Acute sinusitis, commonly known as a sinus infection, is when one or more of your sinuses becomes inflamed because of a viral or, less commonly, bacterial infection. Acute sinusitis is a common infection in some types of PI such as antibody deficiencies. Repeated episodes of acute sinusitis can damage the mucous membranes in the nose and sinuses and lead to chronic sinusitis.

Signs and symptoms of acute sinusitis include runny nose, nasal congestion, facial pain or pressure, especially in the forehead or cheekbones, headache, and, sometimes, a fever. These symptoms may be worse in the morning if your sinuses aren’t draining properly when you sleep.

Viral sinusitis usually gets better in 7-10 days. If acute sinusitis symptoms last for more than 10 days in people with PI, healthcare providers usually prescribe an antibiotic. This is because the symptoms are likely caused by a bacterial infection and the immunodeficiency may make it hard for your immune system to clear the infection. In people with PI, a longer course of antibiotics may be needed to clear the infection than in people who don’t have PI. People with some types of PI or secondary immunodeficiencies may also get fungal infections of the sinuses, which can spread to other tissues.

If you have an ongoing sinus infection that hasn’t gotten better with standard antibiotics, your healthcare provider may do a sinus culture. For this test, the provider takes a sample from your sinuses to see what kind of bacteria or fungus is causing the infection. This can help them choose another, more effective medication to treat the infection. However, the sample needs to be taken from deep inside your sinuses using a thin flexible tube called an endoscope. Swabs from the front of your nose are not accurate and should not be used to decide on treatment.

Chronic rhinosinusitis (CRS)

Chronic rhinosinusitis (CRS) is the term for inflammation of the nose and sinuses that lasts for more than 12 weeks. It is a common health problem that affects more than 10% of the general population [1]. CRS symptoms include:

A stuffy nose or sinus congestion.
A runny nose or constant mucus dripping down the throat (post-nasal drip).
Pain or pressure in the face.
Reduced or lost sense of smell.
A cough that won’t go away (seen more in children than adults).

Some people with CRS have constant sinus issues, sometimes getting slightly better or worse. Others have sinus issues that come and go and short periods with no symptoms in between.

In people with PI, CRS is very common. The sinus infections and increased inflammation that come with many types of PI make it more likely that people with PI will develop CRS. People with antibody deficiencies, like common variable immune deficiency (CVID), or specific antibody deficiency (SAD), often develop CRS. However, people with other types of PI can also develop CRS. In addition, CRS is often one of the first signs of PI, so healthcare providers should test for PI in people who have severe CRS that doesn't get better with standard treatment.

CRS that isn't under control can lead to other issues like feeling tired, trouble sleeping, ear pain or pressure, dizziness, bad breath, and a sore throat. The exact reasons why CRS develops are not fully understood and are still being studied. It's important for people with PI and CRS to talk about all of the factors that might be contributing to their CRS with their healthcare team. It helps to have a team of different specialists, including a primary care provider, an immunologist, an allergist, and an ear, nose, and throat (ENT) specialist (also known as an otolaryngologist), working together to treat CRS in someone with PI.

Known factors, other than PI, that contribute to CRS include:

Allergies: Allergies to things in the environment are the most common risk factor for developing CRS among people in the general population. In people with allergies, the immune system overreacts to things that are normally harmless—like pollen or pet dander. Immunoglobulin E (IgE) antibodies trigger this overreaction.

Allergies cause ongoing inflammation in the nose and sinuses and block sinus drainage, which raises the risk of sinus infections. Most people with allergies who develop CRS are sensitive to year-round allergens with constant exposure, such as pet dander, rather than seasonal allergens.

Note that people with antibody deficiencies that affect their ability to make IgE, such a X-linked agammaglobulinemia (XLA) or CVID, are much less likely to have allergies to environmental allergens than the general population. Seventy-five percent of people with CVID have undetectable IgE and over 95% of people with CVID do not have allergen-specific IgE when tested [2].

If you suspect that you have environmental allergies, you should discuss this issue with your provider to see if you need further allergy testing, such as skin testing.
Physical blockage: Problems with the structure of the nose or sinuses can physically block sinus drainage. When the sinuses can't drain properly, the risk of getting infections that keep coming back and causing inflammation increases. Structural problems include:
- Large nasal polyps (soft, non-cancerous growths in the nose or sinuses).
- Concha bullosa (an air pocket stuck in the bony structures that connect the nose and sinuses).
- A deviated septum (when the structure that divides the nose in half is off-center).
- Sinus cysts (fluid-filled pockets that form on the mucous membrane of the sinuses).

Also, sinus surgeries can sometimes cause structural issues because of scarring or tissue damage.

Smoking and/or vaping: Smoking is a big risk factor for CRS. The particles and chemicals in tobacco or marijuana smoke cause inflammation of the tissues in the nose and sinuses. Vaping is also associated with increased risk of CRS, probably for similar reasons [3].
Airborne chemicals and pollutants: Breathing in irritating chemicals, which is mostly a concern in industrial or agricultural workplaces, might make someone more likely to develop CRS. Being around more common air pollutants like car exhaust and carbon monoxide a lot can make CRS symptoms worse, but it's not clear if these pollutants actually cause CRS.

Diagnosing CRS

If you have symptoms of CRS, a healthcare provider will do a physical exam to check for signs of inflammation in your nose and sinuses. They may find colored mucus, swelling, or growths called polyps in your sinuses. To get a better look inside your nose and sinuses, the provider may use a tool called a rhinoscope. This involves putting a thin, flexible tube with a camera on the end into your nose, usually after spraying medicine in your nose to shrink the tissues.

The provider may also order imaging tests like computed tomography (CT) scans to see the deeper parts of your sinuses. These scans can show if the lining of your sinuses is thicker than normal, if there is a physical blockage, or if there is trapped fluid or mucus.

Managing CRS

Once a healthcare provider has diagnosed CRS, the management plan usually has several parts. Because CRS usually is not just caused by a long-lasting sinus infection, just treating or preventing infections isn't enough to control the symptoms in most cases. Note that CRS generally does not go away, but the right treatment can reduce symptoms and make living with the condition easier. CRS management can include:

Treating PI: The first key step in managing CRS is to properly treat the underlying PI. For many people, this means being on immunoglobulin (Ig) replacement therapy at a dose that prevents infections as much as possible, while also avoiding side effects. Ig replacement therapy can reduce how often and how bad sinus infections are in people with antibody deficiencies. However, it's not clear if higher doses of Ig replacement therapy help with CRS beyond reducing sinus infections. Even people on Ig replacement therapy can develop CRS because many things besides infections contribute to CRS.
Nasal rinses: One of the most helpful ways to manage CRS is to rinse your sinuses daily with a salt water (saline) solution. This helps to physically wash away mucus, small particles, allergens, and germs. Rinsing also helps the cilia in your sinuses work better to naturally clear your sinuses.

Using a larger amount of saline with a neti-pot, squeeze bottle, or water pick designed for nasal rinsing may work better than using saline nasal sprays. You can buy saline packets, or you can make your own buffered saline solution each week from online recipes. Note that it is very important to use water that has been distilled or sterilized by boiling or another method. Using tap water can introduce germs, including amoeba, into your sinuses and common contaminant filters (i.e., Brita or similar filters) do not get rid of these germs.
Treating allergies: Treating allergies is also an important part of managing CRS. Allergy treatment may involve using corticosteroid nasal sprays or antileukotriene medication, in addition to antihistamine medication. Most healthcare providers recommend non-drowsy antihistamines like cetirizine (Zyrtec) or fexofenadine (Allegra) instead of diphenhydramine (Benadryl) to help with itching, sneezing, or a runny nose. Allergy shots or tablets/drops that go under the tongue may be an option to build up the immune system’s tolerance to an allergen, but it's not clear how well they work for people with PI.
Corticosteroids: Corticosteroids are important anti-inflammation medications for treating CRS even if you don’t have allergies. They are usually given as a nasal spray, with different types available over the counter or with a prescription.

Nasal corticosteroids gradually reduce inflammation, so you need to use them daily for several weeks to get the most benefit. Using a nasal rinse before the nasal steroid spray seems to work best. Also, using the correct spray technique is important for the best results and to avoid hurting the front of your nose. Make sure to discuss the proper technique with your healthcare provider.

If symptoms don’t respond to nasal steroid sprays, using nasal rinses with a diluted steroid solution for a short time may be effective in some cases.

Short courses of corticosteroids taken by mouth, like prednisone, may help manage severe flares of CRS. However, because of the significant side effects and risks, oral corticosteroids are rarely used for this purpose, especially in people with PI, since they further weaken the immune system.
Antileukotriene medications: Leukotrienes are chemical signals made by some white blood cells that trigger inflammation. They can worsen symptoms like mucus production and sinus swelling in some people with CRS even if you don’t have allergies. Medications that block the leukotriene signal, like montelukast (Singulair), can help control CRS symptoms.
Biologics for CRS with nasal polyps: Providers may prescribe biologic medications (biologics) called monoclonal antibodies to treat CRS with nasal polyps. These medications block the molecules and cell receptors that experts think cause polyps to develop. Examples include omalizumab, which blocks IgE antibodies, mepolizumab, which blocks the IL-5 receptor, or dupilumab, which blocks IL-4 and IL-13 receptors. A recent analysis of numerous studies using these different medicines suggests that dupilumab may be the most effective [30].
Quitting smoking: Smoking causes ongoing inflammation in the upper and lower airways. Quitting smoking is important for improving CRS symptoms. Household members should also stop smoking since secondhand smoke causes inflammation as well.
Antibiotics: It's not clear if antibiotics help treat CRS. Healthcare providers prescribe antibiotics to treat sinus infections in people with PI because they have a higher chance of developing complications. However, the ongoing sinus symptoms of CRS usually are not caused by a chronic infection. Therefore, experts generally do not recommend long-term antibiotic treatment for ongoing CRS symptoms [4]. Instead, antibiotics should be saved for treating clear, sudden flare-ups from bacterial sinus infections.

However, if there is proof of a chronic infection, such as ongoing colored mucus or CT scan or rhinoscope findings, a 4–6-week course of antibiotics or other antimicrobials may help. Rarely, healthcare providers might prescribe even longer courses, but the risks and side effects should be carefully considered. The healthcare provider should choose antimicrobials based on the germ they think is causing the infection. Symptoms should slowly get better during antimicrobial treatment.

If symptoms don't improve, a culture from the sinuses should be taken to help guide further treatment. CRS can sometimes be made worse by specific infections like Staphylococcus aureus or Pseudomonas aeruginosa that need very specific antibiotic or antifungal medication.
Sinus surgery: Surgery for CRS should only be considered if other management techniques and medications haven't improved symptoms. Sometimes, healthcare providers need to fix structural problems in the sinuses to help them drain properly. In other cases, severe swelling can't be eased with medicine alone, and healthcare providers need to remove the swollen tissue so that medications work better.

If you need sinus surgery, it's very important to keep taking your CRS medications before and after the procedure to maintain the improvements from surgery. People with PI should talk to their immunologist before having any surgery to make sure they get the right care during the whole process.

Pharyngitis and tonsillitis

Pharyngitis describes inflammation of the throat (sore throat). Tonsillitis is when the tonsils, which are located at the back of the throat, become inflamed. Symptoms include a raw or tickling sensation in the back of the throat and, sometimes, difficulty swallowing. Sometimes these symptoms are accompanied by a fever.

The majority of sore throats and tonsillitis are caused by viruses. Aside from influenza and COVID-19, there are no antiviral medications for viruses that cause a sore throat or tonsillitis. Antibiotics will not help for a viral infection.

However, sore throats that are caused by the bacteria Streptococcus pyogenes (strep throat) can cause rheumatic fever or kidney inflammation if they are not treated. If a person with PI has a sore throat, they should contact their healthcare provider to get a strep quick test or culture. Strep throat is usually treated with antibiotics and healthcare providers recommend throwing out toothbrushes and sanitizing water bottles or other objects that could harbor strep bacteria to keep from re-infecting yourself [5].

Sometimes, people have recurrent tonsillitis. In that situation, healthcare providers might suggest removing the tonsils. In children, providers may also recommend removing the adenoids, which are glands at the back of the upper airway, if they are also chronically inflamed. Adults typically do not have any adenoidal tissue or only a very tiny amount because the adenoids shrink in late childhood and adolescence.

Acute bronchitis

Acute bronchitis is inflammation of the bronchi, which are the tubes that carry air from your windpipe into your lungs. Usually, a respiratory virus or, much less commonly, bacteria cause acute bronchitis [6]. Frequently, acute bronchitis happens after a cold or other upper respiratory tract infection.

The most common symptom is a cough that usually lasts 1-3 weeks. The cough may bring up uncolored or colored mucus from the lower airways (sputum). A low-grade fever may occur in some cases of acute bronchitis. If you have a cough, high fever, or increasing shortness of breath, see your healthcare provider as soon as possible because the infection may involve your lungs (pneumonia). Antibiotics are not usually used for acute bronchitis and treatment focuses on controlling symptoms.

Croup

Croup is a general term for an infection, usually in children, that causes inflammation of the voice box (larynx), windpipe (trachea), and airways leading into the lungs (bronchi). Children ages 6 months to 3 years of age are at the highest risk for croup and it is uncommon past 6 years of age. Croup is most commonly caused by parainfluenza viruses, but other viruses can cause croup as well [7]. Bacteria are an uncommon cause of croup.

Croup can start suddenly or slowly. The child might have a normal or slightly high temperature. Sometimes, croup starts at night, and the child might wake up with a tight, barking cough (described as sounding like a seal barking) and trouble breathing. Breathing is hard because the windpipe narrows from inflammation.

Croup can be scary for both caregivers and kids. It’s important for caregivers to stay calm and reassure the child because their breathing can get worse if they become anxious. Home remedies that can help include sitting in a steamy bathroom or, conversely, breathing in cold air, either from outside or by standing in front of an open freezer [8].

If the child’s breathing gets worse, they may need quick medical help. Depending on how bad the symptoms are, caregivers should contact their healthcare provider or go to the emergency room.

Influenza

The flu is a term often used to describe the fever, body aches, cough, and congestion caused by many common respiratory viruses. However, only the influenza virus truly causes the flu.

The flu can be a very serious infection. For example, there were 28,000 flu-related deaths in the U.S. during the 2023-2024 flu season, and most adults hospitalized for the flu had a high-risk underlying medical condition [9], [10]. For most people with PI, the increased risk from the flu comes from complications like chronic lung disease. However, some rare PIs like IRF7 deficiency make a person very high risk for severe flu infections.

Fall and winter are typically flu season in the U.S. Flu symptoms include a sudden high fever, chills, headache, muscle aches, weakness, tiredness, and a runny nose. Vomiting and diarrhea can also occur. Sometimes, a bacterial infection of the ears (otitis media), sinuses (sinusitis), or even lungs (pneumonia) can develop during or after the flu.

You should speak with your healthcare provider right away if you think you have the flu or have been exposed to the flu. If you feel sick, immediately test with an unexpired, rapid antigen test at home. There are now a number of rapid antigen influenza A and B tests, as well as “multiplex” rapid antigen tests that test for COVID-19, influenza A, and influenza B all at the same time.

There are four antiviral drugs available to treat the flu, but they need to be started 1-2 days after symptoms begin to be most effective. All four work on both influenza A and influenza B viruses. If used early, they decrease severe flu infections, hospitalizations, and deaths in people at risk for severe flu (like people with PI). Three of these antiviral medicines can also be used to prevent getting the flu if you are exposed to someone who has the flu.

The best way to prevent the flu is to keep up to date with yearly influenza vaccinations. People with PI and their caregivers should not be immunized with the live, attenuated influenza vaccine (Flu Mist) but should receive one of the inactivated or recombinant flu vaccines every year. Even those on Ig replacement therapy should get a flu vaccine because Ig products typically do not have enough protective antibodies to current flu strains.

COVID-19

People with PI should discuss plans with their healthcare provider for dealing with COVID-19, including:

How and where will you get tested for COVID-19 or other, similar respiratory viruses like influenza?
What antiviral medication(s) does your healthcare provider recommend and how will you get them?
Does your healthcare provider recommend receiving convalescent plasma? If so, where will you get it? Note that only hospital-based providers can order this product.

COVID-19 is a contagious respiratory disease caused by the coronavirus SARS-CoV-2. The SARS-CoV-2 virus spreads mainly through the air when an infected person coughs, sneezes, talks, or exhales [11]. Others then inhale or come in contact with viral particles. The viral particles enter the body through mucous membranes in the nose, mouth, and eyes. Less commonly, COVID-19 can also be spread by touching contaminated surfaces and then touching your nose, mouth, or eyes.

Symptoms of COVID-19 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. At the onset of COVID-19, people may have mild symptoms similar to a cold. However, mild symptoms at the beginning of the infection do not mean you will not develop severe disease later on.

Most commonly, COVID-19 causes respiratory tract infections, and severe pneumonia is a common cause for hospitalizations and death. However, COVID-19 can also affect other parts of the body including the heart, blood vessels, kidneys, and other organs.

People with PI are at higher risk for severe COVID-19 and death than the general population [12]. A study looking at the entire population in Sweden found that people with PI were 3-4 times more likely to be hospitalized and five times more likely to be admitted to the intensive care unit than those without PI [13]. People with PI were also more likely to die from COVID-19.

Other risk factors for severe COVID-19 infections are common to people in the general population and to those with PI. These include, but are not limited to:

Being 65+ years old.
Having chronic lung, liver, kidney, or heart disease, or cancer.
Being on medication that suppresses the immune system.

While all types of PI increase someone’s risk of developing severe COVID-19, there are specific PIs that put individuals at very high risk. Type I interferons are immune system proteins that help fight viral infections and are especially important in preventing severe COVID-19 infections. PIs that disrupt the type I interferon response like TLR7 deficiency place people at very high risk of developing severe COVID-19. In autoimmune polyendocrinopathy syndrome type 1 (APS-1, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy or APECED), the immune system makes antibodies against type I interferons, so people with APS-1/APECED are also a very high risk of severe COVID-19 infections [14].

If you have symptoms of a respiratory tract infection, immediately test for COVID-19 using an unexpired, rapid antigen test at home. Keep in mind that rapid antigen tests may be negative early in an infection even if you really do have COVID-19. If the rapid test is negative, consider getting a more sensitive PCR test (sometimes called a NAAT test) and testing for other respiratory viruses. These tests are typically available at pharmacies, urgent care centers, and healthcare provider offices.

If you test positive for COVID-19 by either a rapid antigen test or a PCR test, contact your healthcare provider to get and start treatment as soon as possible. There are antiviral medications and convalescent plasma available to treat COVID-19, all of which are most effective within 5-8 days of the beginning of symptoms [15]. Nirmatrelvir with ritonavir (trade name Paxlovid) and remdesivir (trade name Verklury) are likely the most effective treatments to prevent severe COVID-19 and death.

Many people delay COVID-19 antiviral treatment because they don’t feel ‘that bad’ at first, but mild symptoms can rapidly become serious. Earlier treatment = better outcome!

covid treatments table — Medications available to treat COVID-19. Note that all treatments work best when started as soon as possible after symptoms begin.

The best way to prevent severe COVID-19 is to get vaccinated and keep up-to-date on boosters recommended by your healthcare provider. A study conducted through the USIDNET patient registry showed that vaccinated people with PI who had COVID-19 were significantly less likely to be hospitalized, be admitted to the ICU, or die than those with PI who were not vaccinated [16]. Household members of people with PI should get vaccinated to create a "protective cocoon" around the person with PI and decrease their exposure to the SARS-CoV-2 virus.

In March 2024, the U.S. Food and Drug Administration (FDA) authorized pemivibart (trade name Pemgarda) to prevent COVID-19 infections in those 12+ years old who are moderately to severely immunocompromised [17]. Pemgarda is a monoclonal antibody, which means that unlike vaccines, it provides protection regardless of how well a person’s immune system works. It is not approved for use after exposure or infection. Pemgarda is given as an intravenous infusion every three months and must be prescribed by a healthcare provider. Infectious Disease Society of America’s clinical guidelines for Pemgarda can help healthcare providers determine if their patients should receive it [18].

Respiratory syncytial virus (RSV)

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. 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 [19]. 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 [20], [21].

The 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.

Infectious Diseases Society of America (IDSA) published recommendations on the prevention of respiratory syncytial virus (RSV) infection specifically in immunocompromised individuals. IDSA recommends that all individuals aged 18 years and older who are immunocompromised receive one dose of an RSV vaccine. In addition, the American Academy of Family Physicians (AAFP) recommends that pregnant individuals who have not received an RSV vaccine previously get vaccinated. These individuals should get one dose of the Abrysvo vaccine when they are 32-36 weeks pregnant from September through January.

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.

Pneumonia

Pneumonia is an infection in the lungs that can be caused by many different types of germs but is usually caused by bacteria, such as Streptococcus pneumoniae (pneumococcus) or Mycoplasma pneumoniae, or respiratory tract viruses. However, certain PIs, like CD40 ligand deficiency or chronic granulomatous disease (CGD), make a person more likely to get pneumonia caused by unusual germs, including fungi like Pneumocystis jirovecii or Aspergillus spp.

Symptoms of pneumonia include chills, high fever, coughing, and chest pain when breathing or coughing. If you have these symptoms, you should see your healthcare provider for the proper diagnosis and treatment. It is important that your healthcare provider check for COVID-19 or influenza if you have pneumonia, as these infections need to be treated early with antiviral medications, not antibiotics. Fungal pneumonia also needs specific treatment and can be very serious if it is not diagnosed and treated quickly.

In addition, healthcare providers should consider that an underlying, undiagnosed PI may be present in people who have:

Recurrent pneumonia, defined as two episodes of pneumonia within a year (with clear lungs on imaging tests in between) or three episodes of pneumonia in a lifetime [22].
Unusually severe pneumonia without other risk factors.
Pneumonia caused by an unusual germ like Pneumocystis jirovecii fungi.

Bronchiectasis

Bronchiectasis is when the airways in the lungs become permanently wider, usually due to damage from recurrent infections in the airways. There are numerous medical problems that can lead to bronchiectasis including PIs. In people with bronchiectasis, it's hard to clear mucus and germs from the airways, which can lead to more frequent and severe pneumonia. A chronic cough that brings up mucus from the lower airways (sputum) is the most common symptom. Other symptoms include fatigue and shortness of breath.

The treatment of bronchiectasis depends on the cause, severity, and other features. Usually, a pulmonologist needs to be part of the team to properly treat this condition.

Non-infectious lung diseases

Lung disease that is not caused by infections or damage from infections is an important cause of illness and even death in people with certain PIs. Interstitial lung disease (ILD) is a type of non-infectious lung disease that happens when there is inflammation or scarring (fibrosis) in a specific part of the lung called the interstitium. The interstitium is the space around the air sacs (alveoli) where oxygen moves from the lung tissue into the blood. In PI, chronic inflammation in the interstitium and other parts of the lung leads to fibrosis. Fibrosis permanently damages the lung's ability to absorb oxygen and cannot be reversed.

CVID is the most common PI that causes ILD and this particular type of ILD is called granulomatous lymphocytic interstitial lung disease (GLILD). In GLILD, the inflammation comes from B cells and T cells as well as granulomas. Granulomas are clusters of white blood cells, mainly macrophages, that gather in tissue. Granulomas can form when the body tries to contain an infection that it can’t get rid of or when the white blood cells aren't controlled properly, which occurs in CVID.

GLILD is not a true autoimmune disease but rather a problem with generalized immune dysregulation. In this case, the immune system is overactive, but it’s not clear exactly what it’s reacting to. Instead of a targeted attack, the immune system causes widespread inflammation in the lungs and, sometimes, other organs in the body.

GLILD occurs in 15-25% of patients with CVID [23]. GLILD is more likely to occur in females (roughly 66%) than males and usually starts after puberty. GLILD can get worse over time and lead to respiratory failure because of fibrosis of the lungs. People with CVID, in particular adults, should be screened for GLILD using a CT scan of the lungs every 3-5 years if they do not have symptoms or loss of lung function.

In the past, GLILD was a major cause of death in CVID. Recent studies show that immunosuppressive medications like rituximab combined with mycophenolate or azathioprine can clear the inflammation in the lungs that causes fibrosis, improving lung function and how the lungs look by CT scan. The majority of patients treated with these medications remain in remission for years after treatment [18].

Another type of ILD happens in people with APS-1/APECED and is called interstitial pneumonia with autoimmune features (IPAF; also called autoimmune pneumonitis) [16].

People with APECED have autoreactive T cells that can cause lung inflammation and ILD. As with GLILD, if the ILD isn't treated properly, the inflammation can be so bad that it causes fibrosis, permanently damaging the lung's ability to absorb oxygen.

In most cases, the symptoms of non-infectious lung disease in people with PI appear slowly over time. People may notice that they don’t have as much endurance during everyday activities. They may have to reduce their exercise, like biking or running, because they become breathless more easily. These changes are often blamed on other things, which can delay the diagnosis of the lung disease.

People with PI who develop non-infectious lung disease often complain of a cough that doesn't bring up any mucus. Fever is not usually present unless there is also an infection. Their toenails and fingernails may get larger and round downward, a sign called clubbing, if they are not getting enough oxygen. Clubbing is not specific to PI or lung damage, but it suggests that a person’s lungs should be checked. In some cases, lung damage can cause a severe drop in blood oxygen, leading to a bluish tint to the skin or mucous membranes. This is known as cyanosis and people with this level of lung damage typically need to be on oxygen.

Diagnosing non-infectious lung disease

During a lung exam, your healthcare provider may hear crackles, wheezes, or a decrease in the amount of air moving in and out of the lungs with breathing. Often, these symptoms lead providers who aren't familiar with non-infectious lung diseases in PI to incorrectly diagnose asthma or a lung infection.

Chest X-rays help healthcare providers diagnose lung infections like pneumonia. But sometimes, a chest X-ray can look normal even if there's still a problem in the lungs. A chest CT scan is a much better way to spot non-infectious lung disease, even when the chest X-ray looks okay. People with CVID and GLILD often have changes on their chest CT scan before they start having symptoms.

Breathing tests, also called pulmonary function tests (PFTs), can show how well the lungs are working. Changes in PFTs can be a sign of ILD and other lung diseases. However, people often lose a lot of lung function before they have symptoms noticeable enough for healthcare providers to order PFTs.

Sometimes, healthcare providers need to do a lung biopsy to figure out the exact problem and how to treat it. A lung biopsy is a surgery where a doctor makes a small cut in the chest and uses tools to remove a small piece of lung tissue. Then, a pathologist (a specialist who studies tissues) looks at the lung tissue under a microscope and does other tests. These tests can show what kind of lung disease is present, like cancer, infection, ILD, or granulomas.

Treating non-infectious lung disease

Changes in the lungs caused by inflammation are usually treated with medications that suppress the immune system. The most common medications for non-infectious lung disease are corticosteroids (like prednisone), which can be taken as pills or given directly into the bloodstream through an IV. Note that inhaled steroids are not effective in treating ILD.

While oral or IV steroids often work well, they might not provide long-term improvement. Using steroids for a long time can also cause problems like high blood pressure, high blood sugar, weak bones (osteopenia), high cholesterol (hyperlipidemia), and stress on the kidneys and eyes.

Other medications that lower immune system activity, like cyclosporine and sirolimus, can sometimes help. Some lung problems get better with one type of immunosuppressive medication but not another. As mentioned previously, rituximab combined with azathioprine or mycophenolate appears to be especially effective in treating GLILD.

If left untreated, non-infectious lung disease can get worse and cause lasting damage to the lungs. While inflammation may be reversible, once fibrosis occurs, it cannot be reversed or fixed. It's very important that your healthcare provider correctly identifies your specific type of lung disease and treats it properly to give you the best chance of protecting your lung function.

Decoding PI: CVID and GLILD

In this December 2025 webinar, Dr. Michael Jordan (Cincinnati Children's Hospital, University of Cincinnati) discusses current issues and clinical trials on the relationship between CVID and granulomatous lymphocytic interstitial lung disease (GLILD).

Watch webinar

Clinical trial explores biologic treatment for CVID lung condition

Researchers are conducting a clinical trial to test the effectiveness of abatacept, a medication used for arthritis, for granulomatous lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID).

Read article

Preventing respiratory infections

There are several strategies that can help you avoid respiratory infections and stay well:

Get vaccinated for both influenza and COVID-19, even if you are on Ig therapy. Also, talk to your immunologist about whether you should get vaccinated against other germs that can cause respiratory infections, such as RSV and Streptococcus pneumoniae.
It’s important for household members or other close contacts to get vaccinated too!
Regularly wash your hands with soap and water, especially after coughing or sneezing, after using the bathroom, and before eating.
Hand sanitizer with at least 60% alcohol can also prevent infections when soap and water are not available. However, hand sanitizer does not kill some germs and may not be as effective as handwashing with soap and water when the hands are greasy or very dirty [24]. When using hand sanitizer, read the label for the correct amount of sanitizer to use and rub the entire hand until completely dry; do not wipe the sanitizer off before it has dried.
Regularly disinfect high-touch surfaces in your home, like door knobs, sink handles, and light switches, especially during cold and flu season.
Avoid individuals who are sick.
Try not to touch your nose, mouth, or eyes, as germs can spread this way.
Avoid crowded indoor areas such as shopping malls, restaurants, and movie theaters, especially during cold and flu season.
During cold and flu season, use a well-fitted N95 or KN95 mask when out in public that completely covers your nose and mouth to avoid inhaling germs [25].

You can also prevent the spread of germs when you have a respiratory infection:

When coughing or sneezing, cover your nose and mouth with a sleeve, elbow, or tissue. Dispose of the tissue after use.
Stay home from work or school until you have been fever-free and your symptoms are improving for 24 hours. Take additional precautions, like wearing a mask and distancing from others, for five days.

Managing respiratory infections

Many different kinds of germs can cause infections in the respiratory system in people with PI. Respiratory infections can be as mild as a cold or as serious as pneumonia. There are antibiotics to treat infections caused by bacteria and antiviral medications for the flu or COVID-19. Home tests for influenza and COVID-19 can help you get diagnosed quickly so that your healthcare provider can prescribe these treatments.

However, treatment for most respiratory infections focuses on easing symptoms and preventing further problems. Your healthcare provider might suggest over-the-counter medicine to lower fever and relieve body aches. Other helpful medications include expectorants, which thin out mucus to make it easier to cough up, and decongestants, which reduce swelling of the mucous membranes in the nose and sinuses.

It's important to drink plenty of fluids to stay hydrated. Drinking different kinds of non-alcoholic drinks is helpful. Drinks with crushed ice or carbonation can soothe a sore throat. Warm drinks, like tea, can help clear nasal passages and ease chest tightness.

During the worst part of a respiratory infection, you may lose your appetite. This usually doesn't last long. Eating small, frequent meals of liquids and light foods is often effective. Once your appetite returns, your healthcare provider might recommend a diet high in calories and protein to replace what your body lost during the illness.

Other ways to feel better include:

Rinsing your mouth with plain water regularly. This can help with dryness and the bad taste that often comes with being sick and breathing through your mouth.
Using a vaporizer or humidifier to increase the moisture in the air and loosen mucus. If you use a vaporizer or humidifier, it's important to clean it daily to prevent mold.
Applying petroleum jelly or lip balm to irritated skin on your lips and nose.
Getting rest. If coughing or a runny nose keeps you from resting, try using extra pillows to raise your head and shoulders while you sleep. Sometimes, a cough suppressant can prevent coughing from waking you up at night.

Page references

Hirsch AG, Stewart WF, Sundaresan AS, Young AJ, Kennedy TL, Scott Greene J, et al. Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample. Allergy. 2017;72: 274–281. Available: https://pubmed.ncbi.nlm.nih.gov/27590749/
Lawrence MG, Palacios-Kibler TV, Workman LJ, Schuyler AJ, Steinke JW, Payne SC, et al. Low serum IgE is a sensitive and specific marker for common variable immunodeficiency (CVID). J Clin Immunol. 2018;38: 225–233. Available: https://pubmed.ncbi.nlm.nih.gov/29453744/
Rha M-S, Cho H-J, Yoon J-H, Kim C-H. Association between the use of electronic cigarettes and the prevalence of chronic rhinosinusitis and allergic rhinitis: a nationwide cross-sectional study. Rhinology. 2022;60: 20–28. Available: https://www.rhinologyjournal.com/download.php?id=2956
Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Kumar KA, Kramper M, et al. Clinical practice guideline (update): Adult Sinusitis Executive Summary. Otolaryngol Head Neck Surg. 2015;152: 598–609. Available: https://pubmed.ncbi.nlm.nih.gov/25833927/
Recurrent Strep Throat: What To Do When Strep Comes Back. In: Cleveland Clinic [Internet]. [cited 6 Jan 2026]. Available: https://health.clevelandclinic.org/recurring-strep-throat
Clark TW, Medina M-J, Batham S, Curran MD, Parmar S, Nicholson KG. Adults hospitalised with acute respiratory illness rarely have detectable bacteria in the absence of COPD or pneumonia; viral infection predominates in a large prospective UK sample. J Infect. 2014;69: 507–515. Available: https://pmc.ncbi.nlm.nih.gov/articles/PMC7112687/
Smith DK, McDermott AJ, Sullivan JF. Croup: Diagnosis and management. Am Fam Physician. 2018;97: 575–580. Available: https://pubmed.ncbi.nlm.nih.gov/29763253/
The Children’s Hospital of Philadelphia. What is Croup? Symptoms, Treatment, and When to Worry. In: Children’s Hospital of Philadelphia [Internet]. 7 Dec 2020 [cited 6 Jan 2026]. Available: https://www.chop.edu/news/health-tip/what-is-croup-symptoms-treatment-and-when-to-worry
Centers for Disease Control and Prevention. Preliminary Estimated Flu Disease Burden 2023–2024 Flu Season. In: Flu Burden [Internet]. 14 Jan 2025 [cited 6 Jan 2026]. Available: https://archive.cdc.gov/#/details?url=https://www.cdc.gov/flu-burden/php/data-vis/2023-2024.html
Centers for Disease Control and Prevention. Laboratory-Confirmed Influenza Hospitalizations. [cited 6 Jan 2026]. Available: https://gis.cdc.gov/grasp/fluview/FluHospChars.html
Indoor Air and Coronavirus (COVID-19). In: Environmental Protection Agency [Internet]. 17 Jun 2020 [cited 6 Jan 2026]. Available: https://www.epa.gov/indoor-air-quality-iaq/indoor-air-and-coronavirus-covid-19
Centers for Disease Control and Prevention. People with Certain Medical Conditions and COVID-19 Risk Factors. In: Covid [Internet]. 17 Nov 2025 [cited 6 Jan 2026]. Available: https://www.cdc.gov/covid/risk-factors/index.html
Lindahl H, Kahn F, Nilsdotter-Augustinsson Å, Fredrikson M, Hedberg P, Killander Möller I, et al. Inborn errors of immunity are associated with increased COVID-19-related hospitalization and intensive care compared to the general population. J Allergy Clin Immunol. 2025;155: 387–397.e6. Available: https://www.jacionline.org/article/S0091-6749(24)01125-4/fulltext
Meager A, Visvalingam K, Peterson P, Möll K, Murumägi A, Krohn K, et al. Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1. PLoS Med. 2006;3: e289. Available: https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0030289
Centers for Disease Control and Prevention. Types of COVID-19 Treatment. In: Covid [Internet]. 6 Jan 2026 [cited 6 Jan 2026]. Available: https://www.cdc.gov/covid/treatment/index.html
McDonnell J, Cousins K, Younger MEM, Lane A, Abolhassani H, Abraham RS, et al. COVID-19 vaccination in patients with inborn errors of immunity reduces hospitalization and critical care needs related to COVID-19: A USIDNET report. J Clin Immunol. 2024;44: 86. Available: https://publications.aap.org/pediatrics/article/154/Supplement%204/S59/200038/COVID-19-Vaccination-in-Patients-With-Inborn
New COVID-19 preventative Pemgarda authorized for immunocompromised. In: Immune Deficiency Foundation [Internet]. [cited 6 Jan 2026]. Available: https://primaryimmune.org/resources/news-articles/new-covid-19-preventative-pemgarda-authorized-immunocompromised
Infectious Diseases Society of America. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. [cited 6 Jan 2026]. Available: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
Kristensen K, Hjuler T, Ravn H, Simões EAF, Stensballe LG. Chronic diseases, chromosomal abnormalities, and congenital malformations as risk factors for respiratory syncytial virus hospitalization: a population-based cohort study. Clin Infect Dis. 2012;54: 810–817. Available: https://pubmed.ncbi.nlm.nih.gov/22247121/
Nanishi E, Hoshina T, Takada H, Ishimura M, Nishio H, Uehara T, et al. A nationwide survey of common viral infections in childhood among patients with primary immunodeficiency diseases. J Infect. 2016;73: 358–368. Available: https://www.journalofinfection.com/article/S0163-4453(16)30203-1/fulltext
Ignacio González-Granado L, Martín-Nalda A, Alsina L, Neth O, Santamaría M. Pere Soler-Palacín. Respiratory syncytial virus infections requiring hospitalization in patients with primary immunodeficiency. Anales de Pediatría. 2022;96. Available: https://pubmed.ncbi.nlm.nih.gov/35637145/
Paredes-Amaya CC, Rengifo de Lima MA, Fernandes-Pineda M, Bonelo-Perdomo A, Matta Cortes L, Ospina-Galíndez JA, et al. Predominantly antibody deficiencies: An important underlying cause of recurrent pneumonia in adults. Can J Respir Crit Care Sleep Med. 2024;8: 270–276. Available: https://perfilesycapacidades.javeriana.edu.co/en/publications/predominantly-antibody-deficiencies-an-important-underlying-cause/
Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. 2004;114: 415–421. Available: https://www.jacionline.org/article/S0091-6749(04)01571-4/fulltext
Centers for Disease Control and Prevention. Hand Sanitizer Facts. In: Clean Hands [Internet]. 13 Jun 2024 [cited 27 Jan 2026]. Available: https://www.cdc.gov/clean-hands/data-research/facts-stats/hand-sanitizer-facts.html
Centers for Disease Control and Prevention. Masks and Respiratory Viruses Prevention. In: Respiratory Illnesses [Internet]. 9 Sep 2025 [cited 27 Jan 2026]. Available: https://www.cdc.gov/respiratory-viruses/prevention/masks.html

This page contains general medical and/or legal information that cannot be applied safely to any individual case. Medical and/or legal knowledge and practice can change rapidly. Therefore, this page should not be used as a substitute for professional medical and/or legal advice. Additionally, links to other resources and websites are shared for informational purposes only and should not be considered an endorsement by the Immune Deficiency Foundation.

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