Primary Immunodeficiency and COVID-19: Treatment and Prevention Tips

When you’re living with a primary immunodeficiency (PI), navigating flu and cold season can be stressful. PI refers to a group of inherited conditions caused by inherited gene mutations (changes) that affect how the immune system works. People with PI may have difficulty fighting infections, and research shows that COVID-19 can cause more severe illness in people with PI than in the general population.

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Understanding your risks, taking steps to protect yourself, and knowing your treatment options can help you feel more prepared for fall and winter. This article covers all of these topics, along with recent research on COVID-19 and PI.

What Is COVID-19?

COVID-19 is an illness caused by the SARS-CoV-2 virus, which is part of the coronavirus family. It mainly spreads through droplets and aerosols (tiny particles) released when an infected person coughs, sneezes, talks, or breathes. The virus can also spread by touching surfaces that someone with COVID-19 has touched and then touching your mouth, nose, or eyes.

Symptoms of COVID-19

COVID-19 symptoms can range from mild to severe, and some people may not have any symptoms at all (this is called being asymptomatic). For most people, symptoms last about seven to 14 days. COVID-19 primarily affects the lungs.

In mild COVID-19, breathing and oxygen levels usually remain normal. In severe COVID-19, the lungs can’t deliver enough oxygen to the body. This often requires hospitalization and may include treatment with supplemental oxygen.

According to the Centers for Disease Control and Prevention (CDC), symptoms of COVID-19 can include:

• Dry cough
• Shortness of breath
• Loss of taste and smell
• Fatigue (exhaustion that doesn’t improve with rest)
• Digestive issues (such as nausea, vomiting, or diarrhea)
• Headache or muscle aches
• Fever or chills
• Coldlike symptoms (such as a stuffy or runny nose)

The symptoms of severe COVID-19 may include:

• Trouble breathing
• Chest pain or pressure that doesn’t go away
• Confusion or disorientation
• Difficulty waking up or staying awake
• Pale, gray, or bluish lips, nails, or skin
• Signs of dehydration (from vomiting or diarrhea)

Call your healthcare provider or seek emergency care right away if you or someone you care for shows these signs.

Do People With PI Get More Severe COVID-19?

Research on COVID-19 in people with PI is limited, in part because PI conditions are rare. This makes large studies difficult — there simply aren’t enough medical records to analyze in many cases. Still, available studies suggest that people with PI may face a higher risk of severe illness or death from COVID-19.

What the Numbers Show

The study reviewed emergency department records from over 1.2 million adults with COVID-19, including more than 800 people with PI. After adjusting for factors like age, sex, race, and chronic conditions, researchers found that people with PI had significantly higher odds of serious outcomes than those without PI:

• About 73 percent of people with PI were hospitalized, compared to 45 percent of those without PI.
• Nearly 19 percent of hospitalized people with PI needed help breathing from a ventilator, compared to 14 percent of those without PI.
• About 18 percent of hospitalized people with PI died of COVID-19, versus 14 percent of hospitalized people without PI.

On average, people with PI also spent nearly two more days in the hospital than those without PI. These findings highlight that PI is a real risk factor for severe COVID-19 outcomes.

Children With PI and COVID-19

Researchers have also looked at the data from many small studies grouped together. One 2022 analysis reviewed about 200 medical records of children with PI and found they may be at higher risk for severe COVID-19. In that group, 23 percent of children with PI were hospitalized during their infection, compared to just 0.18 percent of children in the general population.

Long-Lasting Symptoms

A 2025 study asked people with PI about their experiences after having COVID-19. About 25 percent reported symptoms that continued even after the initial infection cleared. The most common lingering symptoms were fatigue, headaches, and nasal issues (like congestion or a runny nose).

Although the study relied on self-reported data rather than medical records, it suggests that COVID-19 may continue to affect quality of life for some people with PI, even if the infection itself wasn’t severe.

Why Do People With PI Get More Severe COVID-19?

Researchers are still working to understand why people with PI may face more severe illness from COVID-19. Because there are many different types of PI, the reasons likely depend on which parts of the immune system aren’t working properly.

What we do know is that people with certain types of PI appear to be at higher risk for severe COVID-19.

COVID-19 Risk in Specific PI Conditions

Studies have found that people with immune deficiencies related to dealing with viral infections are much more likely to get severe forms of COVID-19. These conditions are known as TLR7 deficiency and autoimmune polyendocrine syndrome type 1 (APS-1), and they’re very rare.

A few other types of PIs were also found to have an increased risk of worse outcomes. Some examples include:

• Agammaglobulinemia
• Common variable immunodeficiency (CVID)
• Combined immunodeficiency
• Severe combined immunodeficiency (SCID)

People with these conditions may experience longer-lasting infections and slower recovery times. Many of these disorders fall into a group known as primary humoral immunodeficiencies (also called antibody deficiencies). These are some of the most frequently diagnosed PI disorders.

PI Treatments and Related Conditions

People with PI often have related conditions that are also known risk factors for severe COVID-19. These medical conditions include:

• Lung conditions such as bronchiectasis or interstitial lung disease
• Diabetes
• Blood cancers, including lymphoma
• Chronic kidney or liver disease

Some of the treatments for PI can also increase the risk of severe infectious diseases, including COVID-19. These include:

• Hematopoietic stem cell transplant (also called a bone marrow transplant)
• Solid organ transplant (such as a kidney or liver transplant)
• Immunosuppressive medications, such as corticosteroids, which weaken the immune system to prevent inflammation or organ rejection

What Happens if I Get COVID-19?

If you or someone you care for is living with PI, COVID-19 can carry a higher risk of serious illness. That’s why it’s important to watch for symptoms and get tested early if you think you may have been exposed.

You may need to test more than once, since at-home COVID-19 tests might not detect the virus right away — especially in the early stages of COVID-19.

If you test positive or develop symptoms, contact your healthcare provider as soon as possible. They understand your medical history and risk factors and can decide whether early treatment is needed to help prevent complications.

What Are COVID-19 Treatment Options for People With PI?

If you have PI and test positive for COVID-19, several treatment options may help reduce the severity of your illness. Your healthcare provider will decide which treatments are right for you, depending on your specific condition, overall health, and timing of symptoms.

Antivirals

Antiviral medications work by stopping the virus from making copies of itself after infection. Some options include:

• Molnupiravir (Lagevrio)
• Nirmatrelvir/ritonavir (Paxlovid)
• Remdesivir (Veklury)

These treatments are most effective when started early. They’re not right for everyone and may interact with other medications, so only take them if prescribed by your doctor.

Convalescent Plasma

Convalescent plasma is a treatment sometimes used for people with weakened immune systems, including those with PI. It involves giving a person an intravenous (IV) infusion of the liquid part of blood (plasma) collected from someone who has recovered from COVID-19.

The donated plasma contains antibodies that can help fight the virus. This approach is similar to immunoglobulin replacement therapy, which many people with PI already receive. For best results, convalescent plasma should be given as early as possible after a confirmed COVID-19 infection.

What Are COVID-19 Prevention Strategies for People With PI?

Preventing infection is one of the most important ways to protect yourself from serious complications of COVID-19. Here are several prevention strategies that can help people with PI lower their risk.

Get Vaccinated, if You’re Eligible

COVID-19 vaccination remains an important prevention tool, even though research is still limited for some PI conditions. Studies suggest that, overall, COVID-19 vaccination reduces the risk of hospitalization among people with PI.

Vaccine recommendations may change as researchers learn more about how people with different types of PI respond. Talk to your healthcare provider about when — and if — you should get vaccinated. You may need to time your vaccine around other treatments that could affect how well it works.

Consider Monoclonal Antibody Treatment

Monoclonal antibodies are lab-made proteins that act like your body’s natural defense system. Unlike convalescent plasma, they’re not taken from donors. One option, pemivibart (Pemgarda), is currently approved to help prevent COVID-19 in people at high risk, including some individuals with PI.

Pemivibart is given as an IV infusion every three months to maintain protection. It’s typically administered in a hospital or clinic setting.

Increase Air Flow Indoors

Because COVID-19 spreads through the air, improving ventilation can lower your risk. You can:

• Open windows and doors when weather allows.
• Use HEPA or high-efficiency air purifiers.
• Upgrade heating, ventilation, and air conditioning (HVAC) systems with high-filtration filters, and replace filters regularly.

Avoid High-Risk Areas

Crowded indoor spaces can raise your risk of infection. If you need to spend time in busy places:

• Wear a well-fitted N95 or KN95 mask.
• Wash your hands regularly with soap and water.
• Avoid touching your face, especially your eyes, nose, and mouth.

Talk With Others Who Understand

On myPIteam, people come together to share their experiences with primary immunodeficiency disorders, get advice, and find support from others who understand.

Have you had a COVID-19 infection? What was your experience like? Let others know in the comments below.