COVID-19 and primary immunodeficiency

What is COVID-19?

COVID-19, sometimes known as COVID or the coronavirus, is a contagious respiratory disease. 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.

When COVID-19 first infected people, it was considered an epidemic health emergency. COVID-19 has since become endemic, which means that it continues to spread widely at low levels around the world. In 2023, the U.S. Centers for Disease Control and Prevention (CDC) estimates that 75,000 people in the U.S. died from COVID-19 complications, which means that COVID-19 continues to be more deadly than the flu. Certain risk factors make people more likely to have a severe infection, but anyone can develop severe disease, even individuals who have had mild COVID-19 in the past.

Seek immediate medical attention if you have any of the following symptoms, which can indicate severe COVID-19:

• Trouble breathing.
• Persistent pain or pressure in the chest.
• New-onset confusion.
• Inability to wake up or stay awake.
• Pale, gray, or blue-colored skin, lips, or nail beds, depending on skin tone.
• Vomiting or diarrhea leading to dehydration.

People who have had COVID-19 can also develop two very different complications after their initial infection—multisystem inflammatory syndrome (MIS-C/MIS-A) 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.

Does PI put you at risk for severe COVID-19, MIS-C/MIS-A, or long COVID?

There is no definitive data on whether those with PI are more likely to get COVID-19 than others. However, there have been studies looking at PI and the course of COVID-19, including severe COVID-19, MIS-C/MIS-A, and long COVID.

Importantly, age, regardless of any other factor, is the single greatest risk factor for developing severe COVID-19. An analysis of adults hospitalized in 2020 that adjusted for chronic conditions found that:

• Those 40 and older still had a higher risk of poor outcomes (intensive care unit (ICU) admission, mechanical ventilation, and/or death) from COVID-19 compared to those ages 18-39.
• The risk was highest for those 65 and older, who 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 definitive. 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 higher than 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.

• Chronic kidney disease.
• Chronic lung diseases:
  • Bronchiectasis.
  • Chronic obstructive pulmonary disease (COPD).
  • Interstitial lung disease.
  • Pulmonary embolism.
  • Pulmonary hypertension.
• Chronic liver diseases:
  • Non-alcoholic fatty liver disease.
  • Alcoholic liver disease.
  • Autoimmune hepatitis.
• Cystic fibrosis.
• Diabetes.
• Heart conditions:
  • Heart failure.
  • Coronary artery disease.
• Leukemia and lymphoma.
• Mood disorders, including depression.

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

• Being a current or former smoker.
• Being the recipient of a hematopoietic 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).

How do you avoid COVID-19?