What Is Common Variable Immunodeficiency (CVID)?
Common Variable Immunodeficiency is a primary immunodeficiency disorder where the body doesn’t make enough antibodies to fight off infections. Unlike allergies, which involve an overactive immune response, CVID is a failure of the immune system to protect you. People with CVID have critically low levels of immunoglobulins-especially IgG, IgA, and sometimes IgM-which are the proteins that act like soldiers in your bloodstream, hunting down bacteria and viruses.
It’s not rare. About 1 in every 25,000 to 50,000 people has it. Most are diagnosed between ages 20 and 40, though symptoms can start earlier. Many people live for years without knowing why they’re always sick. The average time from first symptoms to diagnosis is over eight years. That’s because CVID looks like a string of unrelated problems: chronic sinus infections, pneumonia, stomach bugs, fatigue, and even weight loss.
Why Do Antibodies Drop in CVID?
The problem isn’t that you don’t have B cells-the immune cells that make antibodies. You usually have plenty. The issue is that those B cells are broken. They don’t mature properly. They can’t switch from making basic antibodies to the powerful, targeted ones your body needs to fight off specific threats like pneumonia or foodborne bacteria.
This is called impaired class-switch recombination. Think of it like having a toolbox full of hammers but no screwdrivers or wrenches. You’ve got tools, but they’re useless for the job. In CVID, your body can’t make the right kind of antibodies for the right germ. That’s why even simple infections like strep throat or giardia (a parasite you catch from dirty water) become serious, recurring problems.
Genetics play a role, but it’s messy. Over 20 genes have been linked to CVID, including TACI, BAFF-R, and CD19. But here’s the catch: fewer than 1 in 5 people with CVID have a known genetic mutation. That means for most, we don’t know exactly why it happened. It’s not inherited in a simple way like cystic fibrosis. It’s more like a random glitch in your immune system’s programming.
What Are the Real Symptoms?
People with CVID don’t just get colds. They get repeated infections. The most common are respiratory: sinus infections, bronchitis, and pneumonia. About 35% of pneumonia cases in CVID patients are caused by Haemophilus influenzae, 28% by Streptococcus pneumoniae, and 15% by Staphylococcus aureus. These are bacteria that healthy people easily clear-but for someone with CVID, they stick around, damage lungs, and lead to permanent scarring.
One in three people with CVID also has digestive problems. Chronic diarrhea, bloating, weight loss, and malabsorption aren’t just "bad digestion." They’re often caused by Giardia lamblia, a parasite that thrives when your gut has no antibodies to stop it. In the general population, giardia affects less than 1% of people. In CVID, it’s 12%. That’s a massive difference.
Fatigue is huge. Over 70% of patients report constant tiredness, even when they’re not sick. It’s not laziness-it’s your body burning energy just trying to survive. Many describe it as "feeling like you’re running a marathon every day."
And then there are the hidden dangers. About 25% develop autoimmune diseases-where your immune system attacks your own body. Immune thrombocytopenia (low platelets), autoimmune hemolytic anemia (your body destroys your red blood cells), and rheumatoid arthritis are common. Your immune system, already weak against germs, turns on itself.
How Is CVID Diagnosed?
Diagnosis isn’t based on one test. It’s a puzzle. Doctors look for three things:
- Serum IgG below 500 mg/dL (normal is 700-1600)
- Serum IgA below 7 mg/dL (normal is 70-400)
- Failure to respond to vaccines like pneumococcus or tetanus
They’ll also check IgM levels-often low too. Blood tests will show normal or even high B cell counts, which helps rule out other conditions like X-linked agammaglobulinemia (where B cells are nearly absent).
Doctors may also test for complications: chest CT scans for lung damage, endoscopies for gut inflammation, and blood work for autoimmune markers. It’s not just about counting antibodies-it’s about seeing the damage they’ve left behind.
Because symptoms overlap with asthma, COPD, or even IBS, many patients see three or more doctors before getting the right diagnosis. That’s why awareness among general practitioners is still low.
What’s the Main Treatment?
The only proven treatment is immunoglobulin replacement therapy. This means getting antibodies from donated human plasma. These aren’t drugs-they’re purified proteins that replace what your body can’t make.
There are two ways to get them:
- Intravenous Immunoglobulin (IVIG): Infused into a vein every 3-4 weeks. Takes 2-4 hours. Done at a clinic or hospital.
- Subcutaneous Immunoglobulin (SCIG): Injected under the skin, usually weekly. Can be done at home after training.
Most patients get 400-600 mg per kg of body weight monthly for IVIG, or 100-150 mg/kg weekly for SCIG. The goal? Keep IgG levels above 800 mg/dL. That’s the threshold most doctors agree helps prevent infections.
SCIG is becoming more popular. Why? Fewer side effects. Most people can do it themselves after 3-5 training sessions. Many report better energy, fewer hospital visits, and more control over their lives. But it’s not perfect-25-40% get redness or swelling at injection sites. Rotating locations and slowing the drip rate helps.
What Are the Side Effects and Challenges?
IVIG can cause headaches, chills, nausea, and fever during or right after the infusion. About 32% of patients have these reactions. Some need pre-medication with antihistamines or steroids. Rarely, it can cause kidney problems or blood clots.
SCIG is gentler, but it takes longer. You might spend 1-2 hours a week injecting. Some people find it tiring to stick themselves every week. Others love the independence.
Cost is a huge barrier. In the U.S., IVIG runs $65,000-$95,000 a year. SCIG is slightly more expensive: $70,000-$100,000. Insurance covers most of it, but co-pays and deductibles still hurt. In low-income countries, only 35% of patients get treatment at all.
There’s also a global plasma shortage. Plasma is the source of all immunoglobulin products. Demand is rising, but supply hasn’t kept up. Experts predict treatment costs could jump 15-20% annually through 2028.
What About New Treatments?
Researchers are working on better options. One promising drug is atacicept, a biologic that blocks two signals (BAFF and APRIL) that mess up B cell function. In early trials, it cut severe infections by 37% compared to standard therapy alone. It’s not a cure, but it could mean lower doses of immunoglobulin-or even fewer infusions.
Another hope is gene therapy. Scientists are mapping CVID subtypes. In the next 5 years, we may see treatments tailored to specific genetic flaws-like fixing a software bug instead of replacing the whole system.
For now, though, immunoglobulin therapy remains the gold standard. It’s not glamorous, but it works. Patients who stick with it live longer. In the 1970s, life expectancy for CVID was just 33 years. Today, with consistent treatment, it’s 59-and climbing.
Living With CVID: Daily Realities
People with CVID don’t live like everyone else. They avoid crowded places during flu season. They carry hand sanitizer everywhere. They track their IgG levels like a bank balance. Miss an infusion? You might get sick within days.
But many live full lives. They work, travel, raise kids, and even run marathons. Support groups matter. The Immune Deficiency Foundation has over 200 local chapters and 15,000 members. Their annual conference brings together patients, doctors, and researchers. For many, meeting someone else who gets it is the first time they don’t feel alone.
Education is key. Patients who understand their condition, know their numbers, and advocate for themselves do better. That means knowing your IgG target, recognizing early infection signs, and pushing back when doctors dismiss symptoms as "just allergies" or "stress."
What Should You Do If You Suspect CVID?
If you’ve had:
- Four or more ear or sinus infections in a year
- Two or more pneumonias in a year
- Chronic diarrhea with weight loss
- Autoimmune disease with recurrent infections
- Family history of immune problems
-ask your doctor for a serum immunoglobulin panel. Don’t wait. The earlier you’re diagnosed, the less damage your lungs and gut will take.
There’s no cure yet. But with treatment, CVID is manageable. You can live well. You just need the right diagnosis-and the right support.
Is CVID the same as having low antibodies from aging or cancer?
No. CVID is a genetic disorder where your body can’t make antibodies from birth or early adulthood. Low antibodies from aging (immunosenescence) or cancer treatments like chemotherapy are temporary or acquired. CVID is lifelong and not caused by other diseases. Blood tests can tell the difference by checking B cell counts and vaccine responses.
Can you outgrow CVID?
No. CVID is a lifelong condition. The immune system doesn’t fix the underlying B cell defect. Immunoglobulin therapy replaces what’s missing, but it doesn’t cure the root problem. Stopping treatment leads to a return of infections and complications.
Is CVID contagious?
No. CVID is not contagious. You can’t catch it from someone else. It’s caused by genetic mutations, not germs. People with CVID are more likely to get infections, but they can’t pass CVID to others.
Do I need to avoid vaccines if I have CVID?
You should avoid live vaccines like MMR, varicella, or nasal flu spray. Your immune system can’t handle them safely. But inactivated vaccines (like flu shots, tetanus, or pneumonia vaccines) are safe and often recommended-though they may not work as well. Your doctor will guide you based on your IgG levels and treatment schedule.
Can I have children if I have CVID?
Yes. Many people with CVID have healthy children. The condition isn’t passed on in a simple pattern, so the risk to your kids is low-unless you have a known genetic mutation. Genetic counseling is recommended if you’re planning a family, especially if there’s a family history of immune disorders.
What happens if I miss an immunoglobulin infusion?
Missing one infusion won’t cause immediate danger, but your IgG levels start dropping within days. Most people feel more tired and get sick within 2-3 weeks. Consistency is key. If you miss a dose, contact your clinic right away. They may adjust your next infusion or suggest a temporary boost.
Next Steps for Patients
If you’ve been diagnosed with CVID:
- Find a specialist: Look for an immunologist, not just an allergist. They know the nuances.
- Track your IgG levels: Aim to stay above 800 mg/dL. Ask for copies of your blood work.
- Learn SCIG: If you’re on IVIG, ask about switching to home-based SCIG. It’s more flexible.
- Join a support group: The Immune Deficiency Foundation offers resources, webinars, and peer connections.
- Get annual screenings: Chest CT, lung function tests, and gut checks can catch complications early.
If you suspect you might have CVID but haven’t been tested:
- Request a serum immunoglobulin panel (IgG, IgA, IgM).
- Ask about vaccine response testing (post-pneumococcal or tetanus titers).
- Don’t accept "it’s just allergies" or "you’re always sick" as an answer.
CVID isn’t a death sentence. It’s a challenge-but one that can be managed. Knowledge, consistency, and support make all the difference.
