Infection frequency / susceptibility to infection

Question

Hello,
I am male, 28 years old, and have cystic fibrosis (CF) with the F508d mutation. I am Pseudomonas negative.
For about a year now, I have been taking Kaftrio/Trikafta®, which has resulted in some improvements (almost no sputum, improved digestion, and at least some slight weight gain).

However, my concern is my susceptibility to infections, which is causing me great worry:
Starting with a COVID infection in November 2024, I had about 8-9 colds/flu-like infections last year (2025). In previous years, it was usually about 3-4 infections per year. These usually involved a sore throat, runny nose, headache, sometimes a cough, and lasted for 1-2 weeks.

It's not just the sheer number of infections that's concerning, but also the fact that they now follow a fairly regular pattern: After recovering from an infection, it takes about 5-8 weeks for the next one to occur.

I actually pay close attention to a healthy diet and exercise, but last year I was only able to do a minimal amount of the latter due to my condition.

My comprehensive blood tests have always been normal/unremarkable. I have no vitamin deficiencies, and my white blood cell count and response to infections are normal. My antibody levels have also been normal.

After starting Kaftrio/Trikafta®, the course of the infection has sometimes changed: With three infections, I initially had typical cold symptoms for 4-7 days, before developing a fever of up to about 40 degrees Celsius for 1-3 days, accompanied by a chesty cough. Before Kaftrio/Trikafta®, for example, I would get a fever immediately on the first day of illness with COVID or influenza, whereas with regular colds, I almost never had a fever in the past.

My primary care physicians and the CF clinic see no need to investigate this further, as my blood work is unremarkable, and they say things like, "Many people get sick, some just get sick more often," or "you'll be fine again afterward."

Therefore, I have a few questions, as I find this quite worrying and not normal:

Do you have any ideas what the cause of such susceptibility to infection might be?

What tests would you recommend?

Could the start of Kaftrio therapy be related to this, or is it just a coincidence and there's no further connection?

I would be very grateful for your assessment and feedback.

Answer

Dear questioner,
It is perfectly understandable that you are concerned, as you have noticed an increase in infections over the past year and are looking for possible causes. In particular, you are wondering whether the addition of Kaftrio/Kalydeco (Trikafta®:elexacaftor/tezacaftor/ivacaftor, ETI) to your therapy could be responsible, or if there might be other reasons.

According to current scientific knowledge, treatment with Kaftrio/Kalydeco (Trkafta®)does not lead to an increased susceptibility to infections in the sense of a weakened immune system in people with cystic fibrosis. On the contrary, most studies show that ETI has an overall positive effect on the infection situation. An increased susceptibility to new infections has not been described to date.

However, it is important to know that many pathogens typical of cystic fibrosis, such as Pseudomonas aeruginosa or Staphylococcus aureus, can still be present in the body despite ETI treatment. They may not always be detectable during therapy, and their number often decreases, but they are generally not completely "cured" by ETI. Existing infections can therefore persist and must continue to be medically monitored and treated if necessary.

The causes of increased susceptibility to infection can be very diverse and varied. A definitive explanation cannot be found via the internet or through a general expert assessment. A precise understanding of your individual findings, your medical history, and your personal health situation is necessary.

If you and your CF doctor cannot find a satisfactory explanation or solution, it may be helpful to seek a second opinion at another specialized cystic fibrosis center. We are confident that a thorough and individualized evaluation will provide you with helpful support.

Sincerely,

Dr. Christina Smaczny

20.02.2026