This progression of lung disease accounts for the bulk of morbidity and mortality (approximately 50% of adults have a Forced Expiratory Volume in 1 second  <70%). The underlying lung disease complicated by difficult-to-treat infecting organisms is the primary reason for COVID-19 vulnerability. Other reasons for COVID-19 susceptibility and poor outcomes in people with CF: - Diabetes mellitus: Present in approximately 40% of adults with CF (dysglycemia is present in approximately 65%), and has been shown to be an independent factor for worse outcomes with COVID-19 infection. - Nutritional deficiency: Approximately 85% of people with CF are pancreatic insufficient, with resultant undernutrition in a large proportion of adults with CF. - Chronic liver disease: Affects approximately 30% of people with CF.# 
- Post-transplantation: In Canada, around 1,500 people with CF have received solid organ transplants (predominantly lung) since 2019. People who have received a solid organ transplant take immunosuppressant medications, which are believed to increase risk of serious disease from COVID-19 infection.
There is a growing evidence base available to understand the risk related to COVID-19 infection in people with CF. A recent publication based on data obtained prior to the introduction of COVID-19 vaccines from 22 countries reported on 1452 individuals with CF and confirmed COVID-19 infection. Of those included in the study, 1 in 5 patients required hospitalization, 1 in 30 required intensive care unit (ICU) admission, and 1 in 75 died. 1 Among non-transplanted individuals, worse outcomes were reported for those of older age, non-white race, lower lung function, low body mass index, and concomitant diabetes; this provides direct support for the postulated comorbidities/clinical features listed above. The CF Registry Global Harmonization Group published findings from a global study on the impact of COVID-19 on children with CF. 2 The study included 105 children with CF under the age of 18 from 13 countries; while infection was mild in most cases, a higher number of hospitalizations was noted in individuals with pre-existing advanced lung disease or poor nutrition. 3 Impact of respiratory viruses in people with CF extrapolated from other data People with CF commonly experience infections with a number of respiratory viruses including influenza, adenovirus, respiratory syncytial virus (RSV), enteroviruses, and rhinoviruses. These infections are a common cause of pulmonary exacerbations (estimated at >50%), which drive symptom morbidity and hospitalizations, accelerate lung function decline, and increase mortality. Viral infections may also be associated with acquisition of Pseudomonas aeruginosa pulmonary infection, which is independently associated with the aforementioned negative outcomes.
A previous meta-analysis showed that 50 to 70% of people with CF testing positive for influenza A (H1N1) required hospitalization, as compared to 7 to 20% of the general population. 4 Approximately 40% of patients never recover to their previous baseline lung function after a CF pulmonary exacerbation.
There is every reason to implicate SARS-CoV-2 infection with similar, if not greater, adverse events. Individuals with other chronic lung diseases also are negatively impacted by viral infections, including chronic obstructive pulmonary disease, severe asthma, and bronchiectasis. Although high-quality evidence is not available, influenza immunization is routinely recommended for people with CF worldwide.
Is the COVID-19 vaccine efficacious and safe for people with CF?
As CF is considered to be a severe underlying medical condition, people with CF were excluded from the Pfizer-BioNTech, Moderna, and AstraZeneca COVID-19 vaccine trials. Data is currently limited as to whether COVID-19 vaccines are as efficacious for people with CF as they were found to be for the clinical trial participants. There are data to suggest that the currently available COVID-19 vaccines have efficacy 5 and there is no reason to believe that the antibody response to immunization should be lower in CF compared to the general population.
CF transmembrane conductance regulator (CFTR) gene mutations, which are the cause of CF, do not have clinically relevant impacts on the host and innate immunity. There is no evidence of blunted immune response to other immunizations (e.g., influenza), and immunizations are a routine part of CF care. As well, the relatively younger age of people with CF supports a robust immunological response (65 years of age).

# COVID-19 Vaccines for People with Cystic Fibrosis
Updated: April 18, 2023 3
People with CF are most often not on maintenance/routine medications that would potentially blunt an immune response to immunization (e.g., oral corticosteroids or immunosuppressive therapies). If a patient has received a lung transplant or other solid organ transplant, please refer to the respective clinical guidance for these individuals.
There is no reason to believe that there are specific safety concerns for immunization in people with CF. A study involving 424 people with CF from Italy aged 12 years and older demonstrated that mRNA-based vaccines against SARS-CoV-2 were well-tolerated and safe in the short-term. 6 Individuals with CF invariably have chronic lung disease, some more severe in nature. Therefore, if there was an anaphylactic reaction, there is the potential for more severe symptoms and complications. This would be similar to other patient populations with advanced lung disease (but perhaps less so in CF, as cardiovascular comorbidities are generally not present). As such, it is recommended that healthcare providers counseling people with CF follow the allergy contraindications and advice provided below closely, particularly for people with CF with most severe lung disease (i.e., FEV1 <40% predicted).
Are there any specific contraindications or exceptions for people with CF?
Individuals who have had a severe allergic reaction to an ingredient of one type of COVID-19 vaccine are still able to receive future doses of the other type of vaccine. 7 BCCDC has a list of the individual components and their purpose in the vaccines. For a complete list of components in the vaccine, consult the vaccine monographs found at: www.bccdc.ca/health-info/diseases-conditions/covid-19/covid-19-vaccine/vaccines-for-covid-19.
People with a history of anaphylactic reaction to a previous dose of an mRNA COVID-19 vaccine, revaccination (i.e., administration of a subsequent dose in the series when indicated) may be offered with the same vaccine or the same mRNA platform if a risk assessment deems that the benefits outweigh the potential risks for the individual and if informed consent is provided. Prior to revaccination, consultation with an allergist or another appropriate physician (e.g., Medical Health Officer) is advised. If revaccination is going ahead, vaccine administration should be done in a controlled setting with expertise and equipment to manage anaphylaxis, with an extended period of observation of at least 30 minutes after revaccination.
Health Canada continues to monitor any adverse events following immunization through their post-authorization surveillance process.
Otherwise, there are no specific contraindications or exceptions for people with CF from a disease perspective.
COVID-19 vaccines can be given concomitantly with, or any time before or after any other live or inactivated vaccine.  Are there specific recommendations or considerations for safe and/or most effective administration?
Out of abundance of caution, it is recommended that immunization be delayed in the following circumstances: o If the patient is currently undergoing treatment, including antibiotics for a pulmonary exacerbation of CF; o If patient is hospitalized for a CF-related complication like a bowel obstruction or acute pancreatitis.