Seroprevalence and clinical characteristics of SARS-CoV-2 infection in children with cystic fibrosis

Abstract

Background:

People with cystic fibrosis (PwCF) have chronic lung disease and may be at increased risk of coronavirus disease 2019 (COVID-19)-related morbidity and mortality. This study aimed to determine seroprevalence and clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with cystic fibrosis (CF), and to assess antibody responses following SARS-CoV-2 infection or vaccination.

Methods:

Children and adolescents with CF followed at Seattle Children’s Hospital were enrolled between July 20, 2020 and February 28, 2021. SARS-CoV-2 serostatus was determined on enrollment at 6 and 11 months (±2 months) for nucleocapsid and spike IgG. Participants completed intake and weekly surveys inquiring about SARS-CoV-2 exposures, viral/respiratory illnesses, and symptoms.

Results:

Of 125 PwCF enrolled, 14 (11%) had positive SARS-CoV-2 antibodies consistent with recent or past infection. Seropositive participants were more likely to identify as Hispanic (29% vs. 8%, p = 0.04) and have pulmonary exacerbations requiring oral antibiotics in the year prior (71% vs. 41%, p = 0.04). Five seropositive individuals (35.7%) were asymptomatic, while six (42.9%) reported mild symptoms, primarily cough and nasal congestion. Antispike protein IgG levels were approximately 10-fold higher in participants following vaccination compared with participants who had natural infection alone (p < 0.0001) and resembled levels previously reported in the general population.

Conclusions:

A majority of PwCF have mild or no symptoms of SARS-CoV-2 making it difficult to distinguish from baseline respiratory symptoms. Hispanic PwCF may be disproportionately impacted, consistent with racial and ethnic COVID-19 disparities among the general US population. Vaccination in PwCF generated antibody responses similar to those previously reported in the general population.

1 |. INTRODUCTION

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in the United States in January 2020.¹ Although pediatric cases have represented a minority of total US infections (17.2%), most hospitalized children have underlying medical conditions, including chronic lung disease.^2–4 People with cystic fibrosis (PwCF) have chronic lung disease due to altered airway mucus, chronic airway infection, and airway inflammation, and therefore may be at increased risk of COVID-19-related morbidity and mortality.⁵

Prior studies have examined clinical outcomes following polymerase chain reaction-confirmed SARS-CoV-2 infection in people with cystic fibrosis (CF),^6–8 but because these studies were case-based, they likely underestimated the number of infections while overestimating the frequency of symptoms and severity of disease in PwCF.⁹ To date only three studies (one each from Belgium, Germany, and Northern Italy) have attempted to describe SARS-CoV-2 seroprevalence in PwCF.^10–12 These single-center studies all took place at different stages of the pandemic and found varying SARS-CoV-2 seroprevalence rates (2%–15%) as well as divergent rates of asymptomatic infection (23%–100%). Only one of the three studies examined demographic and clinical characteristics associated with SARS-CoV-2 seroprevalence. Prior literature has suggested that PwCF may have impaired antibody response to vaccination or infection with pathogens such as influenza and pneumococcus, but these seroprevalence studies did not evaluate antibody response or durability following either infection or vaccination.^13–15

This study aimed to define the seroprevalence and rates of symptomatic and asymptomatic SARS-CoV-2 infection in children with CF followed at a large US-based pediatric center. Secondary aims were to determine if demographic or clinical characteristics were associated with SARS-CoV-2 seropositivity and to describe SARS-CoV-2 antibody responses following COVID-19 vaccination and SARS-CoV-2 infection in children and adolescents with CF.

2 |. MATERIALS AND METHODS

2.1 |. Study design and patient population

All children and adolescents with CF followed at Seattle Children’s Hospital were eligible to enroll between July 20, 2020, and February 28, 2021. Human subjects approval was obtained through the Seattle Children’s Hospital Institutional Review Board (Study00001786). PwCF and their families were approached during in-person clinic visits. After provision of verbal informed consent and assent (if applicable), participants or parents completed an intake survey through the Research Electronic Data Capture application (REDCap, hosted at the University of Washington) (Supporting Information: Figure S1).¹⁶ Participants were asked about prior SARS-CoV-2 exposures, results of any prior SARS-CoV-2 testing, symptoms (systemic, respiratory, gastrointestinal, or other) that occurred between February 1, 2020, and study enrollment, as well as any interventions undertaken for treatment. Baseline demographic and clinical data were collected through a review of the electronic medical record (EMR) at enrollment. Participants were then sent weekly follow-up surveys for a total of 56 weeks through REDCap inquiring about SARS-CoV-2 exposures, testing, and symptoms (Supporting Information: Figure S2). Participants reporting symptoms were encouraged to contact their care team after submitting their responses. Vaccination records were obtained through a review of the EMR, which incorporates data from the Washington State Immunization Information System. Vaccines in use in the United States during the study were all targeted against the SARS-CoV-2 spike protein, including the Pfizer-BioNTech BNT162b2 mRNA (Comirnaty), Moderna mRNA-1273 (Spikevax), and Janssen Ad26. COV2.S adenoviral vector vaccines.¹⁷

2.2 |. SARS-CoV-2 serology testing

SARS-CoV-2 serostatus was determined at enrollment a commercial assay for nucleocapsid protein immunoglobulin G (IgG, Abbott SARS-CoV-2 IgG) on the Architect i1000 instrument. After a spike protein receptor binding domain (RBD) IgG assay (Abbott AdviseDx SARS-CoV-2 IgG II) became available during this study it was added to prospective testing and we tested previously stored frozen serum samples, if available. Both assays received Food and Drug Administration emergency use authorization.¹⁸ The estimated sensitivity and specificity of the qualitative nucleocapsid IgG assay are 100% and 99.9%, respectively at least 17 days following symptom onset.¹⁹ For the semi-quantitative spike RBD antibody assay, the estimated sensitivity is 98.0% at 15 days or greater after symptom onset, and specificity is 99.6% based on prepandemic samples.¹⁸ The reference range for a positive spike IgG result is ≥50 arbitrary units (AU)/mL. Follow-up serology testing was performed at 6 and 11 months (±2 months) postenrollment. All samples for antibody testing were collected between July 2020 and March 2022.

2.3 |. Data and statistical analysis

We arbitrarily added 1 AU to all spike IgG measurements so that all spike IgG values were greater than zero for analysis; values above the upper level of quantification (>25,000 AU/mL) were assumed to be 25,001 AU/mL. For comparison to published vaccine antibody responses, we converted AU to Binding Antibody Units (BAU, 7 AU = 1 BAU) based on manufacturer recommendations.²⁰ We defined participants as having evidence of infection with SARS-CoV-2 if they had a positive nucleocapsid antibody result at any point during enrollment, or if they had a positive spike protein antibody result before COVID-19 vaccination. Participants were notified of their serology results, and study investigators directed participants to their care team for medical advice as needed.

Demographic and clinical variables were compared between SARS-CoV-2 seronegative and seropositive study subjects. Continuous variables were summarized with median and interquartile ranges (IQR) unless otherwise noted, and categorical variables were summarized with number and percent. Mann–Whitney tests were used to compare continuous variables across groups, and Fisher’s exact tests were used to compare categorical variables across groups. A logistic regression model was used to regress seropositive status on clinical and demographic variables of interest, using a p value of entry cutoff of 0.15. A two-sided test p < 0.05 was considered statistically significant. The above analyses were performed using R version 4.1.2.

We used survival analysis to estimate the proportion of our study population with serologic evidence of SARS-CoV-2 infection over time with associated 95% confidence intervals (CI) (GraphPad Prism 9.4.1). Participants were censored at the time of their final study serologic testing if results were negative. All spike IgG levels measured at least 14 days after the second Pfizer BNT162b2 vaccine dose were used to fit a single-phase exponential decay model by nonlinear regression (constraints K > 0, plateau = 0, GraphPad Prism 9.4.1).

We used data from the Centers for Disease Control and Prevention (CDC) COVID-19 Nationwide Commercial Lab Seroprevalence data for comparison.^21,22 CDC seroprevalence estimates are based on nucleocapsid antibody testing of a convenience sample of residual serum specimens from individuals presenting to care for reason other than suspected COVID-19, adjusted to represent the population based on US census data. CDC initially used the Abbott SARS-CoV-2 IgG assay used in our study, but then switched to the Roche Elecsys Anti-SARS-CoV-2 assay on 9/30/2021, which has greater sensitivity for more distant infection.²³

3 |. RESULTS

3.1 |. Baseline clinical characteristics and serology testing results

During the study enrollment period, 155 out of approximately 200 children and adolescents receiving care at Seattle Children’s CF clinic were approached, and 125 (81%) were enrolled (Figure 1). Demographic and clinical characteristics for the cohort are described in Table 1. The average age at enrollment was 12 years (IQR 7–17). Approximately half of participants were male (51%, n = 63). Fifty five percent were homozygous for F508del, and 35% were F508del heterozygous. Most patients’ percent predicted forced expiratory volume in one second (ppFEV₁) was in the normal range (median 105%, IQR 93–114), and the median baseline body mass index percentile was 57.3% (IQR 29.9–72.6). All subjects analyzed had serology testing at enrollment (n = 125), with 66% (n = 82) and 70% (n = 88) completing testing at 6-month and 11-month follow-up, respectively.

FIGURE 1.

Flow diagram of cohort selection. PwCF, people with cystic fibrosis.

TABLE 1.

Cohort demographic and clinical characteristics.

Variable	All subjects (n = 125)	SARS-CoV-2 seronegative (n = 111)	SARS-CoV-2 seropositive (n = 14)
Demographics
Age	12 (7–17)	12 (7–16)	15.5 (10.5–18)
Sex
Male	63 (51%)	58 (53%)	5 (36%)
Race
Black	3 (2%)	3 (3%)	0
Asian	3 (2%)	3 (3%)	0
Native Hawaiian/Pacific Islander	2 (2%)	2 (2%)	0
American Indian/Alaska Native	4 (3%)	4 (4%)	0
White	104 (83%)	94 (85%)	10 (71%)
Other	9 (7%)	5 (5%)	4 (29%)
Hispanic ethnicity	13 (10%)	9 (8%)*	4 (29%)*
Clinical characteristics
BMI percentile	57.3 (29.88–72.57)	57.3 (32.25–72.05)	50 (23–80.3)
ppFEV1 at enrollment	105 (93–114)	105 (95–114)	98 (86–108)
1 or 2 copies of F508	113 (90%)	101 (91%)	12 (86%)
Insurance: private or private/public	77 (62%)	69 (62%)	8 (57%)
Pancreatic insufficient	115 (92%)	102 (92%)	13 (93%)
CF-related diabetes	16 (13%)	15 (14%)	1 (7%)
MSSA	90 (72%)	80 (72%)	10 (71%)
MRSA	21 (17%)	16 (15%)	5 (36%)
Pseudomonas aeruginosa	40 (32%)	36 (32%)	4 (29%)
IV antibioitcs for PEx prior 12 months	20 (16%)	18 (16%)	2 (14%)
Oral antibioitics for PEx prior 12 months	55 (44%)	45 (41%)*	10 (71%)*
Dornase alfa use	101 (81%)	90 (82%)	11 (79%)
Hypertonic saline use	86 (69%)	78 (71%)	8 (57%)
Inhaled steroid use	44 (35%)	38 (34%)	6 (43%)
Inhaled antibiotic use	28 (23%)	25 (23%)	3 (23%)
Azithromycin use	30 (24%)	24 (22%)	6 (43%)
Ivacaftor or elexacaftor/tezacaftor/iva-caftor	65 (52%)	56 (50%)	9 (64%)

Note: Results are expressed as the median (interquartile range) or n (%).

Abbreviations: BMI, body mass index; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive S. aureus; PEx, pulmonary exacerbation; ppFEV1, percent predicted forced expiratory volume in one second.

^*Indicates a statistically significant difference with p < 0.05 (Mann-Whitney test).

Fourteen (11%) PwCF had positive SARS-CoV-2 antibodies consistent with prior infection. Six were seropositive on enrollment, five seroconverted between enrollment and 6 months, and three more developed SARS-CoV-2 antibodies by 11 months postenrollment (Figure 2A). One breakthrough infection was identified in a person with CF who received the Janssen Ad26. COV2.S vaccine and subsequently developed nucleocapsid antibodies. There was one death unrelated to COVID-19 disease during the study.

FIGURE 2.

Timeline of serologic evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in persons with cystic fibrosis (CF) and seroprevalence estimates over time in Washington state. (A) Timeline of children and adolescents with CF testing positive for antibodies to SARS-CoV-2. Symbols represent IgG test type (circles for nucleocapsid IgG, triangles for spike protein IgG) and result (closed symbols for positive, open symbols for negative). The timing of vaccine administration is indicated by coronavirus disease 2019 (COVID-19) vaccine type (P, Pfizer BNT162b2; J Janssen Ad26. COV2.S). (B) Estimated seropositivity of children and adolescents with CF compared to the general population of Washington state. The risk of serologic evidence of prior SARS-CoV-2 infection in the study cohort of children and adolescents receiving care at Seattle Children’s Hospital CF Clinic was estimated by survival analysis (triangles, with 95% CI, see Supporting Information: Figure S3). Centers for Disease Control and Prevention (CDC) estimates of the total seropositivity in Washington state ages 0–17 years (shaded area, 95% CI dotted lines) and all ages (open squares, CI not shown) (based on antinucleocapsid antibodies measured in residual samples from commercial labs, arrow indicates the timing of assay switch by CDC, data source ²).

We sought to determine whether any clinical or demographic characteristics of PwCF were associated with increased rates of infection with SARS-CoV-2 as assessed by seroconversion (Table 1). A higher proportion of people in the seropositive group identified as Hispanic (29% vs. 8%, p = 0.04). Seventy one percent of participants who seroconverted had a pulmonary exacerbation requiring oral antibiotics in the year before enrollment compared with 41% of seronegative participants (p = 0.04). In a multivariable regression model with age, race, oral antibiotic use in the prior 12 months for a pulmonary exacerbation, methicillin-resistant Staphylococcus aureus (MRSA) colonization and azithromycin usage, only a history of oral antibiotics for a pulmonary exacerbation demonstrated statistically significant association with SARS-CoV-2 seroconversion (p = 0.046, Supporting Information: Table S2). When included in the multivariate analysis, Hispanic ethnicity produced instability of the model estimates and therefore was excluded from the multivariable model.

3.2 |. Seropositivity over time

Antibody testing in our cohort was longitudinal and asynchronous, so we used a survival analysis approach to estimate the total likelihood of seroconversion to SARS-CoV-2 over time (Supporting Information: Figure S3 and Figure 2B). Our estimated seroprevalence rate was 6.2% (95% CI 3.0–12.5) by February 9, 2021, 14.8% (95% CI 8.4–25.4) by September 30, 2021, and 29.0% (95% CI 11.0–63.6) by December 20, 2021, noting that the estimated uncertainty for SARS-CoV-2 antibody positivity in our cohort became broader over time, as the number of participants remaining enrolled in the study decreased. We compared these estimates to seroprevalence rates for both 0–17 year-olds and all ages in Washington state available from the CDC COVID-19 Nationwide Commercial Lab Seroprevalence data (Figure 2B). Estimated Washington state seroprevalence rates for 0–17 year-olds were 7.9% for the period ending February 20, 2021; 22.6% for September 30, 2021; and 32.3% on December 21, 2022.² Notably, our estimated seroprevalence in children and adolescents with CF follows the general trends in the pediatric and overall populations in Washington state.

3.3 |. Participant reported symptoms and exposures

Eleven participants with positive antibodies for SARS-CoV-2 completed at least one symptom survey during their respective periods of seroconversion. Five participants in the seropositive group reported being asymptomatic during the period when they developed SARS-CoV-2 antibodies (35.7% of all seropositive patients, 45.4% of those completing symptom surveys). Six participants were symptomatic, with cough, rhinorrhea, and sore throat being the most common symptoms reported (42.8% of all seropositive patients, 54.5% of those completing surveys). None of the individuals with serologic evidence of infection required hospitalization for COVID-19.

Ninety nine percent of participants completed the initial enrollment survey (Supporting Information: Table S1). Participants were sent follow-up weekly surveys electronically via email for 56 weeks following enrollment as described in the Methods section. On average, participants completed 66% of weekly surveys. Compared to the SARS-CoV-2 seronegative group, a higher proportion of SARS-CoV-2 positive participants reported SARS-CoV-2 exposures between February 1, 2020 and enrollment (36% vs. 11%) and in the 56 weeks following enrollment (46% vs. 23%). Supporting Information: Table S1 details the types of exposures (i.e., family members, friends, classmates etc.). Only four subjects reported positive COVID testing on enrollment or weekly surveys before final sample collection, three of these were detected by serologic testing.

3.4 |. SARS-CoV-2 antibody responses

Finally, we looked at SARS-CoV-2 antibody responses following vaccination and natural infection. When comparing the first spike protein IgG level after vaccination or infection, spike protein RBD IgG levels were significantly higher in participants who were vaccinated without prior evidence of infection compared with unvaccinated participants who had SARS-CoV-2 infection (geometric mean 1411 BAU/mL vs. 47, p < 0.001, Figure 3A). We estimated the half-life of antispike IgG antibodies to be 74.2 days (95% CI 42.2–164.7) following two doses of BNT162b2 mRNA vaccine using a single-phase exponential decay model (Figure 3B).

FIGURE 3.

Antibody responses to the BNT 162b vaccine in people with cystic fibrosis (PwCF). (A) Antispike protein IgG levels in infected/unvaccinated individuals versus vaccinated subjects without evidence of infection in binding arbitrary units (BAU)/mL. Only results from the first positive spike IgG test at least 14 days after second vaccine dose or evidence of seroconversion are included. Lines represent the geometric mean, with 95% confidence interval of the geometric mean. **** indicates p < 0.0001 by Mann–Whitney test. (B) Antispike IgG levels following two doses of BNT162b2 mRNA vaccine in PwCF. Antibody levels at least 14 days (dotted line) after vaccination in individuals without evidence of infection are included. The half-life (t_½) was estimated to be 74.2 days (95% CI 42. 2–164 days) using a single-phase exponential decay model.

4 |. DISCUSSION

Among the 125 PwCF followed longitudinally for approximately 12 months during the pandemic, we found that 11% (n = 14) of participants had positive SARS-CoV-2 antibodies consistent with prior infection. Furthermore, we estimated the seroprevalence in children and adolescents with CF to closely follow that of the general population over time. This implies that the risk for SARS-CoV-2 exposure and infection in PwCF was similar to that of the general population. Our seroprevalence results fall within the range described in prior single-center European studies evaluating SARS-CoV-2 seroprevalence in people with CF.^10–12 The study from a Belgian CF center of 149 PwCF at the onset of the pandemic (April 2020–May 2020) found an overall seropositive rate of 2.0% (all of whom were asymptomatic, n = 3), while the German (performed between February 2020 and March 2021) and Italian (performed between March 2021 and June 2021) studies found seroprevalence rates of 4.2% and 14.7%, respectively. At least one-third of subjects in our cohort with evidence of infection were asymptomatic, roughly between those observed in the German and Italian cohorts, 23% and 56%, respectively. Symptomatic individuals reported symptoms (cough, rhinorrhea, and sore throat) that are common enough among PwCF to make it difficult to distinguish COVID-19 from respiratory symptoms due to CF lung disease. Our study included prospective weekly symptom surveys, which may have improved our subjects’ accuracy recalling and reporting symptoms.

While only 10% of our enrolled cohort were Hispanic PwCF, 29% of seropositive participants identified as Hispanic. This finding reflects trends in the general US population where Hispanic persons represent 24.5% of reported COVID-19 cases but only 18.45% of the population and the CDC estimates a 1.5-fold increased risk of COVID-19 infection in Hispanic individuals compared to White, non-Hispanic individuals.^2,24 Similar disparities have been reported among people identifying as American Indian or Alaskan Native.²⁴ The underlying cause of this disparity in children with CF is unclear and cannot be addressed with data collected in our surveys. However, it emphasizes the importance of considering possible health disparities in PwCF related to race or ethnicity. Considering other clinical characteristics associated with seroconversion, we found higher rates of oral antibiotic use for pulmonary exacerbation in the year before enrollment among seropositive participants. By contrast, the need for IV antibiotics to treat a pulmonary exacerbation was similar between groups.

Unsurprisingly, we found that participants who seroconverted reported greater numbers of known exposures. Recall bias is unlikely to explain this difference in reported exposures as study participants completed surveys before serology testing.

Among the 14 individuals in our cohort with antibody testing consistent with SARS-CoV-2 infection, we noted that several individuals only had detectable antibodies to the receptor-binding domain of spike protein and not nucleocapsid protein (n = 3, 21%). The same proportion of individuals tested positive for nucleocapsid IgG but reverted to nucleocapsid IgG negative by their 11-month sample (n = 3, 21%). These data are consistent with earlier studies demonstrating that levels of SARS-CoV-2 nucleocapsid antibodies wane faster than the antibody responses to SARS-CoV-2 spike protein, potentially resulting in underestimation of the actual proportion of the population with prior SARS-CoV-2 infection.^9,23,25,26 This phenomenon is a potential limitation of our study, and we may have not detected a small proportion of SARS-CoV-2 infections, especially in vaccinated subjects where spike IgG cannot distinguish infection from vaccination. Our repeated sampling schedule should reduce this limitation, and only a single subject reported a known infection which was not detected by serology testing. It also has implications for future studies using serology to infer SARS-CoV-2 infection history; specifically, without increased sampling frequency or increased assay sensitivity for distant infections, the measured seroprevalence is likely to underestimate the proportion of individuals previously infected with SARS-CoV-2.²³

In our comparison of spike protein antibody levels between those with SARS-CoV-2 infection and vaccinated PwCF without evidence of infection, we found that vaccinated participants had higher spike protein antibody levels. This finding suggests that vaccinated individuals mount a more robust initial antispike IgG response than individuals who were infected but not vaccinated and offers clinicians rationale to encourage PwCF with history of COVID-19 to receive vaccination to boost immunity.

The antispike IgG response after Pfizer-BioNTech BNT162b2 vaccination in our cohort of PwCF (mean 1892 BAU/mL) was similar to an estimated peak level in a large non-CF population-based UK study (mean 959 BAU/mL).²⁷ Furthermore, the durability of antispike IgG as measured by half-life in PwCF (74 days, 95% CI 42–165) was similar in magnitude to that reported after mRNA vaccination in the general population, previously estimated at 51 days following Pfizer-BioNTech BNT162b2 and 52 days following Moderna mRNA1273 vaccination.^27,28 These findings are consistent with a recent report from Italy that found that PwCF mounted an appropriate antibody response following BNT162b2 vaccination.²⁹ Prior studies suggested that PwCF exhibit impaired antibody responses to influenza and pneumococcal vaccination.^13,14 In contrast, our findings suggest that COVID-19 vaccines responses in children and young adults with CF are similar to those of the general population.

Our study has several limitations. As a single pediatric center, our results may not be generalizable to the entire CF community. However, as the first reported seroprevalence study among PwCF living in the United States, we anticipate our findings will provide useful data for other US CF centers. While our sample size is limited, it represents a majority of PwCF at our center and is based on a prospective cohort sample, so it is less likely to have the selection bias inherit in case-based reporting. Furthermore, our single study site protocol allowed for more detailed analyses of participant characteristics with survey data for COVID-19 exposures and potential symptoms before and throughout enrollment. Our estimate of seroprevalence in PwCF represents only a finite period of the pandemic. The majority of our study participants completed the study before the substantial increase in seropositivity associated with the omicron B.1.1.529 variant beginning in December 2021.^22,30 Our measurements of quantitative spike IgG responses and its durability are based on a modest number of subjects that received two doses of BNT162b2 vaccine and had subsequent follow-up antibody testing in our cohort, so they should be viewed as an estimate that requires confirmation in larger studies. Furthermore, cellular immunity also contributes to COVID-19 vaccine protection against severe disease but it was not assessed in our study.¹⁷

5 |. CONCLUSION

Among children and adolescents followed longitudinally at a pediatric CF center, 11% tested positive for antibodies consistent with SARS-CoV-2 infection, and the trend of seropositivity over time closely followed that of the general population. At least 35.7% of participants with evidence of SARS-CoV-2 infection reported no symptoms coincident with infection. Hispanic ethnicity and the need for oral antibiotic use in the year before enrollment were associated with SARS-CoV-2 seroconversion. Antispike protein IgG levels were significantly higher following vaccination compared to SARS-CoV-2 infection in PwCF, and the magnitude and durability of antibody responses in vaccinated PwCF were similar to those previously reported in the general population.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.