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.

Keywords: COVID-19; SARS-CoV-2; antibodies; cystic fibrosis; patient symptoms; seroprevalence.

FIGURE 1

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

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 ).

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.