Humoral and cell-mediated immune responses to BNT162b2 vaccine against SARS-CoV-2 in people with cystic fibrosis.

People with cystic fibrosis (pwCF) were considered to be clinically vulnerable to COVID-19 and were therefore given priority in the vaccination campaign. Vaccines induced a humoral response in these patients that was comparable to the response observed among the general population. However, the role of the cell-mediated immune response in providing long-term protection against SARS-CoV-2 in pwCF has not yet been defined. In this study, humoral (antibody titre) and cell-mediated immune responses (interferon-γ release) to the BNT162b2 vaccine were measured at different time points, from around 6-8 months after the 2nd dose and up to 8 months after the 3rd dose, in 118 CF patients and 26 non-CF subjects. Subjects were sampled between November 2021 and September 2022 and followed-up for breakthrough infection through October 2022. pwCF mounted a cell-mediated response that was similar to that observed in non-CF subjects. Low antibody titres (<1st quartile) were associated with a higher risk of breakthrough infection (HR: 2.39, 95 % CI: 1.17-4.88), while there was no significant association with low INF-γ levels (<0.3 IU/mL) (HR: 1.38, 95 % CI: 0.64-2.99). Further studies are needed in subgroup of pwCF receiving immunosuppressive therapy, such as organ transplant recipients. This data is important for tailoring vaccination strategies for this clinically vulnerable population.

Respiratory outcomes at 6 months follow up after SARSCov-2 infection in people with cystic fibrosis

Background: The severity of Covid-19 and its long-term effects in people with cystic fibrosis (pwCF) are poorly defined. Aim and objectives: To evaluate respiratory outcomes 6 months after SARS-Cov-2 infection in pwCF. Method(s): The study was based on pwCF enrolled from October 15, 2020 to June 30, 2021 in the DECO COVID-19 project, a multicentre prospective study supported by the Italian Ministry of Health (COVID-2020-12371781), that involved 3 Regional Reference Centres for CF (Milan, Rome and Verona). We enrolled pwCF tested with real time polymerase chain reaction (RT-PCR) for SARS-Cov-2 on nasopharyngeal swab for suggestive symptoms of Covid19 and/or for hospital admission. After 6 months follow up, we compared changes in percent predicted forced expiratory volume in one second (ppFEV1) and the rate of pulmonary exacerbations between patients positive or negative for SARS-Cov-2. Result(s): We enrolled 28 pwCF with RT-PCR confirmed infection (median age: 30 years, range: 6-66) and 130 negative to RT-PCR test (median age: 24 years, range: 5-63). The median baseline ppFEV values (range) were 91 (34-114) and 79 (25-117) in those positive and negative to RT-PCR, respectively (P= 0.256). After 6 months ppFEV1 changes were not significantly different between groups (median, interquartile range: 0.8% -5.0;4.0 among positive and +2%, -5.0;6.0 among those who tested negative, P = 0.618). The rates of pulmonary exacerbations were 0.17 per person-month among patients who tested positive and 0.14 in negative pwCF (Incidence rate ratio: 1.19, 95% CI: 0.80-1.76). Conclusion(s): In our CF population, SARS-Cov-2 infection did not impact negatively on respiratory outcomes at 6 months follow up.

Humoral and cell-mediated responses to BNT162b2 mRNA vaccine against SARS-CoV-2 in people with cystic fibrosis

Background: The BNT162b2 mRNAvaccine (Pfizer-BioNTech) was the first anti-SARS-CoV-2 vaccine approved and has shown 95% efficacy against severe COVID-19. The vaccine elicits a combined humoral and cellular adaptive immune response, albeit with high between-subject variability. The humoral response wanes 4 to 6 months after vaccination and, considered alone, does not appear to be indicative of protective immune memory. The role of cell-mediated immune response, which may be more relevant in the long-term protection against SARS-CoV-2, has not been clarified. Our aim was to evaluate the humoral and cell-mediated immune responses induced by administration of the BNT162b2 vaccine 6 to 8 months after the second dose in people with cystic fibrosis (PwCF) and the possible relationship between the anti-SARS-CoV-2 immunoglobulin (Ig)G-S antibodies (Spike protein) titer and the CD4+/CD8+ cell-mediated response. Method(s): One hundred thirteen PwCF (43 male, median age 21, range 11- 64) were enrolled, including 12 patients with virologically confirmed prior SARS-CoV-2 infection. Patients receiving chronic steroid therapy and transplant recipients were excluded. Serum IgG-S was determined by Elecsys anti-SARS-CoV-2 S (Roche) enzyme immunoassay with cut-off for positive response at 0.8 U/mL;cell-mediated immune response was measured using the STANDARDTM F CoviFERON FIA (interferon-gamma) system, a newrapid interferon gamma release assay (IGRA),with cut-off for positive response at 0.30 U/mL on standard F2400 (SD Biosensor, Inc. Korea). Result(s): All patients showed a humoral response 6 to 8 months after the second vaccine dose, with a median antibody titer of 1,288 U/mL (interquartile range [IQR] 610-2397). PwCF who were previously infected by SARS-CoV-2 had higher antibody titers than those naive to the virus (median 6,302, IQR 4272-8349 vs 1,180, IQR 535-1742;p < 0.001). Sixtyone patients (54%) developed a cell-mediated immune response against SARS-CoV-2. Antibody titer was higher in patients with a positive cellmediated response (median 1453, IQR 778-4473) than in those without (median 1054, IQR 510-1498) ( p = 0.01). Conclusion(s): All patients developed an adequate humoral response after two doses of BNT162b2 vaccine;the antibody titer was higher in patients with previous SARS-CoV-2 infection than in naive patients. We documented a cell-mediated response in 54% of patients, and this was associated with a higher antibody titer. Further studies are needed to understand whether development of cell-mediated immune response is elicited with greater protection against severe COVID-19 in PwCF. If this were the case, this rapid and relatively inexpensive test might be a useful tool to determine the best timing for additional vaccine doses in this clinically vulnerable population. Copyright © 2022, European Cystic Fibrosis Society. All rights reserved