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.

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

SARS-CoV-2 infection in cystic fibrosis during the first pandemic wave in Italy: a multi-centre prospective study with a control group

Background: Patients with cystic fibrosis (CF) are at high risk of developing severe forms of viral respiratory infections. This study aimed at comparing symptoms and clinical course of SARS-CoV2 infection with other respiratory infections in patients with CF. Methods: We carried out a prospective multicentre cohort study within the Italian CF Society involving 32 CF centres following 6,597 patients. CF centres were contacted to collect baseline and follow-up data of all patients who had reported symptoms suggestive of COVID-19 or who had had contact with a positive/suspected case between the end of February and July 2020. Symptoms and clinical course of the infection were compared between patients who tested positive by molecular testing (cases) and those who tested negative (controls). Results: Thirty patients were reported from the centres, 16 of whom tested positive and 14 negative. Fever, cough, asthenia and dyspnea were the most frequently reported symptoms and their frequency were not significant different between groups. Eight cases (50%) were hospitalised but none required ICU admission. Two adults with a history of lung transplant required non-invasive ventilation;none required ICU admission. All patients fully recovered without short-term sequelae. Changes in FEV1 (percent of predicted) after recovery were not significantly different between groups (median, interquartile range: 3.0%, –1.5, 5.5 among cases and –3.0%, –8.5, 6.3 among controls, P = 0.48). Conclusions: Symptoms and clinical course of SARS-CoV-2 infection in our patients was not significantly different from other respiratory infections. The clinical course of COVID-19 was relatively favourable, however CF patients with severely impaired respiratory function and organ transplant may develop complications and a negative outcome. The study is ongoing, and we are recruiting patients during the second wave of the pandemic.