Vaccination Against SARS-CoV-2 in Lung Transplant Recipients: Immunogenicity, Efficacy and Safety.

Lung transplant (LuTx) recipients are considered to be at higher risk of developing serious illness from COVID-19. COVID-19 vaccines were shown in randomized clinical trials to substantially reduce the severity of COVID-19, however, patients receiving immunosuppressants were excluded from these trials. Observational studies report a proportion of solid organ transplant (SOT) recipients being able to mount sufficient titers of SARS-CoV-2 specific IgG antibodies, however, other studies demonstrate that more than 90% of the SOT recipients elicit neither humoral nor cellular immune response after vaccination. Currently, the third booster dose of the COVID-19 vaccines was shown to elicit strong immune responses and may, thus, represent a potent tool in the prevention of severe COVID-19 infection in SOT recipients, including patients after lung transplantation. To address the main challenges of SARS-CoV-2 vaccination in LuTx recipients in the era of COVID-19, we have closely collected all available data on the immunogenicity, efficacy and safety of COVID-19 vaccines in LuTx recipients.

How COVID-19 Affects Lung Transplantation: A Comprehensive Review.

Lung transplant (LuTx) recipients are at a higher risk of developing serious illnesses from COVID-19, and thus, we have closely reviewed the consequences of the COVID-19 pandemic on lung transplantation. In most transplant centers, the overall LuTx activity significantly declined and led to a specific period of restricting lung transplantation to urgent cases. Moreover, several transplant centers reported difficulties due to the shortage of ICU capacities. The fear of donor-derived transmission generated extensive screening programs. Nevertheless, reasonable concerns about the unnecessary losses of viable organs were also raised. The overall donor shortage resulted in increased waiting-list mortality, and COVID-19-associated ARDS became an indication of lung transplantation. The impact of specific immunosuppressive agents on the severity of COVID-19 varied. Corticosteroid discontinuation was not found to be beneficial for LuTx patients. Tacrolimus concentrations were reported to increase during the SARS-CoV-2 infection, and in combination with remdesivir, tacrolimus may clinically impact renal functions. Monoclonal antibodies were shown to reduce the risk of hospitalization in SOT recipients. However, understanding the pharmacological interactions between the anti-COVID-19 drugs and the immunosuppressive drugs requires further research.

Immunogenicity of BNT162b2 mRNA COVID-19 vaccine and SARS-CoV-2 infection in lung transplant recipients.

The immunogenicity of the novel mRNA COVID-19 vaccine in immunocompromised lung transplant recipients is still unknown. We compared the antibody response after the first and second doses of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) with the response after natural SARS-CoV-2 infection in lung transplant recipients. None of the vaccinees tested after two doses of the mRNA BNT162b2 vaccine developed anti-SARS-CoV-2 IgG, while 85% patients presented an antibody response after SARS-CoV-2 infection. The absence of antibody response to vaccination led us to investigate the cellular response in a subset of patients. We detected SARS-CoV-2 specific T-cells in 4 out of 12 tested patients. Some patients therefore might have clinical benefit from the vaccine despite an absent antibody response. These results contrast with the excellent antibody response in immunocompetent individuals observed in mRNA BNT162b2 trials and indicate an urgent need to identify the best vaccine type and scheme for immunocompromised transplanted patients.