Transmission and persistent SARS-CoV-2 infection in a lung transplant recipient with Molnupiravirinduced hypermutation

A 58 year-old patient with underlying systemic sclerosis-associated interstitial lung disease (SSc-ILD) was infected with SARS-CoV-2 BA.2. Aggravation of underlying interstitial lung disease leads to the decision to offer lung transplantation to the patient despite non-complete viral clearance. Lung transplantation was successfully performed but despite extensive antiviral therapy the patient remained SARS-CoV-2 positive for additional 165 days. During these period two different virus populations developed in the upper and lower respiratory tract despite antiviral therapy. The patient cleared the virus at the upper respiratory tract whereas the virus persists at the lower respiratory tract. Ex vivo analysis of circulating T cells demonstrated a response to SARS-CoV-2 peptides in recipient-MHC class I-restricted manner whereas a T-cell response targeting SARS-CoV-2 peptides with donor-MHC class I restriction appeared to be limited. This may explain the different clearance capacity towards the virus. Viral persistence with ongoing T-cell dominated alveolitis, mycophenolate mofetile was stopped and molnupiravir was started leading to a decreased virus load. The virus acquired 37 new mutations, mostly transitions, that are most likely caused by molnupiravir. This case shows the feasibility of lung transplantation in a SARS-CoV-2 positive patient despite prolonged infection of the lung tranplant. The different MHC-I restricted T-cell response may cause different clearance kinetics between upper and lower respiratory tract. Changing the immunosuppressive regime and molnupiravir finally lead to complete viral clearance.