Effect of mRNA vaccination on pulmonary sequelae after mild COVID-19

BackgroundPrevious studies indicate a protective role for SARS-CoV-2 vaccination against development of pulmonary post-acute sequelae of COVID (PASC). We compared clinical, imaging, histopathology and ultrastructural features of pulmonary PASC with and without prior vaccination in a consecutive cohort of 54 unvaccinated, 17 partially vaccinated and 28 fully vaccinated patients who presented with dyspnea on exertion after mild COVID-19 (without hospitalization). MethodsPatients underwent full clinical evaluation including autoantibody (ANA/ENA) serology, high-resolution computed tomography (HRCT), bronchioloalveolar lavage fluid (BAL) analysis and transbronchial biopsy followed by histopathological and ultrastructural analysis and SARS-CoV-2 immunohistochemistry. ResultsWhile vaccinated patients were younger (p=0.0056), included more active smokers (p=0.0135) and a longer interval since infection (35 vs. 17 weeks, p=0.0002), dyspnea on exertion and impaired lung function were not different between vaccinated and unvaccinated patients. Ground glass opacities in HRCT and centrilobular fibrosis were more frequent in unvaccinated patients (p=0.0154 and p=0.0353), but presence of autoantibodies, BAL lymphocytosis and bronchiolitis were common findings in all groups. While vaccination against SARS-CoV-2 is associated with a longer time span between infection and consultation along with a reduced frequency of ground glass opacities and centrilobular fibrosis, impaired lung function, bronchiolitis and presence of autoantibodies are comparable between vaccinated and unvaccinated patients. Residual virus was not detected in lung tissue in all but 1 patient. ConclusionWhile differences between the investigated groups with regard to age, smoking status and SARS-CoV-2 variants have to be taken into account, a proposed protective role of SARS-CoV-2 vaccination against pulmonary PASC is so far not fully explained by clinical and histopathology findings. KEY MESSAGESThe role of SARS-CoV-2 vaccination in the protection against pulmonary post-acute sequelae of COVID-19 (PASC) is unclear. Using a multidimensional approach integrating clinical, serological, imaging and histopathology data as well as ultrastructural analyses, we show here that previous vaccination has no impact on lung function, bronchiolitis or the detection of autoantibodies or residual virus in a previously healthy cohort of 99 PASC patients after mild COVID-19. While a higher frequency of ground glass opacities in unvaccinated patients might be due to the longer interval between infection and consultation, the observed fibrotic remodeling should prompt further investigation of a possible pro-fibrotic role of SARS-CoV-2 infection in the lung.