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

Background: Previous 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). Methods: Patients 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. Results: While 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. Conclusion: While 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. ### Competing Interest Statement DG and KS were speakers for Boehringer-Ingelheim. All other authors declare no conflict of interest. ### Funding Statement Funding: This work was in part supported by the German Registry of COVID-19 Autopsies (www.DeRegCOVID.ukaachen.de), funded by the Federal Ministry of Health (ZMVI1-2520COR201), and the Federal Ministry of Education and Research within the framework of the network of university medicine (NATON, No. 01KX2121) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This project was approved by the local ethics committee of the University of Ulm (ref. no. 129-20) and conducted in accordance with the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors