The emergence of the Coronavirus disease 2019 (COVID-19) pandemic in 2020 has profoundly impacted global health systems, particularly affecting vulnerable populations like kidney transplant recipients (KTRs).We prospectively collected blood samples from 17 PCR-confirmed COVID-19 KTR patients and 10 non-COVID-19 KTRs between May and September 2020. Using tandem mass tag-based quantitative proteomics, we characterized peripheral blood mononuclear cells (PBMCs) from KTRs alongside plasma protein biomarkers and lymphocyte counts, followed by bioinformatics analyses. Our study revealed significant proteomic alterations within PBMCs of SARS-CoV-2 infected KTRs, particularly in pathways associated with glycolysis, glucose metabolism, and neutrophil degranulation. Additionally, we observed an altered immune response marked by elevated cytokines and inflammatory mediators, coupled with decreased lymphocyte counts. Notably, patients with acute kidney injury (AKI) exhibited worse outcomes, including higher rates of ICU transfer and mechanical ventilation. Comparison of PBMC proteomic profiles between AKI and non-AKI patients highlighted distinct immune-related pathways, with AKI patients showing pronounced alterations in innate immune responses, particularly in neutrophil degranulation. Moreover, our analysis unveiled a negative correlation between T cell counts and neutrophil degranulation, suggesting potential implications for immune dysregulation in COVID-19. Our findings shed light on the complex proteomic landscape and immune responses in COVID-19-infected KTRs, emphasizing the critical need for studies focused on this population, especially in individuals with AKI. Furthermore, our observations provide valuable insights for further exploration of therapeutic interventions targeting immune dysregulation pathways in this vulnerable population.

The authors have declared no competing interest.

This work was funded by FAPESP (Grants 2017/21052-0 and 2020/05110-2) to R.S. G.G.F.L. has a scholarship from FAPESP (2019/20532-3).

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This prospective cohort study was conducted at Hospital Sao Paulo, the University Hospital of the Federal University of Sao Paulo, located in Sao Paulo, Brazil. The study was submitted to and approved by the National Research Ethics Committee (Comite Nacional de Etica em Pesquisa - CONEP), Process number 3.978.709. All volunteers provided written informed consent prior to enrolment.

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Raw and processed mass spectrometry proteomic data generated in this study are available at ProteomeXchange with the dataset identifier PXD051702.