Evaluation of the Immunomodulatory Effects of Interleukin-10 on Peripheral Blood Immune Cells of COVID-19 Patients: Implication for COVID-19 Therapy

Background: Several therapies with immune-modulatory functions have been proposed to reduce the overwhelmed inflammation associated with COVID-19. Here we investigated the impact of IL-10 in COVID-19, through the ex-vivo assessment of the effect of exogenous IL-10 on SARS-CoV-2-specific-response using a whole-blood platform.Methods: Two cohorts were evaluated: in 'study population A', plasma levels of 27 immune factors were measured by a multiplex analysis in 48 hospitalized 'COVID-19 patients' and 29 'NO COVID-19 controls' all unvaccinated. In 'study population B', 29 COVID-19 patients and 30 NO COVID-19-Vaccinated Controls (NO COVID-19-VC) were prospectively enrolled for the IL-10 study. Whole-blood was stimulated overnight with SARS-COV-2 antigens and then treated with IL-10. Plasma was collected and used for ELISA and Luminex multiplex assay. Remaining blood was used for flow-cytometry analysis.Findings: Baseline levels of several immune factors, including IL-10, were significantly elevated in COVID-19 patients. Exogenous addition of IL-10 significantly downregulated IFN-γ response and several other immune factors in both COVID-19 patients and NO COVID-19-VCs. Importantly, IL-10 did not affect cell survival, but decreased the frequencies of immune cells producing IFN-γ (p<0.05) and down-modulated HLA-DR expression on total CD4+ and NK cells.Interpretation: This study provides important insights into immune modulating effects of IL-10 in COVID-19 and may provide valuable information regarding the further in vivo investigations.Funding Information: This work was supported by: Funding COVID-2020-12371849 (DN), 0000395 del 25/05/2021, COVID-2020-12371675 Ricerca Corrente funded by Italian Ministry of Health, and by generous liberal donations funding for COVID-19 research from Esselunga S.p.A, Camera di Commercio, Industria e Artigianato di Roma, Società Numero Blu Servizi S.p.A., Fineco Bank S.p.A, Associazione magistrati della Corte dei conti, and Società Mocerino Frutta Secca s.r.l. (resolutions n°395 of May 25th 2021, n°254 of April 24th 2021 and n°257 of April 14th 2021).Declaration of Interests: There are no conflicts of interest to declare.Ethics Approval Statement: The present study was approved by the Ethical Committee of Lazzaro Spallanzani National Institute of Infectious Diseases (59/2020, 72/2015, 297/2021) and was conducted between April 15, 2020 and March 22, 2022.