Hydroxychloroquine inhibits trained immunity implications for COVID 19

SARS-CoV-2 infection can cause severe disease for which currently no specific therapy is available. The use of hydroxychloroquine to prevent or treat SARS-CoV-2 infection is controversial and its mode of action poorly understood. We demonstrate that hydroxychloroquine inhibits trained immunity at the functional and epigenetic level and is accompanied by profound changes in the cellular lipidome as well as reduced expression of interferon-stimulated genes. Trained immunity comprises a functional adaptation induced by epigenetic reprogramming which facilitates the anti-viral innate immune response. Our findings therefore suggest that hydroxychloroquine may not have a beneficial effect on the anti-viral immune response to SARS-CoV-2. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by Radboudumc Hypatia grant (to R.D.). MGN was supported by an ERC Advanced grant (833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. SB is supported by the Dutch Heart Foundation (Dekker grant 2018-T028). The Vermeulen lab is part of the Oncode Institute, which is partly funded by the Dutch Cancer Society (KWF). ### 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: Blood from COVID-19 patients was collected after written informed consent at Radboudumc. The study was approved by the local medical ethics committee of the Radboudumc under reference number: 2020-6359. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Please contact corresponding author for data requests.