Anakinra in hospitalized COVID-19 patients guided by baseline soluble urokinase plasminogen receptor plasma levels: a real world, retrospective cohort study

Background In patients with COVID-19 and baseline soluble urokinase plasminogen receptor plasma (suPAR) levels ≥ 6ng/mL, early administration of anakinra, a recombinant interleukin-1 receptor antagonist, may prevent disease progression and death. In case of suPAR testing unavailability, the Severe COvid Prediction Estimate (SCOPE) score may be used as an alternative in guiding treatment decisions. Methods We conducted a monocenter, retrospective cohort study, including patients with SARS-CoV2 infection and respiratory failure. Patients treated with anakinra (anakinra group, AG) were compared to two control groups of patients who did not receive anakinra, respectively with ≥ 6 ng/mL (CG1) and < 6 ng/mL (CG2) baseline suPAR levels. Controls were paired by age, sex, date of admission and vaccination status. Primary endpoint of the study was disease progression at day 14 from admission, as defined by patient distribution on a simplified version of the 11-point World Health Organization Clinical Progression Scale (WHO-CPS). Results Between July, 2021 and January, 2022, 153 patients were included, among which 56 were treated with off-label anakinra, 49 retrospectively fulfilled prescriptive criteria for anakinra and were assigned to CG1, and 48 presented with suPAR levels < 6ng/mL and were assigned to CG2. At day 14, when comparing to CG1, patients who received anakinra had significantly reduced odds of progressing towards worse clinical outcome both in ordinal regression analysis (OR 0.25, 95% CI 0.11-0.54, p<0.001) and in multivariable analysis (OR 0.19, 95% CI 0.03-0.82, p=0.037), and these results were confirmed even when controlling for age, sex, BMI and vaccinal status. Sensitivities of baseline suPAR and SCOPE score in predicting progression towards severe disease or death at day 14 were similar (83% vs 100%, p=0.59). Conclusion This real-word, retrospective cohort study confirmed the safety and the efficacy of suPAR-guided, early use of anakinra in hospitalized COVID-19 patients with respiratory failure. ### Competing Interest Statement I have read the journal's policy and the authors of this manuscript have the following competing interests: E. J. Giamarellos-Bourboulis has received honoraria from Abbott CH, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH, Menarini and Sobi independent educational grants from Abbott CH, AbbVie, bioMérieux Inc, Johnson & Johnson, MSD, UCB and Sobi and funding from the Horizon 2020 European Grants ImmunoSep and RISKinCOVID (granted to the Hellenic Institute for the Study of Sepsis) and the Horizn Health Grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). M. Fantoni has received honoraria from Astra-Zeneca, GSK, Menarini, Sobi and funding from the Horizon 2020 European Grants (Covinform Project). ### Funding Statement The author(s) received no specific funding for this work. ### 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: The study was approved by “Fondazione Policlinico Gemelli IRCCS” ethical committee (protocol number 0010006/22, study ID 4770). 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data cannot be shared publicly because of Ethical Committee requirements. Data are available from the Policlinico Gemelli Institutional Data Access (contact via corresponding author) for researchers who meet the criteria for access to confidential data.