Abstract: pe er re vie we d Efficacy and safety of Ixekizumab vs. low-dose IL-2 vs. Colchicine vs. standard of care on the treatment of patients hospitalized with moderate to critical Covid-19: a pilot randomized clinical trial (STRUCK: Survival Trial Using Cytokine Inhibitors) Running title: Exploring new targets for Covid-19 treatment Lívia Pimenta Bonifácio, Ph.D.,1* Eduardo Ramacciotti, Ph.D.,2,3* Leandro Barile Agati*, Ph.D.,2,3 Fernando Crivelenti Vilar, Ph.D,1 Anna Christina Tojal da Silva, MD.,1 Paulo Louzada Júnior, Ph.D.,1 Benedito Antônio Lopes da Fonseca, Ph.D.,1 Hayala Cristina Cavenague de Souza, Ph.D.,1 Caroline Candida Carvalho de Oliveira, MD.,2,3 Valéria Cristina Resende Aguiar, MD., 2,3 Carlos Augusto de Aguiar Quadros, MD., 3 Cesar Dusilek, MD.,4 Kenji Itinose, MD.,4 Ricardo Gustavo Zill Risson, MD.,4 Lucas Roberto Rivabem Ferreira, MD.,4 Rogério Aparecido Dedivitis, Ph.D.,5 André Sementilli Cortina, MD.,5 Renato Delascio Lopes, Ph.D.,6,7 Esper Georges Kallas, Ph.D.,8 and Fernando Bellissimo-Rodrigues, Ph.D.1 *contributed equally to the present study 1Ribeirão Preto Medical School, University of São Paulo - FMRP / USP. Ribeirão Preto. São ot Paulo. Brazil 2Science Valley Research Institute, São Paulo, SP, Brazil 3Hospital e Maternidade Christóvão da Gama, Grupo Leforte, Santo André, SP, Brazil 4Hospital do Rocio, Campo Largo, Paraná, Brazil 5Irmandade da Santa Casa da Misericórdia de Santos, São Paulo, Brazil 6 Brazilian Clinical Research Institute, São Paulo, SP, Brazil 7Duke University Medical Center – Duke Clinical Research Institute, Durham, North Carolina. 8 Department of Infectious and Parasitic Diseases, School of Medicine, University of São Paulo, SP, Brazil tn Corresponding Author: Fernando Bellissimo-Rodrigues Social Medicine Department, Ribeirão Preto Medical School (USP) Campus Universitário, Monte Alegre 14048-900, Ribeirão Preto, São Paulo, Brazil Phone: (+5516) 3602-2536 Email: fbellissimo@usp.br Pr ep rin Lívia Pimenta Bonifácio Social Medicine Department, Ribeirão Preto Medical School (USP) Campus Universitário, Monte Alegre 14048-900, Ribeirão Preto, São Paulo, Brazil Phone: (+5516) 3602-2536 Email: livia_pb@usp.br This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4095747 d ABSTRACT Pr ep rin tn ot pe er re vie we Background: To evaluate the efficacy and safety of Ixekizumab (IL-17 inhibitor), or low-dose IL-2 or colchicine on top of standard of care (SOC) for Covid-19 treatment. Methods: A multicenter, open-label, randomized, adaptive study of 4 treatment arms conducted in Brazil. Hospitalized patients with moderate to critical Covid-19 were enrolled according to predetermined eligibility criteria. Patients were randomized to one of 4 arms: standard of care (SOC) alone or combined with Ixekizumab, or low-dose IL-2 or colchicine. The primary efficacy outcome was accessed in the “per protocol” population as the proportion of patients with clinical improvement, defined as a two-point decrease on the WHO sevencategory ordinal scale at day 28 after randomization. Findings: 60 patients were enrolled in the study: 16 in the SOC group, 16 in the Ixekizumab group, 14 in the low-dose IL-2 group, and 14 in the colchicine group. Patients assigned to the colchicine arm presented the greatest improvement in the WHO scale (100%) by day 28, while those in the low dose IL-2 had the worse improvement (64.3%). The colchicine arm presented the..