<sec> <title>BACKGROUND</title> Coronavirus disease 19 (COVID-19), the disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is already responsible for more than four and a half million deaths worldwide. With a unique pathophysiology related to respiratory failure due to interstitial pneumonia and acute respiratory distress syndrome, severe COVID-19 is qualitatively different from moderate disease. Since genetics play a crucial role in susceptibility to viral infection and propensity to develop harmful inflammatory conditions, genetic heterogeneity promotes the question of whether gene variants might influence COVID-19 outcomes. The identification of genetic variants associated with severe courses of COVID-19 is a promising option for the improvement of prognostic tools, contemplation of new therapeutic targets and the development of patient’s clinical risk stratification. </sec> <sec> <title>OBJECTIVE</title> We aim to perform a scoping review to assess the extent of the literature regarding the gene variants that could be associated with COVID-19 severity. </sec> <sec> <title>METHODS</title> The proposed scoping review will be conducted in accordance with the methodology from the Joanna Briggs Institute’s Scoping Review Network.12 The search strategy will focus on published studies without discriminating in date or language. A multiple-database search (MEDLINE, LILACS, The Cochrane Library, Science Direct, Google Scholar and OpenGrey) will be done performing the following strategy: ((("COVID-19"[Mesh] OR "SARS-CoV-2"[Mesh]) AND ("Polymorphism, Genetic"[Mesh] OR "Mutation"[Mesh] OR "Antibody Diversity"[Mesh] OR "Antigenic Variation"[Mesh]) AND ("Severity of Illness Index"[Mesh] OR "Death"[Mesh] OR "Critical Care"[Mesh] OR "Critical Illness"[Mesh] OR (severity))). This scoping review will consider observational studies and genome-wide association studies (GWAS) without discriminating in date or language. Additionally, systematic reviews that meet the inclusion criteria will also be considered. Data will be extracted from papers included in the scoping review by two independent reviewers using an already existent data extraction tool. </sec> <sec> <title>RESULTS</title> The conducted search was performed on February 16th in MEDLINE, LILACS, The Cochrane Library, Science Direct, Google Scholar and OpenGrey retrieved a total of 2190 results. Completion of the review is expected in late 2021. </sec> <sec> <title>CONCLUSIONS</title> This scoping review will be the first to map the extent of information regarding the genetic variants associated to the severity of COVID-19. The data gathered by this investigation could lead to biomarkers of severity in COVID-19 and the stratification of patients according to their genetic risk of disease severity. </sec>