{"doi":"10.1101/2020.12.09.416586","title":"Identification of a Novel Susceptibility Marker for SARS-CoV-2 Infection in Human Subjects and Risk Mitigation with a Clinically Approved JAK Inhibitor in Human/Mouse Cells","abstract":"ABSTRACT Coronavirus disease (COVID-19), caused by SARS-CoV-2, has affected over 65 million individuals and killed over 1.5 million persons (December 8, 2020; www.who.int ) 1 . While fatality rates are higher among the elderly and those with underlying comorbidities 2 , host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases. 3–7 We report that the autoimmune PTPN2 risk variant rs1893217 promotes expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry mediated by SARS-CoV-2 spike protein. Elevated ACE2 expression and viral entry were mediated by increased JAK-STAT signalling, and were reversed by the JAK inhibitor, tofacitinib. Collectively, our findings uncover a novel risk biomarker for increased expression of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent to mitigate this risk.","journal":"Anthropos eBooks","year":2020,"id":120586,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":305642,"name":"Rong Hai","orcid":"0000-0002-0577-4676","position":1,"is_corresponding":false},{"id":558550,"name":"Li Jiang","orcid":"0000-0003-2652-0699","position":2,"is_corresponding":false},{"id":260344,"name":"Alina N. Santos","orcid":"0000-0002-9041-7250","position":3,"is_corresponding":false},{"id":331185,"name":"Tara M. Nordgren","orcid":"0000-0001-6398-8528","position":4,"is_corresponding":false},{"id":17881,"name":"Michel L. Tremblay","orcid":"0000-0002-0281-541X","position":5,"is_corresponding":false},{"id":337436,"name":"Lars Eckmann","orcid":"0000-0002-7987-8742","position":6,"is_corresponding":false},{"id":559666,"name":"Elaine Hanson","orcid":null,"position":7,"is_corresponding":false},{"id":260347,"name":"Michael Scharl","orcid":"0000-0002-6729-1469","position":8,"is_corresponding":false},{"id":108571,"name":"Xiwei Wu","orcid":"0000-0002-7071-1671","position":9,"is_corresponding":false},{"id":27732,"name":"Brigid S. Boland","orcid":"0000-0002-5360-8816","position":10,"is_corresponding":false},{"id":260350,"name":"Declan F. McCole","orcid":"0000-0002-6286-0802","position":11,"is_corresponding":false},{"id":260342,"name":"Marianne R. Spalinger","orcid":"0000-0003-4498-0058","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T23:14:38.147936Z","pmid":"33330862","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}