Characteristics of Talaromyces marneffei infection associated with inborn errors of immunity

Abstract

Background: Talaromycosis is a systemic disease caused by Talaromyces marneffei. To capture the characteristics of talaromycosis patients with inborn errors of immunity (IEI) prompts us to develop a systematic review. Objective: To systematically review studies reporting cases of talaromycosis with IEI. We aimed to describe the susceptibility genotypes and clinical characteristics of talaromycosis in IEI patients and understand the underling mechanism of Talaromyces marneffei defence. Methods: A systematic literature review was performed by searching PubMed, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, and Scopus. Data from patients with genetic diagnosis of IEI with talaromycosis, IEI genotypes, immunology, and clinical characteristics were collected. Results: Fifty talaromycosis patients with IEI were included: XHIM (30.00%), STAT3-LOF (20.00%), STAT1-GOF (20.00%), IL2RG (6.00%), IFNGR1 (6.00%), IL12RB1 (4.00%), CARD9 (4.00%), COPA (4.00%), ADA (2.00%), RELB deficiency (2.00%), and NFKB2 (2.00%) were the underlying genetic mutations. mNGS was a rapid and effective diagnostic method. The onset of clinical manifestations included atypical presentations, generally with fever, cough, lymphadenopathy, abdominal discomfort, and pneumonia. Respiratory, skin, lymph node, digestive, and hematologic systems were commonly involved. Variable lung CT findings were commonly misdiagnosed as tuberculosis. Forty-seven patients received antifungal therapy, and 34 patients improved. Conclusions: The XHIM, STAT1-GOF, and STAT3-LOF genotypes exhibited the highest susceptibility to talaromycosis. Pathogen infection should be tested by mNGS in IEI patients with suspected talaromycosis, and antifungal therapy should be rapidly initiated. Immunological and genetic diagnoses are necessary for non-HIV patients with talaromycosis in children.

A genome-wide arrayed CRISPR screen identifies PLSCR1 as an intrinsic barrier to SARS-CoV-2 entry that recent virus variants have evolved to resist

“…To provide a thorough perspective on human genes that impact SARS-CoV-2 infection and to place our arrayed CRISPR KO screen results within the context of existing research, we have compiled a table that includes findings from a selection of 67 large-scale 'omic' studies related to SARS-CoV-2. This compilation encompasses this study and 25 other functional genetic screens for genes that influence SARS-CoV-2 infection [10-12, 14, 17, 18, 26, 29, 60-76], 24 human genetic studies that correlate certain alleles with severe COVID-19 outcomes [4,5,7,23,24,[77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95], ten publications detailing SARS-CoV-2 protein interactomes [96][97][98][99][100][101][102][103][104][105], six focusing on SARS-CoV-2 RNA interactomes [106][107][108][109][110][111], and one that examines proteins with altered phosphorylation states in SARS-CoV-2-infected cells [112] (Supp Tables 9-10 for the full, and summary tables, respectively). This table highlights the depth of resear...…”

“…Approximately 1-5% of critical COVID-19 patients have mutations that compromise the production of or response to type I IFNs, while an additional 15% possess autoantibodies that neutralize type I IFNs [1][2][3][4][5][6][7]. This highlights the essential role of type I IFN in the defense against the SARS-CoV-2 virus that caused the COVID-19 pandemic [8,9].…”