Jason R Andrews
Profile Url: jason-r-andrews
Researcher at Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA
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BackgroundThere is a need to identify scalable tuberculosis screening strategies among high burden populations. The WHO has identified a non-sputum-based triage test as a development priority. MethodsWe performed a diagnostic accuracy study of point-of-care C-reactive protein (CRP) and Xpert-MTB-Host-Response (Xpert-MTB-HR) assays in the context of a mass screening program for tuberculosis in two prisons in Brazil. Incarcerated individuals irrespective of symptoms were screened by sputum Xpert-MTB/RIF and sputum culture. CRP was quantified in serum by a point-of-care assay (iChroma-II) and a 3-gene expression score was quantified from whole blood using the Xpert-MTB-HR cartridge. We evaluated receiver operating characteristic area under the curve (AUC) and assessed specificity at 90% sensitivity and sensitivity at 70% specificity, consistent with WHO target product profile (TPP) benchmarks. FindingsTwo hundred controls controls and 100 culture- or Xpert-positive tuberculosis cases were included. Half of tuberculosis cases and 11% of controls reported any tuberculosis symptoms. AUC for CRP was 0.79 (95% CI: 0.73-0.84) and for Xpert-MTB-HR was 0.84 (95% CI: 0.79-0.89). At 90% sensitivity, Xpert-MTB-HR had significantly higher specificity (53.0%, 95% CI: 45.0-69.0%) than CRP (28.1%, 95% CI: 20.2-41.8%) (p=0.003). Among individuals with medium or high sputum Xpert semi-quantitative load, sensitivity (at 70% specificity) of CRP (90.3%, 95% CI: 74.2-98.0) and Xpert-MTB-HR (96.8%, 95% CI: 83.3-99.9%) was higher. InterpretationFor active case finding in this high tuberculosis-burden setting, CRP and Xpert-MTB-HR did not meet TPP benchmarks for a triage test. However, Xpert-MTB-HR was highly sensitive in detecting individuals with medium or high sputum bacillary burden. FundingNational Institutes of Health (R01 AI130058 and R01 AI149620) and Brazilian National Council for Scientific and Technological Development (CNPq-404182/2019-4). Xpert-MTB-HR cartridges were provided by Cepheid.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can cause Coronavirus Disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that severe COVID-19 patients produced a unique serologic signature, including increased IgG1 with afucosylated Fc glycans. This Fc modification on SARS-CoV-2 IgGs enhanced interactions with the activating Fc{gamma}R, Fc{gamma}RIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including IL-6 and TNF. These results show that disease severity in COVID-19 correlates with the presence of afucosylated IgG1, a pro-inflammatory IgG Fc modification.