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BackgroundThe role of specific blood tests to predict poor prognosis in patients admitted with infection from SARS-CoV2 virus remains uncertain. During the first wave of the global pandemic, an extended laboratory testing panel was integrated into the local pathway to guide triage and healthcare resource utilisation for emergency admissions. We conducted a retrospective service evaluation to determine the utility of extended tests (D-dimer, ferritin, high-sensitivity troponin I, lactate dehydrogenase, procalcitonin) compared to the core panel (full blood count, urea & electrolytes, liver function tests, C-reactive protein). MethodsClinical outcomes for adult patients with laboratory-confirmed COVID-19 admitted between 17th March to 30st June 2020 were extracted, alongside costs estimates for individual tests. Prognostic performance was assessed using multivariable logistic regression analysis with 28-day mortality used as the primary endpoint, and a composite of 28-day intensive care escalation or mortality for secondary analysis. ResultsFrom 13,500 emergency attendances we identified 391 unique adults admitted with COVID-19. Of these, 113 died (29%) and 151 (39%) reached the composite endpoint. "Core" test variables adjusted for age, gender and index of deprivation had a prognostic AUC of 0.79 (95% Confidence Interval, CI: 0.67 to 0.91) for mortality and 0.70 (95% CI: 0.56 to 0.84) for the composite endpoint. Addition of "extended" test components did not improve upon this. ConclusionOur findings suggest use of the extended laboratory testing panel to risk stratify community-acquired COVID-19-positive patients on admission adds limited prognostic value. We suggest laboratory requesting should be targeted to patients with specific clinical indications.
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The outcome of infection is dependent on the ability of viruses to manipulate the infected cell to evade immunity, and the ability of the immune response to overcome this evasion. Understanding this process is key to understanding pathogenesis, genetic risk factors, and both natural and vaccine-induced immunity. SARS-CoV-2 antagonises the innate interferon response, but whether it manipulates innate cellular immunity is unclear. An unbiased proteomic analysis determined how cell surface protein expression is altered on SARS-CoV-2-infected lung epithelial cells, showing downregulation of activating NK ligands B7-H6, MICA, ULBP2, and Nectin1, with minimal effects on MHC-I. This correlated with a reduction in NK cell activation, identifying a novel mechanism by which SARS-CoV2 antagonises innate immunity. Later in the disease process, strong antibody-dependent NK cell activation (ADNKA) developed. These responses were sustained for at least 6 months in most patients, and led to high levels of pro-inflammatory cytokine production. Depletion of spike-specific antibodies confirmed their dominant role in neutralisation, but these antibodies played only a minor role in ADNKA compared to antibodies to other proteins, including ORF3a, Membrane, and Nucleocapsid. In contrast, ADNKA induced following vaccination was focussed solely on spike, was weaker than ADNKA following natural infection, and was not boosted by the second dose. These insights have important implications for understanding disease progression, vaccine efficacy, and vaccine design.