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BackgroundThe worldwide pandemic caused by SARS-CoV-2 has claimed millions of lives and has had a profound effect on global life. Understanding the pathogenicity of the virus and the bodys response to infection is crucial in improving patient management, prognosis, and therapeutic strategies. To address this, we performed functional transcriptomic profiling to better understand the generic and specific effects of SARS-CoV-2 infection. MethodsWhole blood RNA sequencing was used to profile a well characterised cohort of patients hospitalised with COVID-19, during the first wave of the pandemic prior to the availability of approved COVID-19 treatments and who went on to survive or die of COVID-19, and patients hospitalised with influenza virus infection between 2017 and 2019. Clinical parameters between patient groups were compared, and several bioinformatic tools were used to assess differences in transcript abundances and cellular composition. ResultsThe analyses revealed contrasting innate and adaptive immune programmes, with transcripts and cell subsets associated with the innate immune response elevated in patients with influenza, and those involved in the adaptive immune response elevated in patients with COVID-19. Topological analysis identified additional gene signatures that differentiated patients with COVID-19 from patients with influenza, including insulin resistance, mitochondrial oxidative stress and interferon signalling. An efficient adaptive immune response was furthermore associated with patient survival, while an inflammatory response predicted death in patients with COVID-19. A potential prognostic signature was found based on a selection of transcript abundances, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, in the blood transcriptome of COVID-19 patients, upon admission to hospital, which can be used to stratify patients likely to survive or die. ConclusionsThe results identified distinct immunological signatures between SARS-CoV-2 and influenza, prognostic of disease progression and indicative of different targeted therapies. The altered transcript abundances associated with COVID-19 survivors can be used to predict more severe outcomes in patients with COVID-19.
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RationaleManagement of the COVID-19 pandemic is hampered by long delays associated with centralised laboratory PCR testing. In hospitals this leads to poor patient flow and nosocomial transmission and rapid, accurate diagnostic tests are urgently required. The FebriDx is a point-of-care test that detects an antiviral host response protein in finger prick blood within 10 minutes, but its accuracy for the detection of COVID-19 is unknown. ObjectivesTo evaluate the diagnostic accuracy of FebriDx in hospitalised patients during the first wave of the pandemic MethodsMeasures of diagnostic accuracy were calculated based on FebriDx results compared to the reference standard of PCR, and stratified by duration of symptoms. A multivariable predictive model was developed and underwent internal validation. ResultsFebriDx was performed on 251 patients and gave a valid result in 248. 118 of 248 (48%) were PCR positive for COVID-19. Sensitivity of FebriDx for the identification of COVID-19 was 93% (110/118; 95% CI 87 to 97%) and specificity was 86% (112/130; 95%CI 79 to 92%). Positive and negative likelihood ratios were 6.73 (95%CI 4.37 to 10.37) and 0.08 (95%CI 0.04 to 0.15) respectively. In the multivariate model diagnosis of COVID-19 was not significantly influenced by clinical symptoms and signs, and FebriDx accuracy was not improved by restricting testing to those with duration of symptoms of less than seven days. ConclusionsDuring the first wave of the pandemic, FebriDx had high sensitivity for the identification of COVID-19 in hospitalised adults and could be deployed as a front door triage tool. Trial registrationISRCTN14966673