Introduction The COVID-19 pandemic is ongoing, yet, due to the lack of a COVID-19-specific tool, clinicians must use pre-existing illness severity scores for initial prognostication. However, the validity of such scores in COVID-19 is unknown. Methods The North West Collaborative Organisation for Respiratory Research performed a multicentre prospective evaluation of adult patients admitted to the hospital with confirmed COVID-19 during a 2-week period in April 2020. Clinical variables measured as part of usual care at presentation to the hospital were recorded, including the Confusion, Urea, Respiratory Rate, Blood Pressure and Age Above or Below 65 Years (CURB-65), National Early Warning Score 2 (NEWS2) and Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) scores. The primary outcome of interest was 30-day mortality. Results Data were collected for 830 people with COVID-19 admitted across seven hospitals. By 30 days, a total of 300 (36.1%) had died and 142 (17.1%) had been in the intensive care unit. All scores underestimated mortality compared with pre-COVID-19 cohorts, and overall prognostic performance was generally poor. Among the ‘low-risk’ categories (CURB-65 score<2, NEWS2<5 and qSOFA score<2), 30-day mortality was 16.7%, 32.9% and 21.4%, respectively. NEWS2≥5 had a negative predictive value of 98% for early mortality. Multivariable logistic regression identified features of respiratory compromise rather than circulatory collapse as most relevant prognostic variables. Conclusion In the setting of COVID-19, existing prognostic scores underestimated risk. The design of new prognostic tools should focus on features of respiratory compromise rather than circulatory collapse. We provide a baseline set of variables which are relevant to COVID-19 outcomes and may be used as a basis for developing a bespoke COVID-19 prognostication tool.

The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19. Severity of the initial infective insult, postacute psychiatric symptoms and a history of encephalopathy were associated with the greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Longitudinal follow-up in 106 patients demonstrated a trend toward recovery. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 may be immune-mediated, and should guide the development of therapeutic strategies.

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.

The diagnosis of inflammatory bowel disease (IBD) in children and the need to distinguish between subtypes (Crohn’s disease (CD) and ulcerative colitis (UC)) requires lengthy investigative and invasive procedures. Non-invasive, rapid, and cost-effective tests to support these diagnoses are needed. Faecal volatile organic compounds (VOCs) are distinctive in IBD. VOC profiles can be rapidly determined using a gas chromatography–sensor device (OdoReader©). In an inception-cohort of children presenting with suspected IBD, we directly compared the diagnostic fidelity of faecal calprotectin (FCP, a non-specific protein marker of intestinal inflammation) with OdoReader© VOC profiles of children subsequently diagnosed with IBD with matched controls diagnosed with other gastrointestinal conditions. The OdoReader© was 82% (95% confidence interval 75–89%) sensitive and 71% (61–80%) specific but did not outperform FCP (sensitivity 93% (77–99%) and specificity 86% (67–96%); 250 µg/g FCP cut off) in the diagnosis of IBD from other gastrointestinal conditions when validated in a separate sample from the same cohort. However, unlike FCP and better than other similar technologies, the OdoReader© could distinguish paediatric CD from UC (up to 88% (82–93%) sensitivity and 80% (71–89%) specificity in the validation set) and justifies further validation in larger studies. A non-invasive test based on VOCs could help streamline and limit invasive investigations in children.

The spectrum, pathophysiology, and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the one-year cognitive, serum biomarker, and neuroimaging findings from a prospective, national longitudinal study of cognition in 351 COVID-19 patients who had required hospitalisation, compared to 2,927 normative matched controls. Cognitive deficits were global and associated with elevated brain injury markers and reduced anterior cingulate cortex volume one year after admission. The severity of the initial infective insult, post-acute psychiatric symptoms, and a history of encephalopathy were associated with greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Treatment with corticosteroids during the acute phase appeared protective against cognitive deficits. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 is immune-mediated, and should guide the development of therapeutic strategies.

Introduction: The COVID-19 pandemic is ongoing yet, due to the lack of a COVID-19 specific tool, clinicians must use pre-existing illness severity scores for initial prognostication. However, the validity of such scores in COVID-19 is unknown. Methods: The North West Collaborative Organization for Respiratory Research (NW-CORR) performed a multi-centre prospective evaluation of adult patients admitted to hospital with confirmed COVID-19 during a two-week period in April 2020. Clinical variables measured as part of usual care at presentation to hospital were recorded, including the CURB-65, NEWS2, and qSOFA scores. The primary outcome of interest was 30-day mortality. Results: Data were collected for 830 people with COVID-19 admitted across 7 hospitals. By 30 days, a total of 300 (36.1%) had died and 142 (17.1%) had been in ICU. All scores underestimated mortality compared to their original validation in non-COVID-19 populations, and overall prognostic performance was generally poor. Among the ‘low risk’ categories (CURB-65<2, NEWS2<5, qSOFA<2) 30-day mortality was 16.7%, 32.9% and 21.4%, respectively. Multivariable logistic regression identified features of respiratory compromise rather than circulatory collapse as most relevant prognostic variables. Conclusion: All existing prognostic scores evaluated here underestimated adverse outcomes and performed sub-optimally in the COVID-19 setting. New prognostic tools including a focus on features of respiratory compromise rather than circulatory collapse are needed. We provide a baseline set of variables which are relevant to COVID-19 outcomes and may be used as a basis for developing a bespoke COVID-19 prognostication tool. Key Messages: What is the key question? Do well-established illness severity scores have prognostic value in COVID-19? What is the bottom line? All scores appeared to underestimate mortality in COVID-19 and prognostic performance was generally poor, and importantly could not discriminate those patients at very low risk of death within 30 days. Why read on? In this multi-centre prospective evaluation of CURB-65, NEWS2 and qSOFA we comprehensively evaluate score performance and also identify variables which may be of use in COVID-19 prognostication.