Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

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

Three lenses of evidence-based policy

This article discusses recent trends to incorporate the results of systematic research (or ‘evidence’) into policy development, program evaluation and program improvement. This process is consistent with the New Public Management (NPM) emphasis on efficiency and effectiveness. Analysis of evidence helps to answer the questions ‘what works? and ‘what happens if we change these settings?’ Secondly, some of the well known challenges and limitations for ‘evidence-based’ policy are outlined. Policy decisions emerge from politics, judgement and debate, rather than being deduced from empirical analysis. Policy debate and analysis involves an interplay between facts, norms and desired actions, in which ‘evidence’ is diverse and contestable. Thirdly, the article outlines a distinction between technical and negotiated approaches to problem-solving. The latter is a prominent feature of policy domains rich in ‘network’ approaches, partnering and community engagement. Networks and partnerships bring to the negotiation table a diversity of stakeholder ‘evidence’, ie, relevant information, interpretations and priorities. Finally, it is suggested that three types of evidence/perspective are especially relevant in the modern era – systematic (‘scientific’) research, program management experience (‘practice’), and political judgement. What works for program clients is intrinsically connected to what works for managers and for political leaders. Thus, the practical craft of policy development and adjustment involves ‘weaving’ strands of information and values as seen through the lens of these three key stakeholder groups. There is not one evidence-base but several bases. These disparate bodies of knowledge become multiple sets of evidence that inform and influence policy rather than determine it