Detection of SARS-CoV-2-specific mucosal antibodies in saliva following concomitant COVID-19 and influenza vaccination in the ComFluCOV trial

The ComFluCOV trial randomized 679 participants to receive an age-appropriate influenza vaccine, or placebo, alongside their second COVID-19 vaccine. Concomitant administration was shown to be safe, and to preserve systemic immune responses to both vaccines. Here we report on a secondary outcome of the trial investigating SARS-CoV-2-specific mucosal antibody responses. Anti-spike IgG and IgA levels in saliva were measured with in-house ELISAs. Concomitant administration of an influenza vaccine did not affect salivary anti-spike IgG positivity rates to Pfizer/BioNTech BNT162b2 (99.1 cf. 95.6%), or AstraZeneca ChAdOx1 (67.8% cf. 64.9%), at 3-weeks post-vaccination relative to placebo. Furthermore, saliva IgG positively correlated with serum titres highlighting the potential utility of saliva for assessing differences in immunogenicity in future vaccine studies. Mucosal IgA was not detected in response to either COVID-19 vaccine, reinforcing the need for novel vaccines capable of inducing sterilising immunity or otherwise reducing transmission. The trial is registered as ISRCTN 14391248

Future restoration should enhance ecological complexity and emergent properties at multiple scales

Ecological restoration has a paradigm of re-establishing ‘indigenous reference' communities. One resulting concern is that focussing on target communities may not necessarily create systems which function at a high level or are resilient in the face of ongoing global change. Ecological complexity – defined here, based on theory, as the number of components in a system and the number of connections among them – provides a complementary aim, which can be measured directly and has several advantages. Ecological complexity encompasses key ecosystem variables including structural heterogeneity, trophic interactions and functional diversity. Ecological complexity can also be assessed at the landscape scale, with metrics including β diversity, heterogeneity among habitat patches and connectivity. Thus, complexity applies, and can be measured, at multiple scales. Importantly, complexity is linked to system emergent properties, e.g. ecosystem functions and resilience, and there is evidence that both are enhanced by complexity. We suggest that restoration ecology should consider a new paradigm to restore complexity at multiple scales, in particular of individual ecosystems and across landscapes. A complexity approach can make use of certain current restoration methods but also encompass newer concepts such as rewilding. Indeed, a complexity goal might in many cases best be achieved by interventionist restoration methods. Incorporating complexity into restoration policies could be quite straightforward. Related aims such as enhancing ecosystem services and ecological resilience are to the fore in initiatives such as the Sustainable Development Goals and the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services. Implementation in policy and practice will need the development of complexity metrics that can be applied at both local and regional scales. Ultimately, the adoption of an ecological complexity paradigm will be based on an acceptance that the ongoing and unprecedented global environmental change requires new ways of doing restoration that is fit for the future

Blood-based epigenome-wide analyses of cognitive abilities

BACKGROUND: Blood-based markers of cognitive functioning might provide an accessible way to track neurodegeneration years prior to clinical manifestation of cognitive impairment and dementia. RESULTS: Using blood-based epigenome-wide analyses of general cognitive function, we show that individual differences in DNA methylation (DNAm) explain 35.0% of the variance in general cognitive function (g). A DNAm predictor explains ~4% of the variance, independently of a polygenic score, in two external cohorts. It also associates with circulating levels of neurology- and inflammation-related proteins, global brain imaging metrics, and regional cortical volumes. CONCLUSIONS: As sample sizes increase, the ability to assess cognitive function from DNAm data may be informative in settings where cognitive testing is unreliable or unavailable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-021-02596-5

Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health

Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing. These are independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits (N = 1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health