A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2

Background: As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus, whether from infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure antibody-based protection to SARS-CoV-2, ideally with rapid turnaround and without the need for laboratory-based testing. Methods: We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibody (NAb) from whole blood, with a result that can be determined by eye or quantitatively on a small instrument. We compared our lateral flow test with the gold-standard microneutralisation assay, using samples from convalescent and vaccinated donors, as well as immunised macaques. Findings: We show a high correlation between our lateral flow test with conventional neutralisation and that this test is applicable with animal samples. We also show that this assay is readily adaptable to test for protection to newly emerging SARS-CoV-2 variants, including the beta variant which revealed a marked reduction in NAb activity. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (specificity 100% and sensitivity 96% at a microneutralisation cutoff of 1:40) and that fingerprick whole blood samples are sufficient for this test. Interpretation: Taken together, the COVID-19 NAb-testTM device described here provides a rapid readout of NAb based protection to SARS-CoV-2 at the point of care

Bacterial Cyclic Diguanylate Signaling Networks Sense Temperature

Many bacteria use the second messenger cyclic diguanylate (c-di-GMP) to control motility, biofilm production and virulence. Here, we identify a thermosensory diguanylate cyclase (TdcA) that modulates temperature-dependent motility, biofilm development and virulence in the opportunistic pathogen Pseudomonas aeruginosa. TdcA synthesizes c-di-GMP with catalytic rates that increase more than a hundred-fold over a ten-degree Celsius change. Analyses using protein chimeras indicate that heat-sensing is mediated by a thermosensitive Per-Arnt-SIM (PAS) domain. TdcA homologs are widespread in sequence databases, and a distantly related, heterologously expressed homolog from the Betaproteobacteria order Gallionellales also displayed thermosensitive diguanylate cyclase activity. We propose, therefore, that thermotransduction is a conserved function of c-di-GMP signaling networks, and that thermosensitive catalysis of a second messenger constitutes a mechanism for thermal sensing in bacteria

Developmental disabilities among children younger than 5 years in 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016

Background The Sustainable Development Goals (SDGs) mandate systematic monitoring of the health and wellbeing of all children to achieve optimal early childhood development. However, global epidemiological data on children with developmental disabilities are scarce. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 provides a comprehensive assessment of prevalence and years lived with disability (YLDs) for development disabilities among children younger than 5 years in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and YLDs for epilepsy, intellectual disability, hearing loss, vision loss, autism spectrum disorder, and attention deficit hyperactivity disorder. YLDs were estimated as the product of the prevalence estimate and the disability weight for each mutually exclusive disorder, corrected for comorbidity. We used DisMod-MR 2.1, a Bayesian meta-regression tool, on a pool of primary data derived from systematic reviews of the literature, health surveys, hospital and claims databases, cohort studies, and disease-specific registries. Findings Globally, 52·9 million (95% uncertainty interval [UI] 48·7–57·3; or 8·4% [7·7–9·1]) children younger than 5 years (54% males) had developmental disabilities in 2016 compared with 53·0 million (49·0–57·1; or 8·9% [8·2–9·5]) in 1990. About 95% of these children lived in low-income and middle-income countries. YLDs among these children increased from 3·8 million (95% UI 2·8–4·9) in 1990 to 3·9 million (2·9–5·2) in 2016. These disabilities accounted for 13·3% of the 29·3 million YLDs for all health conditions among children younger than 5 years in 2016. Vision loss was the most prevalent disability, followed by hearing loss, intellectual disability, and autism spectrum disorder. However, intellectual disability was the largest contributor to YLDs in both 1990 and 2016. Although the prevalence of developmental disabilities among children younger than 5 years decreased in all countries (except for North America) between 1990 and 2016, the number of children with developmental disabilities increased significantly in sub-Saharan Africa (71·3%) and in North Africa and the Middle East (7·6%). South Asia had the highest prevalence of children with developmental disabilities in 2016 and North America had the lowest. Interpretation The global burden of developmental disabilities has not significantly improved since 1990, suggesting inadequate global attention on the developmental potential of children who survived childhood as a result of child survival programmes, particularly in sub-Saharan Africa and south Asia. The SDGs provide a framework for policy and action to address the needs of children with or at risk of developmental disabilities, particularly in resource-poor countries