Governments are attempting to control the COVID-19 pandemic with nonpharmaceutical interventions (NPIs). However, the effectiveness of different NPIs at reducing transmission is poorly understood. We gathered chronological data on the implementation of NPIs for several European, and other, countries between January and the end of May 2020. We estimate the effectiveness of NPIs, ranging from limiting gathering sizes, business closures, and closure of educational institutions to stay-at-home orders. To do so, we used a Bayesian hierarchical model that links NPI implementation dates to national case and death counts and supported the results with extensive empirical validation. Closing all educational institutions, limiting gatherings to 10 people or less, and closing face-to-face businesses each reduced transmission considerably. The additional effect of stay-at-home orders was comparatively small.

Recent data suggest that NETosis plays a crucial role in the innate immune response and disturbs the homeostasis of the immune system. NETosis is a form of neutrophil-specific cell death characterized by the release of large web-like structures referred to as neutrophil extracellular traps (NETs). NETs are composed of DNA strands associated with histones and decorated with about 20 different proteins, including neutrophil elastase, myeloperoxidase, cathepsin G, proteinase 3, high mobility group protein B1, and LL37. Reportedly, NETosis can be induced by several microbes, and particulate matter including sterile stimuli, via distinct cellular mechanisms. Meanwhile, suicidal NETosis and vital NETosis are controversial. As we enter the second decade of research on NETosis, we have partly understood NETs as double-edged swords of innate immunity. In this review, we will discuss the mechanisms of NETosis, its antimicrobial action, and role in autoimmune diseases, as well as the relatively new field of NET-associated mitochondrial DNA.

Background: Existing analyses of nonpharmaceutical interventions (NPIs) against COVID19 transmission have concentrated on the joint effectiveness of large-scale NPIs. With increasing data, we can move beyond estimating joint effects towards disentangling individual effects. In addition to effectiveness, policy decisions ought to account for the burden placed by different NPIs on the population. Methods: To our knowledge, this is the largest data-driven study of NPI effectiveness to date. We collected chronological data on 9 NPIs in 41 countries between January and April 2020, using extensive fact-checking to ensure high data quality. We infer NPI effectiveness with a novel semi-mechanistic Bayesian hierarchical model, modelling both confirmed cases and deaths to increase the signal from which NPI effects can be inferred. Finally, we study how much perceived burden different NPIs impose on the population with an online survey of preferences using the MaxDiff method. Results: Eight NPIs have a >95% posterior probability of being effective: closing schools (mean reduction in R: 50%; 95% credible interval: 39%-59%), closing nonessential businesses (34%; 16%-49%), closing high-risk businesses (26%; 8%-42%), and limiting gatherings to 10 people or less (28%; 8%-45%), to 100 people or less (17%; -3%-35%), to 1000 people or less (16%; -2%-31%), issuing stay-at-home orders (14%; -2%-29%), and testing patients with respiratory symptoms (13%; -1%-26%). As validation is crucial for NPI models, we performed 15 sensitivity analyses and evaluated predictions on unseen data, finding strong support for our results. We combine the effectiveness and preference results to estimate effectiveness-to-burden ratios. Conclusions: Our results suggest a surprisingly large role for schools in COVID-19 transmission, a contribution to the ongoing debate about the relevance of asymptomatic carriers in disease spreading. We identify additional interventions with good effectiveness-burden tradeoffs, namely symptomatic testing, closing high-risk businesses, and limiting gathering size. Closing most nonessential businesses and issuing stay-at-home orders impose a high burden while having a limited additional effect.

European governments use non-pharmaceutical interventions (NPIs) to control resurging waves of COVID-19. However, they only have outdated estimates for how effective individual NPIs were in the first wave. We estimate the effectiveness of 17 NPIs in Europe’s second wave from subnational case and death data by introducing a flexible hierarchical Bayesian transmission model and collecting the largest dataset of NPI implementation dates across Europe. Business closures, educational institution closures, and gathering bans reduced transmission, but reduced it less than they did in the first wave. This difference is likely due to organisational safety measures and individual protective behaviours—such as distancing—which made various areas of public life safer and thereby reduced the effect of closing them. Specifically, we find smaller effects for closing educational institutions, suggesting that stringent safety measures made schools safer compared to the first wave. Second-wave estimates outperform previous estimates at predicting transmission in Europe’s third wave.

The critical size for strong interaction of hydrophobic particles with phospholipid bilayers has been predicted to be 10 nm. Because of the wide spreading of nonpolar nanoparticles (NPs) in the environment, we aimed to reveal the ability of living organisms to entrap NPs via formation of neutrophil extracellular traps (NETs). Upon interaction with various cell types and tissues, 10-to 40-nmsized NPs induce fast (<20 min) damage of plasma membranes and instability of the lysosomal compartment, leading to the immediate formation of NETs. In contrast, particles sized 100-1,000 nm behaved rather inertly. Resulting NET formation (NETosis) was accompanied by an inflammatory reaction intrinsically endowed with its own resolution, demonstrated in lungs and air pouches of mice. Persistence of small NPs in joints caused unremitting arthritis and bone remodeling. Small NPs coinjected with antigen exerted adjuvant-like activity. This report demonstrates a cellular mechanism that explains how small NPs activate the NETosis pathway and drive their entrapping and resolution of the initial inflammatory response.nanoparticles | size | neutrophils | NETosis | inflammation