Systems-level analysis of innate immunity.

Systems-level analysis of biological processes strives to comprehensively and quantitatively evaluate the interactions between the relevant molecular components over time, thereby enabling development of models that can be employed to ultimately predict behavior. Rapid development in measurement technologies (omics), when combined with the accessible nature of the cellular constituents themselves, is allowing the field of innate immunity to take significant strides toward this lofty goal. In this review, we survey exciting results derived from systems biology analyses of the immune system, ranging from gene regulatory networks to influenza pathogenesis and systems vaccinology.

Public health actions to control new SARS-CoV-2 variants.

Recent reports suggest that some SARS-CoV-2 genetic variants, such as B.1.1.7, might be more transmissible and are quickly spreading around the world. As the emergence of more transmissible variants could exacerbate the pandemic, we provide public health guidance for increased surveillance and measures to reduce community transmission.

Africa Needs a New Public Health Order to Tackle Infectious Disease Threats.

The SARS-CoV-2 pandemic has revealed that Africa needs a new public health order to be resilient, to adapt, and to cope with 21st-century disease threats. The new order will need strengthened continental and national public health institutions; local manufacturing of vaccines, therapeutics, and diagnostics; attraction, training, and retention of a public health workforce; and fostering of respectful local and international partnerships.

Why and How Vaccines Work.

Vaccines save millions of lives from infectious diseases caused by viruses and bacteria. As the world awaits safe and effective COVID-19 vaccines, we celebrate the progresses made and highlight challenges ahead in vaccines and the science behind them.

Malaria: Biology and Disease.

Malaria has been a major global health problem of humans through history and is a leading cause of death and disease across many tropical and subtropical countries. Over the last fifteen years renewed efforts at control have reduced the prevalence of malaria by over half, raising the prospect that elimination and perhaps eradication may be a long-term possibility. Achievement of this goal requires the development of new tools including novel antimalarial drugs and more efficacious vaccines as well as an increased understanding of the disease and biology of the parasite. This has catalyzed a major effort resulting in development and regulatory approval of the first vaccine against malaria (RTS,S/AS01) as well as identification of novel drug targets and antimalarial compounds, some of which are in human clinical trials.

The burden and dynamics of hospital-acquired SARS-CoV-2 in England.

Hospital-based transmission had a dominant role in Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) epidemics1,2, but large-scale studies of its role in the SARS-CoV-2 pandemic are lacking. Such transmission risks spreading the virus to the most vulnerable individuals and can have wider-scale impacts through hospital-community interactions. Using data from acute hospitals in England, we quantify within-hospital transmission, evaluate likely pathways of spread and factors associated with heightened transmission risk, and explore the wider dynamical consequences. We estimate that between June 2020 and March 2021 between 95,000 and 167,000 inpatients acquired SARS-CoV-2 in hospitals (1% to 2% of all hospital admissions in this period). Analysis of time series data provided evidence that patients who themselves acquired SARS-CoV-2 infection in hospital were the main sources of transmission to other patients. Increased transmission to inpatients was associated with hospitals having fewer single rooms and lower heated volume per bed. Moreover, we show that reducing hospital transmission could substantially enhance the efficiency of punctuated lockdown measures in suppressing community transmission. These findings reveal the previously unrecognized scale of hospital transmission, have direct implications for targeting of hospital control measures and highlight the need to design hospitals better equipped to limit the transmission of future high-consequence pathogens.

Global fine-scale changes in ambient NO2 during COVID-19 lockdowns.

Nitrogen dioxide (NO2) is an important contributor to air pollution and can adversely affect human health1-9. A decrease in NO2 concentrations has been reported as a result of lockdown measures to reduce the spread of COVID-1910-20. Questions remain, however, regarding the relationship of satellite-derived atmospheric column NO2 data with health-relevant ambient ground-level concentrations, and the representativeness of limited ground-based monitoring data for global assessment. Here we derive spatially resolved, global ground-level NO2 concentrations from NO2 column densities observed by the TROPOMI satellite instrument at sufficiently fine resolution (approximately one kilometre) to allow assessment of individual cities during COVID-19 lockdowns in 2020 compared to 2019. We apply these estimates to quantify NO2 changes in more than 200 cities, including 65 cities without available ground monitoring, largely in lower-income regions. Mean country-level population-weighted NO2 concentrations are 29% ± 3% lower in countries with strict lockdown conditions than in those without. Relative to long-term trends, NO2 decreases during COVID-19 lockdowns exceed recent Ozone Monitoring Instrument (OMI)-derived year-to-year decreases from emission controls, comparable to 15 ± 4 years of reductions globally. Our case studies indicate that the sensitivity of NO2 to lockdowns varies by country and emissions sector, demonstrating the critical need for spatially resolved observational information provided by these satellite-derived surface concentration estimates.

Wetland emission and atmospheric sink changes explain methane growth in 2020.

Atmospheric methane growth reached an exceptionally high rate of 15.1 ± 0.4 parts per billion per year in 2020 despite a probable decrease in anthropogenic methane emissions during COVID-19 lockdowns1. Here we quantify changes in methane sources and in its atmospheric sink in 2020 compared with 2019. We find that, globally, total anthropogenic emissions decreased by 1.2 ± 0.1 teragrams of methane per year (Tg CH4 yr-1), fire emissions decreased by 6.5 ± 0.1 Tg CH4 yr-1 and wetland emissions increased by 6.0 ± 2.3 Tg CH4 yr-1. Tropospheric OH concentration decreased by 1.6 ± 0.2 per cent relative to 2019, mainly as a result of lower anthropogenic nitrogen oxide (NOx) emissions and associated lower free tropospheric ozone during pandemic lockdowns2. From atmospheric inversions, we also infer that global net emissions increased by 6.9 ± 2.1 Tg CH4 yr-1 in 2020 relative to 2019, and global methane removal from reaction with OH decreased by 7.5 ± 0.8 Tg CH4 yr-1. Therefore, we attribute the methane growth rate anomaly in 2020 relative to 2019 to lower OH sink (53 ± 10 per cent) and higher natural emissions (47 ± 16 per cent), mostly from wetlands. In line with previous findings3,4, our results imply that wetland methane emissions are sensitive to a warmer and wetter climate and could act as a positive feedback mechanism in the future. Our study also suggests that nitrogen oxide emission trends need to be taken into account when implementing the global anthropogenic methane emissions reduction pledge5.

Evolutionary Ecology of Wolbachia Releases for Disease Control.

Wolbachia is an endosymbiotic Alphaproteobacteria that can suppress insect-borne diseases through decreasing host virus transmission (population replacement) or through decreasing host population density (population suppression). We contrast natural Wolbachia infections in insect populations with Wolbachia transinfections in mosquitoes to gain insights into factors potentially affecting the long-term success of Wolbachia releases. Natural Wolbachia infections can spread rapidly, whereas the slow spread of transinfections is governed by deleterious effects on host fitness and demographic factors. Cytoplasmic incompatibility (CI) generated by Wolbachia is central to both population replacement and suppression programs, but CI in nature can be variable and evolve, as can Wolbachia fitness effects and virus blocking. Wolbachia spread is also influenced by environmental factors that decrease Wolbachia titer and reduce maternal Wolbachia transmission frequency. More information is needed on the interactions between Wolbachia and host nuclear/mitochondrial genomes, the interaction between invasion success and local ecological factors, and the long-term stability of Wolbachia-mediated virus blocking.

Beyond empiricism: informing vaccine development through innate immunity research.

Although a great public heath success, vaccines provide suboptimal protection in some patient populations and are not available to protect against many infectious diseases. Insights from innate immunity research have led to a better understanding of how existing vaccines work and have informed vaccine development. New adjuvants and delivery systems are being designed based upon their capacity to stimulate innate immune sensors and target antigens to dendritic cells, the cells responsible for initiating adaptive immune responses. Incorporating these adjuvants and delivery systems in vaccines can beneficially alter the quantitative and qualitative nature of the adaptive immune response, resulting in enhanced protection.

Transcriptional lockdown during acute proteotoxic stress.

Cells experiencing proteotoxic stress downregulate the expression of thousands of active genes and upregulate a few stress-response genes. The strategy of downregulating gene expression has conceptual parallels with general lockdown in the global response to the coronavirus disease 2019 (COVID-19) pandemic. The mechanistic details of global transcriptional downregulation of genes, termed stress-induced transcriptional attenuation (SITA), are only beginning to emerge. The reduction in RNA and protein production during stress may spare proteostasis capacity, allowing cells to divert resources to control stress-induced damage. Given the relevance of translational downregulation in a broad variety of diseases, the role of SITA in diseases caused by proteotoxicity should be investigated in future, paving the way for potential novel therapeutics.

Transitions in development - an interview with Evgeny Kvon.

Evgeny Kvon is an Assistant Professor at the University of California, Irvine (UCI) in the Department of Developmental and Cell Biology, USA. His lab studies non-coding regulatory DNA and its mechanistic role in the control of gene expression to understand more about development, disease and evolution. Last year, Evgeny received the National Institutes of Health Director's New Innovator Award. We spoke to Evgeny over Zoom to learn more about his career and the silver lining to starting a lab during the COVID-19 lockdowns.