Population immunity predicts evolutionary trajectories of SARS-CoV-2.

The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, and antigenic changes that reduce cross-immunity induced by previous infections or vaccinations. How this functional variation shapes global evolution has remained unclear. Here, we establish a predictive fitness model for SARS-CoV-2 that integrates antigenic and intrinsic selection. The model is informed by tracking of time-resolved sequence data, epidemiological records, and cross-neutralization data of viral variants. Our inference shows that immune pressure, including contributions of vaccinations and previous infections, has become the dominant force driving the recent evolution of SARS-CoV-2. The fitness model can serve continued surveillance in two ways. First, it successfully predicts the short-term evolution of circulating strains and flags emerging variants likely to displace the previously predominant variant. Second, it predicts likely antigenic profiles of successful escape variants prior to their emergence.

Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics.

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of "local" when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.

Monkeypox emergency: Urgent questions and perspectives.

Amidst the COVID-19 pandemic, we now face another public health emergency in the form of monkeypox virus. As of August 1, the Centers for Disease Control and Prevention report over 23,000 cases in 80 countries. An inclusive and global collaborative effort to understand the biology, evolution, and spread of the virus as well as commitment to vaccine equity will be critical toward containing this outbreak. We share the voices of leading experts in this space on what they see as the most pressing questions and directions for the community.

Transmission from vaccinated individuals in a large SARS-CoV-2 Delta variant outbreak.

An outbreak of over 1,000 COVID-19 cases in Provincetown, Massachusetts (MA), in July 2021-the first large outbreak mostly in vaccinated individuals in the US-prompted a comprehensive public health response, motivating changes to national masking recommendations and raising questions about infection and transmission among vaccinated individuals. To address these questions, we combined viral genomic and epidemiological data from 467 individuals, including 40% of outbreak-associated cases. The Delta variant accounted for 99% of cases in this dataset; it was introduced from at least 40 sources, but 83% of cases derived from a single source, likely through transmission across multiple settings over a short time rather than a single event. Genomic and epidemiological data supported multiple transmissions of Delta from and between fully vaccinated individuals. However, despite its magnitude, the outbreak had limited onward impact in MA and the US overall, likely due to high vaccination rates and a robust public health response.

Scientific impact in a changing world.

Measuring scientific success has traditionally involved numbers and statistics. However, due to an increasingly uncertain world, more than ever we need to measure the effect that science has on real-world scenarios. We asked researchers to share their points of view on what scientific impact means to them and how impact matters beyond the numbers.

Using virtual interviewing to create a more accessible hybrid academic job market.

Virtual interviewing has become ubiquitous with the academic job market. Here, we highlight the best practices for candidates and departments to consider when using virtual interviewing. We propose how virtual interviews can be leveraged and adapted for hybrid academic job searches combining virtual and in-person activities in a post-pandemic world.

Active learning-based STEM education for in-person and online learning.

The COVID-19 global pandemic has forced the higher education sector to transition to an uncharted remote-learning format. This offers an opportunity to adopt active learning, which increases students' performance compared to lectures, narrows achievement gaps for underrepresented students, and promotes equity and inclusivity, as the basis of STEM education.

Delivering the message: How a novel technology enabled the rapid development of effective vaccines.

This year's Lasker∼Debakey Clinical Research Award honors Katalin Karikó and Drew Weissman for the development of a therapeutic technology based on nucleoside-modification of messenger RNA, enabling the rapid development of the highly effective COVID-19 vaccines.

Persistent progress.

The highly effective and safe mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines draw on decades of painstaking research to overcome the many hurdles for delivering, expressing, and avoiding toxicity of therapeutic mRNA. Cell editor Nicole Neuman talked with Dr. Katalin Karikó and Dr. Drew Weissman, recipients of the 2021 Lasker∼DeBakey Clinical Medical Research Award, to learn more about their quest to develop mRNA-based therapeutics, which led them to the crucial discovery that modification of mRNA could prevent toxicity and increase expression. This conversation has been adapted for print below, with editing for clarity, accuracy, and length.

One world, one health.

The past year has underscored the threat that emerging viruses pose to global health. The 2021 John Dirks Canada Gairdner Global Health award recognizes the contributions of Joseph Sriyal Malik Peiris and Yi Guan toward understanding the origins and options for control of newly emerging infectious disease outbreaks in Asia, notably zoonotic influenza and severe acute respiratory syndrome (SARS). Nicole Neuman of Cell corresponded with Malik Peiris about his path to studying emerging infectious diseases and the challenges of this work. Excerpts of their exchange are included here.

The origins of viral infection sleuth.

The events of the past year have underscored the serious and rapid threat that emerging viruses pose to global health. However, much of the rapid progress in understanding and combating SARS-CoV-2 was made possible because of the decades of important groundwork laid from researchers studying other emergent infectious diseases. The 2021 John Dirks Canada Gairdner Global Health award recognizes the contributions of Joseph Sriyal Malik Peiris and Yi Guan toward understanding the origins and options for control of newly emerging infectious disease outbreaks in Asia, notably zoonotic influenza and severe acute respiratory syndrome (SARS). Cell's Nicole Neuman corresponded with Yi Guan about his path to becoming a viral infection sleuth and the challenges of understanding emerging pathogens and their origins. Excerpts of their exchange are included here.

Coming to America: Genomic surveillance and how B.1.1.7 arrived in the US.

In this issue of Cell, Washington et al. and Alpert et al. demonstrate the value of genomic surveillance when studying the introduction of the B.1.1.7 variant to the US and illustrate the challenge that results from the lack of good sampling strategies.

The emergence and ongoing convergent evolution of the SARS-CoV-2 N501Y lineages.

The independent emergence late in 2020 of the B.1.1.7, B.1.351, and P.1 lineages of SARS-CoV-2 prompted renewed concerns about the evolutionary capacity of this virus to overcome public health interventions and rising population immunity. Here, by examining patterns of synonymous and non-synonymous mutations that have accumulated in SARS-CoV-2 genomes since the pandemic began, we find that the emergence of these three "501Y lineages" coincided with a major global shift in the selective forces acting on various SARS-CoV-2 genes. Following their emergence, the adaptive evolution of 501Y lineage viruses has involved repeated selectively favored convergent mutations at 35 genome sites, mutations we refer to as the 501Y meta-signature. The ongoing convergence of viruses in many other lineages on this meta-signature suggests that it includes multiple mutation combinations capable of promoting the persistence of diverse SARS-CoV-2 lineages in the face of mounting host immune recognition.

Emergence of an early SARS-CoV-2 epidemic in the United States.

The emergence of the COVID-19 epidemic in the United States (U.S.) went largely undetected due to inadequate testing. New Orleans experienced one of the earliest and fastest accelerating outbreaks, coinciding with Mardi Gras. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana had limited diversity compared to other U.S. states and that one introduction of SARS-CoV-2 led to almost all of the early transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras, and the festival dramatically accelerated transmission. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate epidemics.

Generation and transmission of interlineage recombinants in the SARS-CoV-2 pandemic.

We present evidence for multiple independent origins of recombinant SARS-CoV-2 viruses sampled from late 2020 and early 2021 in the United Kingdom. Their genomes carry single-nucleotide polymorphisms and deletions that are characteristic of the B.1.1.7 variant of concern but lack the full complement of lineage-defining mutations. Instead, the remainder of their genomes share contiguous genetic variation with non-B.1.1.7 viruses circulating in the same geographic area at the same time as the recombinants. In four instances, there was evidence for onward transmission of a recombinant-origin virus, including one transmission cluster of 45 sequenced cases over the course of 2 months. The inferred genomic locations of recombination breakpoints suggest that every community-transmitted recombinant virus inherited its spike region from a B.1.1.7 parental virus, consistent with a transmission advantage for B.1.1.7's set of mutations.

Population impact of SARS-CoV-2 variants with enhanced transmissibility and/or partial immune escape.

SARS-CoV-2 variants of concern exhibit varying degrees of transmissibility and, in some cases, escape from acquired immunity. Much effort has been devoted to measuring these phenotypes, but understanding their impact on the course of the pandemic-especially that of immune escape-has remained a challenge. Here, we use a mathematical model to simulate the dynamics of wild-type and variant strains of SARS-CoV-2 in the context of vaccine rollout and nonpharmaceutical interventions. We show that variants with enhanced transmissibility frequently increase epidemic severity, whereas those with partial immune escape either fail to spread widely or primarily cause reinfections and breakthrough infections. However, when these phenotypes are combined, a variant can continue spreading even as immunity builds up in the population, limiting the impact of vaccination and exacerbating the epidemic. These findings help explain the trajectories of past and present SARS-CoV-2 variants and may inform variant assessment and response in the future.

Infodemics: A new challenge for public health.

The COVID-19 information epidemic, or "infodemic," demonstrates how unlimited access to information may confuse and influence behaviors during a health emergency. However, the study of infodemics is relatively new, and little is known about their relationship with epidemics management. Here, we discuss unresolved issues and propose research directions to enhance preparedness for future health crises.

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.

Metabolic consequences of obesity and type 2 diabetes: Balancing genes and environment for personalized care.

The prevalence of type 2 diabetes and obesity has risen dramatically for decades and is expected to rise further, secondary to the growing aging, sedentary population. The strain on global health care is projected to be colossal. This review explores the latest work and emerging ideas related to genetic and environmental factors influencing metabolism. Translational research and clinical applications, including the impact of the COVID-19 pandemic, are highlighted. Looking forward, strategies to personalize all aspects of prevention, management and care are necessary to improve health outcomes and reduce the impact of these metabolic diseases.

Scientific misinformation: A perfect storm, missteps, and moving forward.

The spread of scientific misinformation is not new but rather has long posed threats to human health, environmental well-being, and the creation of a sustainable and equitable future. However, with the COVID-19 pandemic, the need to develop strategies to counteract scientific misinformation has taken on an acute urgency. Cell editor Nicole Neuman sat down with Walter Quattrociocchi and Dietram Scheufele to gain insights on how we got here and what does-and does not-work to fight the spread of scientific misinformation. Excerpts from this conversation, edited for clarity and length, are presented below, and the full conversation is available with the article online.