Phylodynamics of SARS-CoV-2 in France, Europe, and the world in 2020.

Although France was one of the most affected European countries by the COVID-19 pandemic in 2020, the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) movement within France, but also involving France in Europe and in the world, remain only partially characterized in this timeframe. Here, we analyzed GISAID deposited sequences from January 1 to December 31, 2020 (n = 638,706 sequences at the time of writing). To tackle the challenging number of sequences without the bias of analyzing a single subsample of sequences, we produced 100 subsamples of sequences and related phylogenetic trees from the whole dataset for different geographic scales (worldwide, European countries, and French administrative regions) and time periods (from January 1 to July 25, 2020, and from July 26 to December 31, 2020). We applied a maximum likelihood discrete trait phylogeographic method to date exchange events (i.e., a transition from one location to another one), to estimate the geographic spread of SARS-CoV-2 transmissions and lineages into, from and within France, Europe, and the world. The results unraveled two different patterns of exchange events between the first and second half of 2020. Throughout the year, Europe was systematically associated with most of the intercontinental exchanges. SARS-CoV-2 was mainly introduced into France from North America and Europe (mostly by Italy, Spain, the United Kingdom, Belgium, and Germany) during the first European epidemic wave. During the second wave, exchange events were limited to neighboring countries without strong intercontinental movement, but Russia widely exported the virus into Europe during the summer of 2020. France mostly exported B.1 and B.1.160 lineages, respectively, during the first and second European epidemic waves. At the level of French administrative regions, the Paris area was the main exporter during the first wave. But, for the second epidemic wave, it equally contributed to virus spread with Lyon area, the second most populated urban area after Paris in France. The main circulating lineages were similarly distributed among the French regions. To conclude, by enabling the inclusion of tens of thousands of viral sequences, this original phylodynamic method enabled us to robustly describe SARS-CoV-2 geographic spread through France, Europe, and worldwide in 2020.

A shock to the system: entrepreneurial ecosystem resilience and adaptation in a global pandemic

PurposeThis exploratory study uses a punctuated equilibrium paradigm (PEP) framework to examine the impact and adaptation of an entrepreneurial ecosystem (EE) to the COVID-19 pandemic at the organizational and ecosystem level. The aim is to provide guidance to EEs on ways to adapt to future external shocks.Design/methodology/approachAs this study is exploratory in nature, the authors use a sequential mixed method whereby a qualitative method is used first to identify emergent themes from in-depth interviews with EE members, followed by a quantitative method (survey) based on those themes across a broader cross section of EE members.FindingsEntrepreneurial ecosystem's geographical advantages have declined during the pandemic as EE firms adapted to this external shock by developing more digitally distributed organizations.Research limitations/implicationsBased on the findings, the authors propose an emerging model of EEs that extends the traditional clustering model focused on geography to account for more digitally distributed entrepreneurial clusters. However, the results, based on an in-depth study of one ecosystem, may not be fully generalizable to all EEs.Practical implicationsGiven the widespread pandemic impact, the findings may be instructive to EEs and organizations in EEs that aim to become more resilient in the face of potential future external shocks.Social implicationsAs part of the qualitative interview process the interviewees were asked what they would change in San Francisco Bay Area if they had a magic wand right now. They discussed a variety of inspiring ideas, but the most frequently mentioned was their wish to change the focus of business to solve societal problems with a global citizen mindset (e.g. recycling energy, climate change, income inequality, access to education and funding, inequity, wealth gaps, housing crisis and homelessness) to make the world a better place. Additionally, the pandemic exposed some inequality in work conditions across demographics. As firms reorganize to increase resiliency, attention to these issues should be addressed.Originality/valueThis study is unique in applying the PEP to EEs to deepen our understanding about how an EE evolves during periods of sudden external shocks.

Zooanthroponotic transmission of SARS-CoV-2 and host-specific viral mutations revealed by genome-wide phylogenetic analysis.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a generalist virus, infecting and evolving in numerous mammals, including captive and companion animals, free-ranging wildlife, and humans. Transmission among non-human species poses a risk for the establishment of SARS-CoV-2 reservoirs, makes eradication difficult, and provides the virus with opportunities for new evolutionary trajectories, including the selection of adaptive mutations and the emergence of new variant lineages. Here, we use publicly available viral genome sequences and phylogenetic analysis to systematically investigate the transmission of SARS-CoV-2 between human and non-human species and to identify mutations associated with each species. We found the highest frequency of animal-to-human transmission from mink, compared with lower transmission from other sampled species (cat, dog, and deer). Although inferred transmission events could be limited by sampling biases, our results provide a useful baseline for further studies. Using genome-wide association studies, no single nucleotide variants (SNVs) were significantly associated with cats and dogs, potentially due to small sample sizes. However, we identified three SNVs statistically associated with mink and 26 with deer. Of these SNVs, ~⅔ were plausibly introduced into these animal species from local human populations, while the remaining ~⅓ were more likely derived in animal populations and are thus top candidates for experimental studies of species-specific adaptation. Together, our results highlight the importance of studying animal-associated SARS-CoV-2 mutations to assess their potential impact on human and animal health.

The landscape of antibody binding affinity in SARS-CoV-2 Omicron BA.1 evolution.

The Omicron BA.1 variant of SARS-CoV-2 escapes convalescent sera and monoclonal antibodies that are effective against earlier strains of the virus. This immune evasion is largely a consequence of mutations in the BA.1 receptor binding domain (RBD), the major antigenic target of SARS-CoV-2. Previous studies have identified several key RBD mutations leading to escape from most antibodies. However, little is known about how these escape mutations interact with each other and with other mutations in the RBD. Here, we systematically map these interactions by measuring the binding affinity of all possible combinations of these 15 RBD mutations (215=32,768 genotypes) to 4 monoclonal antibodies (LY-CoV016, LY-CoV555, REGN10987, and S309) with distinct epitopes. We find that BA.1 can lose affinity to diverse antibodies by acquiring a few large-effect mutations and can reduce affinity to others through several small-effect mutations. However, our results also reveal alternative pathways to antibody escape that does not include every large-effect mutation. Moreover, epistatic interactions are shown to constrain affinity decline in S309 but only modestly shape the affinity landscapes of other antibodies. Together with previous work on the ACE2 affinity landscape, our results suggest that the escape of each antibody is mediated by distinct groups of mutations, whose deleterious effects on ACE2 affinity are compensated by another distinct group of mutations (most notably Q498R and N501Y).

Genomic diversity of SARS-CoV-2 can be accelerated by mutations in the nsp14 gene.

Coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), encode a proofreading exonuclease, nonstructural protein 14 (nsp14), that helps ensure replication competence at a low evolutionary rate compared with other RNA viruses. In the current pandemic, SARS-CoV-2 has accumulated diverse genomic mutations including in nsp14. Here, to clarify whether amino acid substitutions in nsp14 affect the genomic diversity and evolution of SARS-CoV-2, we searched for amino acid substitutions in nature that may interfere with nsp14 function. We found that viruses carrying a proline-to-leucine change at position 203 (P203L) have a high evolutionary rate and that a recombinant SARS-CoV-2 virus with the P203L mutation acquired more diverse genomic mutations than wild-type virus during its replication in hamsters. Our findings suggest that substitutions, such as P203L, in nsp14 may accelerate the genomic diversity of SARS-CoV-2, contributing to virus evolution during the pandemic.

Evolution of increased positive charge on the SARS-CoV-2 spike protein may be adaptation to human transmission.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and infect individuals. The exterior surface of the SARS-CoV-2 virion is dominated by the spike protein, and the current work examined spike protein biochemical features that have changed during the 3 years in which SARS-CoV-2 has infected humans. Our analysis identified a striking change in spike protein charge, from -8.3 in the original Lineage A and B viruses to -1.26 in most of the current Omicron viruses. We conclude that in addition to immune selection pressure, the evolution of SARS-CoV-2 has also altered viral spike protein biochemical properties, which may influence virion survival and promote transmission. Future vaccine and therapeutic development should also exploit and target these biochemical properties.

Regulatory dissection of the severe COVID-19 risk locus introgressed by Neanderthals.

Individuals infected with the SARS-CoV-2 virus present with a wide variety of symptoms ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via introgression from Neanderthals as the strongest genetic risk factor for the severe response to COVID-19. However, the specific variants along this introgressed haplotype that contribute to this risk and the biological mechanisms that are involved remain unclear. Here, we assess the variants present on the risk haplotype for their likelihood of driving the genetic predisposition to severe COVID-19 outcomes. We do this by first exploring their impact on the regulation of genes involved in COVID-19 infection using a variety of population genetics and functional genomics tools. We then perform a locus-specific massively parallel reporter assay to individually assess the regulatory potential of each allele on the haplotype in a multipotent immune-related cell line. We ultimately reduce the set of over 600 linked genetic variants to identify four introgressed alleles that are strong functional candidates for driving the association between this locus and severe COVID-19. Using reporter assays in the presence/absence of SARS-CoV-2, we find evidence that these variants respond to viral infection. These variants likely drive the locus' impact on severity by modulating the regulation of two critical chemokine receptor genes: CCR1 and CCR5. These alleles are ideal targets for future functional investigations into the interaction between host genomics and COVID-19 outcomes.

Coordinated evolution at amino acid sites of SARS-CoV-2 spike.

SARS-CoV-2 has adapted in a stepwise manner, with multiple beneficial mutations accumulating in a rapid succession at origins of VOCs, and the reasons for this are unclear. Here, we searched for coordinated evolution of amino acid sites in the spike protein of SARS-CoV-2. Specifically, we searched for concordantly evolving site pairs (CSPs) for which changes at one site were rapidly followed by changes at the other site in the same lineage. We detected 46 sites which formed 45 CSP. Sites in CSP were closer to each other in the protein structure than random pairs, indicating that concordant evolution has a functional basis. Notably, site pairs carrying lineage defining mutations of the four VOCs that circulated before May 2021 are enriched in CSPs. For the Alpha VOC, the enrichment is detected even if Alpha sequences are removed from analysis, indicating that VOC origin could have been facilitated by positive epistasis. Additionally, we detected nine discordantly evolving pairs of sites where mutations at one site unexpectedly rarely occurred on the background of a specific allele at another site, for example on the background of wild-type D at site 614 (four pairs) or derived Y at site 501 (three pairs). Our findings hint that positive epistasis between accumulating mutations could have delayed the assembly of advantageous combinations of mutations comprising at least some of the VOCs.

Taxonium, a web-based tool for exploring large phylogenetic trees.

The COVID-19 pandemic has resulted in a step change in the scale of sequencing data, with more genomes of SARS-CoV-2 having been sequenced than any other organism on earth. These sequences reveal key insights when represented as a phylogenetic tree, which captures the evolutionary history of the virus, and allows the identification of transmission events and the emergence of new variants. However, existing web-based tools for exploring phylogenies do not scale to the size of datasets now available for SARS-CoV-2. We have developed Taxonium, a new tool that uses WebGL to allow the exploration of trees with tens of millions of nodes in the browser for the first time. Taxonium links each node to associated metadata and supports mutation-annotated trees, which are able to capture all known genetic variation in a dataset. It can either be run entirely locally in the browser, from a server-based backend, or as a desktop application. We describe insights that analysing a tree of five million sequences can provide into SARS-CoV-2 evolution, and provide a tool at cov2tree.org for exploring a public tree of more than five million SARS-CoV-2 sequences. Taxonium can be applied to any tree, and is available at taxonium.org, with source code at github.com/theosanderson/taxonium.

Since 2020, the SARS-CoV-2 virus has infected billions of people and spread to 185 countries. The virus spreads by making new copies of its genome inside human cells and exploits the cells' machinery to synthesise viral proteins it needs to infect further cells. Each time the virus copies its genetic material there's a chance that the replication process introduces an error to the genetic sequence. Over time, these mutations accumulate which can give rise to new variants with different properties. These new variants, originating from a common ancestor, may spread faster or be able to evade immune systems that have learnt to recognise previous variants. To understand where new variants of SARS-CoV-2 come from and how related they are to each other, scientists build family trees called 'phylogenetic trees' based on similarities in the genetic sequences of different variants of the virus. Looking at these trees researchers can track how a variant spreads geographically, and also attempt to identify new worrying variants that might lead to a new wave of infections. The scale of the COVID-19 pandemic together with the global effort by clinicians and researchers to sequence SARS-CoV-2 genetic material means a library of over 13 million SARS-CoV-2 genomes now exists, making it the largest such collection for any organism. Although phylogenetic trees of viruses have been studied for a long time, exploring the SARS-CoV-2 library presents technical and practical challenges due to its sheer size. Sanderson has developed an open-source web tool called Taxonium that allows users to explore phylogenetic trees with millions of sequences. With help from collaborators at the University of California, Santa Cruz, Sanderson built a website called Cov2Tree, that uses the Taxonium platform to allow immediate access to an expansive tree of all publicly available SARS-CoV-2 sequences. Cov2Tree enables users to visualise all SARS-CoV-2 genomes in a birds-eye view akin to a 'Google Earth for virus sequences' where anyone can zoom in on a related family of viruses down to the level of individual sequences. This can be used to compare variants and follow geographic spread. Using Taxonium, scientists can explore how virus sequences are related to each other. They can also see the individual mutations that have occurred at each branch of the tree, and can search for sequences based on mutation, geographical location, or other factors. Interestingly, a trend appearing in the SARS-CoV-2 phylogenetic tree is the emergence of identical mutations at different branches of the tree without a common origin. These mutations may be a result of convergent evolution, a phenomenon that occurs when a mutation appears independently in different variants as it confers an advantage to the virus making such mutations more likely to persist. This means that scientists may be able to expect certain mutations to appear in more distantly related variants if they have appeared independently in several different variants already. Overall, Taxonium is an important tool for monitoring SARS-CoV-2 genomes, but it also has broader applications. The tool can be used to browse phylogenetic trees of other viruses and organisms. Furthermore, the Taxonium website offers a way to browse a tree of life, with images and links to Wikipedia. The SARS-CoV-2 library might be the largest now, but in the future even bigger datasets will likely be available, highlighting the importance of tools like Taxonium.

Comprehensive fitness landscape of SARS-CoV-2 Mpro reveals insights into viral resistance mechanisms.

With the continual evolution of new strains of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that are more virulent, transmissible, and able to evade current vaccines, there is an urgent need for effective anti-viral drugs. The SARS-CoV-2 main protease (Mpro) is a leading target for drug design due to its conserved and indispensable role in the viral life cycle. Drugs targeting Mpro appear promising but will elicit selection pressure for resistance. To understand resistance potential in Mpro, we performed a comprehensive mutational scan of the protease that analyzed the function of all possible single amino acid changes. We developed three separate high throughput assays of Mpro function in yeast, based on either the ability of Mpro variants to cleave at a defined cut-site or on the toxicity of their expression to yeast. We used deep sequencing to quantify the functional effects of each variant in each screen. The protein fitness landscapes from all three screens were strongly correlated, indicating that they captured the biophysical properties critical to Mpro function. The fitness landscapes revealed a non-active site location on the surface that is extremely sensitive to mutation, making it a favorable location to target with inhibitors. In addition, we found a network of critical amino acids that physically bridge the two active sites of the Mpro dimer. The clinical variants of Mpro were predominantly functional in our screens, indicating that Mpro is under strong selection pressure in the human population. Our results provide predictions of mutations that will be readily accessible to Mpro evolution and that are likely to contribute to drug resistance. This complete mutational guide of Mpro can be used in the design of inhibitors with reduced potential of evolving viral resistance.

Molecular, ecological, and behavioral drivers of the bat-virus relationship.

Bats perform important ecological roles in our ecosystem. However, recent studies have demonstrated that bats are reservoirs of emerging viruses that have spilled over into humans and agricultural animals to cause severe diseases. These viruses include Hendra and Nipah paramyxoviruses, Ebola and Marburg filoviruses, and coronaviruses that are closely related to severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the recently emerged SARS-CoV-2. Intriguingly, bats that are naturally or experimentally infected with these viruses do not show clinical signs of disease. Here we have reviewed ecological, behavioral, and molecular factors that may influence the ability of bats to harbor viruses. We have summarized known zoonotic potential of bat-borne viruses and stress on the need for further studies to better understand the evolutionary relationship between bats and their viruses, along with discovering the intrinsic and external factors that facilitate the successful spillover of viruses from bats.

Genomic epidemiology of the first two waves of SARS-CoV-2 in Canada.

Tracking the emergence and spread of SARS-CoV-2 lineages using phylogenetics has proven critical to inform the timing and stringency of COVID-19 public health interventions. We investigated the effectiveness of international travel restrictions at reducing SARS-CoV-2 importations and transmission in Canada in the first two waves of 2020 and early 2021. Maximum likelihood phylogenetic trees were used to infer viruses' geographic origins, enabling identification of 2263 (95% confidence interval: 2159-2366) introductions, including 680 (658-703) Canadian sublineages, which are international introductions resulting in sampled Canadian descendants, and 1582 (1501-1663) singletons, introductions with no sampled descendants. Of the sublineages seeded during the first wave, 49% (46-52%) originated from the USA and were primarily introduced into Quebec (39%) and Ontario (36%), while in the second wave, the USA was still the predominant source (43%), alongside a larger contribution from India (16%) and the UK (7%). Following implementation of restrictions on the entry of foreign nationals on 21 March 2020, importations declined from 58.5 (50.4-66.5) sublineages per week to 10.3-fold (8.3-15.0) lower within 4 weeks. Despite the drastic reduction in viral importations following travel restrictions, newly seeded sublineages in summer and fall 2020 contributed to the persistence of COVID-19 cases in the second wave, highlighting the importance of sustained interventions to reduce transmission. Importations rebounded further in November, bringing newly emergent variants of concern (VOCs). By the end of February 2021, there had been an estimated 30 (19-41) B.1.1.7 sublineages imported into Canada, which increasingly displaced previously circulating sublineages by the end of the second wave.Although viral importations are nearly inevitable when global prevalence is high, with fewer importations there are fewer opportunities for novel variants to spark outbreaks or outcompete previously circulating lineages.

Developing evolution-resistant drugs for COVID-19.

Analyzing how mutations affect the main protease of SARS-CoV-2 may help researchers develop drugs that are effective against current and future variants of the virus.

Alone, in the dark: The extraordinary neuroethology of the solitary blind mole rat.

On the social scale, the blind mole rat (BMR; Spalax ehrenbergi) is an extreme. It is exceedingly solitary, territorial, and aggressive. BMRs reside underground, in self-excavated tunnels that they rarely leave. They possess specialized sensory systems for social communication and navigation, which allow them to cope with the harsh environmental conditions underground. This review aims to present the blind mole rat as an ideal, novel neuroethological model for studying aggressive and solitary behaviors. We discuss the BMR's unique behavioral phenotype, particularly in the context of 'anti-social' behaviors, and review the available literature regarding its specialized sensory adaptations to the social and physical habitat. To date, the neurobiology of the blind mole rat remains mostly unknown and holds a promising avenue for scientific discovery. Unraveling the neural basis of the BMR's behavior, in comparison to that of social rodents, can shed important light on the underlying mechanisms of psychiatric disorders in humans, in which similar behaviors are displayed.

The effectiveness and limitations of digital images for taxonomic research

In response to the worldwide coronavirus outbreak, which effectively shut down fieldwork, laboratory and herbarium-based studies, an evaluation was made of the effectiveness and limitations of undertaking a virtual taxonomic study using only online herbarium specimen resources related to the genus Madhuca (Sapotaceae) for the Flora of Singapore. The study demonstrated the immense value of digital images to basic taxonomic research but also found that diagnostic micro-morphological characters, often critical in defining species boundaries, cannot be seen in many digital images, even at high resolution. Several recommendations are made on how to maximise the utility of online herbarium specimen images to help facilitate future taxonomic research, though it is clear that physical access to herbarium specimens remains essential.

Protocol to isolate and assess spike protein cleavage in SARS-CoV-2 variants obtained from clinical COVID-19 samples.

For efficient cell entry, SARS-CoV-2 spike protein needs to be cleaved by cellular proteases. Here, we present a comprehensive protocol to assess SARS-CoV-2 spike protein cleavage in viral supernatants from SARS-CoV-2-infected cells. We also include a previous step of SARS-CoV-2 isolation from nasopharyngeal swabs of patients with COVID-19. We optimized the procedures to enhance successful viral isolation and specific spike detection. This protocol facilitates the evaluation of the role of spike mutations in spike protein processing. For complete details on the use and execution of this protocol, please refer to Escalera et al. (2022).

Functional and structural segregation of overlapping helices in HIV-1.

Overlapping coding regions balance selective forces between multiple genes. One possible division of nucleotide sequence is that the predominant selective force on a particular nucleotide can be attributed to just one gene. While this arrangement has been observed in regions in which one gene is structured and the other is disordered, we sought to explore how overlapping genes balance constraints when both protein products are structured over the same sequence. We use a combination of sequence analysis, functional assays, and selection experiments to examine an overlapped region in HIV-1 that encodes helical regions in both Env and Rev. We find that functional segregation occurs even in this overlap, with each protein spacing its functional residues in a manner that allows a mutable non-binding face of one helix to encode important functional residues on a charged face in the other helix. Additionally, our experiments reveal novel and critical functional residues in Env and have implications for the therapeutic targeting of HIV-1.

Selection for infectivity profiles in slow and fast epidemics, and the rise of SARS-CoV-2 variants.

Evaluating the characteristics of emerging SARS-CoV-2 variants of concern is essential to inform pandemic risk assessment. A variant may grow faster if it produces a larger number of secondary infections ("R advantage") or if the timing of secondary infections (generation time) is better. So far, assessments have largely focused on deriving the R advantage assuming the generation time was unchanged. Yet, knowledge of both is needed to anticipate the impact. Here, we develop an analytical framework to investigate the contribution of both the R advantage and generation time to the growth advantage of a variant. It is known that selection on a variant with larger R increases with levels of transmission in the community. We additionally show that variants conferring earlier transmission are more strongly favored when the historical strains have fast epidemic growth, while variants conferring later transmission are more strongly favored when historical strains have slow or negative growth. We develop these conceptual insights into a new statistical framework to infer both the R advantage and generation time of a variant. On simulated data, our framework correctly estimates both parameters when it covers time periods characterized by different epidemiological contexts. Applied to data for the Alpha and Delta variants in England and in Europe, we find that Alpha confers a+54% [95% CI, 45-63%] R advantage compared to previous strains, and Delta +140% [98-182%] compared to Alpha, and mean generation times are similar to historical strains for both variants. This work helps interpret variant frequency dynamics and will strengthen risk assessment for future variants of concern.

Mutations in genes of the SARS-CoV-2 virus have generated new variants of concern, like Alpha, Delta, and more recently Omicron. These strains contain genetic modifications that help the virus spread more easily as well as altering the severity of the illness it causes. This has led to rising numbers of infections, known as epidemic waves, in many parts of the world. Tracking new variants of concern is crucial to protecting the public. To do this, scientists monitor how many people one person with the virus can infect, also known as the number of secondary infections. They may also measure when in the course of the illness an individual may pass along the virus to others. Together, these metrics help determine how fast and large an outbreak caused by a new variant will grow. The more people the new variant infects and the quicker it spreads, the more likely it is to replace existing strains of the virus. So far, most studies have assumed that the growth rate of a new variant solely depends on the number of secondary infections, and the timing of secondary infections is often not considered. To address this, Blanquart et al. built a mathematical model that combines both these parameters to determine the growth rate of new viral strains. The model showed that variants which rapidly cause secondary infections have a larger growth advantage over existing strains when the virus is more easily transmitted between individuals and the epidemic spreads rapidly. But when there is less transmission and the epidemic is declining, variants that generate secondary infections after a longer time have an advantage. For example, when control measures like mask wearing or social distancing are in place, delayed secondary infections may be more advantageous. Blanquart et al. then applied their model to data from the Alpha and Delta variant outbreaks in the United Kingdom. They found that Alpha and Delta did not change the timing of secondary infections compared to previously circulating strains. But the Alpha variant had a 54% transmission advantage over previous strains and the Delta variant had a 140% transmission advantage over Alpha. Taken together, these findings suggest that the timing of secondary infections and transmission rates both play an important role in how quickly a virus spreads. The new mathematical model created by Blanquart et al. may help epidemiologists better predict the trajectory of new SARS-CoV-2 variants and determine how to best control their spread.

Pandemics, past, and present: The role of biological anthropology in interdisciplinary pandemic studies

Biological anthropologists are ideally suited for the study of pandemics given their strengths in human biology, health, culture, and behavior, yet pandemics have historically not been a major focus of research. The COVID-19 pandemic has reinforced the need to understand pandemic causes and unequal consequences at multiple levels. Insights from past pandemics can strengthen the knowledge base and inform the study of current and future pandemics through an anthropological lens. In this paper, we discuss the distinctive social and epidemiological features of pandemics, as well as the ways in which biological anthropologists have previously studied infectious diseases, epidemics, and pandemics. We then review interdisciplinary research on three pandemics-1918 influenza, 2009 influenza, and COVID-19-focusing on persistent social inequalities in morbidity and mortality related to sex and gender;race, ethnicity, and Indigeneity;and pre-existing health and disability. Following this review of the current state of pandemic research on these topics, we conclude with a discussion of ways biological anthropologists can contribute to this field moving forward. Biological anthropologists can add rich historical and cross-cultural depth to the study of pandemics, provide insights into the biosocial complexities of pandemics using the theory of syndemics, investigate the social and health impacts of stress and stigma, and address important methodological and ethical issues. As COVID-19 is unlikely to be the last global pandemic, stronger involvement of biological anthropology in pandemic studies and public health policy and research is vital.