Oscillating spatiotemporal patterns of COVID-19 in the United States.

COVID-19 case rates in the US wax and wane in wave-like patterns over time, but the spatial patterns of these temporal epidemic waves have not been well characterized. By analyzing state- and county-level COVID-19 case rate data for spatiotemporal decomposition modes and oscillatory patterns, we demonstrate that the transmission dynamics of COVID-19 feature recurrent spatiotemporal patterns. In addition to the well-recognized national-level annual mid-winter surges, we demonstrate a prominent but previously unrecognized six-month north-south oscillation in the eastern US (Eastern US COVID-19 Oscillator-EUCO) that gives rise to regional sub-epidemics and travelling epidemic waves.

A Self-Fulfilling Prophecy Pandemic: The 1977 "Russian Flu".

Surprisingly, the 1977 "Russian flu" H1N1 pandemic influenza virus was genetically indistinguishable from strains that had circulated decades earlier but had gone extinct in 1957. This essay puts forward the most plausible chronology to explain the reemergence of the 1977 H1N1 pandemic virus: (1) in January-February 1976, a self-limited small outbreak of a swine H1N1 influenza virus occurred among Army personnel at Fort Dix, New Jersey; (2) in March 1976, the US launched a nationwide H1N1 swine influenza vaccine program; (3) other countries then also launched their own H1N1 R&D efforts; (4) a new H1N1 outbreak, genetically unrelated to the Fort Dix swine virus but indistinguishable from previously extinct H1N1 viruses, was detected early in 1977 in China; (5) the leading Chinese influenza virologist later disclosed that the Chinese military had conducted large H1N1 vaccine R&D studies in 1976. It is likely that the resurrected H1N1 influenza viruses were laboratory-stored strains that were unfrozen and studied as part of the emergency response to a perceived epidemic threat, and that accidentally escaped.

Multiplexed Screening Using Barcoded Aptamer Technology to Identify Oligonucleotide-Based Targeting Reagents.

Recent FDA approvals of mRNA vaccines, short-interfering RNAs, and antisense oligonucleotides highlight the success of oligonucleotides as therapeutics. Aptamers are excellent affinity reagents that can selectively label protein biomarkers, but their clinical application has lagged. When formulating a given aptamer for use, molecular design details can determine biostability and biodistribution; therefore, extensive postselection manipulation is often required for each new design to identify clinically useful reagents harboring improved pharmacokinetic properties.

Identification and characterization of a nonbiological small-molecular mimic of a Zika virus conformational neutralizing epitope.

Antigenic similarities between Zika virus (ZIKV) and other flaviviruses pose challenges to the development of virus-specific diagnostic tools and effective vaccines. Starting with a DNA-encoded one-bead-one-compound combinatorial library of 508,032 synthetic, non-natural oligomers, we selected and characterized small molecules that mimic ZIKV epitopes. High-throughput fluorescence-activated cell sorter-based bead screening was used to select molecules that bound IgG from ZIKV-immune but not from dengue-immune sera.

Origins of the problematic E in SEIR epidemic models.

During the COVID-19 pandemic, over one thousand papers were published on "Susceptible-Exposed-Infectious-Removed" (SEIR) epidemic computational models. The English word "exposed" in its vernacular and public health usage means a state of having been in contact with an infectious individual, but not necessarily infected. In contrast, the term "exposed" in SEIR modeling usage typically stands for a state of already being infected but not yet being infectious to others, a state more properly termed "latently infected.

Differentiation SELEX approach identifies RNA aptamers with different specificities for HIV-1 capsid assembly forms.

The HIV-1 capsid protein (CA) assumes distinct assembly forms during replication, each presenting unique, solvent-accessible surfaces that facilitate multifaceted functions and host factor interactions. However, contributions of individual CA assemblies remain unclear, as the evaluation of CA in cells presents several technical challenges. To address this need, we sought to identify CA assembly form-specific aptamers.

Targeting lung cancer with clinically relevant EGFR mutations using anti-EGFR RNA aptamer.

A significant fraction of non-small cell lung cancer (NSCLC) cases are due to oncogenic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). Anti-EGFR antibodies have shown limited clinical benefit for NSCLC, whereas tyrosine kinase inhibitors (TKIs) are effective, but resistance ultimately occurs. The current landscape suggests that alternative ligands that target wild-type and mutant EGFRs are desirable for targeted therapy or drug delivery development.

Minimizing amplification bias during reverse transcription for in vitro selections.

ystematic volution of igands through ponential enrichment (SELEX) is widely used to identify functional nucleic acids, such as aptamers and ribozymes. Ideally, selective pressure drives the enrichment of sequences that display the function of interest (binding, catalysis, etc.).

Valency and affinity control of aptamer-conjugated nanoparticles for selective cancer cell targeting.

Nanoparticles (NPs) are commonly functionalized using targeting ligands to drive their selective uptake in cells of interest. Typical target cell types are cancer cells, which often overexpress distinct surface receptors that can be exploited for NP therapeutics. However, these targeted receptors are also moderately expressed in healthy cells, leading to unwanted off-tumor toxicities.

FASTAptameR 2.0: A web tool for combinatorial sequence selections.

Combinatorial selections are powerful strategies for identifying biopolymers with specific biological, biomedical, or chemical characteristics. Unfortunately, most available software tools for high-throughput sequencing analysis have high entrance barriers for many users because they require extensive programming expertise. FASTAptameR 2.

An RNA aptamer that shifts the reduction potential of metabolic cofactors.

The discovery of ribozymes has inspired exploration of RNA's potential to serve as primordial catalysts in a hypothesized RNA world. Modern oxidoreductase enzymes employ differential binding between reduced and oxidized forms of redox cofactors to alter cofactor reduction potential and enhance the enzyme's catalytic capabilities. The utility of differential affinity has been underexplored as a chemical strategy for RNA.

Development of Nanomaterial-Modified Impedimetric Aptasensor-A Single-Step Strategy for 3,4-Methylenedioxymethylamphetamine Detection.

Developing rapid, sensitive detection methods for 3,4-Methylenedioxymethylamphetamine (MDMA) is crucial to reduce its current misuse in the world population. With that aim, we developed an aptamer-modified tin nanoparticle (SnNP)-based nanoarchitecture as an electrochemical sensor in this study. This platform exhibited a high electron transfer rate with enhanced conductivity arising from its large surface area in comparison to the bare electrode.

Aptamers Targeting Hallmark Proteins of Neurodegeneration.

Neurodegeneration is a progressive deterioration of neural structures leading to cognitive or motor impairment of the affected patient. There is still no effective therapy for any of the most common neurodegenerative diseases (NDs) such as Alzheimer's or Parkinson's disease. Although NDs exhibit distinct clinical characteristics, many are characterized by the accumulation of misfolded proteins or peptide fragments in the brain and/or spinal cord.

Contribution of Coronavirus-Specific Immunoglobulin G Responses to Complement Overactivation in Patients with Severe Coronavirus Disease 2019.

Background: Excessive complement activation has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19), but the mechanisms leading to this response remain unclear.

Methods: We measured plasma levels of key complement markers, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies against SARS-CoV-2 and seasonal human common cold coronaviruses (CCCs) in hospitalized patients with COVID-19 of moderate (n = 18) and critical severity (n = 37) and in healthy controls (n = 10).

Results: We confirmed that complement activation is systemically increased in patients with COVID-19 and is associated with a worse disease outcome.

Cancer immunomodulation using bispecific aptamers.

Evasion of immune destruction is a major hallmark of cancer. Recent US Food and Drug Administration (FDA) approvals of various immunomodulating therapies underline the important role that reprogramming the immune system can play in combating this disease. However, a wide range of side effects still limit the therapeutic potential of immunomodulators, suggesting a need for more precise reagents with negligible off-target and on-target/off-tumor effects.

Estimating the Impact of Low Influenza Activity in 2020 on Population Immunity and Future Influenza Seasons in the United States.

Background: Influenza activity in the 2020-2021 season was remarkably low, likely due to implementation of public health preventive measures such as social distancing, mask wearing, and school closure. With waning immunity, the impact of low influenza activity in the 2020-2021 season on the following season is unknown.

Methods: We built a multistrain compartmental model that captures immunity over multiple influenza seasons in the United States.

Selection and identification of an RNA aptamer that specifically binds the HIV-1 capsid lattice and inhibits viral replication.

The HIV-1 capsid core participates in several replication processes. The mature capsid core is a lattice composed of capsid (CA) monomers thought to assemble first into CA dimers, then into ∼250 CA hexamers and 12 CA pentamers. CA assembly requires conformational flexibility of each unit, resulting in the presence of unique, solvent-accessible surfaces.

Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques.

Live oral vaccines have been explored for their protective efficacy against respiratory viruses, particularly for adenovirus serotypes 4 and 7. The potential of a live oral vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, remains unclear. In this study, we assessed the immunogenicity of live SARS-CoV-2 delivered to the gastrointestinal tract in rhesus macaques and its protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge.

A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity.

Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV, MERS-CoV and endemic human coronaviruses (HCoVs).