Publications by authors named "Alexander Greninger"

Unlabelled: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues its largely aseasonal spread with millions of cases per year. Highly sensitive, point-of-care testing is critical for rapid detection of coronavirus disease 2019 (COVID-19) cases and initiation of antiviral therapy to avert adverse health outcomes and reduce onward transmission of the virus. While hundreds of COVID-19 diagnostics received emergency use authorization from the FDA during the pandemic, significantly fewer have navigated the course to FDA clearance or approval.

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Unlabelled: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections and hospitalization in infants and the elderly. Newly approved vaccines and the prophylactic antibody nirsevimab have heightened interest in RSV immunologic surveillance, necessitating the development of high-throughput assays assessing anti-RSV neutralizing activity. Quantitative viral neutralization remains the best correlate of protection for RSV infection and the gold standard for RSV immunological testing.

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Congregate homeless shelters are disproportionately affected by infectious disease outbreaks. We describe enterovirus epidemiology across 23 adult and family shelters in King County, Washington, USA, during October 2019-May 2021, by using repeated cross-sectional respiratory illness and environmental surveillance and viral genome sequencing. Among 3,281 participants >3 months of age, we identified coxsackievirus A21 (CVA21) in 39 adult residents (3.

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  • Paramyxoviruses, such as measles and Nipah, pose significant public health risks and have pandemic potential, with HPIV3 being a major cause of illness among vulnerable populations.
  • * There are currently no approved vaccines or treatments for HPIV3, but neutralizing monoclonal antibodies (mAbs) could be a promising strategy despite challenges from viral resistance due to mutations.
  • * The study presents cryo-electron tomography structures showing how mutated HPIV3 can evade neutralization by mAbs by altering the interaction between viral proteins, providing insights that could inform future mAb design.
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  • Human parainfluenza virus 3 (HPIV3) infection relies on the combined actions of the hemagglutinin-neuraminidase (HN) and fusion protein (F) to facilitate virus-cell membrane fusion for infection.
  • Unlike laboratory-adapted strains, field strains of HPIV3 have different cleavage motifs for the F protein, which are cleaved by specific, unidentified proteases found in limited cell types.
  • The study highlights that extracellular serine proteases, like TMPRSS2 and TMPRSS13, can activate the F protein for infectious virus release, suggesting that the activation process depends on the availability of these proteases in host cells.
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Coronavirus disease 2019 (COVID-19) vaccines reduce severe disease and mortality and may lessen transmission, measured by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL). Evaluating vaccine associations in VL at COVID-19 diagnosis in 4 phase 3 randomized, placebo-controlled vaccine trials, July 2020 to July 2021, VL reductions were 2.78 log10 copies/mL (95% confidence interval [CI], 1.

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Little is known about the potential benefits of maternal immunization in the setting of high-risk pregnancies resulting in small-for-gestational-age (SGA) infants. This study compares transplacental transfer of maternal SARS-CoV-2 anti-Spike antibody in pregnancies with SGA compared to appropriate-for-gestational-age infants.

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  • Immunocompromised individuals face a higher risk of prolonged SARS-CoV-2 infections and severe COVID-19, raising concerns about the effectiveness of late-onset antiviral treatments.
  • In a study using an immunocompromised mouse model, it was found that early treatments like nirmatrelvir/ritonavir (paxlovid) or molnupiravir were only moderately effective, while the experimental drug 4'-fluorouridine (4'-FlU) showed significant benefits in reducing viral load.
  • Late-onset direct-acting antiviral (DAA) therapies were shown to effectively shorten the duration of viral replication in immunocompromised hosts, suggesting potential clinical applications to reduce severe disease risks in vulnerable
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The recently discovered methodologies to cultivate and genetically manipulate Treponema pallidum subsp. pallidum (T. pallidum) have significantly helped syphilis research, allowing the in vitro evaluation of antibiotic efficacy, performance of controlled studies to assess differential treponemal gene expression, and generation of loss-of-function mutants to evaluate the contribution of specific genetic loci to T.

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Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence.

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Doxycycline post-exposure prophylaxis (doxy-PEP) could significantly reduce syphilis incidence. However, the increase in intermittent doxycycline usage might select resistant Treponema pallidum (T. pallidum) strains.

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Filoviruses are some of the most lethal viruses in the modern world, and increasing numbers of filovirus species and genera have been discovered in recent years. Despite the potential severity of filovirus outbreaks in the human population, comparably few sensitive pan-filovirus RT-PCR assays have been described that might facilitate early detection and prevention. Here, we present a new pan-filovirus RT-PCR assay targeting the L polymerase gene for detection of all known mammalian filoviruses.

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Article Synopsis
  • Human influenza viruses evolve to avoid detection by the immune system, but the impact of this evolution varies among different age groups.
  • Using a technique called deep mutational scanning, researchers studied how mutations in specific proteins affect antibody neutralization across various ages.
  • Findings indicate that younger individuals' sera are less effective against certain viral mutations that became prevalent after 2020, highlighting the differing immune responses across age demographics and their influence on virus evolution.
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Background: We evaluated the fully human polyclonal antibody product SAB-185 in a phase 3 trial for COVID-19.

Methods: Nonhospitalized high-risk adults within 7 days of symptom onset were randomized 1:1 to open-label SAB-185 3840 units/kg or casirivimab/imdevimab 1200 mg. Noninferiority comparison was undertaken for pre-Omicron population (casirivimab/imdevimab expected to be fully active) and superiority comparison for the Omicron population (casirivimab/imdevimab not expected to be active).

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Doxycycline post-exposure prophylaxis (doxy-PEP) could significantly reduce syphilis incidence. However, the increase in intermittent doxycycline usage might select resistant ( ) strains. To assess whether resistance to doxycycline could be induced in this pathogen, we exposed the SS14 strain in vitro both intermittently and continuously to a sub-bactericidal doxycycline concentration that still exerts antibiotic pressure.

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  • Human rhinoviruses (RV) cause the common cold but can lead to severe health issues, especially in those with weakened immune systems.
  • Researchers sequenced over 1,000 RV genomes from both symptomatic and asymptomatic individuals during two distinct time frames in Washington State to study viral evolution.
  • The study found high genetic diversity, including the presence of various genotypes and recombination events, highlighting the need to explore the relationship between RV genetic variations and immune responses for better long-term strategies.
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Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion are one potential therapeutic approach but have not yet been structurally characterized or advanced to clinical use.

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Background: Histologic and serologic studies suggest the induction of local and systemic Treponema pallidum-specific CD4+ T-cell responses to T. pallidum infection. We hypothesized that T.

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  • Cytomegalovirus (CMV) disease can occur before hematopoietic cell transplantation (HCT) and negatively affect post-transplant outcomes, but the effects of reactivation prior to the procedure were previously unclear.
  • A study found that 11% of HCT candidates experienced pre-HCT CMV reactivation, with lymphopenia identified as a strong risk factor.
  • The presence of pre-HCT CMV reactivation was linked to higher risks of further reactivation and related diseases within the first year after HCT, supporting the need for regular surveillance and potential antiviral therapy in high-risk patients.
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A healthcare provider unknowingly treated a patient with mpox and subsequently developed ocular mpox without rash. She breastfed during illness; her infant was not infected. This report addresses 3 challenges in mpox management and control: diagnosis in the absence of rash, exposures in healthcare settings, and management of lactating patients.

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