Informative Censoring-A Cause of Bias in Estimating COVID-19 Mortality Using Hospital Data.

(1) Background: Several retrospective observational analyzed treatment outcomes for COVID-19; (2) Methods: Inverse probability of censoring weighting (IPCW) was applied to correct for bias due to informative censoring in database of hospitalized patients who did and did not receive convalescent plasma; (3) Results: When compared with an IPCW analysis, overall mortality was overestimated using an unadjusted Kaplan-Meier curve, and hazard ratios for the older age group compared to the youngest were underestimated using the Cox proportional hazard models and 30-day mortality; (4) Conclusions: An IPCW analysis provided stabilizing weights by hospital admission.

Intranasal antisepsis to reduce influenza virus transmission in an animal model.

Background: Seasonal influenza annually causes significant morbidity and mortality, and unpredictable respiratory virus zoonoses, such as the current COVID-19 pandemic, can threaten the health and lives of millions more. Molecular iodine (I ) is a broad-spectrum, pathogen-nonspecific antiseptic agent that has demonstrated antimicrobial activity against a wide range of bacteria, virus, and fungi.

Methods: We investigated a commercially available antiseptic, a non-irritating formulation of iodine (5% povidone-iodine) with a film-forming agent that extends the duration of the iodine's antimicrobial activity, for its ability to prevent influenza virus transmission between infected and susceptible animals in the guinea pig model of influenza virus transmission.

Discovery and intranasal administration of a SARS-CoV-2 broadly acting neutralizing antibody with activity against multiple Omicron subvariants.

Background: The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern, in particular the newly emerged Omicron (B.1.1.

Non-respiratory particles emitted by guinea pigs in airborne disease transmission experiments.

Animal models are often used to assess the airborne transmissibility of various pathogens, which are typically assumed to be carried by expiratory droplets emitted directly from the respiratory tract of the infected animal. We recently established that influenza virus is also transmissible via "aerosolized fomites," micron-scale dust particulates released from virus-contaminated surfaces (Asadi et al. in Nat Commun 11(1):4062, 2020).

Expiratory aerosol particle escape from surgical masks due to imperfect sealing.

Wearing surgical masks or other similar face coverings can reduce the emission of expiratory particles produced via breathing, talking, coughing, or sneezing. Although it is well established that some fraction of the expiratory airflow leaks around the edges of the mask, it is unclear how these leakage airflows affect the overall efficiency with which masks block emission of expiratory aerosol particles. Here, we show experimentally that the aerosol particle concentrations in the leakage airflows around a surgical mask are reduced compared to no mask wearing, with the magnitude of reduction dependent on the direction of escape (out the top, the sides, or the bottom).

The Effect of Convalescent Plasma Therapy on Mortality Among Patients With COVID-19: Systematic Review and Meta-analysis.

To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from 10 randomized clinical trials, 20 matched control studies, 2 dose-response studies, and 96 case reports or case series. Studies published between January 1, 2020, and January 16, 2021, were identified through a systematic search of online PubMed and MEDLINE databases. Random effects analyses of randomized clinical trials and matched control data demonstrated that patients with COVID-19 transfused with convalescent plasma exhibited a lower mortality rate compared with patients receiving standard treatments.

The Effect of Convalescent Plasma Therapy on COVID-19 Patient Mortality: Systematic Review and Meta-analysis.

To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from 10 randomized clinical trials (RCT), 20 matched-control studies, two dose-response studies, and 96 case-reports or case series. Studies published between January 1, 2020 to January 16, 2021 were identified through a systematic search of online PubMed and MEDLINE databases. Random effects analyses of RCT and matched-control data demonstrated that COVID-19 patients transfused with convalescent plasma exhibited a lower mortality rate compared to patients receiving standard treatments.

Transfusion reactions associated with COVID-19 convalescent plasma therapy for SARS-CoV-2.

Background: Convalescent plasma (CP) for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown preliminary signs of effectiveness in moderate to severely ill patients in reducing mortality. While studies have demonstrated a low risk of serious adverse events, the comprehensive incidence and nature of the spectrum of transfusion reactions to CP is unknown. We retrospectively examined 427 adult inpatient CP transfusions to determine incidence and types of reactions, as well as clinical parameters and risk factors associated with transfusion reactions.

Individuals with Down syndrome hospitalized with COVID-19 have more severe disease.

Purpose: Rare genetic conditions like Down syndrome (DS) are historically understudied. Infection is a leading cause of mortality in DS, along with cardiac anomalies. Currently, it is unknown how the COVID-19 pandemic affects individuals with DS.

Humoral response and PCR positivity in patients with COVID-19 in the New York City region, USA: an observational study.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The proportion of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can be detected up to 3 months after symptom resolution.

Efficacy of masks and face coverings in controlling outward aerosol particle emission from expiratory activities.

The COVID-19 pandemic triggered a surge in demand for facemasks to protect against disease transmission. In response to shortages, many public health authorities have recommended homemade masks as acceptable alternatives to surgical masks and N95 respirators. Although mask wearing is intended, in part, to protect others from exhaled, virus-containing particles, few studies have examined particle emission by mask-wearers into the surrounding air.

Convalescent Plasma for the Treatment of Severe COVID-19 Infection in Cancer Patients.

Background: Patients with malignancy are particularly vulnerable to infection with Severe Acute Respiratory Disease-Coronavirus-2 (SARS-CoV-2) given their immunodeficiency secondary to their underlying disease and cancer-directed therapy. We report a case series of patients with cancer who received convalescent plasma, an investigational therapy for severe Coronavirus Disease 2019 (COVID-19).

Methods: Patients with cancer were identified who received convalescent plasma.

Convalescent plasma treatment of severe COVID-19: a propensity score-matched control study.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments. Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus replication before patients have mounted their own humoral immune responses.

Treatment with convalescent plasma in solid organ transplant recipients with COVID-19: Experience at large transplant center in New York City.

Solid organ transplant (SOT) recipients may be at higher risk for poor outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Convalescent plasma is an investigational therapy that may benefit immunosuppressed patients by providing passive immunity. Convalescent plasma was administered to hospitalized patients with coronavirus disease-2019 (COVID-19) at an academic transplant center in New York City.

Influenza A virus is transmissible via aerosolized fomites.

Influenza viruses are presumed, but not conclusively known, to spread among humans by several possible routes. We provide evidence of a mode of transmission seldom considered for influenza: airborne virus transport on microscopic particles called "aerosolized fomites." In the guinea pig model of influenza virus transmission, we show that the airborne particulates produced by infected animals are mainly non-respiratory in origin.

Effect of voicing and articulation manner on aerosol particle emission during human speech.

Previously, we demonstrated a strong correlation between the amplitude of human speech and the emission rate of micron-scale expiratory aerosol particles, which are believed to play a role in respiratory disease transmission. To further those findings, here we systematically investigate the effect of different 'phones' (the basic sound units of speech) on the emission of particles from the human respiratory tract during speech. We measured the respiratory particle emission rates of 56 healthy human volunteers voicing specific phones, both in isolation and in the context of a standard spoken text.

Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs.

Despite efforts to control influenza virus infection and transmission, influenza viruses still cause significant morbidity and mortality in the global human population each year. Most of the current vaccines target the immunodominant hemagglutinin surface glycoprotein of the virus. However, reduced severity of disease and viral shedding have also been linked to antibodies targeting the second viral surface glycoprotein, the neuraminidase.

Aerosol emission and superemission during human speech increase with voice loudness.

Mechanistic hypotheses about airborne infectious disease transmission have traditionally emphasized the role of coughing and sneezing, which are dramatic expiratory events that yield both easily visible droplets and large quantities of particles too small to see by eye. Nonetheless, it has long been known that normal speech also yields large quantities of particles that are too small to see by eye, but are large enough to carry a variety of communicable respiratory pathogens. Here we show that the rate of particle emission during normal human speech is positively correlated with the loudness (amplitude) of vocalization, ranging from approximately 1 to 50 particles per second (0.

The Future of Influenza Vaccines: A Historical and Clinical Perspective.

For centuries, the development of vaccines to prevent infectious disease was an empirical process. From smallpox variolation in Song dynasty China, through the polysaccharide capsule vaccines developed in the 1970s, vaccines were made either from the pathogen itself, treated in some way to render it attenuated or non-infectious, or from a closely related non-pathogenic strain. In recent decades, new scientific knowledge and technologies have enabled rational vaccine design in a way that was unimaginable before.

Antigenic sites in influenza H1 hemagglutinin display species-specific immunodominance.

Hemagglutination inhibition (HI) titers are a major correlate of protection for influenza-related illness. The influenza virus hemagglutinin possesses antigenic sites that are the targets of HI active antibodies. Here, a panel of mutant viruses each lacking a classically defined antigenic site was created to compare the species-specific immunodominance of the antigenic sites in a clinically relevant hemagglutinin.

An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses.

Although vaccines confer protection against influenza A viruses, antiviral treatment becomes the first line of defense during pandemics because there is insufficient time to produce vaccines. Current antiviral drugs are susceptible to drug resistance, and developing new antivirals is essential. We studied host defense peptides from the skin of the South Indian frog and demonstrated that one of these, which we named "urumin," is virucidal for H1 hemagglutinin-bearing human influenza A viruses.

Defining the antibody cross-reactome directed against the influenza virus surface glycoproteins.

Infection with influenza virus induces antibodies to the viral surface glycoproteins hemagglutinin and neuraminidase, and these responses can be broadly protective. To assess the breadth and magnitude of antibody responses, we sequentially infected mice, guinea pigs and ferrets with divergent H1N1 or H3N2 subtypes of influenza virus. We measured antibody responses by ELISA of an extensive panel of recombinant glycoproteins representing the viral diversity in nature.

Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation.

The host innate immune response is the first line of defense against pathogens and is orchestrated by the concerted expression of genes induced by microbial stimuli. Deregulated expression of these genes is linked to the initiation and progression of diseases associated with exacerbated inflammation. We identified topoisomerase 1 (Top1) as a positive regulator of RNA polymerase II transcriptional activity at pathogen-induced genes.