A Drug-Free Pathogen Capture and Neutralizing Nasal Spray to Prevent Emerging Respiratory Infections (preprint)

Respiratory infections pose a global health crisis. Vaccines are pathogen specific, and new vaccines are needed for mutants and emerging pathogens. Here, we report a drug free prophylactic platform - a Pathogen Capture and Neutralizing Spray (PCANS) that acts via a multi-pronged approach to prevent a broad spectrum of respiratory infections. PCANS forms a protective coating in the nasal cavity that enhances the capture of large respiratory droplets. The coating acts as a physical barrier against a broad spectrum of viruses and bacteria, and rapidly neutralizes them, reducing the pathogen load by >99.99%. In mice, PCANS showed nasal retention for at least 8 h and was safe for daily administration. A single prophylactic dose of PCANS protected mice against supra-lethal dosages of a mouse-adapted H1N1 Influenza virus (PR8), reduced lung viral titer by >99.99%, improved survival, and suppressed pathological manifestations. Together, our data suggest PCANS as a promising daily-use prophylactic approach against current and emerging respiratory infections.

Media use and vaccine resistance.

Public health requires collective action-the public best addresses health crises when individuals engage in prosocial behaviors. Failure to do so can have dire societal and economic consequences. This was made clear by the disjointed, politicized response to COVID-19 in the United States. Perhaps no aspect of the pandemic exemplified this challenge more than the sizeable percentage of individuals who delayed or refused vaccination. While scholars, practitioners, and the government devised a range of communication strategies to persuade people to get vaccinated, much less attention has been paid to where the unvaccinated could be reached. We address this question using multiple waves of a large national survey as well as various secondary data sets. We find that the vaccine resistant seems to predictably obtain information from conservative media outlets (e.g. Fox News) while the vaccinated congregate around more liberal outlets (e.g. MSNBC). We also find consistent evidence that vaccine-resistant individuals often obtain COVID-19 information from various social media, most notably Facebook, rather than traditional media sources. Importantly, such individuals tend to exhibit low institutional trust. While our results do not suggest a failure of sites such as Facebook's institutional COVID-19 efforts, as the counterfactual of no efforts is unknown, they do highlight an opportunity to reach those who are less likely to take vital actions in the service of public health.

A 50-state survey study of thoughts of suicide and social isolation among older adults in the United States.

BACKGROUND: We aimed to characterize the prevalence of social disconnection and thoughts of suicide among older adults in the United States, and examine the association between them in a large naturalistic study. METHODS: We analyzed data from 6 waves of a fifty-state non-probability survey among US adults conducted between February and December 2021. The internet-based survey collected the PHQ-9, as well as multiple measures of social connectedness. We applied multiple logistic regression to analyze the association between presence of thoughts of suicide and social disconnection. Exploratory analysis, using generalized random forests, examined heterogeneity of effects across sociodemographic groups. RESULTS: Of 16,164 survey respondents age 65 and older, mean age was 70.9 (SD 5.0); the cohort was 61.4 % female and 29.6 % male; 2.0 % Asian, 6.7 % Black, 2.2 % Hispanic, and 86.8 % White. A total of 1144 (7.1 %) reported thoughts of suicide at least several days in the prior 2 week period. In models adjusted for sociodemographic features, households with 3 or more additional members (adjusted OR 1.73, 95 % CI 1.28-2.33) and lack of social supports, particularly emotional supports (adjusted OR 2.60, 95 % CI 2.09-3.23), were independently associated with greater likelihood of reporting such thoughts, as was greater reported loneliness (adjusted OR 1.75, 95 % CI 1.64-1.87). The effects of emotional support varied significantly across sociodemographic groups. CONCLUSIONS: Thoughts of suicide are common among older adults in the US, and associated with lack of social support, but not with living alone. TRIAL REGISTRATION: NA.

Using General Messages to Persuade on a Politicized Scientific Issue

Politics and science have become increasingly intertwined. Salient scientific issues, such as climate change, evolution, and stem-cell research, become politicized, pitting partisans against one another. This creates a challenge of how to effectively communicate on such issues. Recent work emphasizes the need for tailored messages to specific groups. Here, we focus on whether generalized messages also can matter. We do so in the context of a highly polarized issue: extreme COVID-19 vaccine resistance. The results show that science-based, moral frame, and social norm messages move behavioral intentions, and do so by the same amount across the population (that is, homogeneous effects). Counter to common portrayals, the politicization of science does not preclude using broad messages that resonate with the entire population.

Frequency and degradation of SARS-CoV-2 markers N1, N2, and E in sewage.

Coronavirus disease 2019 (COVID-19) is an infectious disease that is mainly spread through aerosolized droplets containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is excreted in feces by infected individuals. Sewage surveillance has been applied widely to obtain data on the prevalence of COVID-19 in whole communities. We used SARS-CoV-2 gene targets N1, N2, and E to determine the prevalence of COVID-19 at both municipal and building levels. Frequency analysis of wastewater testing indicated that single markers detected only 85% or less of samples that were detected as positive for SARS-CoV-2 with the three markers combined, indicating the necessity of pairing markers to lower the false-negative rate. The best pair of markers in both municipal and building level monitoring was N1 and N2, which correctly identified 98% of positive samples detected with the three markers combined. The degradation rates of all three targets were assessed at two different temperatures (25 and 35 °C) as a possible explanation for observed differences between markers in frequency. Results indicated that all three RNA targets degrade at nearly the same rate, indicating that differences in degradation rate are not responsible for the observed differences in marker frequency.

Depressive symptoms and conspiracy beliefs

Conspiratorial beliefs can endanger individuals and societies by increasing the likelihood of harmful behaviors such as the flouting of public health guidelines. While scholars have identified various correlates of conspiracy beliefs, one factor that has received scant attention is depressive symptoms. We use three large surveys to explore the connection between depression and conspiracy beliefs. We find a consistent association, with the extent of the relationship depending on individual and situational factors. Interestingly, those from relatively advantaged demographic groups (i.e., White, male, high income, educated) exhibit a stronger relationship between depression and conspiracy beliefs than those not from such groups. Furthermore, situational variables that ostensibly increase stress-such as having COVID-19 or parenting during COVID-19-exacerbate the relationship while those that seem to decrease stress, such as social support, vitiate it. The results provide insight about the development of targeted interventions and accentuate the need for theorizing about the mechanisms that lead depression to correlate with conspiracy beliefs. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Optimal spatial evaluation of a pro rata vaccine distribution rule for COVID-19.

The COVID-19 Vaccines Global Access (COVAX) is a World Health Organization (WHO) initiative that aims for an equitable access of COVID-19 vaccines. Despite potential heterogeneous infection levels across a country, countries receiving allotments of vaccines may follow WHO's allocation guidelines and distribute vaccines based on a jurisdictions' relative population size. Utilizing economic-epidemiological modeling, we benchmark the performance of this pro rata allocation rule by comparing it to an optimal one that minimizes the economic damages and expenditures over time, including a penalty representing the social costs of deviating from the pro rata strategy. The pro rata rule performs better when the duration of naturally- and vaccine-acquired immunity is short, when there is population mixing, when the supply of vaccine is high, and when there is minimal heterogeneity in demographics. Despite behavioral and epidemiological uncertainty diminishing the performance of the optimal allocation, it generally outperforms the pro rata vaccine distribution rule.

Siglec-9 Restrains Antibody-Dependent Natural Killer Cell Cytotoxicity against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the immunological profiles of natural killer (NK) cells. However, whether NK antiviral functions are impaired during severe coronavirus disease 2019 (COVID-19) and what host factors modulate these functions remain unclear. We found that NK cells from hospitalized COVID-19 patients degranulate less against SARS-CoV-2 antigen-expressing cells (in direct cytolytic and antibody-dependent cell cytotoxicity [ADCC] assays) than NK cells from mild COVID-19 patients or negative controls. The lower NK degranulation was associated with higher plasma levels of SARS-CoV-2 nucleocapsid antigen. Phenotypic and functional analyses showed that NK cells expressing the glyco-immune checkpoint Siglec-9 elicited higher ADCC than Siglec-9- NK cells. Consistently, Siglec-9+ NK cells exhibit an activated and mature phenotype with higher expression of CD16 (FcγRIII; mediator of ADCC), CD57 (maturation marker), and NKG2C (activating receptor), along with lower expression of the inhibitory receptor NKG2A, than Siglec-9- CD56dim NK cells. These data are consistent with the concept that the NK cell subpopulation expressing Siglec-9 is highly activated and cytotoxic. However, the Siglec-9 molecule itself is an inhibitory receptor that restrains NK cytotoxicity during cancer and other viral infections. Indeed, blocking Siglec-9 significantly enhanced the ADCC-mediated NK degranulation and lysis of SARS-CoV-2-antigen-positive target cells. These data support a model in which the Siglec-9+ CD56dim NK subpopulation is cytotoxic even while it is restrained by the inhibitory effects of Siglec-9. Alleviating the Siglec-9-mediated restriction on NK cytotoxicity may further improve NK immune surveillance and presents an opportunity to develop novel immunotherapeutic tools against SARS-CoV-2 infected cells. IMPORTANCE One mechanism that cancer cells use to evade natural killer cell immune surveillance is by expressing high levels of sialoglycans, which bind to Siglec-9, a glyco-immune checkpoint molecule on NK cells. This binding inhibits NK cell cytotoxicity. Several viruses, such as hepatitis B virus (HBV) and HIV, also use a similar mechanism to evade NK surveillance. We found that NK cells from SARS-CoV-2-hospitalized patients are less able to function against cells expressing SARS-CoV-2 Spike protein than NK cells from SARS-CoV-2 mild patients or uninfected controls. We also found that the cytotoxicity of the Siglec-9+ NK subpopulation is indeed restrained by the inhibitory nature of the Siglec-9 molecule and that blocking Siglec-9 can enhance the ability of NK cells to target cells expressing SARS-CoV-2 antigens. Our results suggest that a targetable glyco-immune checkpoint mechanism, Siglec-9/sialoglycan interaction, may contribute to the ability of SARS-CoV-2 to evade NK immune surveillance.

Assessing uptake of COVID-19 preventive measures among persons aged 13-80 years during lockdown in Wakiso, Uganda: a cross-sectional study

Background: The unprecedented spread of COVID-19 presents a serious public health concern. However, uptake of COVID-19-related preventive behaviors remains unknown. This study aimed to investigate current uptake of COVID-19 preventive measures and their associated factors in Wakiso, Uganda. Subjects and Method: A cross-sectional study was conducted in Wakiso, Uganda from April to September 2020. A total of 1,014 study subjects aged 13-80 years in the population health survey (PHS) who self-reported following any of the COVID-19 preventive behavioral strategies during lockdown was selected. The dependent variable was COVID-19 preventive measures. Independent variables were gender, age, education, marital status, religion, occupation. The data were collected by questionnaire and analyzed using Modified Poisson regression test.

Exertional desaturations after COVID-19: A case for PFO closure.

We present a case of a woman with past medical history notable for mild COVID-19 infection who presented with dyspnea on exertion, then developed progressively worsening exertional desaturations and was found to have a patent foramen ovale (PFO). Extensive cardiopulmonary testing revealed no clear alternate etiology for her symptoms. After much discussion, she underwent successful closure of the PFO with complete resolution of her symptoms and significantly improved exertional desaturation.

Depressive symptoms and conspiracy beliefs

Conspiratorial beliefs can endanger individuals and societies by increasing the likelihood of harmful behaviors such as the flouting of public health guidelines. While scholars have identified various correlates of conspiracy beliefs, one factor that has received scant attention is depressive symptoms. We use three large surveys to explore the connection between depression and conspiracy beliefs. We find a consistent association, with the extent of the relationship depending on individual and situational factors. Interestingly, those from relatively advantaged demographic groups (i.e., White, male, high income, educated) exhibit a stronger relationship between depression and conspiracy beliefs than those not from such groups. Furthermore, situational variables that ostensibly increase stress-such as having COVID-19 or parenting during COVID-19-exacerbate the relationship while those that seem to decrease stress, such as social support, vitiate it. The results provide insight about the development of targeted interventions and accentuate the need for theorizing about the mechanisms that lead depression to correlate with conspiracy beliefs.

Correlation of Binding and Neutralizing Antibodies against SARS-CoV-2 Omicron Variant in Infection-Naïve and Convalescent BNT162b2 Recipients.

In vaccine clinical trials, both binding antibody (bAb) levels and neutralization antibody (nAb) titers have been shown to be correlates of SARS-CoV-2 vaccine efficacy. We report a strong correlation bAb and nAb responses against the SARS-CoV-2 Omicron (BA.1) variant in infection-naïve and previously infected (convalescent) individuals after one and two doses of BNT162b2 vaccination. The vaccine-induced bAb levels against Omicron were significantly lower compared to previous variants of concern in both infection-naive and convalescent individuals, with the convalescent individuals showing significantly higher bAb compared to the naïve individuals at all timepoints. The finding that bAb highly correlated with nAb provides evidence for utilizing binding antibody assays as a surrogate for neutralizing antibody assays. Our data also revealed that after full vaccination, a higher percentage of individuals had undetectable Omicron nAb (58.6% in naive individuals, 7.4% in convalescent individuals) compared to the percentage of individuals who had negative Omicron bAb (0% in naive individuals, 0% in convalescent individuals). The discordance between bAb and nAb activities and the high degree of immune escape by Omicron may explain the high frequency of Omicron infections after vaccination.

New­onset neuropsychiatric sequelae and 'long­COVID' syndrome (Review).

The ongoing coronavirus disease 2019 (COVID-19) pandemic has had a widespread impact on individuals' mental health through indirect psychological and social mechanisms, related to factors such as fear of infection or death, social isolation, lack of social support and financial instability. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has also been associated with the development or recurrence of neuropsychiatric symptoms, both during the acute phase, as well as during the post-acute 'long-COVID' phase. In addition to the COVID-19 survivors with a mental health history that are at a high risk of experiencing a range of neuropsychiatric symptoms following resolution of acute COVID-19, there is accumulating evidence that a diagnosis of COVID-19 may also be associated with new-onset neuropsychiatric morbidity among survivors without pre-existing mental health disorders. In particular, studies investigating the incidence of post-acute neuropsychiatric sequelae, based mostly on retrospective cohort study designs and data from national health registries, have reported the development of new-onset manifestations, including depression, anxiety, psychotic symptoms, sleep disturbances and fatigue. Nevertheless, when COVID-19 survivors were compared with SARS-CoV-2-negative controls and especially survivors of other disorders (such as influenza), the findings regarding the risk of incident neuropsychiatric manifestations varied among studies. While there is evidence of an association between SARS-CoV-2 infection and the subsequent occurrence of new-onset neuropsychiatric symptoms, especially among patients with increased disease severity, further research using methodological approaches less susceptible to confounding bias is required to establish causal relationships.

Digitalization of Online Classes Among Higher Secondary Students in the Emerging Shift of Post Covid-19 (Second Wave)

The second wave of COVID-19 in India has left higher secondary school students befuddled, unhappy, and unsure about their future. During the second wave of the COVID-19 epidemic, a number of factors influence the effectiveness of online learning. Hence, the main objective of this research paper is focused on understanding the factors influencing online learning among higher secondary students. Researchers identified variables such as attitude, tools and technology, and quality of teaching and social support through extensive literature review. The research study adopted snowball sampling technique and used a survey-based online questionnaire for collecting the data;responses were obtained from 394 respondents from the state of Kerala in India. PLS-SEM was used to test the proposed hypotheses. The results of the study indicate that quality of teaching is the only factor that impacts the effectiveness of online classes among higher secondary students. Attitude, technology and tools, and social support are observed to have insignificant impact on online learning effectiveness. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Using General Messages to Persuade on a Politicized Scientific Issue

Politics and science have become increasingly intertwined. Salient scientific issues, such as climate change, evolution, and stem-cell research, become politicized, pitting partisans against one another. This creates a challenge of how to effectively communicate on such issues. Recent work emphasizes the need for tailored messages to specific groups. Here, we focus on whether generalized messages also can matter. We do so in the context of a highly polarized issue: extreme COVID-19 vaccine resistance. The results show that science-based, moral frame, and social norm messages move behavioral intentions, and do so by the same amount across the population (that is, homogeneous effects). Counter to common portrayals, the politicization of science does not preclude using broad messages that resonate with the entire population.