Modeling of ACE2 and antibodies bound to SARS-CoV-2 provides insights into infectivity and immune evasion.

Given the COVID-19 pandemic, there is interest in understanding ligand-receptor features and targeted antibody-binding attributes against emerging SARS-CoV-2 variants. Here, we developed a large-scale structure-based pipeline for analysis of protein-protein interactions regulating SARS-CoV-2 immune evasion. First, we generated computed structural models of the Spike protein of 3 SARS-CoV-2 variants (B.1.1.529, BA.2.12.1, and BA.5) bound either to a native receptor (ACE2) or to a large panel of targeted ligands (n = 282), which included neutralizing or therapeutic monoclonal antibodies. Moreover, by using the Barnes classification, we noted an overall loss of interfacial interactions (with gain of new interactions in certain cases) at the receptor-binding domain (RBD) mediated by substituted residues for neutralizing complexes in classes 1 and 2, whereas less destabilization was observed for classes 3 and 4. Finally, an experimental validation of predicted weakened therapeutic antibody binding was performed in a cell-based assay. Compared with the original Omicron variant (B.1.1.529), derivative variants featured progressive destabilization of antibody-RBD interfaces mediated by a larger set of substituted residues, thereby providing a molecular basis for immune evasion. This approach and findings provide a framework for rapidly and efficiently generating structural models for SARS-CoV-2 variants bound to ligands of mechanistic and therapeutic value.

Predicting Success: An Examination of the Predictive Validity of a Measure of Motivational-Developmental Dimensions in College Admissions.

Amid the COVID-19 pandemic, an unprecedented number of higher education institutions adopted test-optional admissions policies. The proliferation of these policies and the criticism of standardized admissions tests as unreliable predictors of applicants' postsecondary educational promise have prompted the reimagining of evaluative methodologies in college admissions. However, few institutions have designed and implemented new measures of applicants' potential for success, rather opting to redistribute the weight given to other variables such as high school course grades and high school GPA. We use multiple regression to investigate the predictive validity of a measure of non-cognitive, motivational-developmental dimensions implemented as part of a test-optional admissions policy at a large urban research university in the United States. The measure, composed of four short-answer essay questions, was developed based on the social-cognitive motivational and developmental-constructivist perspectives. Our findings suggest that scores derived from the measure make a statistically significant but small contribution to the prediction of undergraduate GPA and 4-year bachelor's degree completion. We also find that the measure does not make a statistically significant nor practical contribution to the prediction of 5-year graduation.

Trends in Euphorbia hirta Research: A 30-year Bibliometric Appraisal of the Present Realities

Euphorbia hirta L., is a common herb with global spread. Different parts of E. hirta are used in traditional medicine for the treatment of a variety of human and animal conditions, such as skin diseases, inflammation, digestive and respiratory disorders. This bibliometric study aimed to provide a panoramic view of the publication landscape in the last thirty years of Euphorbia hirta research. VOSviewer was used to analyze 603 documents retrieved from Scopus database during the period, 1992 to 2021. Dominant research themes in the last thirty years were centred on the application of crude extracts or isolated compounds from E. hirta against diabetes, oxidative stress, inflammation, tuberculosis, snake bite, gastro-intestinal disorders, respiratory infections, skin pathologies, bacterial, fungal and viral infections. Current paradigm shift in E. hirta research are targeted at improving the efficacy of phytomolecules against resistant bacterial pathogens and cancer cells via green synthesis of nanoparticles and the application of in silico technologies in predicting the activities of nano-phytomolecules against SARS-CoV-2 and the Dengue virus. This study recommends further research in the determination of the bioavailability of molecules in in vivo models. Researchers should carry out more preclinical investigations with the aim of establishing the pharmacokinetic and pharmacodynamic properties of phytocompounds instead of relying solely on in silico predictions.

COVID-19 dynamics in an Ohio prison.

Incarcerated individuals are a highly vulnerable population for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the transmission of respiratory infections within prisons and between prisons and surrounding communities is a crucial component of pandemic preparedness and response. Here, we use mathematical and statistical models to analyze publicly available data on the spread of SARS-CoV-2 reported by the Ohio Department of Rehabilitation and Corrections (ODRC). Results from mass testing conducted on April 16, 2020 were analyzed together with time of first reported SARS-CoV-2 infection among Marion Correctional Institution (MCI) inmates. Extremely rapid, widespread infection of MCI inmates was reported, with nearly 80% of inmates infected within 3 weeks of the first reported inmate case. The dynamical survival analysis (DSA) framework that we use allows the derivation of explicit likelihoods based on mathematical models of transmission. We find that these data are consistent with three non-exclusive possibilities: (i) a basic reproduction number >14 with a single initially infected inmate, (ii) an initial superspreading event resulting in several hundred initially infected inmates with a reproduction number of approximately three, or (iii) earlier undetected circulation of virus among inmates prior to April. All three scenarios attest to the vulnerabilities of prisoners to COVID-19, and the inability to distinguish among these possibilities highlights the need for improved infection surveillance and reporting in prisons.

A multistate assessment of population normalization factors for wastewater-based epidemiology of COVID-19.

Wastewater-based epidemiology (WBE) has become a valuable tool for monitoring SARS-CoV-2 infection trends throughout the COVID-19 pandemic. Population biomarkers that measure the relative human fecal contribution to normalize SARS-CoV-2 wastewater concentrations are needed for improved analysis and interpretation of community infection trends. The Centers for Disease Control and Prevention National Wastewater Surveillance System (CDC NWSS) recommends using the wastewater flow rate or human fecal indicators as population normalization factors. However, there is no consensus on which normalization factor performs best. In this study, we provided the first multistate assessment of the effects of flow rate and human fecal indicators (crAssphage, F+ Coliphage, and PMMoV) on the correlation of SARS-CoV-2 wastewater concentrations and COVID-19 cases using the CDC NWSS dataset of 182 communities across six U.S. states. Flow normalized SARS-CoV-2 wastewater concentrations produced the strongest correlation with COVID-19 cases. The correlation from the three human fecal indicators were significantly lower than flow rate. Additionally, using reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) significantly improved correlation values over samples that were analyzed with real-time reverse transcription quantitative polymerase chain reaction (rRT-qPCR). Our assessment shows that utilizing flow normalization with RT-ddPCR generate the strongest correlation between SARS-CoV-2 wastewater concentrations and COVID-19 cases.

Computational design of nanomolar-binding antibodies specific to multiple SARS-CoV-2 variants by engineering a specificity switch of antibody 80R using RosettaAntibodyDesign (RAbD) results in potential generalizable therapeutic antibodies for novel SARS-CoV-2 virus.

The human infectious disease COVID-19 caused by the SARS-CoV-2 virus has become a major threat to global public health. Developing a vaccine is the preferred prophylactic response to epidemics and pandemics. However, for individuals who have contracted the disease, the rapid design of antibodies that can target the SARS-CoV-2 virus fulfils a critical need. Further, discovering antibodies that bind multiple variants of SARS-CoV-2 can aid in the development of rapid antigen tests (RATs) which are critical for the identification and isolation of individuals currently carrying COVID-19. Here we provide a proof-of-concept study for the computational design of high-affinity antibodies that bind to multiple variants of the SARS-CoV-2 spike protein using RosettaAntibodyDesign (RAbD). Well characterized antibodies that bind with high affinity to the SARS-CoV-1 (but not SARS-CoV-2) spike protein were used as templates and re-designed to bind the SARS-CoV-2 spike protein with high affinity, resulting in a specificity switch. A panel of designed antibodies were experimentally validated. One design bound to a broad range of variants of concern including the Omicron, Delta, Wuhan, and South African spike protein variants.

Best Practice Recommendations for Stroke Vascular Imaging During Iodinated Contrast Shortage.

GE Healthcare© announced on April 19, 2022, that their main factory and distributor of iodinated contrast had experienced a temporary shutdown because of COVID-19 outbreak in Shanghai, China. This, along with other supply chain issues, led to a worldwide shortage of iodinated contrast agents, Omnipaque and Visipaque. Our Comprehensive Stroke Center was confronted with the cascading effect of this iodinated contrast material shortage. We took immediate steps to revise our protocols and processes to continue to provide high-quality care to our stroke patients. A multidisciplinary working group comprised of representatives of our stroke center, including vascular neurology, diagnostic neuroradiology, and neurovascular surgery, urgently met to brainstorm how to mitigate the shortage. We established parameters and local guidelines for the use of CT angiography, CT perfusion, and digital subtraction angiography for stroke patients. In this article, we propose "best practice" recommendations from a single Joint Commission approved Comprehensive Stroke Center that can be used as blueprint by other hospital systems when navigating potential future supply chain issues, to provide consistent high-quality stroke care.

Impact of Loneliness and Social Isolation on Mental Health Outcomes Among Individuals With Rheumatic Diseases During the COVID-19 Pandemic.

OBJECTIVE: The study objective was to assess mental and social health outcomes for individuals with rheumatic disease during the COVID-19 pandemic and evaluate the relationship of loneliness and social isolation with depression and anxiety. METHODS: We administered an international cross-sectional online survey to individuals with rheumatic disease(s) (≥18 years) between April 2020 and September 2020, with a follow-up survey from December 2020 to February 2021. We used questionnaires to evaluate loneliness (3-item UCLA Loneliness Scale [UCLA-3]), social isolation (Lubben Social Network Scale [LSNS-6]), depression (Patient Health Questionnaire [PHQ-9]), and anxiety (Generalized Anxiety Disorder 7-item [GAD-7] Scale). We used multivariable linear regression models to evaluate the cross-sectional associations of loneliness and social isolation with depression and anxiety at baseline. RESULTS: Seven hundred eighteen individuals (91.4% women, mean age: 45.4 ± 14.2 years) participated in the baseline survey, and 344 completed the follow-up survey. Overall, 51.1% of participants experienced loneliness (UCLA-3 score ≥6) and 30.3% experienced social isolation (LSNS-6 score <12) at baseline. Depression (PHQ-9 score ≥10) and anxiety (GAD-7 score ≥10) were experienced by 42.8% and 34.0% of participants at baseline, respectively. Multivariable models showed that experiencing both loneliness and social isolation, in comparison to experiencing neither, was significantly associated with an average 7.27 higher depression score (ß = 7.27; 95% confidence interval [CI]: 6.08-8.47) and 5.14 higher anxiety score (ß = 5.14; 95% CI: 4.00-6.28). CONCLUSION: Aside from showing substantial experience of loneliness and social isolation during the COVID-19 pandemic, our survey showed significant associations with depression and anxiety. Patient supports to address social health have potential implications for also supporting mental health.

Longitudinal Trends in Cardiovascular Risk Factor Profiles and Complications Among Patients Hospitalized for COVID-19 Infection: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry.

BACKGROUND: The COVID-19 pandemic has evolved through multiple phases characterized by new viral variants, vaccine development, and changes in therapies. It is unknown whether rates of cardiovascular disease (CVD) risk factor profiles and complications have changed over time. METHODS: We analyzed the American Heart Association COVID-19 CVD registry, a national multicenter registry of hospitalized adults with active COVID-19 infection. The time period from April 2020 to December 2021 was divided into 3-month epochs, with March 2020 analyzed separately as a potential outlier. Participating centers varied over the study period. Trends in all-cause in-hospital mortality, CVD risk factors, and in-hospital CVD outcomes, including a composite primary outcome of cardiovascular death, cardiogenic shock, new heart failure, stroke, and myocardial infarction, were evaluated across time epochs. Risk-adjusted analyses were performed using generalized linear mixed-effects models. RESULTS: A total of 46 007 patient admissions from 134 hospitals were included (mean patient age 61.8 years, 53% male, 22% Black race). Patients admitted later in the pandemic were younger, more likely obese, and less likely to have existing CVD (Ptrend ≤0.001 for each). The incidence of the primary outcome increased from 7.0% in March 2020 to 9.8% in October to December 2021 (risk-adjusted Ptrend=0.006). This was driven by an increase in the diagnosis of myocardial infarction and stroke (Ptrend<0.0001 for each). The overall rate of in-hospital mortality was 14.2%, which declined over time (20.8% in March 2020 versus 10.8% in the last epoch; adjusted Ptrend<0.0001). When the analysis was restricted to July 2020 to December 2021, no temporal change in all-cause mortality was seen (adjusted Ptrend=0.63). CONCLUSIONS: Despite a shifting risk factor profile toward a younger population with lower rates of established CVD, the incidence of diagnosed cardiovascular complications of COVID increased from the onset of the pandemic through December 2021. All-cause mortality decreased during the initial months of the pandemic and thereafter remained consistently high through December 2021.

SARS-CoV-2 Molecular Evolutionary Dynamics in the Greater Accra Region, Ghana.

To assess dynamics of SARS-CoV-2 in Greater Accra Region, Ghana, we analyzed SARS-CoV-2 genomic sequences from persons in the community and returning from international travel. The Accra Metropolitan District was a major origin of virus spread to other districts and should be a primary focus for interventions against future infectious disease outbreaks.

Projecting COVID-19 cases and hospital burden in Ohio.

As the Coronavirus 2019 disease (COVID-19) started to spread rapidly in the state of Ohio, the Ecology, Epidemiology and Population Health (EEPH) program within the Infectious Diseases Institute (IDI) at The Ohio State University (OSU) took the initiative to offer epidemic modeling and decision analytics support to the Ohio Department of Health (ODH). This paper describes the methodology used by the OSU/IDI response modeling team to predict statewide cases of new infections as well as potential hospital burden in the state. The methodology has two components: (1) A Dynamical Survival Analysis (DSA)-based statistical method to perform parameter inference, statewide prediction and uncertainty quantification. (2) A geographic component that down-projects statewide predicted counts to potential hospital burden across the state. We demonstrate the overall methodology with publicly available data. A Python implementation of the methodology is also made publicly available. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

Authorized SARS-CoV-2 molecular methods show wide variability in the limit of detection.

On February 29th, 2020, the U.S. Food and Drug Administration issued the first Emergency Use Authorization (EUA) for a SARS-CoV-2 assay outside of the U.S. Centers for Disease Control and Prevention. As of May 3rd, 2021, 289 total EUAs have been granted. Like influenza, there is no standard for defining limit of detection (LoD), but rather guidance that analytical sensitivity/LoD be established as the level that gives a 95% detection rate in at least 20 replicates. Here we compare the performance characteristics of SARS-CoV-2 tests receiving EUA by standardizing sensitivity to a common unit of measure and assess the variability in LoD between tests. Additionally, we looked at factors that may impact sensitivities due to lack of standardization of the test development process and compare results for a standardized reference panel for comparative analysis within a subset of EUA tests offered by the U.S. Food and Drug Administration.

Selective suppression of de novo SARS-CoV-2 vaccine antibody responses in patients with cancer on B cell-targeted therapy.

We assessed vaccine-induced antibody responses to the SARS-CoV-2 ancestral virus and Omicron variant before and after booster immunization in 57 patients with B cell malignancies. Over one-third of vaccinated patients at the pre-booster time point were seronegative, and these patients were predominantly on active cancer therapies such as anti-CD20 monoclonal antibody. While booster immunization was able to induce detectable antibodies in a small fraction of seronegative patients, the overall booster benefit was disproportionately evident in patients already seropositive and not receiving active therapy. While ancestral virus- and Omicron variant-reactive antibody levels among individual patients were largely concordant, neutralizing antibodies against Omicron tended to be reduced. Interestingly, in all patients, including those unable to generate detectable antibodies against SARS-CoV-2 spike, we observed comparable levels of EBV- and influenza-reactive antibodies, demonstrating that B cell-targeting therapies primarily impair de novo but not preexisting antibody levels. These findings support rationale for vaccination before cancer treatment.

Association between Risk Communication Format and Perceived Risk of Adverse Events after COVID-19 Vaccination among US Adults.

The format used to communicate probability-verbal versus numerical descriptors-can impact risk perceptions and behaviors. This issue is salient for the Coronavirus disease 2019 (COVID-19), where concerns about vaccine-related risks may reduce uptake and verbal descriptors have been widely used by public health, news organizations and on social media, to convey risk. Because the effect of risk-communication format on perceived COVID-19 vaccine-related risks remains unknown, we conducted an online randomized survey among 939 US adults. Participants were given risk information, using verbal or numerical descriptors and were asked to report their perceived risk of experiencing headache, fever, fatigue or myocarditis from COVID-19 vaccine. Associations between risk communication format and perceived risk were assessed using multivariable regression. Compared to numerical estimates, verbal descriptors were associated with higher perceived risk of headache (ß = 5.0 percentage points, 95% CI = 2.0-8.1), fever (ß = 27 percentage points, 95% CI = 23-30), fatigue (ß = 4.9 percentage points, 95% = CI 1.8-8.0) and myocarditis (ß = 4.6 percentage points, 95% CI = 2.1-7.2), as well as greater variability in risk perceptions. Social media influence was associated with differences in risk perceptions for myocarditis, but not side effects. Verbal descriptors may lead to greater, more inaccurate and variable vaccine-related risk perceptions compared to numerical descriptors.

A comprehensive survey of coronaviral main protease active site diversity in 3D: Identifying and analyzing drug discovery targets in search of broad specificity inhibitors for the next coronavirus pandemic (preprint)

Although the rapid development of therapeutic responses to combat SARS-CoV-2 represents a great human achievement, it also demonstrates untapped potential for advanced pandemic preparedness. Cross-species efficacy against multiple human coronaviruses by the main protease (MPro) inhibitor nirmatrelvir raises the question of its breadth of inhibition and our preparedness against future coronaviral threats. Herein, we describe sequence and structural analyses of 346 unique MPro enzymes from all coronaviruses represented in the NCBI Virus database. Cognate substrates of these representative proteases were inferred from their polyprotein sequences. We clustered MPro sequences based on sequence identity and AlphaFold2-predicted structures, showing approximate correspondence with known viral subspecies. Predicted structures of five representative MPros bound to their inferred cognate substrates showed high conservation in protease:substrate interaction modes, with some notable differences. Yeast-based proteolysis assays of the five representatives were able to confirm activity of three on inferred cognate substrates, and demonstrated that of the three, only one was effectively inhibited by nirmatrelvir. Our findings suggest that comprehensive preparedness against future potential coronaviral threats will require continued inhibitor development. Our methods may be applied to candidate coronaviral MPro inhibitors to evaluate in advance the breadth of their inhibition and identify target coronaviruses potentially meriting advanced development of alternative countermeasures.

SARS-CoV-2 infections among asymptomatic individuals contributed to COVID-19 cases: A cross-sectional study among prospective air travelers from Ghana.

Background: The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by asymptomatic individuals has been reported since the early stages of the coronavirus disease 2019 (COVID-19) outbreak in various parts of the world. However, there are limited data regarding SARS-CoV-2 among asymptomatic individuals in Ghana. The aim of the study was to use test data of prospective travelers from Ghana as a proxy to estimate the contribution of asymptomatic cases to the spread of COVID-19. Methods: The study analyzed the SARS-CoV-2 PCR test data of clients whose purpose for testing was classified as "Travel" at the COVID-19 walk-in test center of the Noguchi Memorial Institute for Medical Research (NMIMR) from July 2020 to July 2021. These individuals requesting tests for travel generally had no clinical symptoms of COVID-19 at the time of testing. Data were processed and analyzed using Microsoft Excel office 16 and STATA version 16. Descriptive statistics were used to summarize data on test and demographic characteristics. Results: Out of 42,997 samples tested at the center within that period, 28,384 (66.0%) were classified as "Travel" tests. Of these, 1,900 (6.7%) tested positive for SARS-CoV-2. The majority (64.8%) of the "Travel" tests were requested by men. The men recorded a SARS-CoV-2 positivity of 6.9% compared to the 6.4% observed among women. Test requests for SARS-CoV-2 were received from all regions of Ghana, with a majority (83.3%) received from the Greater Accra Region. Although the Eastern region recorded the highest SARS-CoV-2 positivity rate of 8.35%, the Greater Accra region contributed 81% to the total number of SARS-CoV-2 positive cases detected within the period of study. Conclusion: Our study found substantial SARS-CoV-2 positivity among asymptomatic individuals who, without the requirement for a negative SARS-CoV-2 result for travel, would have no reason to test. These asymptomatic SARS-CoV-2-infected individuals could have traveled to other countries and unintentionally spread the virus. Our findings call for enhanced tracing and testing of asymptomatic contacts of individuals who tested positive for SARS-CoV-2.

Assessment of a mass balance equation for estimating community-level prevalence of COVID-19 using wastewater-based epidemiology in a mid-sized city.

Wastewater-based epidemiology (WBE) has emerged as a valuable epidemiologic tool to detect the presence of pathogens and track disease trends within a community. WBE overcomes some limitations of traditional clinical disease surveillance as it uses pooled samples from the entire community, irrespective of health-seeking behaviors and symptomatic status of infected individuals. WBE has the potential to estimate the number of infections within a community by using a mass balance equation, however, it has yet to be assessed for accuracy. We hypothesized that the mass balance equation-based approach using measured SARS-CoV-2 wastewater concentrations can generate accurate prevalence estimates of COVID-19 within a community. This study encompassed wastewater sampling over a 53-week period during the COVID-19 pandemic in Gainesville, Florida, to assess the ability of the mass balance equation to generate accurate COVID-19 prevalence estimates. The SARS-CoV-2 wastewater concentration showed a significant linear association (Parameter estimate = 39.43, P value < 0.0001) with clinically reported COVID-19 cases. Overall, the mass balance equation produced accurate COVID-19 prevalence estimates with a median absolute error of 1.28%, as compared to the clinical reference group. Therefore, the mass balance equation applied to WBE is an effective tool for generating accurate community-level prevalence estimates of COVID-19 to improve community surveillance.

Alcohol Use.

Unhealthy alcohol use-the consumption of alcohol at a level that has caused or has the potential to cause adverse physical, psychological, or social consequences-is common, underrecognized, and undertreated. For example, data from the 2020 National Survey on Drug Use and Health indicate that 7.0% of adults reported heavy alcohol use in the previous month, and only 4.2% of adults with alcohol use disorder received treatment. Primary care is an important setting for optimizing screening and treatment of unhealthy alcohol use to promote individual and public health.

Impact of the COVID-19 Pandemic on Neurosurgical Transfers: A Single Tertiary Center Study.

OBJECTIVE: Interfacility transfers represent a large proportion of neurosurgical admissions to tertiary care centers each year. In this study, the authors examined the impact of the COVID-19 pandemic on the number of transfers, timing of transfers, demographic profile of transfer patients, and clinical outcomes including rates of surgical intervention. METHODS: A retrospective review of neurosurgical transfer patients at a single tertiary center was performed. Patients transferred from April to November 2020 (the "COVID Era") were compared with an institutional database of transfer patients collected before the COVID-19 pandemic (the "Pre-COVID Era"). During the COVID Era, both emergent and nonemergent neurosurgical services had resumed. A comparison of demographic and clinical factors between the 2 cohorts was performed. RESULTS: A total of 674 patients were included in the study (331 Pre-COVID and 343 COVID-Era patients). Overall, there was no change in the average monthly number of transfers (P = 0.66) or in the catchment area of referral hospitals. However, COVID-Era patients were more likely to be uninsured (1% vs. 4%), had longer transfer times (COVID vs. Pre-COVID Era: 18 vs. 9 hours; P < 0.001), required higher rates of surgical intervention (63% vs. 50%, P = 0.001), had higher rates of spine pathology (17% vs. 10%), and less frequently were admitted to the intensive care unit (34% vs. 52%, P < 0.001). Overall, COVID-Era patients did not experience delays to surgical intervention (3.1 days vs. 3.6 days, P = 0.2). When analyzing the subgroup of COVID-Era patients, COVID infection status did not impact the time of transfer or rates of operation, although COVID-infected patients experienced a longer time to surgery after admission (14 vs. 2.9 days, P < 0.001). CONCLUSION: The COVID-19 pandemic did not reduce the number of monthly transfers, operation rates, or catchment area for transfer patients. Transfer rates of uninsured patients increased during the COVID Era, potentially reflecting changes in access to community neurosurgery care. Shorter time to surgery seen in COVID-Era patients possibly reflects institutional policies that improved operating room efficiency to compensate for surgical backlogs. COVID status affeted time to surgery, reflecting the preoperative care that these patients require before intervention.