Survey of white-footed mice in Connecticut, USA reveals low SARS-CoV-2 seroprevalence and infection with divergent betacoronaviruses (preprint)

Diverse mammalian species display susceptibility to and infection with SARS-CoV-2. Potential SARS-CoV-2 spillback into rodents is understudied despite their host role for numerous zoonoses and human proximity. We assessed exposure and infection among white-footed mice (Peromyscus leucopus) in Connecticut, USA. We observed 1% (6/540) wild-type neutralizing antibody seroprevalence among 2020-2022 residential mice with no cross-neutralization of variants. We detected no SARS-CoV-2 infections via RT-qPCR, but identified non-SARS-CoV-2 betacoronavirus infections via pan-coronavirus PCR among 1% (5/468) of residential mice. Sequencing revealed two divergent betacoronaviruses, preliminarily named Peromyscus coronavirus-1 and -2. Both belong to the Betacoronavirus 1 species and are ~90% identical to the closest known relative, Porcine hemagglutinating encephalomyelitis virus. Low SARS-CoV-2 seroprevalence suggests white-footed mice may not be sufficiently susceptible or exposed to SARS-CoV-2 to present a long-term human health risk. However, the discovery of divergent, non-SARS-CoV-2 betacoronaviruses expands the diversity of known rodent coronaviruses and further investigation is required to understand their transmission extent.

Smoking Status, Nicotine Medication, Vaccination, and COVID-19 Hospital Outcomes: Findings from the COVID EHR Cohort at the University of Wisconsin (CEC-UW) Study.

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown. METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission. RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97). CONCLUSIONS: Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers. IMPLICATIONS: Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

FAIR in action - a flexible framework to guide FAIRification.

The COVID-19 pandemic has highlighted the need for FAIR (Findable, Accessible, Interoperable, and Reusable) data more than any other scientific challenge to date. We developed a flexible, multi-level, domain-agnostic FAIRification framework, providing practical guidance to improve the FAIRness for both existing and future clinical and molecular datasets. We validated the framework in collaboration with several major public-private partnership projects, demonstrating and delivering improvements across all aspects of FAIR and across a variety of datasets and their contexts. We therefore managed to establish the reproducibility and far-reaching applicability of our approach to FAIRification tasks.

Role of Famotidine and Other Acid Reflux Medications for SARS-CoV-2: A Pilot Study.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus-19 disease (COVID-19) pandemic. The H-2 blocker famotidine has been suggested as an FDA-approved drug that could potentially be repurposed for treatment of COVID-19. Famotidine has since been shown to improve patient outcomes and reduce symptom severity in patients acutely ill with COVID-19. Other studies have suggested that proton pump inhibitors (PPIs) might have an association with COVID-19. OBJECTIVE: The purpose of the present study was to determine whether famotidine or any other antireflux medications have a prophylactic or detrimental effect for SARS-CoV-2 infection when taken regularly for the management of acid reflux. METHODS: An anonymous, web-based survey was distributed via email to adult otolaryngology patients to collect demographic data, past medical history, medication history, incidence of symptoms associated with COVID-19, potential exposure to SARS-CoV-2, and results of any PCR or serological testing. Associations between reflux medications and incidence of COVID-19 cases were analyzed. Statistical analysis was performed using SPSS. Chi-square with Fisher's exact test, Point-Biserial correlation, Kendall's-tau-b, independent samples t test, and the Mann-Whitney U test were used as appropriate. A binary logistic regression model was fit to determine probability of COVID-19 cases after adjustment for other risk factors. RESULTS: There were 307 patients who responded to the survey. The average age of respondents was 52.63 ± 17.03. Famotidine use was not associated with incidence of laboratory-confirmed (P= 0.717) or symptomatically suspected (P= 0.876) COVID-19. No other reflux medications were found to be significant predictors for laboratory-confirmed or suspected COVID-19 (P> 0.05). Younger age (odds ratio [OR] = 1.043, 95% CI: 1.020-1.065, P< 0.001), high risk obesity (OR = 4.005, 95% CI: 1.449-11.069, P= 0.007), and use of a corticosteroid nasal spray (OR = 3.529, 95% CI: 1.352-9.211, P= 0.010) were significant predictors for symptomatically suspected COVID-19 cases. CONCLUSIONS: There was no association between incidence of COVID-19 and use of reflux medications, including famotidine at doses used orally to manage reflux and high dose PPIs. Reflux medications did not protect against or increase the risk of COVID-19.

Are researchers in academic medicine flourishing? A survey of midcareer Ph.D. and physician investigators.

Introduction: Midcareer research faculty are a vital part of the advancement of science in U.S. medical schools, but there are troubling trends in recruitment, retention, and burnout rates. Methods: The primary sampling frame for this online survey was recipients of a single R01 or equivalent and/or K-award from 2013 to 2019. Inclusion criteria were 3-14 years at a U.S. medical school and rank of associate professor or two or more years as assistant professor. Forty physician investigators and Ph.D. scientists volunteered for a faculty development program, and 106 were propensity-matched controls. Survey items covered self-efficacy in career, research, work-life; vitality/burnout; relationships, inclusion, trust; diversity; and intention to leave academic medicine. Results: The majority (52%) reported receiving poor mentoring; 40% experienced high burnout and 41% low vitality, which, in turn, predicted leaving intention (P < 0.0005). Women were more likely to report high burnout (P = 0.01) and low self-efficacy managing work and personal life (P = 0.01) and to be seriously considering leaving academic medicine than men (P = 0.003). Mentoring quality (P < 0.0005) and poor relationships, inclusion, and trust (P < 0.0005) predicted leaving intention. Non-underrepresented men were very likely to report low identity self-awareness (65%) and valuing differences (24%) versus underrepresented men (25% and 0%; P < 0.0005). Ph.D.s had lower career advancement self-efficacy than M.D.s (P < .0005). Conclusions: Midcareer Ph.D. and physician investigators faced significant career challenges. Experiences diverged by underrepresentation, gender, and degree. Poor quality mentoring was an issue for most. Effective mentoring could address the concerns of this vital component of the biomedical workforce.

Ten Influential Point-of-Care Ultrasound Papers: 2022 in Review.

Keeping up with the latest developments in the point-of-care ultrasound (POCUS) literature is challenging, as with any area of medicine. Our group of POCUS experts has selected 10 influential papers from the past 12 months and provided a short summary of each. We hope to provide emergency physicians, intensivists, and other acute care providers with a succinct update concerning some key areas of ultrasound interest.

SIGNIFICANCE, MIDTERM RESULTS AND EXPERIENCES OF THE BUDAPEST ONCOLOGY CT AND MR WAITING LISTS REDUCTION PROGRAM

BACKGROUND – High-value medical imaging diagnostic procedures are key elements of the diagnostic process of patients with suspected oncological disease and in determining the effectiveness of the initiated therapy. In Hungary, due to the high diagnostic demands, diagnostic waiting lists for computed tomography (CT) or magnetic resonance imaging (MR) are usually long and result in less transparent reporting times, even in the case of individuals who are potentially suspected of having a malignant disease, or in the case of the follow-up of effectiveness of treatment of diagnosed cancer patients. THE AIM OF THE PRESENT STUDY – Midterm analysis of the onco-diagnostic Program in Budapest implemented within the framework of the Healthy Budapest Program (HBP), gain experiences and presentation of underlying health policy processes. RESULTS – From November 2020 till 31st of December 2022 within the framework of the Program, the Municipality of Budapest has reimbursed 5437 contrast-enhanced CT and 2948 MR examinations with "C” or "D” disease diagnosis. Examinations has been financed in a sector-neutral manner to public and private healthcare providers in the so-called ‘BP' reimbursement category. The report undertaken by Semmelweis University has found, that in Budapest Municipality funded patients, radiological examinations were performed on average 15.2 days sooner (16.1 vs. 31.1 days), than in the case of the National Health Insurance Fund funded patients, the mean waiting time for CT/MR examination was shortened by 13.0 days (4.2 vs. 17.2 days, respectively). In 86% of cases, patients used the Program once, in 14% twice or more. Utilization of the Program shows a significant difference by the different districts of the Capital: the number of cases – originally planned based on demographic, prevalence and incidence data, broken down by district – was utilized between 3-45% for CT, and 8-37% for MR cases, respectively, by district residents mainly referred by district outpatient clinic specialists, between the period of November 2020 and August 2022. CONCLUSION – The Program has been utilised in a smaller scale, than it was originally planned before COVID, in terms of its cases. The program has achieved its aim through the reduction of CT and MR diagnostic waiting times and waiting lists, and it has an indirect effect in generally reducing waiting times at medical imaging. However, this is not sufficient to speed up and provide more efficient service for the entire oncology diagnostic process. Therefore, we wish to further develop the Program in the direction of adding additional diagnostic examinations and developing a patient pathway management module. © 2023 Literatura Medica Publishing House. All rights reserved.

Developmental Epidemiology of Pediatric Anxiety Disorders.

This review summarizes the developmental epidemiology of childhood and adolescent anxiety disorders. It discusses the coronavirus disease of 2019 (COVID-19) pandemic, sex differences, longitudinal course, and stability of anxiety disorders in addition to recurrence and remission. The trajectory of anxiety disorders-whether homotypic (ie, the same anxiety disorder persists over time) or heterotypic (ie, an anxiety disorder shifts to a different diagnosis over time) is discussed with regard to social, generalized, and separation anxiety disorders as well as specific phobia, and panic disorder. Finally, strategies for early recognition, prevention, and treatment of disorders are discussed.

1-O-Octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-GS-441524 (V2043). Evaluation of Oral V2043 in a Mouse Model of SARS-CoV-2 Infection and Synthesis and Antiviral Evaluation of Additional Phospholipid Esters with Enhanced Anti-SARS-CoV-2 Activity.

Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease caused by COVID-19. An orally bioavailable RDV analog may facilitate earlier treatment of non-hospitalized COVID-19 patients. Here we describe the synthesis and evaluation of alkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability and stability in plasma. Oral treatment of SARS-CoV-2-infected BALB/c mice with 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn (60 mg/kg orally, once daily for 5 days starting 12h after infection) reduced lung viral load by 1.5 log10 units versus vehicle at day 2 and to below the limit of detection at day 5. Structure/activity evaluation of additional analogs that have hydrophobic ethers at the sn-2 of glycerol revealed improved in vitro antiviral activity by introduction of a 3-fluoro-4-methoxy-substituted benzyl or a 3- or 4-cyano-substituted benzyl. Collectively, our data support the development of RVn phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections.

Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports.

BACKGROUND: Susac syndrome is an immune-mediated, ischemia-producing, occlusive microvascular endotheliopathy that threatens the brain, retina, and inner ear. There is a need for disease assessment tools that can help clinicians and patients to more easily, accurately, and uniformly track the clinical course and outcome of Susac syndrome. Ideally, such tools should simultaneously facilitate the clinical care and study of Susac syndrome and improve the value of future case reports. To meet this need, two novel clinical assessment tools were developed: the Susac Symptoms Form and the Susac Disease Damage Score. The former is a comprehensive self-report form that is completed by patients/families to serially document the clinical status of a patient. The latter documents the extent of damage perceived by individual patients/families and their physicians. Both forms were initially trialed with two particularly representative and instructive patients. The results of this trial are shared in this report. CASE PRESENTATION: Patient 1 is a 21-year-old Caucasian female who presented with an acute onset of headache, paresthesias, cognitive dysfunction, and emotional lability. Patient 2 is a 14-year-old Caucasian female who presented with an acute onset of headache, cognitive dysfunction, urinary incontinence, ataxia, and personality change. Both patients fulfilled criteria for a definite diagnosis of Susac syndrome: both eventually developed brain, retinal, and inner ear involvement, and both had typical "snowball lesions" on magnetic resonance imaging. The Susac Symptoms Form documented initial improvement in both patients, was sufficiently sensitive in detecting a subsequent relapse in the second patient, and succinctly documented the long-term clinical course in both patients. The Disease Damage Score documented minimal disease damage in the first patient and more significant damage in the second. CONCLUSIONS: The Susac Symptoms Form and the Disease Damage Score are useful disease assessment tools, both for clinical care and research purposes. Their use could enhance the value of future case reports on Susac syndrome and could improve opportunities to learn from a series of such reports.

Boosting compromised SARS-CoV-2-specific T cell immunity in liver transplant recipients by mRNA vaccination

Background and aims Liver transplant recipients (LTR) are threatened by a lower immunogenicity of SARS-CoV-2 mRNA vaccines. However, the interplay between the different branches of the adaptive immune system especially after a third (and fourth) vaccine dose is still poorly understood. Methods Our study longitudinally compares the humoral as well as the cellular response between age-matched LTR (n = 24) and healthy controls (HC, n = 19) after three to four vaccine doses. Therefore, we assessed antibody titers, analyzed the spike-specific T cell epitope repertoire, performed an in-depth characterization of spike-specific CD8 + T cells on a single-epitope level and examined the distribution of different virus-specific CD4 + T cell subpopulations. Results Compared to HC, the development of high antibody titers depended on a third vaccine dose in most LTR. In contrast, spike-specific CD8 + T cells reached a stable level already after the second vaccine dose, albeit with a lower frequency and a narrower epitope repertoire compared to HC. Concerning the CD4 + T cells, the total number of detectable responses as well as the repertoire of targeted epitopes within the spike protein did not signifcantly difer in both cohorts. However, we observed a link between the overall attenuated vaccine response and a reduced frequency of spike-reactive follicular T helper cells (TFH) in LTR. Conclusion Three doses of a COVID-19 mRNA vaccine induce an overall robust humoral and cellular memory response in most LTR. Evaluations of additional booster doses may thus consider the individual vaccine responsiveness as well as the evolution of novel variants of concern.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Medigen COVID-19 Protein Vaccine☆

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group has prepared standardized templates to describe the key considerations for the benefit-risk assessment of several vaccine platform technologies, including protein subunit vaccines. This article uses the BRAVATO template to review the features of the MVC-COV1901 vaccine, a recombinant protein subunit vaccine based on the stabilized pre-fusion SARS-CoV-2 spike protein S-2P, adjuvanted with CpG 1018 and aluminum hydroxide, manufactured by Medigen Vaccine Biologics Corporation in Taiwan. MVC-COV1901 vaccine is indicated for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 12 years of age and older. The template offers details on basic vaccine information, target pathogen and population, characteristics of antigen and adjuvant, preclinical data, human safety and efficacy data, and overall benefit-risk assessment. The clinical development program began in September 2020 and based on demonstration of favorable safety and immunogenicity profiles in 11 clinical trials in over 5,000 participants, it has been approved for emergency use based on immunobridging results for adults in Taiwan, Estwatini, Somaliland, and Paraguay. The main clinical trials include placebo-controlled phase 2 studies in healthy adults (CT-COV-21), adolescents (CT-COV-22), and elderly population (CT-COV-23) as well as 3 immunobridging phase 3 trials (CT-COV-31, CT-COV-32, and CT-COV-34) in which MVC-COV1901 was compared to AZD1222. There are also clinical trials studying MVC-COV1901 as homologous and heterologous boosters (CT-COV-24 and CT-COV-25). The totality of evidence based on ∼3 million vaccinees to date includes a mostly clean safety profile, with adverse events mostly being mild and self-limiting in both clinical development and post-marketing experience, proven immunogenic response, and real-world effectiveness data. The immunogenic profile demonstrates that MVC-COV1901 induces high levels of neutralizing and binding antibodies against SARS-CoV-2. There is a dose-dependent response and a significant correlation between binding and neutralizing antibody activity. Antigen-specific T-cell responses, particularly a Th1-biased immune response characterized by high levels of interferon gamma and IL-2 cytokines, have also been observed. Coupled with this, MVC-COV1901 has favorable thermostability and better safety profiles when compared to other authorized vaccines from different platforms, which make it potentially a good candidate for vaccine supply chains in global markets.

SIGNIFICANCE, MIDTERM RESULTS AND EXPERIENCES OF THE BUDAPEST ONCOLOGY CT AND MR WAITING LISTS REDUCTION PROGRAM

BACKGROUND – High-value medical imaging diagnostic procedures are key elements of the diagnostic process of patients with suspected oncological disease and in determining the effectiveness of the initiated therapy. In Hungary, due to the high diagnostic demands, diagnostic waiting lists for computed tomography (CT) or magnetic resonance imaging (MR) are usually long and result in less transparent reporting times, even in the case of individuals who are potentially suspected of having a malignant disease, or in the case of the follow-up of effectiveness of treatment of diagnosed cancer patients. THE AIM OF THE PRESENT STUDY – Midterm analysis of the onco-diagnostic Program in Budapest implemented within the framework of the Healthy Budapest Program (HBP), gain experiences and presentation of underlying health policy processes. RESULTS – From November 2020 till 31st of December 2022 within the framework of the Program, the Municipality of Budapest has reimbursed 5437 contrast-enhanced CT and 2948 MR examinations with "C” or "D” disease diagnosis. Examinations has been financed in a sector-neutral manner to public and private healthcare providers in the so-called ‘BP' reimbursement category. The report undertaken by Semmelweis University has found, that in Budapest Municipality funded patients, radiological examinations were performed on average 15.2 days sooner (16.1 vs. 31.1 days), than in the case of the National Health Insurance Fund funded patients, the mean waiting time for CT/MR examination was shortened by 13.0 days (4.2 vs. 17.2 days, respectively). In 86% of cases, patients used the Program once, in 14% twice or more. Utilization of the Program shows a significant difference by the different districts of the Capital: the number of cases – originally planned based on demographic, prevalence and incidence data, broken down by district – was utilized between 3-45% for CT, and 8-37% for MR cases, respectively, by district residents mainly referred by district outpatient clinic specialists, between the period of November 2020 and August 2022. CONCLUSION – The Program has been utilised in a smaller scale, than it was originally planned before COVID, in terms of its cases. The program has achieved its aim through the reduction of CT and MR diagnostic waiting times and waiting lists, and it has an indirect effect in generally reducing waiting times at medical imaging. However, this is not sufficient to speed up and provide more efficient service for the entire oncology diagnostic process. Therefore, we wish to further develop the Program in the direction of adding additional diagnostic examinations and developing a patient pathway management module. © 2023 Literatura Medica Publishing House. All rights reserved.

COVID-19: Impact on the Musician and Returning to Singing; A Literature Review.

OBJECTIVE: The purpose of this study was to review current literature of the impact of COVID-19 on musicians and returning to singing. METHODS: A comprehensive search of peer-review articles was completed using PubMed, GoogleScholar, Scopus, and Web of Science. The search was completed using many key terms including voice, hoarseness, dysphonia, aphonia, cough, singers, and public speakers. The bibliography from each article found was searched to find additional articles. The search process revealed 56 peer-reviewed articles, 18 primary articles, ranging from the years 2019 to 2020. CONCLUSION: COVID-19 has had a major impact on singers and other musicians worldwide. It can affect the voice and can lead to paresis/paralysis of laryngeal nerves to long-term changes in respiratory function. There is a risk from aerosolization/droplet formation transmission with singing, and with playing wind and brass instruments that can be mitigated by following COVID-19 guidelines. Ways to reduce possible transmission during singing and instrument play include virtual rehearsals or performances, mask-wearing, instrument covers, smaller choirs, performing outside, excellent ventilation being socially distanced, shorter rehearsals, regularly cleaning commonly touched surfaces and washing hands, avoiding contact with others, and temperature screening.

Impact of sedentary behavior and emotional support on prenatal psychological distress and birth outcomes during the COVID-19 pandemic.

Abstract. BACKGROUND: Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics. METHODS: Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report. RESULTS: After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed. CONCLUSIONS: There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Medigen COVID-19 protein vaccine.

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group has prepared standardized templates to describe the key considerations for the benefit-risk assessment of several vaccine platform technologies, including protein subunit vaccines. This article uses the BRAVATO template to review the features of the MVC-COV1901 vaccine, a recombinant protein subunit vaccine based on the stabilized pre-fusion SARS-CoV-2 spike protein S-2P, adjuvanted with CpG 1018 and aluminum hydroxide, manufactured by Medigen Vaccine Biologics Corporation in Taiwan. MVC-COV1901 vaccine is indicated for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 12 years of age and older. The template offers details on basic vaccine information, target pathogen and population, characteristics of antigen and adjuvant, preclinical data, human safety and efficacy data, and overall benefit-risk assessment. The clinical development program began in September 2020 and based on demonstration of favorable safety and immunogenicity profiles in 11 clinical trials in over 5,000 participants, it has been approved for emergency use based on immunobridging results for adults in Taiwan, Estwatini, Somaliland, and Paraguay. The main clinical trials include placebo-controlled phase 2 studies in healthy adults (CT-COV-21), adolescents (CT-COV-22), and elderly population (CT-COV-23) as well as 3 immunobridging phase 3 trials (CT-COV-31, CT-COV-32, and CT-COV-34) in which MVC-COV1901 was compared to AZD1222. There are also clinical trials studying MVC-COV1901 as homologous and heterologous boosters (CT-COV-24 and CT-COV-25). The totality of evidence based on ∼3 million vaccinees to date includes a mostly clean safety profile, with adverse events mostly being mild and self-limiting in both clinical development and post-marketing experience, proven immunogenic response, and real-world effectiveness data. The immunogenic profile demonstrates that MVC-COV1901 induces high levels of neutralizing and binding antibodies against SARS-CoV-2. There is a dose-dependent response and a significant correlation between binding and neutralizing antibody activity. Antigen-specific T-cell responses, particularly a Th1-biased immune response characterized by high levels of interferon gamma and IL-2 cytokines, have also been observed. Coupled with this, MVC-COV1901 has favorable thermostability and better safety profiles when compared to other authorized vaccines from different platforms, which make it potentially a good candidate for vaccine supply chains in global markets.

Early Identification of Autism Spectrum Disorder Among Children Aged 4 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020.

Problem/Condition: Autism spectrum disorder (ASD). Period Covered: 2020. Description of System: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates prevalence and characteristics of ASD and monitors timing of ASD identification among children aged 4 and 8 years. In 2020, a total of 11 sites (located in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin) conducted surveillance of ASD among children aged 4 and 8 years and suspected ASD among children aged 4 years. Surveillance included children who lived in the surveillance area at any time during 2020. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement in an evaluation, 2) a special education classification of autism (eligibility), or 3) an ASD International Classification of Diseases (ICD) code (revisions 9 or 10). Children aged 4 years were classified as having suspected ASD if they did not meet the case definition for ASD but had a documented qualified professional's statement indicating a suspicion of ASD. This report focuses on children aged 4 years in 2020 compared with children aged 8 years in 2020. Results: For 2020, ASD prevalence among children aged 4 years varied across sites, from 12.7 per 1,000 children in Utah to 46.4 in California. The overall prevalence was 21.5 and was higher among boys than girls at every site. Compared with non-Hispanic White children, ASD prevalence was 1.8 times as high among Hispanic, 1.6 times as high among non-Hispanic Black, 1.4 times as high among Asian or Pacific Islander, and 1.2 times as high among multiracial children. Among the 58.3% of children aged 4 years with ASD and information on intellectual ability, 48.5% had an IQ score of ≤70 on their most recent IQ test or an examiner's statement of intellectual disability. Among children with a documented developmental evaluation, 78.0% were evaluated by age 36 months. Children aged 4 years had a higher cumulative incidence of ASD diagnosis or eligibility by age 48 months compared with children aged 8 years at all sites; risk ratios ranged from 1.3 in New Jersey and Utah to 2.0 in Tennessee. In the 6 months before the March 2020 COVID-19 pandemic declaration by the World Health Organization, there were 1,593 more evaluations and 1.89 more ASD identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. After the COVID-19 pandemic declaration, this pattern reversed: in the 6 months after pandemic onset, there were 217 fewer evaluations and 0.26 fewer identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. Patterns of evaluation and identification varied among sites, but there was not recovery to pre-COVID-19 pandemic levels by the end of 2020 at most sites or overall. For 2020, prevalence of suspected ASD ranged from 0.5 (California) to 10.4 (Arkansas) per 1,000 children aged 4 years, with an increase from 2018 at five sites (Arizona, Arkansas, Maryland, New Jersey, and Utah). Demographic and cognitive characteristics of children aged 4 years with suspected ASD were similar to children aged 4 years with ASD. Interpretation: A wide range of prevalence of ASD by age 4 years was observed, suggesting differences in early ASD identification practices among communities. At all sites, cumulative incidence of ASD by age 48 months among children aged 4 years was higher compared with children aged 8 years in 2020, indicating improvements in early identification of ASD. Higher numbers of evaluations and rates of identification were evident among children aged 4 years until the COVID-19 pandemic onset in 2020. Sustained lower levels of ASD evaluations and identification seen at a majority of sites after the pandemic onset could indicate disruptions in typical practices in evaluations and identification for health service providers and schools through the end of 2020. Sites with more recovery could indicate successful strategies to mitigate service interruption, such as pivoting to telehealth approaches for evaluation. Public Health Action: From 2016 through February of 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing ASD evaluation and identification 4 years earlier (from 2012 until March 2016) among the cohort of children aged 8 years in 2020 . From 2016 to March 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing that among children aged 8 years in 2020 from 2012 until March 2016. The disruptions in evaluation that coincided with the start of the COVID-19 pandemic and the increase in prevalence of suspected ASD in 2020 could have led to delays in ASD identification and interventions. Communities could evaluate the impact of these disruptions as children in affected cohorts age and consider strategies to mitigate service disruptions caused by future public health emergencies.

Patient and Process Outcomes among Pediatric Patients Undergoing Appendectomy during the COVID-19 Pandemic: An International Retrospective Cohort Study.

BACKGROUND: COVID-19 forced healthcare systems to make unprecedented changes in clinical care processes. The authors hypothesized that the COVID-19 pandemic adversely impacted timely access to care, perioperative processes, and clinical outcomes for pediatric patients undergoing primary appendectomy. METHODS: A retrospective, international, multicenter study was conducted using matched cohorts within participating centers of the international PEdiatric Anesthesia COVID-19 Collaborative (PEACOC). Patients younger than 18 yr old were matched using age, American Society of Anesthesiologists Physical Status, and sex. The primary outcome was the difference in hospital length of stay of patients undergoing primary appendectomy during a 2-month period early in the COVID-19 pandemic (April to May 2020) compared with prepandemic (April to May 2019). Secondary outcomes included time to appendectomy and the incidence of complicated appendicitis. RESULTS: A total of 3,351 cases from 28 institutions were available with 1,684 cases in the prepandemic cohort matched to 1,618 in the pandemic cohort. Hospital length of stay was statistically significantly different between the two groups: 29 h (interquartile range: 18 to 79) in the pandemic cohort versus 28 h (interquartile range: 18 to 67) in the prepandemic cohort (adjusted coefficient, 1 [95% CI, 0.39 to 1.61]; P < 0.001), but this difference was small. Eight centers demonstrated a statistically significantly longer hospital length of stay in the pandemic period than in the prepandemic period, while 13 were shorter and 7 did not observe a statistically significant difference. During the pandemic period, there was a greater occurrence of complicated appendicitis, prepandemic 313 (18.6%) versus pandemic 389 (24.1%), an absolute difference of 5.5% (adjusted odds ratio, 1.32 [95% CI, 1.1 to 1.59]; P = 0.003). Preoperative SARS-CoV-2 testing was associated with significantly longer time-to-appendectomy, 720 min (interquartile range: 430 to 1,112) with testing versus 414 min (interquartile range: 231 to 770) without testing, adjusted coefficient, 306 min (95% CI, 241 to 371; P < 0.001), and longer hospital length of stay, 31 h (interquartile range: 20 to 83) with testing versus 24 h (interquartile range: 14 to 68) without testing, adjusted coefficient, 7.0 (95% CI, 2.7 to 11.3; P = 0.002). CONCLUSIONS: For children undergoing appendectomy, the COVID-19 pandemic did not significantly impact hospital length of stay.

Cancer, more than a "COVID-19 co-morbidity".

Patients with cancer represent a particularly vulnerable population at risk of adverse outcomes related to COVID-19. Collectively, the initial studies, including patients with and without cancer, confirmed that patients with cancer had a higher risk of complications and death related to COVID-19. Subsequent studies on patients with COVID-19 and cancer investigated patient and disease-related factors associated with COVID-19 severity and morality. Multiple interconnected factors include demographics, comorbidities, cancer-associated variables, treatment side effects, and other parameters. However, there is a lack of clarity on the contributions of any one factor. In this commentary, we deconvolute the data of specific risk factors associated with worse outcomes due to COVID-19 in cancer patients and focus on understanding the recommended guidelines to mitigate COVID-19 risk in this vulnerable population. In the first section, we highlight the key parameters, including age and race, cancer status, type of malignancy, cancer therapy, smoking status and comorbidities that impact outcomes for cancer patients with COVID-19. Next, we discuss efforts made at the patient, health system, and population levels to mitigate the effects of the ongoing outbreak for patients with cancer, including (1) screening, barrier and isolation strategies (2), Masking/PPE (3), vaccination, and (4) systemic therapies (e.g., evusheld) to prevent disease onset in patients. In the last section, we discuss optimal treatment strategies for COVID-19, including additional therapies for patients with COVID-19 and cancer. Overall, this commentary focuses on articles with high yield and impact on understanding the evolving evidence of risk factors and management guidelines in detail. We also emphasize the ongoing collaboration between clinicians, researchers, health system administrators and policymakers and how its role will be important in optimizing care delivery strategies for patients with cancer. Creative patient-centered solutions will be critical in the coming years, post the pandemic.

Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics (preprint)

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of SARS-CoV-2 lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of 'local' when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.