Can endorsement by religious leaders move the needle on vaccine hesitancy?

Existing research, including work specific to COVID-19, suggests that endorsement by medical practitioners increases vaccine uptake. Yet, vaccine hesitancy persists despite health professionals continuing to widely endorse multiple vaccines to combat COVID-19 since late 2020. Could endorsement by other trusted leaders reduce vaccine hesitancy? Although some studies suggest that trust in religious leaders can influence individuals' health attitudes and behaviors, the evidence is mixed. Our study explores the potential added value of messaging by religious leaders across religious traditions - specifically, it asks whether their endorsement of the COVID-19 vaccine might increase vaccine uptake in an environment where health professionals are already endorsing vaccines. To investigate this question, we conducted an online survey experiment with 6,000 respondents across five countries with different dominant religions (Buddhism, Christianity, and Islam). Respondents were randomly assigned to either a control group that only included endorsement by medical practitioners or a treatment group that added either endorsement by religious leaders or, for comparative purposes, endorsement by political leaders. We found that endorsement by religious leaders reduced vaccine hesitancy only in one country. These findings corroborate existing research that medical practitioners are the best line of defense to combat vaccine hesitancy. They also suggest the limitations of endorsement by non-experts.

A systematic review of caries risk in children <6 years of age.

BACKGROUND: For caries risk assessment (CRA) tools for young children to be evidence-based, it is important to systematically review the literature to identify factors associated with the onset of early childhood caries (ECC). AIM: This updated systematic review aimed to identify current evidence on caries risk in young children. DESIGN: A comprehensive and systematic literature search of relevant databases was conducted to update a previous systematic review and identify risk factors associated with ECC. Potential risk factors were identified based on strength of association using odds ratios, hazard ratios, relative risk, etc. GRADE was used for rating quality evidence through consensus. RESULTS: Twenty-two studies met inclusion criteria for the search from mid-2017 to 2021. Twenty-five publications from the prior systematic review, from 1997 to mid-2017, were also included. Several socioeconomic, behavioral, and clinical variables were identified as ECC risk factors. Factors included the following: age, socioeconomic status, frequency of and supervised toothbrushing, fluoride exposure, breast- and bottle-feeding, feeding habits, absence of a dental home, past caries experience, active non-cavitated lesions, visible plaque, enamel defects, and microbiome. CONCLUSION: This study provides updated evidence of risk factors for ECC that could be included in CRA tools.

Coexistence of human immunodeficiency virus infection and autoimmune hepatitis: A double trouble.

A wide spectrum of hepatobiliary manifestations occur in Human Immunodeficiency Virus (HIV)-infected patients. Among the common causes are the infectious hepatitis, drug-related hepatitis, opportunistic infections, non-alcoholic steatohepatitis, HIV cholangiopathy and neoplasm. Auto-immune hepatitis (AIH) is rarely reported in this setting. We present two different presentations of auto immune hepatitis in HIV positive patients. One developed jaundice and ascites as a consequence of liver decompensation and other exhibited cholestatic pattern. Their serology and liver biopsy confirmed autoimmune hepatitis as underlying aetiology. We would like to share the clinical improvement with simultaneous immunosuppressive therapy and combination Anti Retroviral Therapy (cART). There are no documented cases on this issue from the Indian subcontinent that we are aware of.

Immunovirological discordance among people living with human immunodeficiency virus at a center in Western India: A retrospective study.

Background and Objectives: Treatment of people living with human immunodeficiency virus (HIV) (PLHIV) is monitored using plasma HIV viral load levels and CD4 counts. Patients with either immunological nonresponse (virological suppression achieved) or virological nonresponse (immune reconstitution achieved) are termed as having a discordant response. These patients are at higher risk for acquired immunodeficiency syndrome (AIDS)-related infections/diseases/neoplasms, non-AIDS-related illnesses (cardiovascular, neurological, renal, hepatic diseases), and all-cause death. This study was conducted to assess the prevalence of immunovirological discordance among PLHIV after completion of at least 1 year of combination antiretroviral therapy (cART) at an antiretroviral therapy (ART) plus center in India and analyze contributory factors. Methods: The study was a retrospective study of PLHIV receiving cART at the ART plus clinic in Western India from January 18 to December 21. Four hundred and ninety-six patients were studied based on sample size calculated and assessed for CD4 and viral load response at 0, 6, and 12 months of ART. Results: Of the 496 patients, 48 patients (9.7%) had immunovirological discordance. Out of them, 36 patients (75%) had a virological response (immunological nonresponse) and 12 (25%) patients had an immunological response (virological nonresponse). The factors contributing to immunological nonresponse were as follows - low baseline CD4 levels (<100 cells) (36.1%), adherence <95% (33.3%), presence of opportunistic infections (16.6%), and failure on first-line therapy (11.1%). Other factors noted included higher baseline viral load (2.7%), chronic kidney disease (5.5%), and chronic hepatitis B virus co-infection (5.5%). Virological nonresponse was associated with poor adherence to therapy <95% (33%) and failure of first-line regimen (33%). Opportunistic infections were noted among 33% of patients and 8.3% of patients were found to have higher baseline viral load. Interpretation and Conclusion: Immunovirological discordance is an important factor influencing response to cART and is associated with many complications such as AIDS and non-AIDS-related events and even death. Improved adherence and timely identification and management of opportunistic infections are measures that are beneficial in reducing the incidence of immunovirological discordance.

Layperson Physiological Tolerance and Operational Performance in Centrifuge-Simulated Spaceflight.

INTRODUCTION: Prior study has indicated that individuals of varied age, medical history, and limited-to-no experience tolerate spaceflight conditions. We sought to expand upon the understanding of layperson response to hypergravity conditions expected in commercial spaceflight by exposing subjects, following minimal training, to centrifuge-simulated, high-fidelity commercial spaceflight profiles. We further explored how these individuals perform in simulated operational activities during and following hypergravity.METHODS: Volunteer subjects participated in up to five centrifuge runs (maximum +4.0 Gz, +4.5 Gx, 6.1 G resultant; onset rate <0.5 Gz · s-1, ≤1 Gx · s-1). Profiles included two winged spacecraft simulations with sequential and combined +Gx/+Gz and two capsule simulations representing nominal +Gx launch and reentry. The final profile simulated a capsule launch abort, with a more dynamic cycling of +Gx exposures and oscillatory multi-axis exposures simulating parachutes and water motion. Touchscreen tablets were used to administer pattern-replication tasks during and after profiles.RESULTS: A total of 46 subjects participated, including 4 diabetics and 9 with cardiac disease. There was increased frequency of motion sickness, subjectively associated with capsule-type profiles, and increased termination of participation compared to prior studies. There was no association between medical history, age, sex, or motion sickness history and tolerance or noncompletion. Tablet test errors were common; accuracy and time to completion were associated with age. There was no association between any time metric or accuracy and sex.DISCUSSION: This study improves understanding of layperson tolerance in commercial spaceflight analog conditions, and the capsular profiles broaden the applicability of the findings. The frequency of task errors highlights the potential for mistakes in operational activities when performed by laypersons.Blue RS, Ong KM, Ray K, Menon A, Mateus J, Auñón-Chancellor S, Shah R, Powers W. Layperson physiological tolerance and operational performance in centrifuge-simulated spaceflight. Aerosp Med Hum Perform. 2023; 94(8):584-595.

An investigation of data from the first year of the interim Canada Dental Benefit for children <12 years of age.

Introduction: In 2022, the federal government announced a commitment of $5.3B to provide dental care for the uninsured, beginning with children <12 years of age. Now referred to as the Interim Canada Dental Benefit (CDB), the program targets those <12 years of age from families with annual incomes <$90,000 without private dental insurance. The purpose of this study was to review federal data from the Government of Canada on public uptake and applications made to the Canada Revenue Agency (CRA) during the first year of the Interim CDB. Methods: Data for the first year of the Interim CDB (up to June 30, 2023) were accessed from the Government of Canada Open Data Portal through Open Government Licence-Canada. Rates of children receiving the Interim CDB per 1,000 were calculated by dividing the number of beneficiaries by the total number of children 0-11 years by province or territory, available from Statistics Canada for the year 2021. Results: During the first year of the program, a total of 204,270 applications were approved, which were made by 188,510 unique applicants for 321,000 children <12 years of age. Over $197M was distributed by the CRA. Overall, the national rate for receiving the Interim CDB was 67.8/1,000 children. Ontario (82.5/1,000), Manitoba (77.1/1,000), Nova Scotia (73.4/1,000), and Saskatchewan (72.3%), all had rates of children with the Interim CDB above the national rate. Conclusions: Data from the first year of the Interim CDB suggests that this federal funding is increasing access to care for children <12 years by addressing the affordability of dental care. Governments and the oral health professions need to address other dimensions of access to care including accessibility, availability, accommodation, awareness, and acceptability of oral health care.

Fever of Unknown Origin and Hepatitis as the Initial Presentation of Anti-MDA-5 Positive Dermatomyositis: A Case Report.

Petersdorf and Beeson first defined fever of unknown origin (FUO) in 1961, and subsequently, over the next 60 years, the definition of FUO has changed considerably. In the western world, non-infectious inflammatory diseases are the most common cause of FUO; however, in developing countries, infections remain the leading cause of FUO. Dermatomyositis (DM) is an autoimmune inflammatory disease of unknown aetiology which mainly affects skin and muscles. Anti-melanoma differentiation-associated protein 5 (MDA-5) positive DM generally presents with classical cutaneous manifestations, early interstitial lung disease, and patients generally do not have clinical features of muscle involvement. We present a case of a 39-year-old male who presented with FUO and hepatitis and was diagnosed as clinically amyopathic DM after two weeks of admission. Subsequently, he was found to have a high titre of Anti-MDA-5 antibody. This is the first case of Anti-MDA-5 positive DM presenting as FUO and hepatitis with a favourable outcome to the best of our knowledge.

Epistaxis, paroxysmal anxiety episodes, and hypertension in a child with SDHB-associated paraganglioma: A case report.

A child presented with anxiety and weight gain which were overlooked until she had epistaxis. She was found to have hypertension secondary to paraganglioma. She was managed with curative surgery involving multidisciplinary care. The tumor removal led to the amelioration of symptoms and marked control of hypertension.

Symptomatic hypoglycemia in a nondiabetic adult female recovering from mild COVID-19 infection: A case report.

A 38-year-old lady, recently recovered from SARS-CoV-2 infection and taking grape seed extract, suffered multiple episodes of severe postprandial hyperinsulinemic hypoglycemia. A careful evaluation ruled out the common etiologies of hypoglycemia and identified grape seed extract consumption as a possible cause. She recovered after stopping the nutritional supplements. In her, hypoglycemia could have resulted from transient beta cell dysfunction associated with SARS-CoV-2 infection or proanthocyanidins in the grape seed extract.

Relationship of Computed Tomography Severity Score With Patient Characteristics and Survival in Hypoxemic COVID-19 Patients.

Background Computed tomography (CT) scans and CT severity scores (CTSS) are widely used to assess the severity and prognosis in coronavirus disease 2019 (COVID-19). CTSS has performed well as a predictor in differentiating severe from non-severe cases. However, it is not known if CTSS performs similarly in hospitalized severe cases with hypoxia at admission. Methods We conducted a retrospective comparative study at a COVID-care center from Western India between 25th April and 31st May 2021, enrolling all consecutive severe COVID-19 patients with hypoxemia (peripheral oxygen saturation < 94%). Neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, ferritin, and CT thorax were done within 24h of admission before being initiated on any anti-COVID-19 therapy. CTSS was calculated by visual assessment and categorized into three severity categories and was correlated with laboratory markers and overall survival (OS). Statistical analysis was done using John's Macintosh Project (JMP) 15.0.0 ver. 3.0.0 (Cary, North Carolina). Results The median age of the study population (n-298) was 59 years (24-95) with a male preponderance (61.41%, n=183). The 15 and 30-day survivals were 67.64% and 59.90%, respectively. CTSS did not correlate with age, gender, time from vaccination, symptoms, or comorbidities but had a significant though weak correlation with LDH (p=0.009), D-dimer (p=0.006), and NLR (p=0.019). Comparing demographic and laboratory aspects using CT severity categories, only NLR (p=0.0146) and D-dimer (p=0.0006) had significant differences. The 15d-OS of mild, moderate, and severe CT categories were 88.62%, 70.39%, and 52.62%, respectively, while 30d-OS of three categories were 59.08%, 63.96%, and 49.12%, respectively. Conclusion Among hospitalized severe COVID-19 patients with hypoxemia at admission, CT severity categories correlate well with outcomes but not inflammatory markers at admission.

mRNA-1273 and BNT162b2 COVID-19 vaccines elicit antibodies with differences in Fc-mediated effector functions.

The successful development of several coronavirus disease 2019 (COVID-19) vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants that are able to evade vaccine-induced neutralizing antibodies, real-world vaccine efficacy has begun to show differences across the two approved mRNA platforms, BNT162b2 and mRNA-1273; these findings suggest that subtle variation in immune responses induced by the BNT162b2 and mRNA-1273 vaccines may confer differential protection. Given our emerging appreciation for the importance of additional antibody functions beyond neutralization, we profiled the postboost binding and functional capacity of humoral immune responses induced by the BNT162b2 and mRNA-1273 vaccines in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to variants of concern. However, differences emerged across epitope-specific responses, with higher concentrations of receptor binding domain (RBD)- and N-terminal domain-specific IgA observed in recipients of mRNA-1273. Antibodies eliciting neutrophil phagocytosis and natural killer cell activation were also increased in mRNA-1273 vaccine recipients as compared to BNT162b2 recipients. RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector functions induced across the mRNA vaccines. These data provide insights into potential differences in protective immunity conferred by these vaccines.

Headache of Wearing PPE; A Survey for Neurological Symptoms with PPE amongst Health Care Workers.

Background: The COVID-19 pandemic has put the entire medical fraternity into a very challenging and demanding situation. Along with always being at the risk of COVID infection, healthcare workers (HCWs) are also facing neurological problems due to long working hours in personal protective equipment (PPE). These symptoms and their characteristics need to be observed and studied in-depth to understand the problems experienced by HCWs and to design new solutions to overcome such problems. Objectives: This study intends to evaluate the various neurological manifestations among the HCWs wearing PPE for prolonged periods. Materials and Methods: We conducted a questionnaire-based cross-sectional study at a Covid care center from western India from April 20 to June 01, 2021 by using a self-administered web-based questionnaire. A total of 256 HCWs were surveyed. The de-identified data were analyzed using JMP 15.0.0. Results: Among a total of 256 HCWs surveyed for this study, the majority (58.6%) were aged 24-35 years, with a male preponderance (65.62%, n = 168). Participants included doctors (41%), nurses (35%), paramedical staff (22%), and housekeeping staff (1%). The symptoms encountered among the HCWs wearing the PPE were headache, classified further as donning headache in 112 (44.98%), doffing headache in 56 (26.24%), slowed mentation in 48 (21.05%), and excessive sleepiness in 86 (38.74%), which affected their work performance. The age of the HCWs had a significant correlation with all the symptoms. Conclusion: Headache, slowed mentation, and excessive sleepiness was encountered among the HCWs wearing PPE, which depended upon the duration of PPE usage. The most common symptom was headache, which was of moderate to severe intensity.

SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.

Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.

mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern.

SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization.

Serological Markers of SARS-CoV-2 Reinfection.

As public health guidelines throughout the world have relaxed in response to vaccination campaigns against SARS-CoV-2, it is likely that SARS-CoV-2 will remain endemic, fueled by the rise of more infectious SARS-CoV-2 variants. Moreover, in the setting of waning natural and vaccine immunity, reinfections have emerged across the globe, even among previously infected and vaccinated individuals. As such, the ability to detect reexposure to and reinfection by SARS-CoV-2 is a key component for global protection against this virus and, more importantly, against the potential emergence of vaccine escape mutations. Accordingly, there is a strong and continued need for the development and deployment of simple methods to detect emerging hot spots of reinfection to inform targeted pandemic response and containment, including targeted and specific deployment of vaccine booster campaigns. In this study, we identify simple, rapid immune biomarkers of reinfection in rhesus macaques, including IgG3 antibody levels against nucleocapsid and FcγR2A receptor binding activity of anti-RBD antibodies, that are recapitulated in human reinfection cases. As such, this cross-species analysis underscores the potential utility of simple antibody titers and function as price-effective and scalable markers of reinfection to provide increased resolution and resilience against new outbreaks. IMPORTANCE As public health and social distancing guidelines loosen in the setting of waning global natural and vaccine immunity, a deeper understanding of the immunological response to reexposure and reinfection to this highly contagious pathogen is necessary to maintain public health. Viral sequencing analysis provides a robust but unrealistic means to monitor reinfection globally. The identification of scalable pathogen-specific biomarkers of reexposure and reinfection, however, could significantly accelerate our capacity to monitor the spread of the virus through naive and experienced hosts, providing key insights into mechanisms of disease attenuation. Using a nonhuman primate model of controlled SARS-CoV-2 reexposure, we deeply probed the humoral immune response following rechallenge with various doses of viral inocula. We identified virus-specific humoral biomarkers of reinfection, with significant increases in antibody titer and function upon rechallenge across a range of humoral features, including IgG1 to the receptor binding domain of the spike protein of SARS-CoV-2 (RBD), IgG3 to the nucleocapsid protein (N), and FcγR2A receptor binding to anti-RBD antibodies. These features not only differentiated primary infection from reexposure and reinfection in monkeys but also were recapitulated in a sequencing-confirmed reinfection patient and in a cohort of putatively reinfected humans that evolved a PCR-positive test in spite of preexisting seropositivity. As such, this cross-species analysis using a controlled primate model and human cohorts reveals increases in antibody titers as promising cross-validated serological markers of reinfection and reexposure.

Understanding Vaccine Hesitancy in the Context of COVID-19: The Role of Trust and Confidence in a Seventeen-Country Survey.

Objectives: An effective vaccine to SARS-CoV-2 cannot be successfully deployed if a significant number of people worldwide are unwilling to accept it. We investigated the relationship between trust in scientists and medical professionals and perceptions of vaccine safety and effectiveness. We also build on past studies by exploring the relationship between confidence in global health organizations and vaccine hesitancy. Methods: We conducted an online survey in seventeen countries/territories across five world regions between May -June 2020. We assessed the relationship between COVID19 vaccine hesitancy, confidence in public health organizations, and trust in key experts and leaders. Results: Our findings strongly suggest that confidence in the World Health Organization combined with trust in domestic scientists and healthcare professionals is a strong driver of vaccine acceptance across multiple countries/territories. Conclusion: We find that hesitancy is widespread, and uptake would be insufficient to achieve herd immunity. There is widespread confidence in how public health organizations have responded to the current pandemic and this is related to vaccine acceptance. Our results also highlight the important role of trust in health care providers and scientists in reducing COVID19 vaccine hesitancy.

Epidemiological and Immunological Features of Obesity and SARS-CoV-2.

Obesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response remain poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups; we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection; and remarkably homogenous immune activity across BMI categories suggests immune protection across these groups may be similar.

Early cross-coronavirus reactive signatures of humoral immunity against COVID-19.

The introduction of vaccines has inspired hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against SARS-CoV-2, thus we profiled the earliest humoral signatures in a large cohort of acutely ill (survivors and nonsurvivors) and mild or asymptomatic individuals with COVID-19. Although a SARS-CoV-2­specific immune response evolved rapidly in survivors of COVID-19, nonsurvivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibodies. Given the conservation of S2 across ß-coronaviruses, we found that the early development of SARS-CoV-2­specific immunity occurred in tandem with preexisting common ß-coronavirus OC43 humoral immunity in survivors, which was also selectively expanded in individuals that develop a paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.