Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection.

Virus-neutralizing antibodies are often accepted as a correlate of protection against infection, though questions remain about which components of the immune response protect against SARS-CoV-2 infection. In this small observational study, we longitudinally measured spike receptor binding domain (RBD)-specific and nucleocapsid (NP)-specific serum IgG in a human cohort immunized with the Pfizer BNT162b2 vaccine. NP is not encoded in the vaccine, so an NP-specific response is serological evidence of natural infection. A greater than fourfold increase in NP-specific antibodies was used as the serological marker of infection. Using the RBD-specific IgG titers prior to seroconversion for NP, we calculated a protective threshold for RBD-specific IgG. On average, the RBD-specific IgG response wanes below the protective threshold 169 days following vaccination. Many participants without a history of a positive test result for SARS-CoV-2 infection seroconverted for NP-specific IgG. As a group, participants who seroconverted for NP-specific IgG had significantly higher levels of RBD-specific IgG following NP-seroconversion. RBD-specific IgG titers may serve as one correlate of protection against SARS-CoV-2 infection. These titers wane below the proposed protective threshold approximately six months following immunization. Based on serological evidence of infection, the frequency of breakthrough infections and consequently the level of SARS-CoV-2-specific immunity in the population may be higher than what is predicted based on the frequency of documented infections.

The 80th anniversary of Annals of Allergy, Asthma & Immunology (1943-2023).

The year 2023 marks the 80th year of publication of Annals of Allergy, Asthma & Immunology. To celebrate this important milestone, we look back on the history of the journal from its inception to the present day. This special article explores the rationale and people involved in creating the journal and highlights major advances in Annals history. Our celebration of Annals' 80th year of publication concludes with a glimpse into the potential future of Annals.

The pathophysiology of postacute sequelae of COVID-19 (PASC): Possible role for persistent inflammation.

As the SARS-CoV-2-induced pandemic wanes, a substantial number of patients with acute Corona Virus-induced disease (COVID-19 continue to have symptoms for a prolonged time after initial infection. These patients are said to have postacute sequelae of COVID (PASC) or "long COVID". The underlying pathophysiology of this syndrome is poorly understood and likely quite heterogeneous. The role of persistent, possibly deviant inflammation as a major factor in comorbidity is suspected. Objective: To review data that address the relative importance of inflammation in the pathophysiology spectrum of PASC and to address how this would impact diagnosis and approach to therapy in patients identified as having such inflammatory abnormalities. Methods: A review of public databases, including PubMed, MeSH, NLM catalog, and clinical trial databases such as clinicaltrials.gov. Results: The literature supports a prominent role for various forms and types of inflammation in the pathophysiologic spectrum of PASC. Such inflammation can be persistent ant CoV-2-specific responses, new onset autoimmune responses, or a loss of normal immunoregulation resulting in widespread, sustained inflammatory pathologies that can affect both broad constitutional symptoms (such as fatigue, neurocognitive dysfunction, and anxiety/depression) and organ-specific dysfunction and/or failure. Conclusions: PASC is a significant clinical entity with similarities to and differences from other postviral syndromes. Significant research efforts are ongoing to better understand specific aberrant inflammatory pathways present in individual patients for the purpose of developing and implementing effective therapies and ultimately prophylaxis strategies to prevent the progression of COVID-19 as well as likely future viral illnesses and pandemics.

Is Baikiain in Tara Flour a Causative Agent for the Adverse Events Associated with the Recalled Frozen French Lentil & Leek Crumbles Food Product? - A Working Hypothesis.

The French Lentil & Leek Crumbles frozen food product was recently recalled due to reports of gastrointestinal issues. So far, 393 adverse illness complaints and 133 hospitalizations have been reported from consumption of this food, and the tara (Tara spinosa) protein flour ingredient is hypothesized to be responsible. A multipronged approach resulted in identification of (S)-(-)-baikiain in tara as a compound of interest due to its abundance, possible metabolic fate, and close resemblance to irreversible inhibitors of L-pipecolate oxidase. Oral administration of baikiain in ND4 mice showed a statistically significant increase in blood ALT levels and a reduction in liver GSH.

An Update on Monoclonal Antibody Therapy to Treat Moderate-to-Severe Asthma: Benefits, Choices, and Limitations.

Moderate or severe asthma is a complex disease process clinically manifesting as at least partially reversible airway obstruction due to airway hyperresponsiveness. Asthma therapy was based primarily on symptom control until recent studies of its mechanisms have led to a host of new targeted, safe, and effective therapies. These biologic therapies directly attack culprit inflammatory mediators at the molecular level. In this article we review currently available biologic agents for the treatment of moderate-to-severe asthma. We provide information deemed necessary to optimally consult with an asthma specialist to choose, assist in financial arrangements for, and coordinate the use of these new, promising, Food and Drug Administration-approved biologic agents. We will also briefly review the molecular pathways targeted with each class of biologic to provide a more in-depth understanding of why these targeted therapies are effective. These biologics are the first of many to come that modify newly discovered components of the immune system with which many physicians are unfamiliar.

Predictors of Metformin Failure: Repurposing Electronic Health Record Data to Identify High-Risk Patients.

CONTEXT: Metformin is the first-line drug for treating diabetes but has a high failure rate. OBJECTIVE: To identify demographic and clinical factors available in the electronic health record (EHR) that predict metformin failure. METHODS: A cohort of patients with at least 1 abnormal diabetes screening test that initiated metformin was identified at 3 sites (Arizona, Mississippi, and Minnesota). We identified 22 047 metformin initiators (48% female, mean age of 57 ± 14 years) including 2141 African Americans, 440 Asians, 962 Other/Multiracial, 1539 Hispanics, and 16 764 non-Hispanic White people. We defined metformin failure as either the lack of a target glycated hemoglobin (HbA1c) (<7%) within 18 months of index or the start of dual therapy. We used tree-based extreme gradient boosting (XGBoost) models to assess overall risk prediction performance and relative contribution of individual factors when using EHR data for risk of metformin failure. RESULTS: In this large diverse population, we observed a high rate of metformin failure (43%). The XGBoost model that included baseline HbA1c, age, sex, and race/ethnicity corresponded to high discrimination performance (C-index of 0.731; 95% CI 0.722, 0.740) for risk of metformin failure. Baseline HbA1c corresponded to the largest feature performance with higher levels associated with metformin failure. The addition of other clinical factors improved model performance (0.745; 95% CI 0.737, 0.754, P < .0001). CONCLUSION: Baseline HbA1c was the strongest predictor of metformin failure and additional factors substantially improved performance suggesting that routinely available clinical data could be used to identify patients at high risk of metformin failure who might benefit from closer monitoring and earlier treatment intensification.

Respiratory psychophysiology and COVID-19: A research agenda.

After multiple waves of the COVID-19 pandemic, it has become clear that the impact of SARS-CoV-2 will carry on for years to come. Acutely infected patients show a broad range of disease severity, depending on virus variant, vaccination status, age and the presence of underlying medical and physical conditions, including obesity. Additionally, a large number of patients who have been infected with the virus present with post-COVID syndrome. In September 2020, the International Society for the Advancement of Respiratory Psychophysiology organized a virtual interest meeting on 'Respiratory research in the age of COVID-19', which aimed to discuss how research in respiratory psychophysiology could contribute to a better understanding of psychophysiological interactions in COVID-19. In the resulting current paper, we propose an interdisciplinary research agenda discussing selected research questions on acute and long-term neurobiological, physiological and psychological outcomes and mechanisms related to respiration and the airways in COVID-19, as well as research questions on comorbidity and potential treatment options, such as physical rehabilitation.

IgG Antibody Response to the Pfizer BNT162b2 SARS-CoV-2 Vaccine in Healthcare Workers with Healthy Weight, Overweight, and Obesity.

Obesity is a significant factor for increased morbidity and mortality upon infection with SARS-CoV-2. Because of the higher potential for negative outcomes following infection of individuals with obesity, the impact of body mass index (BMI) on vaccine immunogenicity and efficacy is an important public health concern. Few studies have measured the magnitude and durability of the vaccine-specific response in relation to BMI. We measured the receptor binding domain (RBD)-specific serum IgG and surrogate neutralizing titers in a cohort of 126 vaccinated individuals with no clinical history or serological evidence of previous SARS-CoV-2 infection 50 and 200 days following vaccination. BMI had no significant impact on RBD-specific IgG titers and surrogate neutralizing titers 50 days following immunization, and leptin levels had no correlation with the response to immunization. Two hundred days following immunization, antibody titers in all groups had declined by approximately 90%. The responses were also similar between male and female participants and did not significantly vary across age groups. These results indicate that the magnitude and durability of the antibody response to mRNA-based vaccines are unaffected by BMI in this cohort.

Experimental methods to study sleep disruption and immune balance in urban children with asthma.

Study Objectives: We describe research methods developed to examine effects of sleep disruption on changes in immune balance, lung function, and cognitive performance in a sample of urban, ethnically diverse children with persistent asthma. Two case examples (8- and 10-year-old males) are presented to highlight methods of the current study and illustrate effects of experimentally disrupted sleep on the immune balance profile (Th1/Th2 cytokines), key sleep variables from polysomnography data, and lung function in our sample. Methods: Children follow an individualized structured sleep schedule consistent with their habitual sleep need (≥9.5 hours' time in bed) for six days before a laboratory-based experimental sleep protocol. Children then spend two successive nights in the sleep lab monitored by polysomnography: a baseline night consisting of uninterrupted sleep, and a disruption night, during which they are awoken for 2 minutes between 20-minute intervals of uninterrupted sleep. Evening and morning blood draws bracket baseline and disruption nights for immune biomarker assessment. Results: A shift towards immune imbalance following the sleep disruption protocol was observed in these illustrative cases. Conclusions: Data from these case examples provide evidence that the experimental protocol caused disruptions in sleep as observed on polysomnography and had the hypothesized downstream effects on immune balance associated with clinical asthma control. Documenting the effects of sleep disruption on immune function in children with persistent asthma is a crucial step towards understanding associations between sleep, immune balance, and asthma outcomes and provides important information for developing novel interventions for youth with asthma and suboptimal sleep. Clinical Trials: Not applicable.

Effective screening of SARS-CoV-2 neutralizing antibodies in patient serum using lentivirus particles pseudotyped with SARS-CoV-2 spike glycoprotein.

Pseuodotyped particles have significant importance and use in virology as tools for studying the biology of highly pathogenic viruses in a lower biosafety environment. The biological, chemical, and serological studies of the recently emerged SARS-CoV-2 will be greatly aided by the development and optimization of a suitable pseudotyping system. Here, we pseudotyped the SARS-CoV-2 Spike glycoprotein (SPG) on a traditional retroviral (MMLV) as well as a third generation lentiviral (pLV) vector and tested the transduction efficiency in several mammalian cell lines expressing SARS-CoV-2 receptor hACE2. While MMLV pseudotyped the vesicular stomatitis virus G glycoprotein (VSV-G) efficiently, it could not pseudotype the full-length SPG. In contrast, pLV pseudotyped both glycoproteins efficiently; however, much higher titers of pLV-G particles were produced. Among all the tested mammalian cells, 293Ts expressing hACE2 were most efficiently transduced using the pLV-S system. The pLV-S particles were efficiently neutralized by diluted serum (>:640) from recently recovered COVID-19 patients who showed high SARS-CoV-2 specific IgM and IgG levels. In summary, pLV-S pseudotyped virus provides a valid screening tool for the presence of anti SARS-CoV-2 specific neutralizing antibodies in convalescent patient serum.