Laboratory markers of severity across three COVID-19 outbreaks in Australia: has Omicron and vaccinations changed disease presentation?

COVID-19 has rapidly evolved since it was first discovered in December 2019. We aimed to retrospectively review our experience with COVID-19 infection across 2020-2022, focusing on differences in laboratory markers at presentation. Consecutive adult patients admitted to hospital with confirmed COVID-19 infection were retrospectively reviewed across three periods (29/3/2020-29/9/2020, 16/8/2021-13/10/2021 and 1/1/2022-31/1/2022), correlating with the lineages B.1.338, Delta (B.1.617.2) and Omicron (B.1.1.159), respectively. Laboratory findings of the first requested blood test within 24 h of presentation were recorded and correlated with patient outcome. The primary outcome was requirement for oxygen therapy at any point. Inflammatory markers, namely serum ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) were significantly lower on presentation during 2022 compared to 2021, corresponding to a milder disease course. More than 80% of 2022 patients had received 2 or more vaccine doses and fully vaccinated patients displayed significantly lower inflammatory markers at presentation. Using 2022 data, a multivariate prediction model was constructed to predict for oxygen requirement, with c-statistic 0.86. Patients in 2022, corresponding with the Omicron variant, displayed a milder disease course, even in hospitalised patients, with the majority not requiring oxygen and lower inflammatory markers. We constructed a simple-to-use risk prediction model with c-statistic 0.86 which may identify individuals who can be safely managed as outpatients in the era of highly transmissible variants.

Food Allergies in Inner-City Schools: Addressing Disparities and Improving Management.

OBJECTIVE: Food allergy (FA) affects approximately 8% of children in the United States. Management comprises both preventing and treating allergic reactions, which poses unique challenges in the inner-city school setting. In this article, we review the epidemiology of FA in school-aged children and management challenges and opportunities specific to the inner-city population. DATA SOURCES: A literature search of the PubMed database was performed to identify published literature on FA epidemiology, FA management, school policies, disparities, inner-city, race, ethnicity, and socioeconomic status. STUDY SELECTIONS: Relevant articles on FA management best practices and challenges in schools, with a particular emphasis on inner-city schools and populations and socioeconomic, racial, and ethnic disparities, were reviewed in detail. RESULTS: Disparities in FA prevalence, management, and treatment exist. Additional research is needed to better characterize these disparities and elucidate the mechanisms leading to them. There is a lack of evidence-based interventions for the prevention and treatment of food allergic reactions in schools and specifically in inner-city schools, in which a greater proportion of students may rely on school food. CONCLUSION: There are opportunities for partnership among health care providers, schools, and communities to address unmet needs in FA management and disparities in the inner-city school setting.

Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios

PURPOSE OF THE STUDY: To assess the association between maternal and neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody concentrations. STUDY POPULATION: Mother and newborn dyads (n = 1471) from 1714 parturient women at a single, urban, hospital center in Pennsylvania from April 9, 2020 to August 8, 2020. METHODS: Pregnant women who delivered at Pennsylvania Hospital were screened for SARS-CoV-2 by nasopharyngeal polymerase chain reaction (PCR) upon admission, SARS-CoV-2 exposure, and development of coronavirus disease 2019 (COVID-19) symptoms. Residual maternal and cord blood sera routinely collected at delivery were used for SARS-CoV-2 spike protein antibody measurement using a validated enzyme-linked immunosorbent assay. Antibody (IgG, IgM) concentrations and transplacental transfer ratios were analyzed along with demographic and clinical data obtained from electronic medical record review. RESULTS: The study cohort of 1714 women who delivered included White non-Hispanic (51.3%), Black non-Hispanic (26.3%), Hispanic (11.8%), Asian (7.3%), and other (3.3%) participants with a median age of 32 years. SARS-CoV-2 IgG and/or IgM antibodies were detected in 83 of 1471 (6%) mothers with matched mother and newborn sera available at delivery. Among newborns born to seropositive women, IgG was detected in 72 of 83 (87%) newborns. Infants born to seronegative mothers did not have any detectable antibodies, and IgM antibodies were not detected in any cord blood sample. Most seropositive women (60%) were asymptomatic for COVID-19. None of the infants born to seropositive mothers tested positive to SARS-CoV-2 by PCR between 24 and 48 hours after birth. Neonatal cord blood IgG concentrations were positively correlated to maternal IgG concentrations (r = 0.886, P < .001). Placental transfer ratios were associated with time elapsed from maternal infection, defined as time of symptom-prompted PCR testing, to delivery (r = 0.620, P < .001). Transfer ratios were not associated with infection severity. Ratios more than 1.0 were observed among all disease severities, including those asymptomatic. Antibody transfer ratios increased as time increased between onset of maternal infection and delivery. CONCLUSIONS: Maternal IgG antibodies to SARS-CoV-2 were transferred across the placenta in symptomatic and asymptomatic infection in pregnancy. Neonatal cord blood antibody concentrations correlated with maternal antibody concentrations and with the length of time between onset of infection and delivery.

A Synopsis of the Synopses, 2021–2022

An introduction is presented in which the editor discusses various reports within the issue on topics including asthma in children, how to improve recognition and diagnosis of important immunologic disorders, and the immune response and clinical manifestations of COVID-19.

Impaired Fibrinolytic Potential Predicts Oxygen Requirement in COVID-19.

Abnormal coagulation and fibrinolysis contributes to the respiratory distress syndrome in COVID-19. We aimed to explore the association of impaired fibrinolytic potential with disease severity and oxygen requirement in hospitalized patients. Adults admitted to hospital with confirmed COVID-19 infection between 1-31 January 2022 were included, corresponding to the first Omicron outbreak in Melbourne, Victoria. The first citrated plasma sample requested within 24 h of the patient's presentation was obtained and analyzed by the overall hemostatic potential (OHP) assay, a spectrophotometric assay in which fibrin formation (triggered by small amounts of thrombin (OCP)) and fibrinolysis (by the addition of thrombin and tissue plasminogen activator (OHP and OFP%)) were simultaneously measured. There were 266 patients (median 72 years, 52.9% male), of which 49.6% did not require oxygen therapy. COVID-19 severity and requirement for oxygen was significantly associated with higher OCP, OHP, and lower OFP%. Vaccinated individuals compared with non-vaccinated individuals had significantly lower OHP (16.5 vs. 23.1, p = 0.015) and higher OFP (72.0% vs. 65.1%, p = 0.005), as well as significantly lower AST, ferritin, LDH, CRP, and D-dimer. A multivariate model containing OHP was constructed with the outcome of oxygen requirement, with c-statistic of 0.85 (95%CI 0.81-0.90). In this pilot study, we show a significant correlation between OHP results and requirement for oxygen supplementation in hospitalized patients during a period dominated by the Omicron variant. The results were incorporated into a multivariate model that predicted for oxygen requirement, with high discriminative ability.

Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity in Healthy Controls and Patients with Cardiovascular Risk Factors and/or Disease.

Angiotensin converting enzyme 2 (ACE2) is an endogenous negative regulator of the renin-angiotensin system, a key factor in the development of cardiovascular disease (CVD). ACE2 is also used by SARS-CoV-2 for host cell entry. Given that COVID-19 is associated with hypercoagulability, it is timely to explore the potential relationship between plasma ACE2 activity and the coagulation profile. In this cross-sectional study, ACE2 activity and global coagulation assays (GCA) including thromboelastography, thrombin, and fibrin generation were measured in adult healthy controls (n = 123; mean age 41 ± 17 years; 35% male) and in patients with cardiovascular risk factors and/or disease (n = 258; mean age 65 ± 14 years; 55% male). ACE2 activity was significantly lower in controls compared to patients with cardiovascular risk factors and/or disease (median 0.10 (0.02, 3.33) vs. 5.99 (1.95, 10.37) pmol/mL/min, p < 0.001). Of the healthy controls, 48% had undetectable ACE2 activity. Controls with detectable ACE2 had lower maximum amplitude (p < 0.001). In patients with cardiovascular risk factors and/or disease, those in the 3rd tertile were older and male (p = 0.002), with a higher Framingham grade and increased number of cardiovascular risk factors (p < 0.001). In conclusion, plasma ACE2 activity is undetectable to very low in young healthy controls with minimal clinically relevant associations to GCA. Patients with cardiovascular risk factors and/or disease have increased plasma ACE2 activity, suggesting that it may be an important biomarker of endothelial dysfunction and atherosclerosis.

Acute At-Home Management of Anaphylaxis: 911: What Is the Emergency?

The appropriate at-home management of anaphylaxis begins with patient education on recognition and treatment, especially when and how to use epinephrine. Delayed administration of epinephrine as well as having severe symptoms and needing multiple doses of epinephrine to treat symptoms are risk factors for biphasic anaphylaxis. The successful implementation of at-home management of anaphylaxis requires appropriate patient selection and an algorithmic approach that recommends activation of emergency medical services (EMS) when the patient does not adequately respond to at-home administration of epinephrine or there are extenuating patient-related circumstances. Fortunately, approximately 98% of anaphylactic episodes respond to 2 or fewer doses of epinephrine, the standard prescription used for epinephrine autoinjectors; fatal anaphylaxis is very rare, as low as 0.002 deaths/million person-years; and biphasic reactions are uncommon (∼5%), and only extremely rarely lethal. Thus, most common concerns leading to recommended EMS activation and emergency department visits after epinephrine administration are generally unsubstantiated. Furthermore, emergency department visits do not always lead to better treatment and drive health care costs higher. Open communications with patients and families regarding risks and benefits of at-home management and observation versus EMS activation and emergency department evaluation after epinephrine administration for anaphylaxis are essential. However, we believe the data indicate that it is time to reconsider the often used and taught approach that recommends EMS activation whenever epinephrine is used.

Asthma, from mild to severe, is an independent prognostic factor for mild to severe Coronavirus disease 2019 (COVID-19).

BACKGROUND: Chronic illnesses were reported to be poor prognostic factors associated with severe illness and mortality in Coronavirus disease 2019 (COVID-19) infection. The association with asthma, however, is limited and controversial, especially for mild asthma. METHODS: A territory wide retrospective study was conducted to investigate the association between asthma and the prognosis of COVID-19. All patients with laboratory confirmed in Hong Kong for COVID-19 from the 23 January to 30 September 2020 were included in the study. Severe diseases were defined as those who develop respiratory complications, systemic complications, and death. RESULTS: Among the 4498 patients included in the analysis, 165 had asthma, with 141 having mild asthma. Patients with asthma were significantly more likely to require invasive mechanical ventilation (incidence = 17.0% odds ratio [OR] = 4.765, p < 0.001), oxygen therapy (incidence = 39.4%, OR = 3.291, p < 0.001), intensive care unit admission (incidence = 21.2%, OR = 3.625, p < 0.001), and systemic steroid treatment (incidence = 34.5%, OR = 4.178, p < 0.001) and develop shock (incidence = 16.4%, OR = 4.061, p < 0.001), acute kidney injury (incidence = 6.1%, OR = 3.281, p = 0.033), and secondary bacterial infection (incidence = 56.4%, OR = 2.256, p < 0.001). They also had significantly longer length of stay. Similar findings were also found in patients with asthma of the Global Initiative for Asthma (GINA) steps 1 and 2 upon subgroup analysis. CONCLUSIONS: Asthma, regardless of severity, is an independent prognostic factor for COVID-19 and is associated with more severe disease with respiratory and systemic complications.

Territory-Wide Study on Hospital Admissions for Asthma Exacerbations in the COVID-19 Pandemic.

Rationale: Patients with asthma were advised to avoid coronavirus disease (COVID-19) and comply with medication during the COVID-19 pandemic. Respiratory tract infection is a common cause of asthma exacerbations. There has not been evidence suggesting the link between COVID-19 and asthma exacerbation, especially in places with dramatic responses in infection control with universal masking and aggressive social distancing. Objectives: To assess the number for admissions of asthma exacerbations in January to April 2020 in Hong Kong with reference to admission in the past 5 years. Methods: Admission records of asthma exacerbations were retrieved from the Clinical Data Analysis and Reporting System. Patients aged 18 years or older with a known history of asthma admitted for asthma exacerbation were included. Log-linear was used to model count, with year and masking used as covariate and further analysis on ambient temperature and length of hospital stays. Fisher's exact test was used to compare the mortality rate and mechanical ventilation between the periods. Admissions for myocardial infarction, ischemic stroke, and gastric ulcer were included as controls. Results: The number of admissions for asthma exacerbations significantly decreased by 53.2% (95% confidence interval [CI], 50.4-55.8%) in 2020 compared with monthly average admission in 2015-2019, with a higher magnitude of decrease compared with control diagnoses. Admissions for asthma exacerbations decreased by 2.0% (95% CI, 1.8-2.2%) with every 1°C (1.8°F) increase in temperature and by 0.8% with every 1% increase in masking (95% CI, 0.8-0.9%). Conclusions: Hospitalization number for asthma exacerbations significantly decreased in early 2020, with similar length of stay. This was observed with concomitant practice of universal masking and social distancing during the COVID-19 pandemic in Hong Kong. We proposed that universal masking and social distancing reduced respiratory viral infection, leading to fewer hospital admissions for asthma exacerbations.

Health disparities in allergic and immunologic conditions in racial and ethnic underserved populations: A Work Group Report of the AAAAI Committee on the Underserved.

Health disparities are health differences linked with economic, social, and environmental disadvantage. They adversely affect groups that have systematically experienced greater social or economic obstacles to health. Renewed efforts are needed to reduced health disparities in the United States, highlighted by the disparate impact on racial minorities during the coronavirus pandemic. Institutional or systemic patterns of racism are promoted and legitimated through accepted societal standards, and organizational processes within the field of medicine, and contribute to health disparities. Herein, we review current evidence regarding health disparities in allergic rhinitis, asthma, atopic dermatitis, food allergy, drug allergy, and primary immune deficiency disease in racial and ethnic underserved populations. Best practices to address these disparities involve addressing social determinants of health and adopting policies to improve access to specialty care and treatment for the underserved through telemedicine and community partnerships, cross-cultural provider training to reduce implicit bias, inclusion of underserved patients in research, implementation of culturally competent patient education, and recruitment and training of health care providers from underserved communities. Addressing health disparities requires a multilevel approach involving patients, health providers, local agencies, professional societies, and national governmental agencies.

A Cyclodextrin-Stabilized Spermine-Tagged Drug Triplex that Targets Theophylline to the Lungs Selectively in Respiratory Emergency.

Ion-pairing a lifesaving drug such as theophylline with a targeting moiety could have a significant impact on medical emergencies such as status asthmaticus or COVID-19 induced pneumomediastinum. However, to achieve rapid drug targeting in vivo the ion-pair must be protected against breakdown before the entry into the target tissue. This study aims to investigate if inserting theophylline, when ion-paired to the polyamine transporter substrate spermine, into a cyclodextrin (CD), to form a triplex, could direct the bronchodilator to the lungs selectively after intravenous administration. NMR demonstrates that upon the formation of the triplex spermine protruded from the CD cavity and this results in energy-dependent uptake in A549 cells (1.8-fold enhancement), which persists for more than 20 min. In vivo, the triplex produces a 2.4-fold and 2.2-fold increase in theophylline in the lungs 20 min after injection in rats and mice, respectively (p < 0.05). The lung targeting is selective with no increase in uptake into the brain or the heart where the side-effects of theophylline are treatment-limiting. Selectively doubling the concentration of theophylline in the lungs could improve the benefit-risk ratio of this narrow therapeutic index medicine, which continues to be important in critical care.

Novel Approaches to Food Allergy Management During COVID-19 Inspire Long-Term Change.

The SARS-CoV2 pandemic has prompted a re-evaluation of our current practice of medicine. The seemingly abrupt worldwide spread of this disease resulted in immediate changes and a reduction in many allergy-focussed services and procedures. The reality of the long-term circulation of this virus in our communities requires us to evolve as a specialty. In this article, we outline current and future challenges in the management of food allergy in light of coronavirus disease 2019 (COVID-19). We focus on infant food allergy prevention, management of anaphylaxis, accurate diagnosis with oral food challenges, and active management of food allergy with oral immunotherapy. This article identifies the challenges of conflicting guidelines, shortcomings of acute management approaches, and inherent system deficiencies. We offer perspectives and strategies that can be implemented now, including an evaluation of virtual care and telemedicine for the management of food allergy. The use of a shared decision-making model results in novel approaches that can benefit our patients and our specialty for years to come. COVID-19 has forced us to re-evaluate our current way of thinking about food allergy management to better treat our patients.

Managing Food Allergy in Schools During the COVID-19 Pandemic.

In the wake of the COVID-19 pandemic and massive disruptions to daily life in the spring of 2020, in May 2020, the Centers for Disease Control (CDC) released guidance recommendations for schools regarding how to have students attend while adhering to principles of how to reduce the risk of contracting SARS-CoV-2. As part of physical distancing measures, the CDC is recommending that schools who traditionally have had students eat in a cafeteria or common large space instead have children eat their lunch or other meals in the classroom at already physically distanced desks. This has sparked concern for the safety of food-allergic children attending school, and some question of how the new CDC recommendations can coexist with recommendations in the 2013 CDC Voluntary Guidelines on Managing Food Allergy in Schools as well as accommodations that students may be afforded through disability law that may have previously prohibited eating in the classroom. This expert consensus explores the issues related to evidence-based management of food allergy at school, the issues of managing the health of children attending school that are acutely posed by the constraints of an infectious pandemic, and how to harmonize these needs so that all children can attend school with minimal risk from both an infectious and allergic standpoint.