A randomized controlled trial to evaluate outcomes with Aggrenox in patients with SARS-CoV-2 infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an immunoinflammatory and hypercoagulable state that contributes to respiratory distress, multi-organ dysfunction, and mortality. Dipyridamole, by increasing extracellular adenosine, has been postulated to be protective for COVID-19 patients through its immunosuppressive, anti-inflammatory, anti-coagulant, vasodilatory, and anti-viral actions. Likewise, low-dose aspirin has also demonstrated protective effects for COVID-19 patients. This study evaluated the effect of these two drugs formulated together as Aggrenox in hospitalized COVID-19 patients. METHODS: In an open-label, single site randomized controlled trial (RCT), hospitalized COVID-19 patients were assigned to adjunctive Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally) with standard of care treatment compared to standard of care treatment alone. Primary endpoint was illness severity according to changes on the eight-point COVID ordinal scale, with levels of 1 to 8 where higher scores represent worse illness. Secondary endpoints included all-cause mortality and respiratory failure. Outcomes were measured through days 14, 28, and/or hospital discharge. RESULTS: From October 1, 2020 to April 30, 2021, a total of 98 patients, who had a median [IQR] age of 57 [47, 62] years and were 53.1% (n = 52) female, were randomized equally between study groups (n = 49 Aggrenox plus standard of care versus n = 49 standard of care alone). No clinically significant differences were found between those who received adjunctive Aggrenox and the control group in terms of illness severity (COVID ordinal scale) at days 14 and 28. The overall mortality through day 28 was 6.1% (3 patients, n = 49) in the Aggrenox group and 10.2% (5 patients, n = 49) in the control group (OR [95% CI]: 0.40 [0.04, 4.01], p = 0.44). Respiratory failure through day 28 occurred in 4 (8.3%, n = 48) patients in the Aggrenox group and 7 (14.6%, n = 48) patients in the standard of care group (OR [95% CI]: 0.21 [0.02, 2.56], p = 0.22). A larger decrease in the platelet count and blood glucose levels, and larger increase in creatinine and sodium levels within the first 7 days of hospital admission were each independent predictors of 28-day mortality (p < 0.05). CONCLUSION: In this study of hospitalized patients with COVID-19, while the outcomes of COVID illness severity, odds of mortality, and chance of respiratory failure were better in the Aggrenox group compared to standard of care alone, the data did not reach statistical significance to support the standard use of adjuvant Aggrenox in such patients.

Fellows in Training Wellness in Allergy and Immunology: AAAAI Workgroup Report.

Physician health and wellness can be negatively affected by burnout, which in turn can lead to multiple potential professional and personal issues. Burnout issues can start in medical school and progress during residency and fellowship, and throughout a physician's career. A previous survey of allergists and immunologists reported a burnout rate of 35%. However, there are currently few data regarding health and wellness specifically for fellows-in-training (FIT) in allergy and immunology. This workgroup report was developed to assess health and wellness among FIT in our specialty. The American Academy of Allergy, Asthma & Immunology electronically distributed an anonymous questionnaire using the validated mini-Z survey to a total of 388 allergy and immunology FIT. In addition to the mini-Z items, the survey queried personal and professional demographic characteristics and included open-ended wellness questions. A total of 82 FIT completed the survey, yielding a 24% response rate. The burnout rate was 39%, which is lower than the national average among US physicians. Overall job satisfaction was 82%, and 72% reported satisfactory or better control over workload. Our results identify FIT-specific concerns in our specialty that can be used to develop tailored interventions to improve wellness and minimize burnout among this group. However, future surveys are needed to continue to address allergy and immunology FIT-specific wellness challenges.

Pulmonary Procedures During the COVID-19 Pandemic: A Work Group Report of the AAAAI Asthma Diagnosis and Treatment (ADT) Interest Section.

The COVID-19 pandemic has placed increased demands on the ability to safely perform pulmonary procedures in keeping with Centers for Disease Control and Prevention (CDC), American Thoracic Society (ATS), and the Occupational Safety and Health Administration (OSHA) recommendations. Accordingly, the American Academy of Allergy, Asthma & Immunology (AAAAI) Asthma Diagnosis and Treatment convened this work group to offer guidance. The work group is composed of specialist practitioners from academic and both large and small practices. Individuals with special expertise were assigned sections on spirometry, fractional exhaled nitric oxide, nebulized treatments, and methacholine challenge. The work group met periodically to achieve consensus. This resulting document has recommendations for the allergy/asthma/immunology health care setting based on available evidence including reference documents from the CDC, ATS, and OSHA.

Cannabis-related allergies: An international overview and consensus recommendations.

Cannabis is the most widely used recreational drug in the world. Cannabis sativa and Cannabis indica have been selectively bred to develop their psychoactive properties. The increasing use in many countries has been accelerated by the COVID-19 pandemic. Cannabis can provoke both type 1 and type 4 allergic reactions. Officially recognized allergens include a pathogenesis-related class 10 allergen, profilin, and a nonspecific lipid transfer protein. Other allergens may also be relevant, and recognition of allergens may vary between countries and continents. Cannabis also has the potential to provoke allergic cross-reactions to plant foods. Since cannabis is an illegal substance in many countries, research has been hampered, leading to challenges in diagnosis since no commercial extracts are available for testing. Even in countries such as Canada, where cannabis is legalized, diagnosis may rely solely on the purchase of cannabis for prick-to-prick skin tests. Management consists of avoidance, with legal issues hindering the development of other treatments such as immunotherapy. Education of healthcare professionals is similarly lacking. This review aimed to summarize the current status of cannabis allergy and proposes recommendations for the future management of this global issue.

Delayed allergic skin reactions to vaccines.

Background: Recent advances in vaccination against the severe acute respiratory syndrome coronavirus 2 pandemic have brought allergists and dermatologists to the forefront because both immediate and delayed hypersensitivity reactions have been reported. Objective: This literature review focused on delayed reactions to vaccines, including possible causative agents and practical information on how to diagnose, evaluate with patch testing, and manage subsequent dose administration. Methods: Currently published reviews and case reports in PubMed, along with data on vaccines from the Centers for Disease Control and Prevention web site. Relevant case reports and reviews that focused on delayed reactions to vaccines were selected. Results: Most delayed hypersensitivity reactions to vaccines include cutaneous manifestations, which vary from local persistent pruritic nodules to systemic rashes. The onset is usually within a few days but can be delayed by weeks. Multiple excipients have been identified that have been implicated in delayed vaccine reactions, including thimerosal, formaldehyde, aluminum, antibiotics, and gelatin. Treatment with antihistamines, topical corticosteroids, or systemic corticosteroids alleviates symptoms in most patients. Such reactions are generally not contraindications to future vaccination. However, for more-severe reactions, patch testing for causative agents can be used to aid in diagnosis and approach further vaccination. Conclusion: Delayed-type hypersensitivity reactions to vaccines are not uncommon. If needed, patch testing can be used to confirm agents, including antibiotics, formaldehyde, thimerosal, and aluminum. In most cases, delayed cutaneous reactions are not contraindications to further vaccine administration.

Incidence, Characteristics and Outcomes of Large Vessel Stroke in COVID-19 Cohort: An International Multicenter Study

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The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.

Incidence, Characteristics and Outcomes of Large Vessel Stroke in COVID-19 Cohort: An International Multicenter Study.

BACKGROUND: While there are reports of acute ischemic stroke (AIS) in coronavirus disease 2019 (COVID-19) patients, the overall incidence of AIS and clinical characteristics of large vessel occlusion (LVO) remain unclear. OBJECTIVE: To attempt to establish incidence of AIS in COVID-19 patients in an international cohort. METHODS: A cross-sectional retrospective, multicenter study of consecutive patients admitted with AIS and COVID-19 was undertaken from March 1 to May 1, 2020 at 12 stroke centers from 4 countries. Out of those 12 centers, 9 centers admitted all types of strokes and data from those were used to calculate the incidence rate of AIS. Three centers exclusively transferred LVO stroke (LVOs) patients and were excluded only for the purposes of calculating the incidence of AIS. Detailed data were collected on consecutive LVOs in hospitalized patients who underwent mechanical thrombectomy (MT) across all 12 centers. RESULTS: Out of 6698 COVID-19 patients admitted to 9 stroke centers, the incidence of stroke was found to be 1.3% (interquartile range [IQR] 0.75%-1.7%). The median age of LVOs patients was 51 yr (IQR 50-75 yr), and in the US centers, African Americans comprised 28% of patients. Out of 66 LVOs, 10 patients (16%) were less than 50 yr of age. Among the LVOs eligible for MT, the average time from symptom onset to presentation was 558 min (IQR 82-695 min). A total of 21 (50%) patients were either discharged to home or discharged to acute rehabilitation facilities. CONCLUSION: LVO was predominant in patients with AIS and COVID-19 across 2 continents, occurring at a significantly younger age and affecting African Americans disproportionately in the USA.

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.

Physician wellness in allergy and immunology: Personal resiliency.

OBJECTIVE: Physician burnout and wellness are vital and current issues in medicine, including allergy and immunology. Resilience involves the ability to rebound from personal and professional adversities. Improving individual resilience can be used to combat many of these stresses. DATA SOURCES: PubMed database and the worldwide web were searched for articles on physician wellness and resilience. STUDY SELECTIONS: Peer-reviewed scholarly review articles, peer-reviewed scientific research articles, and articles from internet websites on wellness and resilience were utilized as study selections. RESULTS: Physicians deal with many occupational stresses, including bureaucratic tasks, employment change, discrimination, difficult personalities, financial issues, and retirement. Personal stresses may include marital or relationship issues, loss of a family member, and mental and physical conditions. A variety of techniques can be used to improve personal resilience. These include addressing individual mental and physical health care issues; focusing on adequate sleep, nutrition, and exercise; maintaining a positive and hopeful outlook; addressing spirituality; and adding daily humor. CONCLUSION: As we address our own wellness and improve our resilience as physicians, the healthier we become and the better we can advocate for our patients and our specialty of allergy and immunology.

Outcomes and Spectrum of Major Neurovascular Events Among COVID-19 Patients: A 3-Center Experience.

BACKGROUND: Preliminary data suggest that Coronavirus Disease-2019 (COVID-19) is associated with hypercoagulability and neurovascular events, but data on outcomes is limited. OBJECTIVE: To report the clinical course and outcomes of a case series of COVID-19 patients with a variety of cerebrovascular events. METHODS: We performed a multicentric, retrospective chart review at our three academic tertiary care hospitals, and identified all COVID-19 patients with cerebrovascular events requiring neuro-intensive care and/or neurosurgical consultation. RESULTS: We identified 26 patients between March 1 and May 24, 2020, of whom 12 (46%) died. The most common event was a large-vessel occlusion (LVO) in 15 patients (58%), among whom 8 died (8/15, 53%). A total of 9 LVO patients underwent mechanical thrombectomy, of whom 5 died (5/9, 56%). A total of 7 patients (27%) presented with intracranial hemorrhage. Of the remaining patients, 2 had small-vessel occlusions, 1 had cerebral venous sinus thrombosis, and another had a vertebral artery dissection. Acute Respiratory Distress Syndrome occurred in 8 patients, of whom 7 died. Mortalities had a higher D-dimer on admission (mean 20 963 ng/mL) than survivors (mean 3172 ng/mL). Admission Glasgow Coma Scale (GCS) score was poor among mortalities (median 7), whereas survivors had a favorable GCS at presentation (median 14) and at discharge (median 14). CONCLUSION: COVID-19 may be associated with hemorrhage as well as ischemia, and prognosis appears poorer than expected-particularly among LVO cases, where outcome remained poor despite mechanical thrombectomy. However, a favorable neurological condition on admission and lower D-dimer may indicate a better outcome.

Clinician Wellness During the COVID-19 Pandemic: Extraordinary Times and Unusual Challenges for the Allergist/Immunologist.

The global spread of coronavirus disease 2019 (COVID-19) has caused sudden and dramatic societal changes. The allergy/immunology community has quickly responded by mobilizing practice adjustments and embracing new paradigms of care to protect patients and staff from severe acute respiratory syndrome coronavirus 2 exposure. Social distancing is key to slowing contagion but adds to complexity of care and increases isolation and anxiety. Uncertainty exists across a new COVID-19 reality, and clinician well-being may be an underappreciated priority. Wellness incorporates mental, physical, and spiritual health to protect against burnout, which impairs both coping and caregiving abilities. Understanding the stressors that COVID-19 is placing on clinicians can assist in recognizing what is needed to return to a point of wellness. Clinicians can leverage easily accessible tools, including the Strength-Focused and Meaning-Oriented Approach to Resilience and Transformation approach, wellness apps, mindfulness, and gratitude. Realizing early warning signs of anxiety, depression, substance abuse, and posttraumatic stress disorder is important to access safe and confidential resources. Implementing wellness strategies can improve flexibility, resilience, and outlook. Historical parallels demonstrate that perseverance is as inevitable as pandemics and that we need not navigate this unprecedented time alone.