Childhood asthma diagnoses declined during the COVID-19 pandemic in the United States.

BACKGROUND: Prior studies have documented declines in pediatric asthma exacerbations and asthma-related health care utilization during the COVID-19 pandemic, but less is known about the incidence of asthma during the pandemic. METHODS: We conducted a retrospective cohort study of children under age 18 without a prior diagnosis of asthma within a large US commercial claims database. Incident asthma was defined using a combination of diagnosis codes, location of services, and medication dispensing. Crude quarterly rates of asthma diagnosis per 1000 children were calculated, and the incidence rate ratio and 95% confidence interval were estimated for newly diagnosed asthma during versus before the pandemic using negative binomial regression, adjusted for age, sex, region, and season. RESULTS: Compared with 3 years prior to the pandemic, crude incident diagnosis rates of asthma decreased by 52% across the first four quarters of the US pandemic. The covariate-adjusted pandemic-associated incidence rate ratio was 0.47 (95% confidence interval 0.43, 0.51). CONCLUSIONS: New diagnoses of childhood asthma in the US declined by half during the first year of the pandemic. These findings raise important questions whether pandemic-related changes in infectious or other triggers truly altered the incidence of childhood asthma beyond the well-described disruptions in healthcare access.

Biologic use and outcomes among adults with severe asthma treated by US subspecialists.

BACKGROUND: Multiple biologics are now available for severe asthma (SA) treatment and can improve outcomes for patients. However, few available data describe the real-world use and effectiveness of multiple approved biologics, including biologic switching, among subspecialists in the United States. OBJECTIVE: To evaluate biologic use and associated exacerbation outcomes in a large cohort of subspecialist-treated US adults with SA. METHODS: CHRONICLE is an ongoing, noninterventional study of subspecialist-treated US adults with SA receiving biologics, maintenance systemic corticosteroids, or those persistently uncontrolled by high-dose inhaled corticosteroids with additional controllers. For enrolled patients, sites report asthma exacerbations and medication use starting 12 months before enrollment. For patients enrolled between February 2018 and February 2021, biologic use and exacerbation outcomes before and after biologic initiation are described. RESULTS: Among 2793 enrolled patients, 66% (n = 1832) were receiving biologics. The most used biologic (> 1 biologic use per patient allowed) was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), dupilumab (18%), and reslizumab (3%). Overall, 16% of patients had biologic switches, 13% had stops, and 89% had ongoing biologic use. Patients starting and switching biologics experienced a 58% (1.80 vs 0.76 per patient-year) and 49% (1.47 vs 0.75 per patient-year) reduction in exacerbations, respectively (both P < .001), with a numerically greater reduction observed among those starting non-anti-immunoglobulin E biologics compared with anti-immunoglobulin E. CONCLUSION: Real-world starting and switching of biologic therapies for SA were associated with meaningful reductions in exacerbations. With increasing biologic options available, individualized approaches to therapy may improve patient outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03373045.

Development of an aerosol intervention for COVID-19 disease: Tolerability of soluble ACE2 (APN01) administered via nebulizer.

As ACE2 is the critical SARS-CoV-2 receptor, we hypothesized that aerosol administration of clinical grade soluble human recombinant ACE2 (APN01) will neutralize SARS-CoV-2 in the airways, limit spread of infection in the lung, and mitigate lung damage caused by deregulated signaling in the renin-angiotensin (RAS) and Kinin pathways. Here, after demonstrating in vitro neutralization of SARS-CoV-2 by APN01, and after obtaining preliminary evidence of its tolerability and preventive efficacy in a mouse model, we pursued development of an aerosol formulation. As a prerequisite to a clinical trial, we evaluated both virus binding activity and enzymatic activity for cleavage of Ang II following aerosolization. We report successful aerosolization for APN01, retaining viral binding as well as catalytic RAS activity. Dose range-finding and IND-enabling repeat-dose aerosol toxicology testing were conducted in dogs. Twice daily aerosol administration for two weeks at the maximum feasible concentration revealed no notable toxicities. Based on these results, a Phase I clinical trial in healthy volunteers has now been initiated (NCT05065645), with subsequent Phase II testing planned for individuals with SARS-CoV-2 infection.

Experiences of Black and Latinx health care workers in support roles during the COVID-19 pandemic: A qualitative study.

Black and Latinx individuals, and in particular women, comprise an essential health care workforce often serving in support roles such as nursing assistants and dietary service staff. Compared to physicians and nurses, they are underpaid and potentially undervalued, yet play a critical role in health systems. This study examined the impact of the coronavirus disease 2019 (COVID-19) pandemic from the perspective of Black and Latinx health care workers in support roles (referred to here as HCWs). From December 2020 to February 2021, we conducted 2 group interviews (n = 9, 1 group in English and 1 group in Spanish language) and 8 individual interviews (1 in Spanish and 7 in English) with HCWs. Participants were members of a high-risk workforce as well as of communities that suffered disproportionately during the pandemic. Overall, they described disruptive changes in responsibilities and roles at work. These disruptions were intensified by the constant fear of contracting COVID-19 themselves and infecting their family members. HCWs with direct patient care responsibilities reported reduced opportunities for personal connection with patients. Perspectives on vaccines reportedly changed over time, and were influenced by peers' vaccination and information from trusted sources. The pandemic has exposed the stress endured by an essential workforce that plays a critical role in healthcare. As such, healthcare systems need to dedicate resources to improve the work conditions for this marginalized workforce including offering resources that support resilience. Overall working conditions and, wages must be largely improved to ensure their wellbeing and retain them in their roles to manage the next public health emergency. The role of HCWs serving as ambassadors to provide accurate information on COVID-19 and vaccination among their coworkers and communities also warrants further study.

Highly versatile antibody binding assay for the detection of SARS-CoV-2 infection and vaccination.

Monitoring the burden and spread of infection with the new coronavirus SARS-CoV-2, whether within small communities or in large geographical settings, is of paramount importance for public health purposes. Serology, which detects the host antibody response to the infection, is the most appropriate tool for this task, since virus-derived markers are most reliably detected during the acute phase of infection. Here we show that our ELISA protocol, which is based on antibody binding to the Receptor Binding Domain (RBD) of the S1 subunit of the viral Spike protein expressed as a novel fusion protein, detects antibody responses to SARS-CoV-2 infection and vaccination. We also show that our ELISA is accurate and versatile. It compares favorably with commercial assays widely used in clinical practice to determine exposure to SARS-CoV-2. Moreover, our protocol accommodates use of various blood- and non-blood-derived biospecimens, such as breast milk, as well as dried blood obtained with microsampling cartridges that are appropriate for remote collection. As a result, our RBD-based ELISA protocols are well suited for seroepidemiology and other large-scale studies requiring parsimonious sample collection outside of healthcare settings.

Determinants and Dynamics of SARS-CoV-2 Infection in a Diverse Population: 6-Month Evaluation of a Prospective Cohort Study.

BACKGROUND: We studied risk factors, antibodies, and symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a diverse, ambulatory population. METHODS: A prospective cohort (n = 831) previously undiagnosed with SARS-CoV-2 infection underwent serial testing (SARS-CoV-2 polymerase chain reaction, immunoglobulin G [IgG]) for 6 months. RESULTS: Ninety-three participants (11.2%) tested SARS-CoV-2-positive: 14 (15.1%) asymptomatic, 24 (25.8%) severely symptomatic. Healthcare workers (n = 548) were more likely to become infected (14.2% vs 5.3%; adjusted odds ratio, 2.1; 95% confidence interval, 1.4-3.3) and severely symptomatic (29.5% vs 6.7%). IgG antibodies were detected after 79% of asymptomatic infections, 89% with mild-moderate symptoms, and 96% with severe symptoms. IgG trajectories after asymptomatic infections (slow increases) differed from symptomatic infections (early peaks within 2 months). Most participants (92%) had persistent IgG responses (median 171 days). In multivariable models, IgG titers were positively associated with symptom severity, certain comorbidities, and hospital work. Dyspnea and neurologic changes (including altered smell/taste) lasted ≥ 120 days in ≥ 10% of affected participants. Prolonged symptoms (frequently more severe) corresponded to higher antibody levels. CONCLUSIONS: In a prospective, ethnically diverse cohort, symptom severity correlated with the magnitude and trajectory of IgG production. Symptoms frequently persisted for many months after infection.Clinical Trials Registration. NCT04336215.

Black and Latinx Community Perspectives on COVID-19 Mitigation Behaviors, Testing, and Vaccines.

Importance: Black and Latinx communities have been disproportionately affected by the COVID-19 pandemic, yet little work has sought to understand their perspectives. Objective: To explore the experiences of Black and Latinx communities during the pandemic to better understand their perspectives on COVID-19 mitigation behaviors (eg, mask wearing), testing, and vaccines. Design, Setting, and Participants: In this community-engaged qualitative study conducted with 18 community-based organizations and 4 health care organizations between November 19, 2020, and February 5, 2021, in New Jersey counties severely affected by the pandemic, group and individual interviews were used to purposively sample 111 Black and Latinx individuals. A total of 13 group interviews were organized by race/ethnicity and language: 4 English-speaking groups with Black participants (n = 34), 3 Spanish-speaking groups with Latinx participants (n = 24), and 4 English-speaking groups with Black and Latinx participants (n = 36). To understand the views of health care workers from these communities, 2 additional groups (n = 9) were convened and supplemented with individual interviews. Main Outcomes and Measures: Description of Black and Latinx participants' experiences during the COVID-19 pandemic and their perspectives on mitigation behaviors, testing, and vaccines. Results: The study included 111 participants (87 women [78.4%]; median age, 43 years [range, 18-93 years]). Participants described the devastating effects of the pandemic on themselves, loved ones, and their community. Their experiences were marked by fear, illness, loss, and separation. These experiences motivated intense information seeking, mitigation behaviors, and testing. Nevertheless, vaccine skepticism was high across all groups. Participants did not trust the vaccine development process and wanted clearer information. Black participants expressed that they did not want to be subjects of experiments. Conclusions and Relevance: The remaining unknowns about new vaccines need to be acknowledged and described for Black and Latinx communities to make informed decisions. Ultimately, scientists and public officials need to work transparently to address unanswered questions and work collaboratively with trusted community leaders and health professionals to foster partnered approaches, rather than focusing on marketing campaigns, to eliminate vaccine skepticism.

Managing the risks and benefits of clinical research in response to a pandemic.

Introduction: The coronavirus disease 2019 (COVID-19) created major disruptions at academic centers and healthcare systems globally. Clinical and Translational Science Awards (CTSA) fund hubs supported by the National Center for Advancing Translational Sciences provideinfrastructure and leadership for clinical and translational research at manysuch institutions. Methods: We surveyed CTSA hubs and received responses from 94% of them regarding the impact of the pandemic and the processes employed for the protection of research personnel and participants with respect to the conduct of research, specifically for studies unrelated to COVID-19. Results: In this report, we describe the results of the survey findings in the context of the current understanding of disease transmission and mitigation techniques. Conclusions: We reflect on common practices and provide recommendations regarding lessons learned that will be relevant to future pandemics, particularly with regards to staging the cessation and resumption of research activities with an aim to keep the workforce, research participants, and our communities safe in future pandemics.

Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospital Workers: Results From a Screening Study in New Jersey, United States in Spring 2020.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a critical concern among healthcare workers (HCWs). Other studies have assessed SARS-CoV-2 virus and antibodies in HCWs, with disparate findings regarding risk based on role and demographics. METHODS: We screened 3904 employees and clinicians for SARS-CoV-2 virus positivity and serum immunoglobulin (Ig)G at a major New Jersey hospital from April 28 to June 30, 2020. We assessed positive tests in relation to demographic and occupational characteristics and prior coronavirus disease 2019 symptoms using multivariable logistic regression models. RESULTS: Thirteen participants (0.3%) tested positive for virus and 374 (9.6%) tested positive for IgG (total positive: 381 [9.8%]). Compared with participants with no patient care duties, the odds of positive testing (virus or antibodies) were higher for those with direct patient contact: below-median patient contact, adjusted odds ratio (aOR) = 1.71 and 95% confidence interval [CI] = 1.18-2.48; above-median patient contact, aOR = 1.98 and 95% CI = 1.35-2.91. The proportion of participants testing positive was highest for phlebotomists (23.9%), maintenance/housekeeping (17.3%), dining/food services (16.9%), and interpersonal/support roles (13.7%) despite lower levels of direct patient care duties. Positivity rates were lower among doctors (7.2%) and nurses (9.1%), roles with fewer underrepresented minorities. After adjusting for job role and patient care responsibilities and other factors, Black and Latinx workers had 2-fold increased odds of a positive test compared with white workers. Loss of smell, taste, and fever were associated with positive testing. CONCLUSIONS: The HCW categories at highest risk for SARS-CoV-2 infection include support staff and underrepresented minorities with and without patient care responsibilities. Future work is needed to examine potential sources of community and nosocomial exposure among these understudied HCWs.

Prevalence of SARS-CoV-2 infection in previously undiagnosed health care workers in New Jersey, at the onset of the U.S. COVID-19 pandemic.

BACKGROUND: Healthcare workers (HCW) are presumed to be at increased risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection due to occupational exposure to infected patients. However, there has been little epidemiological research to assess these risks. METHODS: We conducted a prospective cohort study of HCW (n = 546) and non-healthcare workers (NHCW; n = 283) with no known prior SARS-CoV-2 infection who were recruited from a large U.S. university and two affiliated university hospitals. In this cross-sectional analysis of data collected at baseline, we examined SARS-CoV-2 infection status (as determined by presence of SARS-CoV-2 RNA in oropharyngeal swabs) by healthcare worker status and role. RESULTS: At baseline, 41 (5.0%) of the participants tested positive for SARS-CoV-2 infection, of whom 14 (34.2%) reported symptoms. The prevalence of SARS-CoV-2 infection was higher among HCW (7.3%) than in NHCW (0.4%), representing a 7.0% greater absolute risk (95% confidence interval for risk difference 4.7, 9.3%). The majority of infected HCW (62.5%) were nurses. Positive tests increased across the two weeks of cohort recruitment in line with rising confirmed cases in the hospitals and surrounding counties. CONCLUSIONS: Overall, our results demonstrate that HCW had a higher prevalence of SARS-CoV-2 infection than NHCW. Continued follow-up of this cohort will enable us to monitor infection rates and examine risk factors for transmission.

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Is Comparable in Clinical Samples Preserved in Saline or Viral Transport Medium.

As the coronavirus disease 2019 (COVID-19) pandemic sweeps across the world, the availability of viral transport medium (VTM) has become severely limited, contributing to delays in diagnosis and rationing of diagnostic testing. Given that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA has demonstrated stability, we posited that phosphate-buffered saline (PBS) may be a viable transport medium, as an alternative to VTM, for clinical real-time quantitative PCR (qPCR) testing. The intra-individual reliability and interindividual reliability of SARS-CoV-2 qPCR were assessed in clinical endotracheal secretion samples transported in VTM or PBS to evaluate the stability of the qPCR signal for three viral targets (N gene, ORF1ab, and S gene) when samples were stored in these media at room temperature for up to 18 hours. We report that the use of PBS as a transport medium allows high intra-individual and interindividual reliability, maintains viral stability, and compares with VTM in the detection of the three SARS-CoV-2 genes through 18 hours of storage. This study establishes PBS as a clinically useful medium that can be readily deployed for transporting and short-term preservation of specimens containing SARS-CoV-2. Use of PBS as a transport medium has the potential to increase testing capacity for SARS-CoV-2, aiding more widespread screening and early diagnosis of COVID-19.