Disparities in COVID-19 testing and outcomes among Asian American and Pacific Islanders: an observational study in a large health care system.

BACKGROUND: The COVID-19 pandemic has disproportionately impacted racial and ethnic minorities in the United States, including Asian Americans, Native Hawaiians and Pacific Islanders (Asian Americans and NH/PIs). However, few studies have highlighted nor disaggregated these disparities by Asian Americans and NH/PIs ethnic subgroups. METHODS: This retrospective, cross-sectional observational study aimed to assess variation of Asian Americans and NH/PIs COVID-19 testing and outcomes compared to non-Hispanic Whites (NHW). The study utilized data from the electronic health records (EHR) and the COVID-19 Universal Registry for Vital Evaluations (CURVE) from all patients tested for SARS-CoV-2 (n = 556,690) at a large, health system in Northern and Central California between February 20, 2020 and March 31, 2021. Chi-square tests were used for testing differences in the severity of COVID-19 (hospitalization, ICU admission, death) and patient demographic and clinical characteristics across the Asian Americans and NH/PIs subgroups and NHW. Unadjusted and adjusted Odds Ratios (ORs) were estimated for measuring effect of race ethnicity on severity of COVID-19 using multivariable logistic regression. RESULTS: Of the entire tested population, 70,564/556,690 (12.7%) tested positive for SARS-CoV-2. SARS-CoV-2 positivity of Asian subgroups varied from 4% in the Chinese and Korean populations, to 11.2%, 13.5%, and 12.5% for Asian Indian, Filipino, and "other Asian" populations respectively. Pacific Islanders had the greatest subgroup test positivity at 20.1%. Among Asian Americans and NH/PIs patients with COVID-19 disease, Vietnamese (OR = 2.06, 95% CI = 1.30-3.25), "Other Asian" (OR = 2.13, 95% CI = 1.79-2.54), Filipino (OR = 1.78, 95% CI = 1.34-2.23), Japanese (OR = 1.78, 95% CI = 1.10-2.88), and Chinese (OR = 1.73, 95% CI = 1.34-2.23) subgroups had almost double the odds of hospitalization compared to NHW. Pacific Islander (OR = 1.58, 95% CI = 1.19-2.10) and mixed race subgroups (OR = 1.55, 95% CI = 1.10-2.20) had more than one and a half times odds of hospitalization compared to NHW. Adjusted odds of ICU admission or death among hospitalized patients by different Asian subgroups varied but were not statistically significant. CONCLUSIONS: Variation of COVID-19 testing and hospitalization by Asian subgroups was striking in our study. A focus on the Asian Americans and NH/PIs population with disaggregation of subgroups is crucial to understand nuances of health access, utilization, and outcomes among subgroups to create health equity for these underrepresented populations.

Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CLpro).

Starting from the MLPCN probe compound ML300, a structure-based optimization campaign was initiated against the recent severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (3CLpro). X-ray structures of SARS-CoV-1 and SARS-CoV-2 3CLpro enzymes in complex with multiple ML300-based inhibitors, including the original probe ML300, were obtained and proved instrumental in guiding chemistry toward probe compound 41 (CCF0058981). The disclosed inhibitors utilize a noncovalent mode of action and complex in a noncanonical binding mode not observed by peptidic 3CLpro inhibitors. In vitro DMPK profiling highlights key areas where further optimization in the series is required to obtain useful in vivo probes. Antiviral activity was established using a SARS-CoV-2-infected Vero E6 cell viability assay and a plaque formation assay. Compound 41 demonstrates nanomolar activity in these respective assays, comparable in potency to remdesivir. These findings have implications for antiviral development to combat current and future SARS-like zoonotic coronavirus outbreaks.

"Could we have predicted this?" The association of a future mental health need in young people with a non-specific complaint and frequent emergency department visits.

OBJECTIVE: Mental health emergencies among young people are increasing. There is growing pressure for emergency departments to screen patients for mental health needs even when it is not their chief complaint. We hypothesized that young people with an initial non-specific condition and emergency department (ED) revisits have increased mental health needs. METHODS: Retrospective, observational study of the California Office of Statewide Health Planning and Development Emergency Department Discharge Dataset (2010-2014) of young people (11-24 years) with an index visit for International Classification of Diseases, Ninth Revision diagnostic codes of "Symptoms, signs, and ill-defined conditions" (Non-Specific); "Diseases of the respiratory system" (Respiratory) and "Unintentional injury" (Trauma) who were discharged from a California ED. Patients were excluded if they had a prior mental health visit, chronic disease, or were pregnant. ED visit frequency was counted over 12 months. Regression models were created to analyze characteristics associated with a mental health visit. RESULTS: Patients in the Non-Specific category compared to the Respiratory category had 1.2 times the odds of a future mental health visit (OR 1.20; 95% CI 1.17-1.24). Patients with ≥1 ED revisit, regardless of diagnostic category, had 1.3 times the odds of a future mental health visit. Patients with both a Non-Specific index visit and 1, 2, and 3 or more revisits with non-specific diagnoses had increasing odds of a mental health visit (OR 1.38; 95% CI 1.29-1.47; OR 1.70; 95% CI 1.46-1.98; OR 2.20; 95% CI 1.70-2.87, respectively.). CONCLUSIONS: Young people who go to the ED for non-specific conditions and revisits may benefit from targeted ED mental health screening.

Consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors.

Expanding the US Food and Drug Administration-approved indications for immune checkpoint inhibitors in patients with cancer has resulted in therapeutic success and immune-related adverse events (irAEs). Neurologic irAEs (irAE-Ns) have an incidence of 1%-12% and a high fatality rate relative to other irAEs. Lack of standardized disease definitions and accurate phenotyping leads to syndrome misclassification and impedes development of evidence-based treatments and translational research. The objective of this study was to develop consensus guidance for an approach to irAE-Ns including disease definitions and severity grading. A working group of four neurologists drafted irAE-N consensus guidance and definitions, which were reviewed by the multidisciplinary Neuro irAE Disease Definition Panel including oncologists and irAE experts. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND/University of California Los Angeles (UCLA) Appropriateness Method with prespecified definitions. 27 panelists from 15 academic medical centers voted on a total of 53 rating scales (6 general guidance, 24 central and 18 peripheral nervous system disease definition components, 3 severity criteria and 2 clinical trial adjudication statements); of these, 77% (41/53) received first round consensus. After revisions, all items received second round consensus. Consensus definitions were achieved for seven core disorders: irMeningitis, irEncephalitis, irDemyelinating disease, irVasculitis, irNeuropathy, irNeuromuscular junction disorders and irMyopathy. For each disorder, six descriptors of diagnostic components are used: disease subtype, diagnostic certainty, severity, autoantibody association, exacerbation of pre-existing disease or de novo presentation, and presence or absence of concurrent irAE(s). These disease definitions standardize irAE-N classification. Diagnostic certainty is not always directly linked to certainty to treat as an irAE-N (ie, one might treat events in the probable or possible category). Given consensus on accuracy and usability from a representative panel group, we anticipate that the definitions will be used broadly across clinical and research settings.

Optimal preparation of SARS-CoV-2 viral transport medium for culture.

INTRODUCTION: The sudden arrival of the COVID-19 pandemic placed significant stresses on supply chains including viral transport medium (VTM). The VTM that was urgently required needed to support viral replication, as well as other routine diagnostic approaches. We describe the preparation and validation testing of VTM for rapidly expanding diagnostic testing, where the capacity of the VTM to preserve viral integrity, for culture, isolation and full sequence analysis, was maintained. METHODS: VTM was prepared using different methods of sterilization then 'spiked' with virus. The VTM was investigated using viral culture in Vero cells, and for nucleic acid detection by quantitative PCR. RESULTS: The best results were obtained by filter and autoclave-based sterilization. The VTM proved robust for culture-based analyses provided the inoculated VTM was stored at 4 °C, and tested within 48 h. The filtered VTM also supported PCR-based diagnosis for at least 5 days when the mock inoculated VTM was held at room temperature. DISCUSSION: The manual handling of VTM production, including filling and sterilization, was optimized. SARS-CoV-2 was spiked into VTM to assess different sterilization methods and measure the effects of storage time and temperature upon VTM performance. While most diagnostic protocols will not require replication competent virus, the use of high quality VTM will allow for the next phase of laboratory analysis in the COVID-19 pandemic, including drug and antibody susceptibility analysis of re-isolated SARS-CoV-2, and for the testing of vaccine escape mutants.

Communication Chaos from Discrepancies in Personal Protective Equipment and Preoperative Guidelines.

OBJECTIVES/HYPOTHESIS: To compare personal protective equipment (PPE) guidelines, specifically respirator use, among international public health agencies, academic hospitals, and otolaryngology-head and neck surgery (OHNS) departments in the United States for the care of coronavirus-19 (COVID-19) patients. STUDY DESIGN: Cross sectional survey. METHODS: Review of publicly available public health and academic hospitals guidelines along with review of communication among otolaryngology departments. RESULTS: Among 114 academic institutions affiliated with OHNS residencies, 20 (17.5%) institutions provided public access to some form of guidance on PPE and 73 (64%) provided information on screening or diagnostic testing. PPE guidelines were uniquely described based on several variables: location of care, COVID-19 status, involvement of aerosol generating or high-risk procedures, and physical distance from the patient. Six hospital guidelines were highlighted. Across these six institutions, there was agreement that N95 respirators were needed for high-risk patients undergoing high-risk procedures. Variations existed among institutions for scenarios with low-risk patients. Definitions of the low-risk patient and high-risk procedures were inconsistent among institutions. Three of the highlighted institutions had OHNS departments recommending higher level of airway protection than the institution. CONCLUSIONS: OHNS departments typically had more stringent PPE guidance than their institution. Discrepancies in communicating PPE use were frequent and provide inconsistent information on how healthcare workers should protect themselves in the COVID-19 pandemic. Identification of these inconsistencies serves as an opportunity to standardize communication and develop evidence-based guidelines. LEVEL OF EVIDENCE: V Laryngoscope, 131:E746-E754, 2021.