Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia.

BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

U.S. county-level characteristics to inform equitable COVID-19 response

BackgroundThe spread of Coronavirus Disease 2019 (COVID-19) across the United States confirms that not all Americans are equally at risk of infection, severe disease, or mortality. A range of intersecting biological, demographic, and socioeconomic factors are likely to determine an individuals susceptibility to COVID-19. These factors vary significantly across counties in the United States, and often reflect the structural inequities in our society. Recognizing this vast inter-county variation in risks will be critical to mounting an adequate response strategy. Methods and FindingsUsing publicly available county-specific data we identified key biological, demographic, and socioeconomic factors influencing susceptibility to COVID-19, guided by international experiences and consideration of epidemiological parameters of importance. We created bivariate county-level maps to summarize examples of key relationships across these categories, grouping age and poverty; comorbidities and lack of health insurance; proximity, density and bed capacity; and race and ethnicity, and premature death. We have also made available an interactive online tool that allows public health officials to query risk factors most relevant to their local context. Our data demonstrate significant inter-county variation in key epidemiological risk factors, with a clustering of counties in certain states, which will result in an increased demand on their public health system. While the East and West coast cities are particularly vulnerable owing to their densities (and travel routes), a large number of counties in the Southeastern states have a high proportion of at-risk populations, with high levels of poverty, comorbidities, and premature death at baseline, and low levels of health insurance coverage. The list of variables we have examined is by no means comprehensive, and several of them are interrelated and magnify underlying vulnerabilities. The online tool allows readers to explore additional combinations of risk factors, set categorical thresholds for each covariate, and filter counties above different population thresholds. ConclusionCOVID-19 responses and decision making in the United States remain decentralized. Both the federal and state governments will benefit from recognizing high intra-state, inter-county variation in population risks and response capacity. Many of the factors that are likely to exacerbate the burden of COVID-19 and the demand on healthcare systems are the compounded result of long-standing structural inequalities in US society. Strategies to protect those in the most vulnerable counties will require urgent measures to better support communities attempts at social distancing and to accelerate cooperation across jurisdictions to supply personnel and equipment to counties that will experience high demand.

The demand for inpatient and ICU beds for COVID-19 in the US: lessons from Chinese cities

BackgroundSustained spread of SARS-CoV-2 has happened in major US cities. Capacity needs in Chinese cities could inform the planning of local healthcare resources. MethodsWe described the intensive care unit (ICU) and inpatient bed needs for confirmed COVID-19 patients in two Chinese cities (Wuhan and Guangzhou) from January 10 to February 29, 2020, and compared the timing of disease control measures in relation to the timing of SARS-CoV-2 community spread. We estimated the peak ICU bed needs in US cities if a Wuhan-like outbreak occurs. ResultsIn Wuhan, strict disease control measures were implemented six weeks after sustained local transmission of SARS-CoV-2. Between January 10 and February 29, COVID-19 patients accounted for an average of 637 ICU patients and 3,454 serious inpatients on each day. During the epidemic peak, 19,425 patients (24.5 per 10,000 adults) were hospitalized, 9,689 (12.2 per 10,000 adults) were considered to be in serious condition, and 2,087 patients (2.6 per 10,000 adults) needed critical care per day. In Guangzhou, strict disease control measures were implemented within one week of case importation. Between January 24 and February 29, COVID-19 accounted for an average of 9 ICU patients and 20 inpatients on each day. During the epidemic peak, 15 patients were in critical condition, and 38 were classified as serious. If a Wuhan-like outbreak were to happen in a US city, the need for healthcare resources may be higher in cities with a higher prevalence of vulnerable populations. ConclusionEven after the lockdown of Wuhan on January 23, the number of seriously ill COVID-19 patients continued to rise, exceeding local hospitalization and ICU capacities for at least a month. Plans are urgently needed to mitigate the effect of COVID-19 outbreaks on the local healthcare system in US cities.

Modeling the Comparative Impact of Individual Quarantine vs. Active Monitoring of Contacts for the Mitigation of COVID-19

BackgroundVoluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases, such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible, and broader mitigation measures must be implemented. MethodsTo estimate the comparative efficacy of these case-based interventions to control COVID-19, we fit a stochastic branching model to reported parameters for the dynamics of the disease. Specifically, we fit to the incubation period distribution and each of two sets of the serial interval distribution: a shorter one with a mean serial interval of 4.8 days and a longer one with a mean of 7.5 days. To assess variable resource settings, we consider two feasibility settings: a high feasibility setting with 90% of contacts traced, a half-day average delay in tracing and symptom recognition, and 90% effective isolation; and low feasibility setting with 50% of contacts traced, a two-day average delay, and 50% effective isolation. FindingsOur results suggest that individual quarantine in high feasibility settings where at least three-quarters of infected contacts are individually quarantined contains an outbreak of COVID-19 with a short serial interval (4.8 days) 84% of the time. However, in settings where this performance is unrealistically high and the outbreak continues to grow, so too will the burden of the number of contacts traced for active monitoring or quarantine. When resources are prioritized for scalable interventions such as social distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to mitigation efforts. InterpretationOur model highlights the urgent need for more data on the serial interval and the extent of presymptomatic transmission in order to make data-driven policy decisions regarding the cost-benefit comparisons of individual quarantine vs. active monitoring of contacts. To the extent these interventions can be implemented they can help mitigate the spread of COVID-19. FundingThis work was supported in part by Award Number U54GM088558 from the US National Institute Of General Medical Sciences.

The effect of human mobility and control measures on the COVID-19 epidemic in China

The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19.