Bebtelovimab for High-Risk Outpatients With Early COVID-19 in a Large US Health System.
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ABSTRACT:
SUBMITTER: Dryden-Peterson S
PROVIDER: S-EPMC9620388 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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Bebtelovimab for High-Risk Outpatients With Early COVID-19 in a Large US Health System.
Dryden-Peterson Scott S Kim Andy A Joyce Mary-Ruth MR Johnson Jennifer A JA Kim Arthur Y AY Baden Lindsey R LR Woolley Ann E AE
Open forum infectious diseases 20221027 11
There are limited data for the clinical efficacy of bebtelovimab in preventing severe coronavirus disease 2019. Among outpatients unable to take nirmatrelvir-ritonavir at a large health system, 10 of 377 (2.7%) patients who received bebtelovimab and 17 of 377 (4.5%) matched untreated patients were hospitalized or died. The 43% observed risk reduction with bebtelovimab was not statistically significant (<i>P</i> = 0.14). ...[more]
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Project description:BackgroundEarly administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19.MethodsIn this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause.ResultsA total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups.ConclusionsThe administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.).
| S-EPMC8385553 | biostudies-literature
Project description:IntroductionThis real-world study assessed the effectiveness of bebtelovimab (BEB) versus nirmatrelvir/ritonavir (NR) among outpatients with COVID-19 during the Omicron variant era.MethodsWe conducted a cohort study evaluating patients treated with BEB or NR from February to August 2022 (study period). Follow-up began the day after treatment and continued for 30 days. Cohorts were constructed using de-identified electronic health record data from TriNetX Dataworks USA. The study assessed 30-day all-cause hospitalization or death (composite) using the risk difference (RD) and 95% confidence interval (95% CI).ResultsUnmatched cohorts included 12,920 BEB- and 70,741 NR-treated patients. After exact matching on key baseline covariates (age > 65 years, immunocompromised, recent emergency department [ED] visit, and COVID-19 vaccination) and high-dimensional propensity score matching (1:1) on a broader set of covariates, 5827 patients were included in each cohort. BEB-treated patients were older and had more comorbidities compared to NR-treated patients prior to matching. After matching, baseline characteristics were well balanced. The cumulative incidence of the primary outcome (hospitalization or death) was 2.0% and 1.8% for BEB and NR, respectively (RD 0.2%; 95% CI - 0.3%, 0.7%). The upper bound of the RD 95% CI (0.7%) excluded the noninferiority margin (1.795%), demonstrating that BEB was not inferior to NR. The RDs of the secondary outcomes were (BEB vs NR): hospitalization (RD 0.1%; 95% CI - 0.4%, 0.6%); ED visit (RD 0.5%; 95% CI - 0.3%, 1.3%); and death (RD 0.09%; 95% CI - 0.003%, 0.2%). Results from subgroup, sensitivity, and linked analyses (EHR + claims + mortality data) were consistent with the main results.ConclusionTreatment with BEB was not inferior to NR with respect to 30-day all-cause hospitalization or death. The risk of secondary outcomes was not different for patients treated with BEB compared to NR.
| S-EPMC11861768 | biostudies-literature
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| S-EPMC9695104 | biostudies-literature
Project description:BackgroundEndothelial damage induces myofibrillar breakdown and muscle degradation in COVID-19 infection. There is a relationship between increased endothelin-1 synthesis and sarcopenia. We evaluated the preventive effect of early bosentan therapy as an endothelin receptor blocker in sarcopenia in high-risk outpatients with COVID-19 infection.MethodsFrom 15 December 2021 to 15 August 2023, patients within 3 days of the onset of signs and symptoms were randomly assigned to receive bosentan, 62.5 mg, or placebo, twice daily from enrollment for 30 days. The primary outcome was disease progression (death or hospitalization within 15 days after randomization), and the data for this outcome have been previously published. Sarcopenia as a secondary outcome was assessed prospectively at 3, 6, 9 and 12 months after randomization using the criteria of the Asian Working Group for Sarcopenia (AWGS) 2019 (IRCT.ir, IRCT20211203053263N1).ResultsA total of 313 patients (156 bosentan group, 157 controls) were included in the analyses, which were performed under the intent-to-treat principle. Overall, the incidence of sarcopenia was 8.6% (n = 27). Nineteen (73%) had severe sarcopenia. At the 3-month follow-up, the incidence of sarcopenia was 8.3% in the total population, with the significant risk difference (RD) of -10.17% in the bosentan group versus the control group. The incidence in the total population and RD in the bosentan group versus the control group at months 6, 9 and 12 were 8.6% (RD: -10.81%, p < 0.001), 8.3% (RD: -10.17%, p = 0.001) and 5.4% (RD: -6.99%, p = 0.003), respectively. During the study, 29 people developed severe COVID-19 and were hospitalized. At follow-up, sarcopenia occurred in four inpatients and 23 outpatients (p = 0.23). Mortality occurred in 5.1% (n = 16) of the total population, including 4 (1.3%) of the patients in the bosentan group and 12 (3.8%) of the patients in the placebo group (p = 0.069). None of the patients who died had sarcopenia. Bosentan did not cause any severe adverse events and was well tolerated.ConclusionEarly administration of bosentan may prevent sarcopenia in high-risk outpatients with COVID-19.
| S-EPMC11876846 | biostudies-literature
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| S-EPMC9753458 | biostudies-literature
Project description:BackgroundRemdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain.MethodsWe conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28.ResultsA total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group.ConclusionsAmong nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).
| S-EPMC8757570 | biostudies-literature
Project description:ImportanceThe influence of sleep-disordered breathing (SDB) and sleep-related hypoxemia in SARS-CoV-2 viral infection and COVID-19 outcomes remains unknown. Controversy exists regarding whether to continue treatment for SDB with positive airway pressure given concern for aerosolization with limited data to inform professional society recommendations.ObjectiveTo investigate the association of SDB (identified via polysomnogram) and sleep-related hypoxia with (1) SARS-CoV-2 positivity and (2) World Health Organization (WHO)-designated COVID-19 clinical outcomes while accounting for confounding including obesity, underlying cardiopulmonary disease, cancer, and smoking history.Design, setting, and participantsThis case-control study was conducted within the Cleveland Clinic Health System (Ohio and Florida) and included all patients who were tested for COVID-19 between March 8 and November 30, 2020, and who had an available sleep study record. Sleep indices and SARS-CoV-2 positivity were assessed with overlap propensity score weighting, and COVID-19 clinical outcomes were assessed using the institutional registry.ExposuresSleep study-identified SDB (defined by frequency of apneas and hypopneas using the Apnea-Hypopnea Index [AHI]) and sleep-related hypoxemia (percentage of total sleep time at <90% oxygen saturation [TST <90]).Main outcomes and measuresOutcomes were SARS-CoV-2 infection and WHO-designated COVID-19 clinical outcomes (hospitalization, use of supplemental oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation, and death).ResultsOf 350 710 individuals tested for SARS-CoV-2, 5402 (mean [SD] age, 56.4 [14.5] years; 3005 women [55.6%]) had a prior sleep study, of whom 1935 (35.8%) tested positive for SARS-CoV-2. Of the 5402 participants, 1696 were Black (31.4%), 3259 were White (60.3%), and 822 were of other race or ethnicity (15.2%). Patients who were positive vs negative for SARS-CoV-2 had a higher AHI score (median, 16.2 events/h [IQR, 6.1-39.5 events/h] vs 13.6 events/h [IQR, 5.5-33.6 events/h]; P < .001) and increased TST <90 (median, 1.8% sleep time [IQR, 0.10%-12.8% sleep time] vs 1.4% sleep time [IQR, 0.10%-10.8% sleep time]; P = .02). After overlap propensity score-weighted logistic regression, no SDB measures were associated with SARS-CoV-2 positivity. Median TST <90 was associated with the WHO-designated COVID-19 ordinal clinical outcome scale (adjusted odds ratio, 1.39; 95% CI, 1.10-1.74; P = .005). Time-to-event analyses showed sleep-related hypoxia associated with a 31% higher rate of hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005).Conclusions and relevanceIn this case-control study, SDB and sleep-related hypoxia were not associated with increased SARS-CoV-2 positivity; however, once patients were infected with SARS-CoV-2, sleep-related hypoxia was an associated risk factor for detrimental COVID-19 outcomes.
| S-EPMC8581726 | biostudies-literature
Project description:ObjectivesTo evaluate rapid COVID-19 vaccine clinic implementation from January-April 2021 in the Los Angeles County Department of Health Services (LACDHS), the second-largest US safety net health system. During initial vaccine clinic implementation, LACDHS vaccinated 59,898 outpatients, 69% of whom were Latinx (exceeding the LA County Latinx population of 46%). LACDHS is a unique safety net setting to evaluate rapid vaccine implementation due to system size, geographic breadth, language/racial/ethnic diversity, limited health staffing resources, and socioeconomic complexity of patients.MethodsImplementation factors were assessed through semi-structured interviews of staff from all twelve LACDHS vaccine clinics from August-November 2021 using the Consolidated Framework for Implementation Research (CFIR) and themes analyzed using rapid qualitative analysis.ResultsOf 40 potential participants, 25 health professionals completed an interview (27% clinical providers/medical directors, 23% pharmacist, 15% nursing staff, and 35% other). Qualitative analysis of participant interviews yielded ten narrative themes. Implementation facilitators included bidirectional communication between system leadership and clinics, multidisciplinary leadership and operations teams, expanded use of standing orders, teamwork culture, use of active and passive communication structures, and development of patient-centered engagement strategies. Barriers to implementation included vaccine scarcity, underestimation of resources needed for patient outreach, and numerous process challenges encountered.ConclusionPrevious studies focused on robust advance planning as a facilitator and understaffing and high staff turnover as barriers to implementation in safety net health systems. This study found facilitators that can mitigate lack of advance planning and staffing challenges present during public health emergencies such as the COVID-19 pandemic. The ten identified themes may inform future implementations in safety net health systems.
| S-EPMC10277563 | biostudies-literature
Project description:ObjectiveMultiple states have reported increases in opioid overdose deaths during the coronavirus disease 2019 (COVID-19) pandemic, however little is known about opioid-related presentations to the emergency department (ED).MethodsThis was a time series analysis of visits to 7 EDs in greater Chicago, Illinois from October 20, 2019 to July 25, 2020. We compared the number of ED visits for opioid-related diagnoses in the time period preceding the World Health Organization pandemic declaration (prepandemic period, October 20, 2019-July 3, 2020) to the time period following the World Health Organization declaration (pandemic period, March 8, 2020 to July 25, 2020) using a single-group interrupted time series analysis with Newey-West standard errors. We also present data on alcohol-related ED visits for comparison.ResultsWe evaluated a total of 177,405 visits across the 7 EDs during the study period. The mean number of weekly ED visits in the prepandemic and pandemic periods was 4841 and 4029 weekly visits, respectively. In the interrupted time series analysis, there was no significant immediate effect of the pandemic start on opioid-related ED visits (-0.44 visits per 1000 ED visits, 95% CI -2.47 to 1.58, P = 0.66), however, there was a significant immediate effect of the pandemic start on alcohol-related ED visits (-4.1, 95% CI: -8.25 to -0.01, P < 0.05).ConclusionsDespite reductions in overall ED visit volumes and alcohol-related visits during COVID-19, the number of opioid-related visits was not significantly reduced during the early pandemic. These data reinforce the need to provide comprehensive treatment services for opioid use disorder during the co-occurring COVID-19 and opioid crises.
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