Dataset Information

Clinical Characteristics and Outcomes of Coronavirus Disease 2019 Patients Who Received Compassionate-Use Leronlimab.

ABSTRACT:

Background

Leronlimab, a monoclonal antibody blocker of C-C chemokine receptor type 5 originally developed to treat human immunodeficiency virus infection, was administered as an open-label compassionate-use therapeutic for coronavirus disease 2019 (COVID-19).

Methods

Twenty-three hospitalized severe/critical COVID-19 patients received 700 mg leronlimab subcutaneously, repeated after 7 days in 17 of 23 patients still hospitalized. Eighteen of 23 received other experimental treatments, including convalescent plasma, hydroxychloroquine, steroids, and/or tocilizumab. Five of 23 received leronlimab after blinded, placebo-controlled trials of remdesivir, sarilumab, selinexor, or tocilizumab. Outcomes and results were extracted from medical records.

Results

Mean age was 69.5 ± 14.9 years; 20 had significant comorbidities. At baseline, 22 were receiving supplemental oxygen (3 high flow, 7 mechanical ventilation). Blood showed markedly elevated inflammatory markers (ferritin, D-dimer, C-reactive protein) and an elevated neutrophil-to-lymphocyte ratio. By day 30 after initial dosing, 17 were recovered, 2 were still hospitalized, and 4 had died. Of the 7 intubated at baseline, 4 were fully recovered off oxygen, 2 were still hospitalized, and 1 had died.

Conclusions

Leronlimab appeared safe and well tolerated. The high recovery rate suggested benefit, and those with lower inflammatory markers had better outcomes. Some, but not all, patients appeared to have dramatic clinical responses, indicating that unknown factors may determine responsiveness to leronlimab. Routine inflammatory and cell prognostic markers did not markedly change immediately after treatment, although interleukin-6 tended to fall. In some persons, C-reactive protein clearly dropped only after the second leronlimab dose, suggesting that a higher loading dose might be more effective. Future controlled trials will be informative.

SUBMITTER: Yang B

PROVIDER: S-EPMC7665416 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ImportanceRisk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities.ObjectiveTo describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity.Design, setting, and participantsThe Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020.ExposuresCOVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms.Main outcomes and measuresThe main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes.ResultsA total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01).Conclusions and relevanceIn this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.

Project description:Adult patients with cancer have a greater likelihood of developing severe illness and death from coronavirus disease 2019 compared with patients without cancer. We sought to characterize the clinical characteristics and outcomes of cancer patients who tested positive for severe acute respiratory syndrome coronavirus 2 and were admitted to the ICU at the peak of the first wave of the pandemic in the United States.DesignA single-center retrospective cohort study.SettingTwo medical-surgical ICUs of a tertiary-care cancer center.Patients/subjectsAll consecutive adult patients (≥ 18 yr) with current or past (< 2 yr) diagnosis of cancer who were admitted to the ICU with coronavirus disease 2019 between March 1, and June 30, 2020.InterventionsNone.Measurements and main resultsDemographic, clinical, and laboratory data of 89 critically ill cancer patients were extracted from electronic medical records. Median age was 65 years (interquartile range, 57-70 yr), 66% were White, and 58% male. Approximately a third of patients had three or more comorbidities. Fifty-one patients (57%) had solid tumors, and 38 (42%) had hematologic malignancies. Sixty-one patients (69%) received cancer-directed therapy within the previous 90 days. Sixty patients (67%) required mechanical ventilation, 56% required prone positioning, 28% underwent tracheostomy, and 71% required vasopressors. Hospital mortality was 45% (40/89). Among those who required mechanical ventilation, mortality was 53% (32/60). Hospital mortality was significantly higher among patients with hematologic malignancies, higher severity of illness and organ failure scores, need for invasive mechanical ventilation and vasopressor therapy, lower hemoglobin and platelet count, and higher d-dimer levels at ICU admission. ICU and hospital length of stay were 10 and 26 days, respectively. At 9-month follow-up, the mortality rate was 54% (48/89).ConclusionsWe report the largest case series and intermediate-term follow-up of cancer patients with coronavirus disease 2019 who were admitted to the ICU. Hospital mortality was 45%. Intermediate-term outcome after hospital discharge was favorable.