RESUMO
As of October 2021, coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global emergency, and novel therapeutics are urgently needed. Here we describe human single chain variable fragment (scFv) antibodies (76clAbs) that block an epitope of the SARS-CoV-2 spike protein essential for ACE2-mediated entry into cells. 76clAbs neutralize the delta variant and other variants being monitored (VBMs) and inhibit spike-mediated pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. In two independent animal models, intranasal administration counteracted the infection. Due to high efficiency, remarkable stability, resilience to nebulization and low production cost, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.
RESUMO
Despite the extracorporeal cytokine hemadsorption device CytoSorb was granted FDA emergency approval for critically ill COVID19 patients, to our knowledge no published studies are currently available to support its use. This manuscript reports the experience of the use of CytoSorb during COVID19 pandemic in Bergamo, Italy. In our pilot study, eleven COVID19 patients requiring invasive mechanical ventilation for a rapidly progressive ARDS were treated with 24 to 48 hours of extracorporeal cytokine hemadsorption. Respiratory and laboratory parameters, including a full set of inflammatory cytokines, were evaluated at different time points. A significant but transient reduction of the hyperinflammatory status was observed, along with the amelioration of the clinical and respiratory parameters. We believe that this manuscript will provide them with important preliminary data on the use of cytokine hemadsorption devices.
RESUMO
BackgroundSevere COVID-19 is characterised by interstitial pneumonia and hyperinflammation, with elevated levels of pro-inflammatory cytokines, such as IL-6. Effective treatments are urgently needed, and IL-6 is a rational target to reduce hyperinflammation. MethodsAn observational, control cohort, single-centre study initiated at the Papa Giovanni XXIII Hospital in Bergamo, Italy included patients with COVID-19 confirmed by a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2 RNA and interstitial pneumonia requiring ventilatory support. Patients were treated with either best supportive care and siltuximab or best supportive care alone. Propensity score matching was applied to minimise differences in baseline covariates between patient cohorts. The main outcome was mortality in siltuximab-treated patients compared with patients in the matched-control cohort. This study (Siltuximab in Severe COVID-19, SISCO) is registered with ClinicalTrials.gov, identifier NCT04322188. FindingsThirty patients received siltuximab, while 188 control patients received only best supportive care. Siltuximab-treated patients were matched to 30 control patients using the propensity score analysis of baseline covariates. The 30-day mortality rate was significantly lower in the siltuximab-treated than the matched-control cohort patients (HR 0{middle dot}462, 95% CI 0{middle dot}221- 0{middle dot}965); p=0{middle dot}0399). The mean follow-up was 33{middle dot}3 days (range 7-58 days) for the siltuximab-treated patients and 22{middle dot}8 days (range 2-45 days) for the control cohort. Sixteen siltuximab-treated patients were discharged from hospital, four remained on mechanical ventilation, and 10 patients died. InterpretationPatients with rapidly progressing COVID-19 respiratory failure requiring ventilatory support may benefit from treatment with siltuximab to reduce mortality and cytokine-driven hyperinflammation associated with severe disease. These findings require validation in a randomised controlled clinical trial. FundingPapa Giovanni XXIII Hospital and the Italian Association for Cancer Research funded the study. EUSA Pharma supplied siltuximab, and provided funding for data collection, analysis, and development of the publication.
