Recombinant human plasma gelsolin (rhu-pGSN) in a patient hospitalized with critical COVID-19 pneumonia.
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ABSTRACT:
SUBMITTER: Catteeuw JV
PROVIDER: S-EPMC8353968 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Risk of severe disease and death due to coronavirus 2019 (COVID-19) is increased in certain patient demographic groups, including those who are of advanced age, male sex, and obese body mass index. Investigations of the biological variations that contribute to this risk have been hampered by heterogeneous severity, with immunologic features of critical disease potentially obscuring differences between risk groups. To examine immune heterogeneity related to demographic risk factors, we enrolled 38 patients hospitalized with clinically homogeneous COVID-19 pneumonia – defined as oxygen saturation <94% on room air without respiratory failure, septic shock, or multiple organ dysfunction – and performed single-cell RNA-sequencing of leukocytes collected at admission. Examination of individual risk factors identified strong shifts within neutrophil and monocyte/dendritic cell compartments, revealing altered immune cell type-specific responses in higher-risk COVID-19 patient subgroups. Specifically, we found transcriptional evidence of altered neutrophil maturation in aged versus young patients and enhanced cytokine responses in monocytes/dendritic cells of male versus female patients. Such innate immune cell alterations may contribute to outcome differences linked to these risk factors. They also highlight the importance of diverse patient cohorts in studies of therapies targeting the immune response in COVID-19.
2023-10-11 | GSE236177 | GEO
Project description:Coronavirus disease 2019 (COVID-19) can be asymptomatic or lead to a wide spectrum of symptoms, ranging from mild upper respiratory system involvement to acute respiratory distress syndrome, multi-organ damage and death. In this study, we explored the potential of microRNAs (miRNA) in delineating patient condition and in predicting clinical outcome. Analysis of the circulating miRNA profile of COVID-19 patients, sampled at different hospitalization intervals after admission, allowed to identify miR-144-3p as a dynamically regulated miRNA in response to COVID-19.
2023-01-27 | GSE195898 | GEO
Project description:The lack of available biomarkers for diagnosing and predicting different stages of coronavirus disease 2019 (COVID-19) is currently one of the main challenges that clinicians are facing. Recent evidence indicates that the plasma levels of specific miRNAs may be significantly modified in COVID-19 patients. Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 40 patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (between March and May 2020) (median 13.50 [IQR 9–24] days since symptoms initiation) and 21 healthy noninfected individuals. Patients were categorized as hospitalized not requiring oxygen therapy (n = 6), hospitalized requiring low-flow oxygen (n = 23), and hospitalized requiring high-flow oxygen support (n = 11). A total of 1218 different micro(mi)RNAs were identified. When compared with healthy noninfected donors, SARS-CoV-2 infected patients showed significantly (fold change [FC] >1.2 and adjusted p [padj] <0.05) altered expression of 190 miRNAs. The top 10 differentially expressed (DE) miRNAs were miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, and miR-191-5p, which displayed FC and padj values ranging from 153 to 5 and 2.51 × 10-32 to 2.21 × 10-21, respectively, which unequivocally diagnosed SARS-CoV-2 infection. No differences in blood cell counts and biochemical plasma parameters, including interleukin 6, ferritin and D-dimer, were observed between COVID-19 patients on high-flow oxygen therapy, low-flow oxygen therapy, or not requiring oxygen therapy. Notably, 31 significantly deregulated miRNAs were found when patients on high- and low-flow oxygen therapy were compared. Similarly, 6 DE miRNAs were identified between patients on high flow and those not requiring oxygen therapy. SARS-CoV-2 infection generates a specific miRNA signature in hospitalized patients. Furthermore, specific miRNA profiles are associated with COVID-19 prognosis in severe patients.
2024-04-03 | GSE230092 | GEO
Project description:Background:Plasma gelsolin (pGSN) is an abundant circulating protein quickly consumed by extensive tissue damage. Marked depletion is associated with later poor outcomes in diverse clinical circumstances. Repletion with recombinant human (rhu)-pGSN in animal models of inflammation lessens mortality and morbidity. Methods:Neutropenic mice were treated with different meropenem doses ±12 mg of rhu-pGSN commencing 1 day before an intratracheal challenge with multidrug-resistant Pseudomonas aeruginosa. Survival, bacterial counts, and pulmonary pathology were compared between corresponding meropenem groups with and without rhu-pGSN. Results:Overall survival was 35/64 (55%) and 46/64 (72%) in mice given meropenem without and with rhu-pGSN, respectively (??=?17%; 95% CI, 1-34). In control mice receiving meropenem 1250 mg/kg/d where the majority died, the addition of rhu-pGSN increased survival from 5/16 (31%) to 12/16 (75%) (??=?44%; 95% CI, 13-75). Survival with minor lung injury was found in 26/64 (41%) mice receiving only meropenem, vs 38/64 (59%) in mice given meropenem plus rhu-pGSN (??=?19%; 95% CI, 2-36). Conclusions:In a series of dose-ranging experiments, both mortality and lung injury were reduced by the addition of rhu-pGSN to meropenem against carbapenem-resistant P. aeruginosa. Rhu-pGSN offers a novel candidate therapy for antibiotic-resistant pneumonia.
| S-EPMC7397834 | biostudies-literature
Project description:Proteomics analysis of exosomes isolated from four temporal phases of COVID-19
2021-05-19 | PXD026091 | Pride
Project description:BackgroundCoronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear.MethodsWe randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28.ResultsA total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P?=?0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, -?5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group.ConclusionsIn hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.).
| S-EPMC7781101 | biostudies-literature
Project description:BackgroundThe efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear.MethodsWe randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed.ResultsA total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P = 0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group.ConclusionsAmong patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114.).
| S-EPMC8220898 | biostudies-literature
Project description:The combination of coronavirus disease 2019 (COVID-19) pneumonia and pulmonary-renal syndrome due to ANCA-associated vasculitis (AAV) poses diagnostic uncertainty and a therapeutic dilemma. According to current limited knowledge of COVID-19, the application of commonly used drugs in AAV, cyclophosphamide (CYC) and rituximab (RTX), must be weighed carefully in active COVID-19 infection. We report a case of a 52-year-old male patient with concurrent severe COVID-19 pneumonia and acute relapse of pulmonary-renal syndrome due to AAV after recent RTX maintenance dose. The patient presented with severe hypoxaemia, complete B-cell depletion and severe acute respiratory syndrome coronavirus 2 viraemia. He was successfully treated with therapeutic plasma exchange employing COVID-19 convalescent plasma.
| S-EPMC8244539 | biostudies-literature
Project description:BackgroundCoronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.MethodsIn this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo.ResultsOf the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, -1.0; 95% CI, -2.5 to 0; P = 0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points; 95% CI, -7.6 to 8.2; nominal P = 0.94).ConclusionsIn this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann-La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov number, NCT04320615.).
| S-EPMC7953459 | biostudies-literature
Project description:BACKGROUNDPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive.METHODSWe conducted a randomized, open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high-flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (noninvasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7 (death) at 14 days. Primary analysis was performed in the intention-to-treat population.RESULTSBetween April 4, 2020, and February 5, 2021, 350 patients were randomly assigned to either CP (n = 179) or SOC (n = 171). At 14 days, proportion of patients in categories 5, 6, or 7 was 11.7% in the CP group versus 16.4% in the control group (P = 0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5-7 in the CP group versus 17.0% in the control group (P = 0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95% CI 0.19-1.14, log-rank P = 0.087).CONCLUSIONCP showed a significant benefit in preventing progression to noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant.TRIAL REGISTRATIONClinicaltrials.gov, NCT04345523.FUNDINGGovernment of Spain, Instituto de Salud Carlos III.
| S-EPMC8516461 | biostudies-literature