Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19

Clinical Infectious Diseases, Год журнала: 2024, Номер 78(6), С. 1490 - 1503

Опубликована: Фев. 20, 2024

Abstract Background Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was evaluate which virus host response factors were associated with risk among participants Therapeutics for Inpatients (TICO/ACTIV-3) trials. Methods A secondary analysis 2625 SARS-CoV-2 infection randomized 1 5 antiviral products or matched placebo 114 centers on 4 continents. Uniform, site-level collection participant baseline clinical variables performed. Research laboratories assayed upper respiratory swabs viral RNA plasma anti–SARS-CoV-2 antibodies, nucleocapsid antigen (viral Ag), interleukin-6 (IL-6). Associations between time by 90 days assessed using univariate multivariable Cox proportional hazards models. Results Viral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29–3.34), (<35 000 copies/mL [aHR, 2.42; 1.09–5.34], ≥35 2.84; 1.29–6.28], vs below detection), support (<4 L O2 1.84; 1.06–3.22]; ≥4 4.41; 2.63–7.39], noninvasive ventilation/high-flow nasal cannula 11.30; 6.46–19.75] no oxygen), renal impairment (aHR, 1.77; 1.29–2.42), IL-6 >5.8 2.54 [1.74–3.70] ≤5.8 ng/L) significantly final analyses. Ag, RNA, not measured real-time. Conclusions Baseline virus-specific, clinical, biological are strongly within days, revealing pathogen host-response therapeutic targets disease.

Язык: Английский

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Three hospitalized non-critical COVID-19 subphenotypes and change in intubation or death over time: A latent class analysis with external and longitudinal validation

PLoS ONE, Год журнала: 2025, Номер 20(3), С. e0316434 - e0316434

Опубликована: Март 19, 2025

There are two subphenotypes of COVID-19 acute respiratory distress syndrome with differential responses to corticosteroids, but whether similar hospitalized non-critical patients exist remains unknown. To identify and validate at hospital admission that may elucidate pathobiology facilitate heterogeneity-of-treatment effect analyses clinical trials patients. We conducted a multi-center retrospective cohort study adults who were not intubated or did die within 24 hours admission. derived externally longitudinally validated during the wild-type delta severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV2) waves via latent class analysis using laboratory data trained XGBoost machine learning models predict subphenotype. analyzed for 4,827 patients: 2,077 wave Columbia University Medical Center (CUMC) affiliate derivation patients; 1,214 Cornell external validation 1,536 CUMC longitudinal A three-class model best fit each identifying low-inflammatory, intermediate-inflammatory, high-inflammatory fibrinolysis, increasing 90-day risk intubation death across in wave. However, wave, intermediate-inflammatory subphenotype had lowest death. area under receiver-operating-curve was 0.96 testing dataset, biomarkers inflammation cardiorenal dysfunction strongest predictors identified three persisted through SARS-CoV2 waves. The greatest relative improvement survival over time standardized use corticosteroids other interventions. Our can COVID-19.

Язык: Английский

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Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19

Annals of Internal Medicine, Год журнала: 2022, Номер 175(9), С. 1266 - 1274

Опубликована: Авг. 8, 2022

Ensovibep (MP0420) is a designed ankyrin repeat protein, novel class of engineered proteins, under investigation as treatment SARS-CoV-2 infection.To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared care alone.Double-blind, randomized, placebo-controlled, trial. (ClinicalTrials.gov: NCT04501978).Multinational, multicenter trial.Adults COVID-19.Intravenous 600 mg, or placebo.Ensovibep was assessed for early futility on the basis pulmonary ordinal scores at day 5. The primary outcome time sustained recovery through 90, defined 14 consecutive days home place usual residence after hospital discharge. A composite safety that included death, serious adverse events, end-organ disease, infections 90.An independent data monitoring board recommended enrollment be halted 485 were randomly assigned received an infusion ensovibep (n = 247) placebo 238). odds ratio (OR) more favorable (vs. placebo) group 5 0.93 (95% CI, 0.67 1.30; P 0.68; OR > 1 would favor ensovibep). 90-day cumulative incidence 82% 80% (subhazard [sHR], 1.06 [CI, 0.88 1.28]; sHR 90 occurred 78 participants (32%) 70 (29%) (HR, 1.07 0.77 1.47]; HR < ensovibep).The trial prematurely stopped because futility, limiting power outcome.Compared placebo, did not improve receiving including remdesivir; no concerns identified.National Institutes Health.

Язык: Английский

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Management of patients with lymphoma and COVID‐19: Narrative review and evidence‐based practical recommendations

Hematological Oncology, Год журнала: 2022, Номер 41(1), С. 3 - 15

Опубликована: Окт. 17, 2022

Patients with hematologic malignancies can be immunocompromized because of their disease, anti-cancer therapy, and concomitant immunosuppressive treatment. Furthermore, these patients are usually older than 60 years have comorbidities. For all reasons they highly vulnerable to infection severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) an increased risk developing severe/critical Coronavirus disease 2019 (COVID-19) compared the general population. Although COVID-19 vaccination has proven effective in reducing incidence vaccinated lymphoma may not protected as often fail develop a sufficient antiviral immune response. There is therefore urgent need address management setting ongoing pandemic. Passive immunization monoclonal antibodies against SARS-CoV-2 currently available complementary drug strategy active for patients, while drugs (remdesivir, ritonavir-boosted nirmatrelvir, molnupiravir) preventing progression COVID-19. In this narrative review we present most recent data documenting characteristics outcomes Our ultimate goal provide practice-oriented guidance from diagnosis treatment follow-up lymphoma. To purpose, will first overview main concerning prognostic factors fatality rate who COVID-19; also addressed. We then discuss current prophylaxis options patients. Finally, based on literature our multidisciplinary experience, summarize set indications how manage according exposure, level severity former history infection, typically encountered clinical practice.

Язык: Английский

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Tixagevimab and Cilgavimab (Evusheld™) Prophylaxis Prevents Breakthrough COVID-19 Infections in Immunosuppressed Population: 6-Month Prospective Study

Vaccines, Год журнала: 2023, Номер 11(2), С. 350 - 350

Опубликована: Фев. 3, 2023

Persons with neuroinflammatory diseases (pwNID) treated potent immunosuppressives are at risk of severe COVID-19 outcomes and reduced vaccine seroconversion. We aimed determining the real-world efficacy tixagevimab cilgavimab (Evusheld™) in immunosuppressed pwNID preventing breakthrough infections.31 were followed for 6 months after administration as a prophylactic medication (January 2022-July 2022). Only anti-CD20 monoclonal antibodies sphingosine-1-phosphate modulators considered eligible study. A control group 126 (38 seropositive 88 seronegative SARS-CoV-2 vaccination) included. Breakthrough infections rate their severity was determined over follow-up.The had more comorbidities when compared total (54.8% vs. 30.2% 27.3%, p = 0.02 0.005, respectively). After 6-month follow-up, significantly lower numbers (6.5% 34.1%, 0.002) 38.6%, < 0.001). All Evusheld-treated mild, whereas 9/43 moderate/severe. No side effects to recorded.In immunosuppressive therapies, during Omicron (BA.2-BA.5 variants) wave.

Язык: Английский

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