Therapeutic strategies for COVID-19: progress and lessons learned

Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(6), С. 449 - 475

Опубликована: Апрель 19, 2023

Язык: Английский

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Insights for COVID-19 in 2023

Revista Española de Quimioterapia, Год журнала: 2022, Номер 36(2), С. 114 - 124

Опубликована: Дек. 12, 2022

Predictions for a near end of the pandemic by World Health Organization should be interpreted with caution. Current evidence indicates that efficacy fourth dose classical mRNA vaccines (BT162b2 or mRNA-1273) is low and short-lived in preventing SARS-CoV-2 infection its predominant variant (Omicron). However, high against severe symptomatic infection, hospitalization death. The new being introduced are bivalent active Omicron variants. Potential to coming year include vaccine based on recombinant protein emulates receptor binding domain Spike under development Spanish company Hipra, as well nasal oral administration. Available information suggests COVID-19 can administered association influenza vaccination without particular complications. New drugs COVID-19, both antiviral anti-inflammatory, investigation, but this does not seem case monoclonal antibodies. indication use masks some circumstances will maintained next view accumulation scientific data their efficacy. Finally, long COVID Post-COVID syndrome may continue affect very proportion patients who have had disease, requiring combined diagnostic therapeutic resources.

Язык: Английский

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The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19

Annals of Internal Medicine, Год журнала: 2022, Номер 175(10), С. 1401 - 1410

Опубликована: Авг. 29, 2022

Background: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding the pathogenesis COVID-19. Objective: To evaluate whether levels can predict short-term clinical outcomes identify viral factors associated hospitalized SARS-CoV-2. Design: Cross-sectional study baseline level from 2540 participants enrolled TICO (Therapeutics for Inpatients With COVID-19) platform trial August 2020 to November 2021, additional data on day 5 outcome time discharge. Setting: 114 centers 10 countries. Participants: Adults acute infection 12 days or less symptoms. Measurements: Baseline N was measured at a central laboratory. Delta variant status determined nasal swabs using reverse transcriptase polymerase chain reaction. Associations between patient characteristics were assessed both unadjusted multivariable modeling. Association elevated 1000 ng/L greater outcomes, including worsening ordinal pulmonary scale hospital discharge, evaluated logistic regression Fine–Gray models, respectively. Results: Plasma below quantification 5% enrollment, 57%. severity illness strongly level, mean 3.10-fold higher among those requiring noninvasive ventilation high-flow cannula compared room air (95% CI, 2.22 4.34). who lacked antispike antibodies (6.42 fold; 5.37 7.66) (1.73 1.41 2.13). Additional included male sex, shorter since admission, decreased remdesivir, renal impairment. In contrast, race, ethnicity, body mass index, immunocompromising conditions not levels. markedly odds worsened (odds ratio, 5.06 [CI, 3.41 7.50]) longer discharge (median, 7 vs. 4 days; subhazard 0.51 0.45 0.57]), ratios similar across all severity. Limitations: samples drawn presentation. No point-of-care test measure is currently available. Conclusion: Elevated highly clinically outcomes. Multiple are These support potential role ongoing replication patients. Primary Funding Source: U.S. government Operation Warp Speed National Institute Allergy Infectious Diseases.

Язык: Английский

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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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Ritonavir: 25 Years’ Experience of Concomitant Medication Management. A Narrative Review

Infectious Diseases and Therapy, Год журнала: 2024, Номер 13(5), С. 1005 - 1017

Опубликована: Апрель 12, 2024

Ritonavir is a potent inhibitor of the cytochrome P450 3A4 enzyme and commonly used as pharmacokinetic (PK) enhancer in antiviral therapies because it increases bioavailability concomitantly administered antivirals. Decades experience with ritonavir-enhanced HIV and, more recently, COVID-19 demonstrate that boosting doses ritonavir are well tolerated, an established safety profile. The mechanisms PK enhancement by result potential for drug–drug interactions (DDIs) several classes drugs, thus making co-medication management important consideration enhanced therapies. However, rates DDIs contraindicated medications low, suggesting these risks manageable infectious disease specialists who have use enhancers. In this review, we provide overview ritonavir's action describe approaches resources available to mitigate adverse events manage concomitant medication both chronic short-term settings.

Язык: Английский

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SARS-CoV-2 spike protein in infectivity

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 21 - 56

Опубликована: Янв. 1, 2025

Язык: Английский

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Blood absolute lymphocyte count and trajectory are important in understanding severe COVID-19

BMC Infectious Diseases, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 15, 2025

Abstract Background Low blood absolute lymphocyte count (ALC) may predict severe COVID-19 outcomes. Knowledge gaps remain regarding the relationship of ALC trajectory with clinical outcomes and factors associated lymphopenia. Methods Our post hoc analysis Therapeutics for Inpatients platform trial utilized proportional hazards models to assess relationships between Day (D) 0 lymphopenia (ALC < 0.9 cells/uL), D0 0.5 cells/uL) or D5 mortality secondary infections, sustained recovery using Fine-Gray models. Logistic regression was used variables trajectory. Results (1426/2579) (636/2579) were increased (aHR 1.48; 1.08, 2.05, p = 0.016 aHR 1.60; 1.20, 2.14, 0.001) decreased (aRRR 0.90; 0.82, 0.99, 0.033 aRRR 0.78; 0.70, 0.87, 0.001 respectively). Trial participants persistent had mortality, new impaired recovery, as compared no Persistent older age, male sex; prior immunosuppression, heart failure, aspirin use, normal body mass index; biomarkers organ damage (renal lung), ineffective immune response (elevated IL-6 viral nucleocapsid antigen levels). Similar results observed Conclusions Lymphopenia predictive outcomes, particularly when during hospitalization. A better understanding underlying risk will help illuminate disease pathogenesis guide management strategies.

Язык: Английский

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Long-term outcomes of passive immunotherapy for COVID-19: A pooled analysis of a large multinational platform randomized clinical trial

Clinical Microbiology and Infection, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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SARS-Cov-2 vaccination strategies in hospitalized recovered COVID-19 patients: a randomized clinical trial (VATICO Trial)

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 22, 2025

The impact on immunogenicity and efficacy of SARS-CoV-2 vaccination in people with prior COVID-19 could differ depending timing number doses. VATICO study randomized 66 hospitalized recovered individuals to receive either immediate or deferred vaccination, one two doses mRNA vaccines. We measured binding neutralizing antibodies against at enrollment longitudinally. Median (IQR) time from infection first was 68 (53–75) days the group, 151 (137–173) group. At week 48, vaccine did not influence change antibody levels relative baseline. Adherence assigned regimen lower particularly participants receiving Although ultimately lacked adequate power draw firm conclusions, these results suggest possible benefits prompt after recovery COVID-19.

Язык: Английский

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Physicochemical Characteristics of Antimicrobials and Practical Recommendations for Intravenous Administration: A Systematic Review

Antibiotics, Год журнала: 2023, Номер 12(8), С. 1338 - 1338

Опубликована: Авг. 19, 2023

Most antimicrobial drugs need an intravenous (IV) administration to achieve maximum efficacy against target pathogens. IV is related complications, such as tissue infiltration and thrombo-phlebitis. This systematic review aims provide practical recommendations about diluent, pH, osmolarity, dosage, infusion rate, vesicant properties, phlebitis rate of the most commonly used evaluated in randomized controlled studies (RCT) till 31 March 2023. The authors searched for available RCT PUBMED EMBASE®, EBSCO® CINAHL®, Cochrane Controlled Clinical trials. Drugs’ chemical features were online, drug data sheets, scientific papers, establishing that with a pH <5 or >9, osmolarity >600 mOsm/L, high incidence reported literature, adoption utmost caution during administration. We 931 papers; 232 included. A total 82 antimicrobials identified. Regarding antibiotics, 37 reach “caution” criterion, well seven antivirals, 10 antifungals, three antiprotozoals. In this subgroup antimicrobials, correct vascular access device (VAD) selection essential avoid complications due through peripheral vein. Knowing physicochemical characteristics crucial improve patient’s safety significantly, thus avoiding errors local side effects.

Язык: Английский

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