Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 387(9), P. 790 - 798

Published: Aug. 24, 2022

The oral protease inhibitor nirmatrelvir has shown substantial efficacy in high-risk, unvaccinated patients infected with the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data regarding effectiveness preventing disease 2019 (Covid-19) outcomes from B.1.1.529 (omicron) are limited.We obtained data for all members Clalit Health Services who were 40 years age or older at start study period and assessed as being eligible to receive therapy during omicron surge. A Cox proportional-hazards regression model time-dependent covariates was used estimate association treatment hospitalization death due Covid-19, adjustment sociodemographic factors, coexisting conditions, previous SARS-CoV-2 immunity status.A total 109,254 met eligibility criteria, whom 3902 (4%) received period. Among 65 older, rate Covid-19 14.7 cases per 100,000 person-days among treated compared 58.9 untreated (adjusted hazard ratio, 0.27; 95% confidence interval [CI], 0.15 0.49). adjusted ratio 0.21 (95% CI, 0.05 0.82). 64 age, 15.2 15.8 0.74; 0.35 1.58). 1.32 0.16 10.75).Among rates significantly lower those than did not. No evidence benefit found younger adults.

Language: Английский

---

VV116 versus Nirmatrelvir–Ritonavir for Oral Treatment of Covid-19

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 388(5), P. 406 - 417

Published: Dec. 28, 2022

Nirmatrelvir-ritonavir has been authorized for emergency use by many countries the treatment of coronavirus disease 2019 (Covid-19). However, supply falls short global demand, which creates a need more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome 2 (SARS-CoV-2).We conducted phase 3, noninferiority, observer-blinded, randomized trial during outbreak caused B.1.1.529 (omicron) variant SARS-CoV-2. Symptomatic adults mild-to-moderate Covid-19 high risk progression were assigned to receive 5-day course either or nirmatrelvir-ritonavir. The primary end point was time sustained clinical recovery through day 28. Sustained defined as alleviation all Covid-19-related target symptoms total score 0 1 sum each symptom (on scale from higher scores indicating greater severity; on 11-item range 33) consecutive days. A lower boundary two-sided 95% confidence interval hazard ratio than 0.8 considered indicate noninferiority (with >1 shorter nirmatrelvir-ritonavir).A 822 participants underwent randomization, and 771 received (384 participants) nirmatrelvir-ritonavir (387 participants). respect established in analysis (hazard ratio, 1.17; [CI], 1.01 1.35) maintained final (median, 4 days 5 nirmatrelvir-ritonavir; CI, 1.02 1.36). In analysis, resolution (score 11 days) first negative SARS-CoV-2 test did not differ substantially between two groups. No group had died incidence adverse events (67.4% vs. 77.3%).Among who at progression, noninferior recovery, fewer safety concerns. (Funded Vigonvita Life Sciences others; ClinicalTrials.gov number, NCT05341609; Chinese Clinical Trial Registry ChiCTR2200057856.).

Language: Английский

---

Real-world COVID-19 vaccine effectiveness against the Omicron BA.2 variant in a SARS-CoV-2 infection-naive population

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(2), P. 348 - 357

Published: Jan. 18, 2023

The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. Although first-generation vaccines remain effective against severe disease death, robust evidence on vaccine effectiveness (VE) all infections, irrespective symptoms, remains sparse. We used a community-wide serosurvey with 5,310 subjects to estimate how vaccination histories modulated risk infection in infection-naive Hong Kong during large wave BA.2 epidemic January-July 2022. estimated that infected 45% (41-48%) the local population. Three four doses BNT162b2 or CoronaVac were 7 days after (VE 48% (95% credible interval 34-64%) 69% (46-98%) for three BNT162b2, respectively; VE 30% (1-66%) 56% (6-97%) CoronaVac, respectively). At 100 immunization, waned 26% (7-41%) 35% (10-71%) 6% (0-29%) 11% (0-54%) CoronaVac. rapid waning conferred by an increasingly complex viral evolutionary landscape highlight necessity rapidly deploying updated followed vigilant monitoring VE.

Language: Английский

---

Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114367 - 114367

Published: Feb. 6, 2023

Despite the need for novel, effective therapeutics COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like 3 C-like protease (3CLpro) or major (Mpro), have been identified as promising targets antiviral drugs. The Mpro has a role in protein processing well pathogenesis of virus, could be useful therapeutic target. drug nirmatrelvir can keep from replicating through inhibiting Mpro. Nirmatrelvir was combined with another HIV inhibitor, ritonavir, create Paxlovid (Nirmatrelvir/Ritonavir). metabolizing enzyme cytochrome P450 A inhibited by ritonavir lengthen half-life nirmatrelvir, so rintonavir acts pharmacological enhancer. exhibits potent activity against current coronavirus variants, despite significant alterations viral genome. Nevertheless, there still several unanswered questions. This review summarizes literature efficacy treating infection, also their safety possible side effects.

Language: Английский

---

Effectiveness of COVID-19 Treatment With Nirmatrelvir–Ritonavir or Molnupiravir Among U.S. Veterans: Target Trial Emulation Studies With One-Month and Six-Month Outcomes

Annals of Internal Medicine, Journal Year: 2023, Volume and Issue: 176(6), P. 807 - 816

Published: June 1, 2023

Information about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes setting Omicron variant transmission COVID-19 vaccination is limited.

Language: Английский

---

Efficacy and safety of Paxlovid for COVID-19:a meta-analysis

Journal of Infection, Journal Year: 2022, Volume and Issue: 86(1), P. 66 - 117

Published: Sept. 30, 2022

Language: Английский

---

SARS-CoV-2 Virologic Rebound With Nirmatrelvir–Ritonavir Therapy

Annals of Internal Medicine, Journal Year: 2023, Volume and Issue: 176(12), P. 1577 - 1585

Published: Nov. 13, 2023

Background: Data are conflicting regarding an association between treatment of acute COVID-19 with nirmatrelvir−ritonavir (N-R) and virologic rebound (VR). Objective: To compare the frequency VR in patients without N-R for COVID-19. Design: Observational cohort study. Setting: Multicenter health care system Boston, Massachusetts. Participants: Ambulatory adults use N-R. Intervention: Receipt 5 days versus no therapy. Measurements: The primary outcome was VR, defined as either a positive SARS-CoV-2 viral culture result after prior negative or 2 consecutive loads above 4.0 log10 copies/mL that were also at least 1.0 higher than load below copies/mL. Results: Compared untreated persons (n = 55), those taking 72) older, received more vaccinations, commonly had immunosuppression. Fifteen participants (20.8%) 1 (1.8%) who (absolute difference, 19.0 percentage points [95% CI, 9.0 to 29.0 points]; P 0.001). All result. In multivariable models, only associated (adjusted odds ratio, 10.02 [CI, 1.13 88.74]; 0.038). Virologic common among started therapy within symptom onset (26.3%) (0%) (P 0.030). Among receiving N-R, prolonged shedding replication-competent virus compared did not have (median, 14 vs. 3 days). Eight 16 (50% 25% 75%]) reported rebound; completely asymptomatic. No post-VR resistance mutations detected. Limitations: study design differences treated groups; used surrogate marker risk ongoing transmission. Conclusion: occurred approximately people often rebound, virus. Primary Funding Source: National Institutes Health.

Language: Английский

---

Viral burden rebound in hospitalised patients with COVID-19 receiving oral antivirals in Hong Kong: a population-wide retrospective cohort study

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(6), P. 683 - 695

Published: Feb. 13, 2023

Language: Английский

---

Association of nirmatrelvir for acute SARS‐CoV‐2 infection with subsequent Long COVID symptoms in an observational cohort study

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(1)

Published: Jan. 1, 2024

Oral nirmatrelvir/ritonavir is approved as treatment for acute COVID-19, but the effect of during infection on risk Long COVID unknown. We hypothesized that nirmatrelvir SARS-CoV-2 reduces developing and rebound after associated with COVID. conducted an observational cohort study within Covid Citizen Science (CCS) study, online over 100 000 participants. included vaccinated, nonhospitalized, nonpregnant individuals who reported their first positive test March-August 2022. was ascertained infection. Patient-reported symptoms, symptom test-positivity were asked subsequent surveys at least 3 months A total 4684 met eligibility criteria, whom 988 (21.1%) treated 3696 (78.9%) untreated; 353/988 (35.7%) 1258/3696 (34.0%) untreated responded to survey (n = 1611). Among 1611 participants, median age 55 years 66% female. At 5.4 ± 1.3 infection, not symptoms (odds ratio [OR]: 1.15; 95% confidence interval [CI]: 0.80-1.64; p 0.45). 666 answered questions, or positivity (OR: 1.34; CI: 0.74-2.41; 0.33). Within this nonhospitalized individuals, oral more than 90 days

Language: Английский

---

Oral Antiviral Treatment for COVID-19: A Comprehensive Review on Nirmatrelvir/Ritonavir

Viruses, Journal Year: 2022, Volume and Issue: 14(11), P. 2540 - 2540

Published: Nov. 17, 2022

Despite the rapid development of efficient and safe vaccines against COVID-19, need to confine pandemic treat infected individuals on an outpatient basis has led approval oral antiviral agents. Taking into account viral kinetic pattern SARS-CoV-2, it is high importance intervene at early stages disease. A protease inhibitor called nirmatrelvir coupled with ritonavir (NMV/r), which acts as a CYP3A inhibitor, delivered formulation, shown much promise in preventing disease progression high-risk patients no for supplemental oxygen administration. Real-world data seem confirm drug combination’s efficacy safety all variants concern adult populations. Although, not fully clarified, rebound recurrence COVID-19 symptoms have been described following treatment; however, more potential resistance issues concerning Mpro gene, drug’s therapeutic target, are needed. NMV/r gamechanger fight by hospitalizations halting severity; therefore, research future greater awareness its use warranted.

Language: Английский

---