Conv. Plasma
Nigella Sativa
Peg.. Lambda

All paxlovid studies
Meta analysis
Home COVID-19 treatment researchPaxlovidPaxlovid (more..)
Melatonin Meta
Bromhexine Meta Metformin Meta
Budesonide Meta
Cannabidiol Meta Molnupiravir Meta
Colchicine Meta
Conv. Plasma Meta
Curcumin Meta Nigella Sativa Meta
Ensovibep Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Peg.. Lambda Meta
Fluvoxamine Meta Quercetin Meta
Hydroxychlor.. Meta Remdesivir Meta
Ivermectin Meta
Lactoferrin Meta

All Studies   All Outcomes   Recent:  
0 0.5 1 1.5 2+ Viral rebound -761% Improvement Relative Risk Paxlovid for COVID-19  POSITIVES  EARLY TREATMENT Is early treatment with paxlovid beneficial for COVID-19? Prospective study of 127 patients in the USA Worse viral clearance with paxlovid (p=0.038) Edelstein et al., medRxiv, June 2023 Favors paxlovid Favors control

SARS-CoV-2 virologic rebound with nirmatrelvir-ritonavir therapy

Edelstein et al., medRxiv, doi:10.1101/2023.06.23.23288598, POSITIVES
Jun 2023  
  Source   PDF   All Studies   Meta AnalysisMeta
Prospective study of 127 COVID-19 patients in the USA showing higher risk of replication-competent virologic rebound with paxlovid treatment.
Authors note that rebound substantially increases the duration of shedding of replication-competent virus.
When compared with previous studies, authors believe the higher frequency of rebound detected is due to the frequent sampling and culture analysis. When authors restrict to 3 timepoints with PCR only, as in prior studies, they detect a similar rate of rebound as in previous studies, but miss 80% of rebound events detected in this study.
viral rebound, 760.8% higher, RR 8.61, p = 0.04, treatment 15 of 72 (20.8%), control 1 of 55 (1.8%), adjusted per study, odds ratio converted to relative risk, replication-competent virological rebound, multivariable.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Edelstein et al., 27 Jun 2023, prospective, USA, preprint, 22 authors, POSITIVES trial.
All Studies   All Outcomes   Submit Updates or Corrections
This PaperPaxlovidAll
SARS-CoV-2 virologic rebound with nirmatrelvir-ritonavir therapy
Gregory E Edelstein, Julie Boucau, Rockib Uddin, Caitlin Marino, May Y Liew, M.D Mamadou Barry, Ph.D Manish C Choudhary, Rebecca F Gilbert, Zahra Reynolds, Yijia Li, Dessie Tien, Shruti Sagar, Tammy D Vyas, M.D Yumeko Kawano, Jeffrey A Sparks, M.D Sarah P Hammond, M.D. M.Sc Zachary Wallace, M.D. Ph.D Jatin M Vyas, Amy K Barczak, Jacob E Lemieux, Jonathan Z Li, MD MPH Mark J Siedner
Objective: To compare the frequency of replication-competent virologic rebound with and without nirmatrelvir-ritonavir treatment for acute COVID-19. Secondary aims were to estimate the validity of symptoms to detect rebound and the incidence of emergent nirmatrelvir-resistance mutations after rebound. Design: Observational cohort study. Setting: Multicenter healthcare system in Boston, Massachusetts. Participants: We enrolled ambulatory adults with a positive COVID-19 test and/or a prescription for nirmatrelvir-ritonavir. Exposures: Receipt of 5 days of nirmatrelvir-ritonavir treatment versus no COVID-19 therapy. Main Outcome and Measures: The primary outcome was COVID-19 virologic rebound, defined as either (1) a positive SARS-CoV-2 viral culture following a prior negative culture or (2) two consecutive viral loads ≥4.0 log10 copies/milliliter after a prior reduction in viral load to <4.0 log10 copies/milliliter. Results: Compared with untreated individuals (n=55), those taking nirmatrelvir-ritonavir (n=72) were older, received more COVID-19 vaccinations, and were more commonly immunosuppressed. Fifteen individuals (20.8%) taking nirmatrelvir-ritonavir experienced virologic rebound versus one (1.8%) of the untreated (absolute difference 19.0% [95%CI 9.0-29.0%], P=0.001). In multivariable models, only N-R was associated with VR (AOR 10.02, 95%CI 1.13-88.74). VR occurred more commonly among those with earlier nirmatrelvirritonavir initiation (29.0%, 16.7% and 0% when initiated days 0, 1, and ≥2 after diagnosis, respectively, P=0.089). Among participants on N-R, those experiencing rebound had prolonged shedding of replication-competent virus compared to those that did not rebound (median: 14 vs 3 days). Only 8/16 with virologic rebound reported worsening symptoms (50%, 95%CI 25%-75%); 2 were completely asymptomatic. We detected no post-rebound nirmatrelvir-resistance mutations in the NSP5 protease gene. Conclusions and Relevance: Virologic rebound occurred in approximately one in five people taking nirmatrelvir-ritonavir and often occurred without worsening symptoms. Because it is associated with replication-competent viral shedding, close monitoring and potential isolation of those who rebound should be considered.
Anderson, Caubel, Rusnak, Nirmatrelvir-ritonavir and viral load rebound in COVID-19
Boucau, Uddin, Marino, Characterization of Virologic Rebound Following Nirmatrelvir-Ritonavir Treatment for Coronavirus Disease 2019 (COVID-19), Clin Infect Dis, doi:10.1093/cid/ciac512
Charness, Gupta, Stack, Rebound of SARS-CoV-2 Infection after Nirmatrelvir-Ritonavir Treatment, N Engl J Med, doi:10.1056/NEJMc2206449
Deo, Choudhary, Moser, Symptom and Viral Rebound in Untreated SARS-CoV-2 Infection, Ann Intern Med, doi:10.7326/M22-2381
Epling, Rocco, Boswell, Clinical, Virologic, and Immunologic Evaluation of Symptomatic Coronavirus Disease 2019 Rebound Following Nirmatrelvir/Ritonavir Treatment, Clin Infect Dis, doi:10.1093/cid/ciac663
Goyal, Reeves, Cardozo-Ojeda, Schiffer, Mayer, Viral load and contact heterogeneity predict SARS-CoV-2 transmission and super-spreading events, Walczak AM, doi:10.7554/eLife.63537
North, Barczak, Goldstein, Determining the Incidence of Asymptomatic SARS-CoV-2 Among Early Recipients of COVID-19 Vaccines (DISCOVER-COVID-19): A Prospective Cohort Study of Healthcare Workers Before, During and After Vaccination, Clin Infect Dis, doi:10.1093/cid/ciab643
Pandit, Radin, Chiang, The COVID-19 Rebound Study: A Prospective Cohort Study to Evaluate Viral and Symptom Rebound Differences in Participants Treated with Nirmatrelvir Plus Ritonavir Versus Untreated Controls, Clin Infect Dis. Published online February, doi:10.1093/cid/ciad102
Perelson, Ribeiro, Phan, National Institutes of Health. A Study to Learn About the Study Medicines (Nirmatrelvir Plus Ritonavir) in People Aged 12 Years or Older With COVID-19 and a Compromised Immune System (NCT05438602), doi:10.1101/2023.05.30.2329074713
Wong, Lau, Au, Viral burden rebound in hospitalised patients with COVID-19 receiving oral antivirals in Hong Kong: a population-wide retrospective cohort study, Lancet Infect Dis. Published online February, doi:10.1016/S1473-3099(22)00873-8
Wong, Yip, Lai, Wong, Hui et al., Incidence of Viral Rebound After Treatment With Nirmatrelvir-Ritonavir and Molnupiravir, JAMA Netw Open, doi:10.1001/jamanetworkopen.2022.45086
Wölfel, Corman, Guggemos, Virological assessment of hospitalized patients with COVID-2019, Nature, doi:10.1038/s41586-020-2196-x
Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop