Evidence map›Paper›PMID 42228900›Full record

ArticleInteractive journal of medical research2026

COVID-19 Rebound in Nirmatrelvir Plus Ritonavir Treatment and Control Groups: Prospective Cohort Study.

Jacqueline K Kueper, Kalyani Kottilil, Giorgio Quer, Danielle C Chiang, Emily G Spencer, Jyothi Purushotham, Edward Ramos, Leila Roumani, Kristian G Andersen, Eric J Topol and 2 more

Abstract read
In one paragraph

Article in Interactive journal of medical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Jacqueline K KueperScripps Research Translational Institute, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, United States, 1 858-784-1000.ORCID http://orcid.org/0000-0002-6690-1552
Kalyani KottililScripps Research Translational Institute, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, United States, 1 858-784-1000.ORCID http://orcid.org/0000-0002-7035-4547
Giorgio QuerScripps Research Translational Institute, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, United States, 1 858-784-1000.ORCID http://orcid.org/0000-0003-2208-7912
Danielle C ChiangScripps Research Translational Institute, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, United States, 1 858-784-1000.ORCID http://orcid.org/0000-0003-0919-9303
Emily G SpencerScripps Research Translational Institute, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, United States, 1 858-784-1000.ORCID http://orcid.org/0000-0003-2650-4357
Jyothi PurushothamScripps Research Translational Institute, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, United States, 1 858-784-1000.ORCID http://orcid.org/0000-0002-6190-4199
Edward RamosScripps Research Translational Institute, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, United States, 1 858-784-1000.ORCID http://orcid.org/0000-0003-1675-7094
Leila RoumanieMed, Miami, FL, United States.
Kristian G AndersenScripps Research Translational Institute, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, United States, 1 858-784-1000.ORCID http://orcid.org/0000-0001-6431-5982
Eric J TopolScripps Research Translational Institute, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, United States, 1 858-784-1000.ORCID http://orcid.org/0000-0002-1478-4729
Jay A Pandit *Scripps Research Translational Institute, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, United States, 1 858-784-1000.ORCID http://orcid.org/0000-0003-0119-0881
Michael J Mina *eMed, Miami, FL, United States.ORCID http://orcid.org/0000-0002-0674-5762

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Observation of COVID-19 rebound after nirmatrelvir plus ritonavir (NPR) has driven important questions surrounding one of the only direct-acting antiviral treatments for COVID-19. Objective: The objective of this study was to examine the epidemiology of COVID-19 rebound among COVID-19-positive outpatients in the United States who independently decided whether or not to take NPR. Methods: This prospective, decentralized observational cohort study was conducted from August 2022 through December 2023 and included frequent proctored COVID-19 rapid antigen tests and self-report symptom surveys for 15 days. The primary outcome was the incidence of viral and symptom rebound. Secondary outcomes included time to initial viral and symptom clearance, rebound probability among patients who cleared by day 15, and symptom frequency. Results: Of 917 consenting participants, 669 (73%) were eligible for inclusion in the analysis (n=443, 66% in the NPR group; n=226, 34% in the control group). The mean age was 46.1 (SD 12.9) years, 62.6% (n=419) of participants were female, and 49.2% (n=329) had at least one preexisting condition. Overall, 15-day cumulative incidence was higher in the NPR group than the control group for both viral (70/443, 15.8% vs 12/226, 5.3%) and symptom (73/443, 16.5% vs 19/226, 8.4%) rebound. Time to initial viral and symptom clearance was similar between groups, and among those who experienced clearance by day 15, the probability of viral rebound (NPR: 19.1%, 95% CI 15.1%-24.0% vs control: 7%, 95% CI 4.0%-12.6%; P<.001) and symptom rebound (NPR: 47.7%, 95% CI 36.1%-60.8% vs control: 16.9%, 95% CI 10.9%-25.7%; P<.001) was higher in the NPR group than the control group. Conclusions: This study demonstrates that while COVID-19 rebound occurs in both NPR-treated and untreated outpatients, the incidence is higher in the NPR group.

Indexed as

COVID-19COVID-19 reboundnirmatrelvir plus ritonavirsymptom reboundviral rebound

Identifiers

PMID42228900
PMCPMC13229391

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.