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May 9, 2024 · What is Paxlovid rebound? Paxlovid rebound typically happens within a week after you've taken Paxlovid to treat COVID-19. With Paxlovid rebound, either your COVID-19 symptoms return or you test positive after testing negative. Sometimes it's both. Paxlovid rebound is usually milder than the initial illness. The main concern is spreading the ...
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Feb 20, 2024 · What initially was referred to as “Paxlovid rebound”—a return of COVID symptoms or test positivity after starting a course of the antiviral—is now more accurately referred to as “COVID rebound,” because rebound can happen regardless of whether someone takes antivirals.
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- How does Paxlovid work? Paxlovid is an antiviral therapy that consists of two separate medications packaged together. When you take your three-pill dose, two of those pills will be nirmatrelvir, which inhibits a key enzyme that the COVID virus requires in order to make functional virus particles.
- When should I take Paxlovid? You have to take Paxlovid within five days of developing symptoms. Like all antivirals, Paxlovid works best early in the course of an illness—in this case, within the first five days of symptom onset, says Jeffrey Topal, MD, a Yale Medicine infectious diseases specialist who is involved in determining COVID-19 treatment protocols for Yale New Haven Hospital patients.
- How often do I take Paxlovid? The standard dose is three Paxlovid pills twice daily for five days for a full course that adds up to 30 pills. It helps that the pills are packaged in a “dose card,” basically a medication blister pack that allows you to punch out the pills as needed.
- Is Paxlovid similar to Tamiflu? “I think it's a good comparison,” says Dr. Roberts. Tamiflu is an antiviral drug that reduces flu symptoms. Both are prescription-only oral antiviral pills given early in illness.
Sep 26, 2023 · The theory behind Paxlovid rebound is that the treatment is so effective at suppressing the virus that the immune system does not ramp up its cellular and antibody...
- Dani Blum
- Overview
- Abstract
- Introduction
- Review Methodology
- Review Findings
- Discussion
- References
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Figure 1
Early treatment with a first-line therapy (nirmatrelvir/ritonavir [Paxlovid] or remdesivir) or second-line therapy (molnupiravir) prevents hospitalization and death among patients with mild-to-moderate COVID-19 who are at risk for severe disease and is recommended by the National Institutes of Health COVID-19 Treatment Guidelines. On May 25, 2023, ...
COVID-19 has caused approximately 6.5 million hospitalizations and 1.1 million deaths in the United States.* Although hospitalizations and deaths are currently much lower than they were during the peak of the pandemic, COVID-19 continues to cause substantial morbidity and mortality. As of December 9, 2023, approximately 23,000 hospitalizations per ...
CDC reviewed SARS-CoV-2 rebound studies published during February 1, 2020–November 29, 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used (9). PubMed, JSTOR, and Google Scholar were searched using keywords “Paxlovid rebound,” “SARS-CoV-2 viral rebound,” “SARS-CoV-2 rebound,” “nirmatrelvir/ritonavir rebound,” “mol...
Studies of Rebound in Patients Who Did and Did Not Receive Antiviral Treatment
SARS-CoV-2 rebound with and without the use of antiviral treatment were described in previous studies (10–16). The definition of and methods assessing SARS-CoV-2 rebound, including frequency and duration of specimen collection, varied among studies (Table 2). No hospitalizations or deaths were reported among outpatients who experienced rebound, because symptoms were mild. Four retrospective cohort studies found similar frequencies of viral rebound among persons who did and did not receive COVID-19 antiviral treatment (10,12,15–16). Three studies found higher frequencies of rebound among treated persons: the first study examined persons with chronic lymphocytic leukemia (14); the second examined treated persons who were older (median age = 57 years versus 39 years; p<0.001), received more COVID-19 vaccine doses (4 versus 3; p<0.001), and had higher rates of immunosuppression (32% versus 9%; p<0.001) than did untreated persons (11); and the third used propensity score matching to ensure the treated and untreated groups were well matched, but had limited follow-up time (13). A large retrospective, observational study found similar rates of rebound and no statistically significant differences among patients treated with nirmatrelvir/ritonavir (6.6%; 95% CI = 4.1%–10.5%), molnupiravir (4.8%; 95% CI = 3.3%–6.9%) and those who received no treatment (4.5%; 95% CI = 3.9%–5.2%) (Table 2) (15). Persons with immunocompromising conditions had higher odds of viral rebound regardless of treatment status: nirmatrelvir/ritonavir (odds ratio [OR] = 7.37; 95% CI = 2.56–21.26), molnupiravir (OR = 3.05; 95% CI = 1.28–7.25), and no treatment (OR = 2.21; 95% CI = 1.50–3.27). Among patients receiving nirmatrelvir/ritonavir, the odds of virologic rebound were higher among those aged 18–65 years compared with those aged >65 years (OR = 3.09; 95% CI = 1.00–9.53), those with high comorbidity prevalence (score >6 on the Charlson Comorbidity Index [OR = 6.02; 95% CI = 2.09–17.38]), and those concomitantly taking corticosteroids (OR = 7.51; 95% CI = 1.67–33.82), whereas the odds were lower among those who were not fully vaccinated (OR = 0.16; 95% CI = 0.04–0.67). Initial analysis of EPIC-HR trial data showed that viral rebound rates were low and similar between the treated and untreated groups (Table 2) (10). In addition, rebound was not associated with low nirmatrelvir/ritonavir levels, hospitalization or death, severe symptom relapse, vaccination or serologic status, or emergent mutations (8,10).
Infectivity, Resistance, and Immune Response
One observational study demonstrated that duration of shedding of infectious virus was longer among persons with rebound (14 days) compared with those without rebound (3 days), but found no evidence of resistance-associated mutations using genomic sequencing (11). Another study of biomarkers among six patients with rebound after treatment with nirmatrelvir/ritonavir demonstrated that a robust immune response was present during rebound, likely reducing risk for disease progression (17). This study also found no evidence of resistance.
Onset and Duration of Rebound
Among 22 patients (from three studies) with available virologic data and who received treatment, median time to negative test results was 6 days (IQR = 5–7 days) after initial positive test result (18–20) (Figure 2). Median time to viral rebound was 9 days (IQR = 9–13 days) after diagnosis, and to resolution was 16 days (IQR = 16–19 days) into the viral illness. Rebound occurred during the course of illness when there was variability in viral load because of host factors (21).
Current evidence, including randomized controlled trial and observational data, suggests that SARS-CoV-2 rebound occurs initially as a mild illness 3–7 days after resolution of the initial acute illness, occurs in both treated and untreated patients, and is not associated specifically with receiving nirmatrelvir/ritonavir. Moreover, rebound occurs when there is variable, host-mounted immune response to infection during the course of illness. Finally, no hospitalizations or deaths were reported among outpatients who experienced rebound.
Some observational studies demonstrated a higher frequency of rebound among treated persons (10%–14%) (11,14,22) than reported by the randomized controlled trial, EPIC-HR (8,10) (Supplementary Table, https://stacks.cdc.gov/view/cdc/137156). Viral rebound might occur in persons on antiviral treatment because they are at high risk for severe disease and might have host factors, such as immunosuppression, that contribute to the natural variability in viral dynamics (21). Risk factors for rebound appear to be similar to risk for severe disease, but further studies are needed to understand whether persons with certain characteristics or underlying medical conditions are predisposed to experiencing rebound. Another important consideration is that persons receiving antiviral treatment might be at higher risk for experiencing rebound given the viral suppression related to use of treatment early in the disease course and resumption of viral replication after completion of treatment because of delayed viral clearance. This elevated risk could be due to early discontinuation of antiviral treatment or the need for longer courses of treatment among certain persons, such as those who are immunocompromised (14). Two ongoing clinical trials of nirmatrelvir/ritonavir will further characterize the frequency of rebound after different durations of nirmatrelvir/ritonavir treatment among immunocompromised subjects¶¶ and the potential benefit of nirmatrelvir/ritonavir retreatment among subjects with posttreatment rebound.***
1.National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. Washington, DC: US Department of Health and Human Services, National Institutes of Health. https://www.covid19treatmentguidelines.nih.gov/ Accessed December 5, 2023.
2.Hammond J, Leister-Tebbe H, Gardner A, et al.; EPIC-HR Investigators. Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19. N Engl J Med 2022;386:1397–408. https://doi.org/10.1056/NEJMoa2118542 PMID:35172054
3.Gottlieb RL, Vaca CE, Paredes R, et al.; GS-US-540-9012 (PINETREE) Investigators. Early remdesivir to prevent progression to severe COVID-19 in outpatients. N Engl J Med 2022;386:305–15. https://doi.org/10.1056/NEJMoa2116846 PMID:34937145
4.Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al.; MOVe-OUT Study Group. Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients. N Engl J Med 2022;386:509–20. https://doi.org/10.1056/NEJMoa2116044 PMID:34914868
5.Yan L, Streja E, Li Y, et al. Anti-SARS-CoV-2 pharmacotherapies among nonhospitalized U.S. veterans, January 2022 to January 2023. JAMA Netw Open 2023;6:e2331249. https://doi.org/10.1001/jamanetworkopen.2023.31249 PMID:37651140
6.Gousseff M, Penot P, Gallay L, et al.; COCOREC study group. Clinical recurrences of COVID-19 symptoms after recovery: viral relapse, reinfection or inflammatory rebound? J Infect 2020;81:816–46. https://doi.org/10.1016/j.jinf.2020.06.073 PMID:32619697
Feb 1, 2024 · Paxlovid rebound is a term used to describe when a person experiences worsening of COVID symptoms after initially getting better after taking Paxlovid (nirmatrelvir / ritonavir). But COVID rebound isn’t a side effect of Paxlovid.
This Medical News story examines the latest information about rebound, treatment eligibility, optimal dosing, and other questions related to.
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related to: what is paxlovid rebound therapyFind Important Safety Information And Review Possible Side Effects Of A Medication Option. Get Helpful HIV Medication Patient Resources Here & Talk With Your Doctor About Treatment.
