Characterization of Virologic Rebound Following Nirmatrelvir-Ritonavir Treatment for Coronavirus Disease 2019 (COVID-19)

Boucau, Julie; Uddin, Rockib; Marino, Caitlin; Regan, James; Flynn, James P.; Choudhary, Manish; Chen, Geoffrey; Stuckwisch, Ashley; Mathews, Josh; Liew, May Y.; Singh, Arshdeep; Reynolds, Zahra; Iyer, Surabhi; Chamberlin, Grace; Vyas, Tammy D.; Vyas, Jatin M.; Turbett, Sarah E; Li, Jonathan Z.; Lemieux, Jacob E.; Barczak, Amy K.; Siedner, Mark J.

doi:10.1093/cid/ciac512

Cited by 83 publications

(77 citation statements)

References 8 publications

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“…Additional data are needed to determine the cause, frequency, duration, and spectrum of rebound symptoms along with the relation to antiviral treatment. During rebound, the findings of a higher viral load, the ease of viral culture, 4 , 5 and possible viral transmission suggest that patients are likely to be contagious during the rebound period.…”

mentioning

confidence: 99%

Rebound of SARS-CoV-2 Infection after Nirmatrelvir–Ritonavir Treatment

Charness¹,

Gupta²,

Stack

et al. 2022

N Engl J Med

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confidence: 99%

Rebound of SARS-CoV-2 Infection after Nirmatrelvir–Ritonavir Treatment

Charness¹,

Gupta²,

Stack

et al. 2022

N Engl J Med

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“…A further explanation may be the persistence of a high viral load of SARS-CoV-2 in individuals who are no longer symptomatic, irrespective of antiviral treatment. This latter explanation is supported by studies showing the presence of culturable SARS-CoV-2 virus in nasal swabs for up to 2 weeks after symptomatic COVID-19 [ 21 ]. This finding has future implications for viral surveillance and isolation of treated patients, with revision of current public health guidelines.…”

mentioning

confidence: 76%

Editorial: Rebound COVID-19 and Cessation of Antiviral Treatment for SARS-CoV-2 with Paxlovid and Molnupiravir

Parums¹

2022

Med Sci Monit

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One of the most recently described clinical associations with SARS-CoV-2 infection is rebound COVID-19, which occurs between five and eight days following the cessation of antiviral treatment. Most case reports of rebound COVID-19 have been associated with cessation of treatment with the combined oral antiviral agent nirmatrelvir/ritonavir (Paxlovid). On 24 May 2022, the US Centers for Disease Control and Prevention (CDC) issued a Health Alert Network (HAN) Health Advisory update for patients, healthcare providers, and public health departments on COVID-19 rebound or recurrence of COVID-19. However, population data from the US showed no significant differences in the risk of developing rebound COVID-19 between patients treated with Paxlovid and Molnupiravir. The mechanisms of rebound COVID-19 remain unclear but may involve the development of resistance to the antiviral drug, impaired immunity to the virus, or insufficient drug dosing. A further explanation may be the persistence of a high viral load of SARS-CoV-2 in individuals who are no longer symptomatic. This Editorial aims to provide an update on what is known about rebound COVID-19 and the current public health implications.

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“…Her symptoms and antigen positivity resumed 4 weeks post-nirmatrelvir/ritonavir treatment along with enhanced T cell and antibody responses to SARS-CoV-2 (Figures 2, 3), suggestive of viral reactivation after antiviral treatment. SARS-CoV-2 viral rebound has been reported after a 5-day course of nirmatrelvir/ritonavir during acute infection (18,19). A similar mechanism could be at play in the case of Neuro-PASC given evidence of a persistent SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS-CoV-2 antigen persistence

2022

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IntroductionLong COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC) in ∼30% of all infected individuals. Here, we present a case of PASC in a patient with rheumatoid arthritis characterized by viral persistence in the nasopharynx for 6 months after acute infection. We demonstrate transient disappearance of antigen persistence and decreased antiviral and autoimmune T cell responses after nirmatrelvir/ritonavir and tocilizumab treatment.Case presentationA 37-year-old female with a 7-year history of rheumatoid arthritis enrolled in a COVID-19 research study was found to continuously test SARS-CoV-2 antigen positive in the nasopharynx for 6 months after acute infection. She simultaneously presented with new-onset PASC symptoms including chronic occipital headache and periods of intense fatigue 8 weeks after acute infection. The patient was prescribed nirmatrelvir/ritonavir to treat SARS-CoV-2 persistence at 3.5 months post-acute infection and observed a reduction in PASC symptoms 3 weeks after completing antiviral treatment. After resurgence of PASC symptoms, she stopped treatment with tocilizumab for rheumatoid arthritis to attempt complete SARS-CoV-2 viral clearance. The severity of the patient’s PASC symptoms subsequently increased, and she developed new-onset brain fog in addition to previous symptoms, which resolved after resumption of tocilizumab treatment. Assessment of adaptive immune responses demonstrated that nirmatrelvir/ritonavir and tocilizumab treatment decreased antiviral and autoreactive T cell activation. After resuming tocilizumab treatment, the patient’s PASC symptoms were significantly reduced, but nasopharyngeal antigen positivity remained.ConclusionThese data suggest that nirmatrelvir/ritonavir should be considered in the treatment of PASC in patients who have SARS-CoV-2 antigen persistence, though care must be taken to monitor the patient for symptom resurgence or viral reactivation. In addition, the IL-6 inhibitor tocilizumab may ameliorate PASC symptoms in patients with persistent headache, fatigue, and brain fog.

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Characterization of Virologic Rebound Following Nirmatrelvir-Ritonavir Treatment for Coronavirus Disease 2019 (COVID-19)

Cited by 83 publications

References 8 publications

Rebound of SARS-CoV-2 Infection after Nirmatrelvir–Ritonavir Treatment

Rebound of SARS-CoV-2 Infection after Nirmatrelvir–Ritonavir Treatment

Editorial: Rebound COVID-19 and Cessation of Antiviral Treatment for SARS-CoV-2 with Paxlovid and Molnupiravir

Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS-CoV-2 antigen persistence

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