Combination regimen of nirmatrelvir/ritonavir and molnupiravir for the treatment of persistent SARS-CoV-2 infection: A case report and a scoping review of the literature

Marangoni, Davide; Antonello, Roberta Maria; Coppi, Marco; Palazzo, Marianna; Nassi, Luca; Streva, Noemi; Povolo, Laura; Malentacchi, Francesca; Zammarchi, Lorenzo; Rossolini, Gian María; Vannucchi, Alessandro M.; Bartoloni, Alessandro; Spinicci, Michele

doi:10.1016/j.ijid.2023.04.412

Cited by 21 publications

(16 citation statements)

References 18 publications

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“…Our population was composed mainly of onco-hematological patients, in accordance with previously reported experiences [7,[20][21][22][23]. Interestingly, to our knowledge, this is the first report including up to four PLWHA with persistent SARS-CoV-2 infection treated with sequential or combined antiviral/antibody therapies.…”

Section: Discussionsupporting

confidence: 73%

Sequential or Combination Treatments as Rescue Therapies in Immunocompromised Patients with Persistent SARS-CoV-2 Infection in the Omicron Era: A Case Series

Longo,

Venuti,

Gaviraghi

et al. 2023

Antibiotics

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Prolonged SARS-CoV-2 infections are widely described in immunosuppressed patients, but safe and effective treatment strategies are lacking. We aimed to outline our approach to treating persistent COVID-19 in patients with immunosuppression from different causes. In this case series, we retrospectively enrolled all immunosuppressed patients with persistent SARS-CoV-2 infections treated at our centers between March 2022 and February 2023. Patients received different sequential or combination regimens, including antivirals (remdesivir, nirmatrelvir/ritonavir, or molnupiravir) and/or monoclonal antibodies (mAbs) (tixagevimab/cilgavimab or sotrovimab). The main outcome was a complete virological response (negative SARS-CoV-2 RT-PCR on nasopharyngeal swabs) at the end of treatment. Fifteen patients were included as follows: eleven (11/15; 73%) with hematological disease and four (4/15; 27%) with recently diagnosed HIV/AIDS infection. Six patients (6/15; 40%) received a single antiviral course, four patients (4/15; 27%) received an antiviral and mAbs sequentially, and two patients (13%) received three lines of treatment (a sequence of three antivirals or two antivirals and mAbs). A combination of two antivirals or one antiviral plus mAbs was administered in three cases (3/15, 20%). One patient died while still positive for SARS-CoV-2, while fourteen (14/15; 93%) tested negative within 16 days after the end of treatment. The median time to negativization since the last treatment was 2.5 days. Both sequential and combination regimens used in this study demonstrated high efficacy and safety in the high-risk group of immunosuppressed patients.

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Section: Discussionsupporting

confidence: 73%

Sequential or Combination Treatments as Rescue Therapies in Immunocompromised Patients with Persistent SARS-CoV-2 Infection in the Omicron Era: A Case Series

Longo,

Venuti,

Gaviraghi

et al. 2023

Antibiotics

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“…There were some reports of patients with hematological malignancies who were refractory to conventional therapy and continued to shed viral RNA. Two of these cases were treated with remdesivir, which inhibits RNA polymerase by a similar mechanism to molnupiravir, repeatedly and for a long time [ 19 , 20 ]; the other was treated with a combination of nirmatrelvir/ritonavir and molnupiravir for a prolonged period [ 21 ]. These atypical treatments resulted in the improvement of persistent COVID-19 infection.…”

Section: Discussionmentioning

confidence: 99%

Chimeric antigen receptor T-cell therapy after COVID-19 in refractory high-grade B-cell lymphoma

Hayashino,

Seike,

Fujiwara

et al. 2024

Int J Hematol

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Although chimeric antigen receptor T-cell (CAR-T) therapies have dramatically improved the outcomes of relapsed/refractory B-cell malignancies, recipients suffer from severe humoral immunodeficiencies. Furthermore, patients with coronavirus disease 2019 (COVID-19) have a poor prognosis, as noted in several case reports of recipients who had COVID-19 before the infusion. We report the case of a 70-year-old woman who developed COVID-19 immediately before CAR-T therapy for high-grade B-cell lymphoma. She received Tixagevimab−Cilgavimab chemotherapy and radiation therapy but never achieved remission. She was transferred to our hospital for CAR-T therapy, but developed COVID-19. Her symptoms were mild and she was treated with long-term molnupiravir. On day 28 post-infection, lymphodepleting chemotherapy was restarted after a negative polymerase chain reaction (PCR) test was confirmed. The patient did not experience recurrence of COVID-19 symptoms or severe cytokine release syndrome. Based on the analysis and comparison of the previous reports with this case, we believe that CAR-T therapy should be postponed until a negative PCR test is confirmed. In addition, Tixagevimab−Cilgavimab and long term direct-acting antiviral agent treatment can be effective prophylaxis for severe COVID-19 and shortening the duration of infection.

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“…Recently, a case report study by Marangoni et al, reported that a 73-year-old man with follicular lymphoma with persistent SARS-CoV-2 infection was successfully treated with 10-day coadministration oral antivirals molnupiravir and nirmatrelvir plus ritonavir. Importantly, the study’s therapists stated that this combination therapy was well tolerated both clinically and biochemically, and no signs of toxicity were observed …”

Section: Combination Therapy: the Latest Strategy For The Treatment O...mentioning

confidence: 96%

An Overview on Anti-COVID-19 Drug Achievements and Challenges Ahead

Valipour,

Irannejad,

Keyvani

2023

ACS Pharmacol. Transl. Sci.

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The appearance of several coronavirus pandemics/ epidemics during the last two decades (SARS-CoV-1 in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019) indicates that humanity will face increasing challenges from coronaviruses in the future. The emergence of new strains with similar transmission characteristics as SARS-CoV-2 and mortality rates similar to SARS-CoV-1 (∼10% mortality) or MERS-CoV (∼35% mortality) in the future is a terrifying possibility. Therefore, getting enough preparations to face such risks is an inevitable necessity. The present study aims to review the drug achievements and challenges in the fight against SARS-CoV-2 with a combined perspective derived from pharmacology, pharmacotherapy, and medicinal chemistry insights. Appreciating all the efforts made during the past few years, there is strong evidence that the desired results have not yet been achieved and research in this area should still be pursued seriously. By expressing some pessimistic possibilities and concluding that the drug discovery and pharmacotherapy of COVID-19 have not been successful so far, this short essay tries to draw the attention of responsible authorities to be more prepared against future coronavirus epidemics/pandemics.

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Combination regimen of nirmatrelvir/ritonavir and molnupiravir for the treatment of persistent SARS-CoV-2 infection: A case report and a scoping review of the literature

Cited by 21 publications

References 18 publications

Sequential or Combination Treatments as Rescue Therapies in Immunocompromised Patients with Persistent SARS-CoV-2 Infection in the Omicron Era: A Case Series

Sequential or Combination Treatments as Rescue Therapies in Immunocompromised Patients with Persistent SARS-CoV-2 Infection in the Omicron Era: A Case Series

Chimeric antigen receptor T-cell therapy after COVID-19 in refractory high-grade B-cell lymphoma

An Overview on Anti-COVID-19 Drug Achievements and Challenges Ahead

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