Early combination therapy of COVID-19 in high-risk patients

Orth, Hans Martin; Flasshove, Charlotte; Berger, Moritz; Hattenhauer, Tessa; Biederbick, Kaja D.; Mispelbaum, Rebekka; Klein, Uwe; Stemler, Jannik; Fisahn, Matthis; Doleschall, Anna D.; Baermann, Ben-Niklas; Koenigshausen, Eva; Tselikmann, Olga; Killer, Alexander; de Angelis, Clara; Gliga, Smaranda; Stegbauer, Johannes; Spuck, Nikolai; Silling, Gerda; Rockstroh, Jürgen K.; Strassburg, Christian P.; Brossart, Peter; Panse, Jens P.; Jensen, Björn-Erik Ole; Luedde, Tom; Boesecke, Christoph; Heine, Annkristin; Cornely, Oliver A.; Monin, Malte B.

doi:10.1007/s15010-023-02125-5

Cited by 13 publications

(1 citation statement)

References 24 publications

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“…18 In vivo data also demonstrated prolonged viral clearance in patients with severe immunocompromise, including the hematooncology population. 19 Prolonged positivity in SOT recipients is less frequently described; however, it is unclear whether this represents a lower burden of prolonged positivity in this population or publication bias. Some multicentre studies have demonstrated higher numbers of SOT recipients than those with haematologic malignancies, but this may reflect the underlying patient populations seen at these institutions.…”

Section: Prolonged Sars-cov-2 Test Positivitymentioning

confidence: 94%

Antiviral therapies for the management of persistent coronavirus disease 2019 in immunocompromised hosts: A narrative review

Kinsella,

Moso,

Morrissey

et al. 2024

Transplant Infectious Dis

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Antiviral agents with activity against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) have played a critical role in disease management; however, little is known regarding the efficacy of these medications in the treatment of SARS‐CoV‐2 infection in immunocompromised patients, particularly in the management of persistent SARS‐CoV‐2 positivity.This narrative review discusses the management of persistent coronavirus disease 2019 in immunocompromised hosts, with a focus on antiviral therapies. We identified 84 cases from the literature describing a variety of approaches, including prolonged antiviral therapy (n = 11), combination antivirals (n = 13), and mixed therapy with antiviral and antibody treatments (n = 60). A high proportion had an underlying haematologic malignancy (n = 67, 80%), and were in receipt of anti‐CD20 agents (n = 51, 60%). Success was reported in 70 cases (83%) which varied according to the therapy type. Combination therapies with antivirals may be an effective approach for individuals with persistent SARS‐CoV‐2 positivity, particularly those that incorporate treatments aimed at increasing neutralizing antibody levels. Any novel approaches taken to this difficult management dilemma should be mindful of the emergence of antiviral resistance.

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Section: Prolonged Sars-cov-2 Test Positivitymentioning

confidence: 94%

Antiviral therapies for the management of persistent coronavirus disease 2019 in immunocompromised hosts: A narrative review

Kinsella,

Moso,

Morrissey

et al. 2024

Transplant Infectious Dis

View full text Add to dashboard Cite

show abstract

Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections

Nooruzzaman,

Johnson,

Rani

et al. 2024

Nat Commun

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We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n = 15). All patients received remdesivir and some also received nirmatrelvir-ritonavir (n = 3) or therapeutic monoclonal antibodies (n = 4). Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient sequentially treated with nirmatrelvir-ritonavir and remdesivir. In vitro characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo.

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Early combination of sotrovimab with nirmatrelvir/ritonavir or remdesivir is associated with low rate of persisting SARS CoV-2 infection in immunocompromised outpatients with mild-to-moderate COVID-19: a prospective single-centre study

Gentile,

Viceconte,

Cuccurullo

et al. 2024

Annals of Medicine

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Background Immunocompromised patients are at high risk of developing persisting/prolonged COVID-19. Data on the early combined use of antivirals and monoclonal antibodies in this population are scarce. Research design and methods We performed an observational, prospective study, enrolling immunocompromised outpatients with mild-to-moderate COVID-19, treated with a combination of sotrovimab plus one antiviral (remdesivir or nirmatrelvir/ritonavir) within 7 days from symptom onset. Primary outcome was hospitalization within 30 days. Secondary outcomes were: needing for oxygen therapy; development of persistent infection; death within 60 days and reinfection or relapse within 90 days. Results We enrolled 52 patients. No patient was hospitalized within 30 days of disease onset, required oxygen administration, died within 60 days, or experienced a reinfection or clinical relapse within 90 days. The clearance rates were 67% and 97% on the 14th day after the end of therapy and at the end of the follow-up period, respectively. Factors associated with longer infection were initiation of therapy 3 days after symptom onset and enrollment for more than 180 days from the beginning of the study. However, only the latter factor was independently associated with a longer SARS-CoV-2 infection, suggesting a loss of efficacy of this strategy with the evolution of SARS-CoV-2 variants. Conclusions Early administration of combination therapy with a direct antiviral and sotrovimab seems to be effective in preventing hospitalization, progression to severe COVID-19, and development of prolonged/persisting SARS-CoV-2 infection in immunocompromised patients.

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Early combination therapy of COVID-19 in high-risk patients

Cited by 13 publications

References 24 publications

Antiviral therapies for the management of persistent coronavirus disease 2019 in immunocompromised hosts: A narrative review

Antiviral therapies for the management of persistent coronavirus disease 2019 in immunocompromised hosts: A narrative review

Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections

Early combination of sotrovimab with nirmatrelvir/ritonavir or remdesivir is associated with low rate of persisting SARS CoV-2 infection in immunocompromised outpatients with mild-to-moderate COVID-19: a prospective single-centre study

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