tetano
Editor, Senior Moderator
Infection
. 2023 Nov 29.
doi: 10.1007/s15010-023-02125-5. Online ahead of print. Early combination therapy of COVID-19 in high-risk patients
Hans Martin Orth[SUP] #[/SUP][SUP] 1 2 [/SUP], Charlotte Flasshove[SUP] #[/SUP][SUP] 1 2 [/SUP], Moritz Berger[SUP] 3 [/SUP], Sandra Tessa Hattenhauer[SUP] 1 4 [/SUP], Kaja D Biederbick[SUP] 1 4 [/SUP], Rebekka Mispelbaum[SUP] 1 4 [/SUP], Uwe Klein[SUP] 1 4 [/SUP], Jannik Stemler[SUP] 1 5 6 7 [/SUP], Matthis Fisahn[SUP] 1 5 6 7 [/SUP], Anna D Doleschall[SUP] 1 8 [/SUP], Ben-Niklas Baermann[SUP] 1 9 [/SUP], Eva Koenigshausen[SUP] 10 [/SUP], Olga Tselikmann[SUP] 10 [/SUP], Alexander Killer[SUP] 1 2 [/SUP], Clara de Angelis[SUP] 1 2 [/SUP], Smaranda Gliga[SUP] 1 2 [/SUP], Johannes Stegbauer[SUP] 10 [/SUP], Nikolai Spuck[SUP] 3 [/SUP], Gerda Silling[SUP] 1 8 [/SUP], Jürgen K Rockstroh[SUP] 1 11 12 [/SUP], Christian P Strassburg[SUP] 1 11 [/SUP], Peter Brossart[SUP] 1 4 [/SUP], Jens P Panse[SUP] 1 8 [/SUP], Björn-Erik Ole Jensen[SUP] 1 2 [/SUP], Tom Luedde[SUP] 1 2 [/SUP], Christoph Boesecke[SUP] 1 11 12 [/SUP], Annkristin Heine[SUP] 1 4 [/SUP], Oliver A Cornely[SUP] 1 5 6 7 [/SUP], Malte B Monin[SUP] 13 14 15 16 [/SUP]
Affiliations
Purpose: Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect.
Methods: This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 10[SUP]6[/SUP] copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 10[SUP]6[/SUP] copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher's tests or Kaplan-Meier analysis and long-rank tests. Multivariable regression analysis was performed.
Results: 144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 10[SUP]6[/SUP] copies/ml of 8.0 days (IQR 6.0-15.3). Underlying haematological malignancies (HM) (p = 0.03) and treatment initiation later than five days after diagnosis (p < 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (n = 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2-9.9; p = 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment.
Conclusion: Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients.
Keywords: COVID-19; Dual anti-SARS-CoV-2 therapies; Immunocompromised host; Individualized therapeutic approaches; Prolonged viral shedding.
. 2023 Nov 29.
doi: 10.1007/s15010-023-02125-5. Online ahead of print. Early combination therapy of COVID-19 in high-risk patients
Hans Martin Orth[SUP] #[/SUP][SUP] 1 2 [/SUP], Charlotte Flasshove[SUP] #[/SUP][SUP] 1 2 [/SUP], Moritz Berger[SUP] 3 [/SUP], Sandra Tessa Hattenhauer[SUP] 1 4 [/SUP], Kaja D Biederbick[SUP] 1 4 [/SUP], Rebekka Mispelbaum[SUP] 1 4 [/SUP], Uwe Klein[SUP] 1 4 [/SUP], Jannik Stemler[SUP] 1 5 6 7 [/SUP], Matthis Fisahn[SUP] 1 5 6 7 [/SUP], Anna D Doleschall[SUP] 1 8 [/SUP], Ben-Niklas Baermann[SUP] 1 9 [/SUP], Eva Koenigshausen[SUP] 10 [/SUP], Olga Tselikmann[SUP] 10 [/SUP], Alexander Killer[SUP] 1 2 [/SUP], Clara de Angelis[SUP] 1 2 [/SUP], Smaranda Gliga[SUP] 1 2 [/SUP], Johannes Stegbauer[SUP] 10 [/SUP], Nikolai Spuck[SUP] 3 [/SUP], Gerda Silling[SUP] 1 8 [/SUP], Jürgen K Rockstroh[SUP] 1 11 12 [/SUP], Christian P Strassburg[SUP] 1 11 [/SUP], Peter Brossart[SUP] 1 4 [/SUP], Jens P Panse[SUP] 1 8 [/SUP], Björn-Erik Ole Jensen[SUP] 1 2 [/SUP], Tom Luedde[SUP] 1 2 [/SUP], Christoph Boesecke[SUP] 1 11 12 [/SUP], Annkristin Heine[SUP] 1 4 [/SUP], Oliver A Cornely[SUP] 1 5 6 7 [/SUP], Malte B Monin[SUP] 13 14 15 16 [/SUP]
Affiliations
- PMID: 38017344
- DOI: 10.1007/s15010-023-02125-5
Purpose: Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect.
Methods: This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 10[SUP]6[/SUP] copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 10[SUP]6[/SUP] copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher's tests or Kaplan-Meier analysis and long-rank tests. Multivariable regression analysis was performed.
Results: 144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 10[SUP]6[/SUP] copies/ml of 8.0 days (IQR 6.0-15.3). Underlying haematological malignancies (HM) (p = 0.03) and treatment initiation later than five days after diagnosis (p < 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (n = 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2-9.9; p = 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment.
Conclusion: Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients.
Keywords: COVID-19; Dual anti-SARS-CoV-2 therapies; Immunocompromised host; Individualized therapeutic approaches; Prolonged viral shedding.
