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Immunocompromised patients with persistent SARS-CoV-2 viral shedding ≥8 weeks, clinical outcomes, and virological
Clémentine de La Porte des Vaux1, Nicolas Veyrenche2, Kevin Da Silva3
1Department of Infectious and Tropical Diseases, Hôpital Necker Enfants Malades, Assistance Publique des Hôpitaux de Paris (APHP), IHU Imagine, Université Paris Cité, Paris, France.
Abstract:
Immunocompromised patients (ICPs) infected with SARS-CoV-2 are at higher risk of severe illness. Some experience persistent viral shedding beyond eight weeks, which is associated with increased mortality and invasive fungal infections. However, data on the clinical profile, treatment impact, and standardized management for these patients remain limited. We conducted a retrospective cohort study at Groupe Hospitalier Paris Centre between March 1, 2020, and February 10, 2024. We assessed symptomatic ICPs with persistent SARS-CoV-2 shedding (>8 weeks), analyzing clinical progression, time to viral clearance, and emergence of resistance mutations in relation to treatment regimens. Fifty-three patients were included: 53% were solid organ transplant (SOT) recipients, 42% had hematological malignancies (HMs), and 5% had other immunosuppressive conditions. Severe infections occurred in 32%, 91% required hospitalization, and 17% (n = 9) presented invasive mold infections. SOT recipients achieved clinical cure faster than HM patients (P < 0.01). Patients treated with direct antivirals showed significantly faster viral clearance (P = 0.03) than those treated with monoclonal antibodies (mAbs) or convalescent plasma. No resistance mutations emerged against remdesivir or nirmatrelvir/ritonavir. However, 54% of viral strains showed initial or acquired spike protein resistance to mAbs. Direct antiviral therapies, particularly remdesivir and nirmatrelvir/ritonavir, appear safe and effective in promoting faster viral clearance and clinical recovery in ICPs with persistent symptomatic SARS-CoV-2 infection.
Insights
Immunocompromised patients with persistent SARS-CoV-2 infection benefit from direct antivirals. These treatments promote faster viral clearance and clinical recovery, with no observed resistance mutations against key drugs.
Area of Science:
- Infectious Diseases
- Virology
- Immunology
Background:
- Immunocompromised patients (ICPs) face severe SARS-CoV-2 illness and prolonged viral shedding.
- Persistent shedding (>8 weeks) correlates with mortality and invasive fungal infections.
- Limited data exists on clinical profiles and management strategies for these ICPs.
Purpose of the Study:
- To analyze the clinical profile of symptomatic ICPs with persistent SARS-CoV-2 shedding.
- To evaluate the impact of different treatment regimens on viral clearance and clinical outcomes.
- To assess the emergence of antiviral resistance mutations in ICPs.
Main Methods:
- Retrospective cohort study of 53 symptomatic ICPs with SARS-CoV-2 shedding >8 weeks.
- Analysis of clinical progression, time to viral clearance, and resistance mutations.
- Comparison of outcomes based on treatment regimens: direct antivirals, monoclonal antibodies (mAbs), convalescent plasma.
Main Results:
- 32% experienced severe infections; 91% required hospitalization; 17% developed invasive mold infections.
- Direct antiviral therapy led to significantly faster viral clearance compared to mAbs or convalescent plasma (P=0.03).
- No resistance mutations emerged against remdesivir or nirmatrelvir/ritonavir; however, 54% of strains showed spike protein resistance to mAbs.
Conclusions:
- Direct antivirals, including remdesivir and nirmatrelvir/ritonavir, are safe and effective for persistent SARS-CoV-2 infection in ICPs.
- These therapies accelerate viral clearance and clinical recovery.
- Monoclonal antibodies showed limited efficacy due to emerging spike protein resistance.
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