Infectious Disease · Medical Literature
Convalescent Plasma Restores Viral Clearance After Anti-Spike Monoclonal Antibody Failure in Immunocompromised COVID-19 Patients: A Systematic Review and Meta-Analysis of Individual Patient Data.
Abstract
Anti-Spike monoclonal antibodies (mAbs) progressively lost efficacy during the COVID-19 pandemic due to the emergence and predominance of resistant SARS-CoV-2 variants. By contrast, high-titre COVID-19 convalescent plasma (CCP) collected from vaccinated donors recently recovered from infection provides a polyclonal source of antibodies that remains effective in clearing SARS-CoV-2 in immunosuppressed patients, unable to mount an adequate immune response against the virus. We conducted a systematic review and individual participant data meta-analysis to examine the effect of CCP in immunocompromised patients persistently positive for SARS-CoV-2 viraemia following mAb therapy, and to evaluate possible biological factors associated with a favourable outcome. Electronic databases were searched for studies published from January 2020 to January 2026. All studies including eligible cases were considered in the systematic review. Unpublished cases were also collected from investigators of the selected studies. The protocol was registered at PROSPERO (CRD420251142891). Forty-seven cases (30 cases from 12 published studies and 17 unpublished cases) were included. In 33 out of 47 patients (70.2%) with a mAb-resistant infection, SARS-CoV-2 clearance occurred following CCP transfusion, with a mean of 2.7 CCP units administered. In logistic regression, total CCP volume transfused was positively associated with SARS-CoV-2 clearance. In conclusion, CCP transfusion was associated with SARS-CoV-2 clearance in persistently positive immunocompromised patients following failure of anti-Spike mAb therapy.
Clinical relevance
This systematic review and individual patient data meta-analysis addresses a critical therapeutic gap for immunocompromised patients with persistent SARS-CoV-2 viremia who have failed anti-Spike monoclonal antibody (mAb) therapy — a scenario rendered increasingly common by the dominance of mAb-resistant variants. The affected population includes immunosuppressed individuals (e.g., hematologic malignancy, solid organ transplant, primary immunodeficiency) who cannot mount adequate endogenous humoral responses and lack viable alternative antiviral options. Clinicians managing refractory COVID-19 in immunocompromised hosts should be aware that high-titre, vaccinated-donor convalescent plasma (CCP) represents an evidence-informed rescue strategy in this specific context.
Key findings
1. Viral clearance was achieved in 33 of 47 immunocompromised patients (70.2%) with mAb-resistant SARS-CoV-2 infection following CCP transfusion, representing the primary efficacy outcome. 2. The mean number of CCP units administered across the cohort was 2.7 units, providing a practical dosing benchmark for clinical reference. 3. On logistic regression analysis, total CCP volume transfused was the only identified factor positively associated with SARS-CoV-2 clearance, suggesting a dose-response relationship — though specific odds ratios, confidence intervals, and p-values were not reported in the abstract. 4. The analysis incorporated 47 cases in total — 30 from 12 published studies and 17 previously unpublished cases contributed by study investigators — reflecting an individual participant data (IPD) methodology that enhances analytical granularity over aggregate meta-analysis. 5. CCP used was specifically high-titre product collected from vaccinated donors recently recovered from infection, providing a polyclonal antibody repertoire theoretically capable of neutralizing variant-resistant strains that escape mAb binding. 6. NOTE — Effect sizes (OR, HR, RR), confidence intervals, p-values, and NNT/NNH were not reported in the available abstract; quantitative precision of findings beyond the 70.2% clearance rate and mean dose cannot be confirmed and were not fabricated.
Practice implications
In immunocompromised patients with persistent SARS-CoV-2 viremia following documented or suspected anti-Spike mAb failure, escalation to high-titre COVID-19 convalescent plasma — sourced from vaccinated, recently recovered donors — should be considered as a rescue transfusion strategy, particularly given the 70.2% viral clearance rate observed in this IPD meta-analysis. The dose-response association between total CCP volume and clearance suggests that clinicians should not limit therapy to a single unit; a mean of 2.7 units was administered in cleared cases, supporting multi-unit dosing protocols pending patient-specific tolerability assessment. Patient selection should prioritize those with confirmed mAb-resistant variant infection and quantifiable viremia, with serial viral load monitoring used to gauge treatment response and guide decisions regarding additional CCP units.