Haploidentical CD3+ TCR αβ/CD19+-depleted HSCT for MHC class II deficiency and persistent SARS-CoV-2 pneumonitis
Subramaniam Ramanathan1, Liz Veramendi-Espinoza2, Benjamin Shillitoe1
1Children's Hematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
Insights
Hematopoietic stem cell transplant (HSCT) combined with novel antiviral therapies successfully treated a child with combined immunodeficiency and persistent SARS-CoV-2 infection. This approach led to viral clearance and improved clinical outcomes in a challenging case.
Area of Science:
- Immunology
- Virology
- Pediatric Hematology/Oncology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, ranging from mild to severe respiratory distress.
- Children with combined immunodeficiencies may have impaired immune responses and persistent SARS-CoV-2 infections.
Purpose of the Study:
- To describe a case of successful haploidentical hematopoietic stem cell transplant (HSCT) in a child with combined immunodeficiency and persistent SARS-CoV-2 infection.
- To evaluate the role of novel antiviral strategies in managing persistent viral infections post-HSCT.
Main Methods:
- A 13-month-old girl with MHC class II deficiency and persistent SARS-CoV-2 infection underwent a maternal haploidentical HSCT.
- The patient received regdanvimab (monoclonal antibody) and remdesivir for SARS-CoV-2 treatment peri-HSCT.
- Adoptive transfer of maternal CD45RO+ memory T lymphocytes was performed post-HSCT.
Main Results:
- The patient showed increasing cycle threshold values, indicating reduced viral RNA load.
- Concomitant expansion of CD3+ lymphocytes was observed.
- Clinical and radiological improvements were noted post-HSCT.
Conclusions:
- A combination of haploidentical HSCT, antiviral therapy (regdanvimab, remdesivir), and T-cell addback therapy contributed to successful viral clearance.
- Novel antiviral strategies, including monoclonal antibodies and T-cell therapy, are crucial for managing challenging viral infections in immunocompromised pediatric patients.
Background:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to coronavirus disease 2019 (COVID-19), which can range from a mild illness to a severe phenotype characterized by acute respiratory distress needing mechanical ventilation. Children with combined immunodeficiencies might be unable to mount a sufficient cellular and humoral immune response against COVID-19 and have persistent disease.
Objective:
Our aim was to describe a child with combined immunodeficiency and a favorable post-hematopoietic stem cell transplant (HSCT) course following a haploidentical HSCT in the presence of persistent SARS-CoV-2 infection.
Methods:
A 13-month-old girl with MHC class II deficiency developed persistent pre-HSCT SARS-CoV-2 infection. Faced with a significant challenge of balancing the risk of progressive infection due to an incompetent immune system with the danger of inflammatory pneumonitis peri-immune reconstitution after HSCT, the patient's physicians performed a maternal (with a recent history of COVID-19 infection) haploidentical HSCT. The patient received regdanvimab (after stem cell infusion) and remdesivir (before and after stem cell infusion).
Results:
The patient exhibited a gradual increase in her cycle threshold values, implying a reduction in viral RNA with concomitant expansion in the CD3 lymphocyte subset and clinical and radiologic improvement.
Conclusions:
Combination of adoptive transfer of maternal CD45RO+ memory addback T lymphocytes after haploidentical HSCT and use of regdanvimab (a SARS-CoV-2-neutralizing mAb) and remdesivir may have led to the successful outcome in our patient with severe immunodeficiency after she had undergone HSCT. This case highlights the role of novel antiviral strategies (mAbs and CD45RO+ memory T lymphocytes) in contributing to viral clearance in a challenging clinical scenario.
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