SARS-CoV-2 neutralising mAbs(The Scripps Research Institute/International AIDS Vaccine Initiative)

The rapid adaptation of SARS‐CoV‐2 within the host species and the increased viral transmission triggered the evolution of different SARS‐CoV‐2 variants. Though numerous monoclonal antibodies (mAbs) have been identified as prophylactic therapy for SARS‐CoV‐2, the ongoing surge in the number of SARS‐CoV‐2 infections shows the importance of understanding the mutations in the spike and developing novel vaccine strategies to target all variants. Here, we report the map of experimentally validated 74 SARS‐CoV‐2 neutralizing mAb binding epitopes of all variants. The majority (87.84%) of the potent neutralizing epitopes are localized to the receptor‐binding domain (RBD) and overlap with each other, whereas limited (12.16%) epitopes are found in the N‐terminal domain (NTD). Notably, 69 out of 74 mAb targets have at least one mutation at the epitope sites. The potent epitopes found in the RBD show higher mutations (4‐10aa) compared to lower or modest neutralizing antibodies, suggesting that these epitopes might co‐evolve with the immune pressure. The current study shows the importance of determining the critical mutations at the antibody recognition epitopes, leading to the development of broadly reactive immunogens targeting multiple SARS‐CoV‐2 variants. Further, vaccines inducing both humoral and cell‐mediated immune responses might prevent the escape of SARS‐CoV‐2 variants from neutralizing antibodies.

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.

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.

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).

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.

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.