SARS-COOV-2 Infection in An Adolescent Patient after Haploidentical Stem Cell Transplantation

Background: Patients that undergo Hematopoietic Stem Cell Transplantation (HSCT) are easily susceptible to respiratory viral infections (RVIs), most of which possibly fatal. Indeed, the current spread of the COVID-19 pandemic, which has already infected almost 69 million and killed more than 1.5 million people worldwide, is a concerning topic for the hematologists. The positivity to SARSCoV2 (usually checked by nasopharyngeal swabs), even as an incidental finding before the HSCT in the patient or in the donor inevitably leads to postpone the procedure, with all the easily imaginable risks implicated. To date, there are very few reports on the clinical course and outcome of the coronavirus disease after HSCT, even less in pediatric patients. The role of the immune system in SARS-CoV-2 infection is partially unclear, especially the connection between virus replication, inflammatory response and tissue damage. Methods: The case we report is that of a 14 y/o patient, affected by T acute lymphoblastic leukemia with extramedullary (optical neuritis) and medullary relapse, who contracted SARS-CoV2 at day +110 from maternal haploidentical NK-alloreactive HSCT with regulatory and conventional T-cell adoptive immunotherapy, and successfully recovered without severe acute respiratory syndrome and/or apparent sequelae. The neutrophil engraftment was observed at day +11 from HSCT, the platelet engraftment at day +20. Chimerism was 100% donor, and CD3+/CD4 + lymphocyte count was 137 per mmc, CD3+/CD8+ 1644 per mmc, CD3-/CD56+ 521 per mmc at day +30. At day +15 from HSCT, the patient developed grade 1 cutaneous and gastrointestinal acute GvHD, treated with hydrocortisone 100 mg/day (for one week) and extracorporeal photopheresis as first-line therapy, then beclomethasone dipropionate 10 mg/day and Ruxolitinib 5 mg bid. At day +110 from HSCT the RT-PCR on nasopharyngeal swab showed positivity for SARS-CoV2. Results: The patient, admitted in the Infectious Disease Department, was treated with Remdesivir and intravenous immunoglobulins;he also received 3 hyperimmune plasma infusions. The immunosuppressive therapy was interrupted to stimulate the immune response and facilitate the virus clearance, since the SARS-CoV2 swabs were persistently positive with high viral load, without the production of specific antibodies. Except for a bacterial sepsis, the hospital stay was substantially uneventful: the patient was apyretic, without any need of oxygen support (arterial blood gas analysis was normal) and no relevant sign or symptom. Given these clinical features, after 40 days of hospital stay, he was discharged, in spite of the persistent SARS-CoV2 positivity and the low title of antibodies (20.1 AU/mL). After 72 days, the patient finally tested negative for SARSCoV-2 by PCR on nasopharyngeal swab, with an elevated title of SARS-Cov-2 antibodies (78.6 AU/mL). Conclusions: SARS-CoV-2 appears to differ from other respiratory viruses, since the role of the immune response, rather than protective, can be harmful. Our report suggests that in this patient, the immunocompromised condition may have acted as a protective factor against the COVID-19, which would corroborate the hypothesis of the major role played by the immune response in the development of the severity and mortality of the disease.