ABSTRACT
Background: Data on SARS-CoV-2 infection in Hemoglobinopathies are still scarce and controversial. Since March 2020, we, as Italian Society for Thalassemia and Hemoglobinopathies (SITE), recommended close monitoring and set up an Italian survey to verify the impact of SARSCoV- 2 infection on patients with Hemoglobinopathies (EMO AER COVID-19 NCT04746066) among Italian Centers. Aims: To explore the hypothesis of an increased vulnerability of Hemoglobinopathies to SARS-COV2 infection. Methods: After SITE proposal and Ethics Committee approval, each participating Center entered data on a specific electronic Case Report Form (eCRF) (https://covid19.site-italia.org). Inclusion criteria included positive swab or serology and at least 15 days of follow-up from either the onset of symptoms or SARS-CoV2 positivity. This cut-off is updated to February 15, 2021. Results: Twenty-seven Centers that provide care to 6121 patients with Hemoglobinopathy (65% of the Italian population) recorded a total of 275 SARS-CoV2 infections (overall, prevalence 4.5%), in 191 transfusion- dependent thalassemia cases (TDT, prevalence 5.8%), 36 non-transfusion- dependent thalassemia (NTDT, prevalence 2.3%) and 48 sickle cell disease patients (SCD, prevalence 3.7%). Median age was 41 years (IQR: 30-48, range: 9 months-85 year). Twenty-eight patients (10 %) were pediatrics (median age: 6.5 years, IQR: 4-11). Most patients (72%) had comorbidities;134 (49%) had splenectomy or functional asplenia. We observed a broad spectrum of disease severity, ranging from no symptoms in 65 patients (24%) to multisystem organ failure and death in 5 patients: 2 TDT (age: 49 and 56 years), 1 NTDT (age: 45 years), 2 SCD (age: 57 years both). Overall, 56 (20%) patients required hospitalization, 12 in high-intensity care unit;10 required support by oxygen, 11 needed more intensive ventilation support with continuous positive airway pressure (CPAP), and 7 required intubation. Nine patients required ad hoc transfusion or more than scheduled. Two SCD patients of 9 and 20 months of age, respectively, recovered after a long and life-treating disease. One TDT patient experienced reinfection after 3 months from the first;one 30w-pregnant SCD woman developed COVID-19 without consequences for herself and the fetus. Overall clinical severity has been higher in SCD than in thalassemia patients. Summary/Conclusion: The prevalence of COVID-19 in Hemoglobinopathies apparently overlaps the general population (4.5% vs 4.6%), however, these patients are more strictly observed and we could postulate that the precautions suggested or self-applied by the patients were effective. The overall mortality is 1.8% vs 3.4% and the difference may be due to the younger age of patients with Hemoglobinopathies. Our data confirm the higher risk of severe disease and death in SCD.
ABSTRACT
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.