Spotlight on the impact of viral infections on Hematopoietic Stem Cells (HSCs) with a focus on COVID-19 effects.

Hematopoietic stem cells (HSCs) are known for their significant capability to reconstitute and preserve a functional hematopoietic system in long-term periods after transplantation into conditioned hosts. HSCs are thus crucial cellular targets for the continual repair of inherited hematologic, metabolic, and immunologic disorders. In addition, HSCs can undergo various fates, such as apoptosis, quiescence, migration, differentiation, and self-renewal. Viruses continuously pose a remarkable health risk and request an appropriate, balanced reaction from our immune system, which as well as affects the bone marrow (BM). Therefore, disruption of the hematopoietic system due to viral infection is essential. In addition, patients for whom the risk-to-benefit ratio of HSC transplantation (HSCT) is acceptable have seen an increase in the use of HSCT in recent years. Hematopoietic suppression, BM failure, and HSC exhaustion are all linked to chronic viral infections. Virus infections continue to be a leading cause of morbidity and mortality in HSCT recipients, despite recent advancements in the field. Furthermore, whereas COVID-19 manifests initially as an infection of the respiratory tract, it is now understood to be a systemic illness that significantly impacts the hematological system. Patients with advanced COVID-19 often have thrombocytopenia and blood hypercoagulability. In the era of COVID-19, Hematological manifestations of COVID-19 (i.e., thrombocytopenia and lymphopenia), the immune response, and HSCT may all be affected by the SARS-CoV-2 virus in various ways. Therefore, it is important to determine whether exposure to viral infections may affect HSCs used for HSCT, as this, in turn, may affect engraftment efficiency. In this article, we reviewed the features of HSCs, and the effects of viral infections on HSCs and HSCT, such as SARS-CoV-2, HIV, cytomegalovirus, Epstein-Barr virus, HIV, etc. Video Abstract.

Journey of a hematopoietic stem cell transplantation center through COVID-19 pandemic: one-year experience

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for oncological, hematologi-cal and non-malignant disorders. Despite global trend for a decrease of transplantation activity in view of the COVID-19 pandemic, we tried to maintain it by taking preventive measures and optimizing infection control in our center. Patients and methods This is an observational study. We collected the performance data of our transplant center from April 2020 to July 2021, i.e., during two waves of the pandemic. The main objectives were to study the influence of COVID-19 pandemic on the workflow of the HSCT center, including morbidity among employees and HSCT recipients, as well as on the transplant activity. Results The first case of COVID-19 infection in St. Petersburg was recorded on March 8, 2020. On March 30, 2020, a national lockdown had been imposed in the Russian Federation. The second wave of COVID-19 started in October 2020. Weekly screening of staff and patients was the main diagnostic tool, in addition to the governmental requirements. In sum, a total of 21702 PCR tests for SARS-CoV-2 were performed over the study period. As for July 1, 2021, 69.7% of employees became immune to the virus, due to previous COVID-19 disease, or by vaccination. In 2020, we managed to perform 419 HSCT, including 136 autologous and 283 allogeneic transplants. For comparison, 415 HSCTs were carried out in 2019, with 144 autologous and 271 allogeneic transplants. In 2020, the HSC donorship was shifted towards unrelated donors from the Russian Registry and haploidentical donors. Incidence of COVID-19 among HSCT recipients between April 2020 and July 2021 was 7.3% (n=39), being 8.6% (n=31) after allogeneic HSCT, and 4.5% (n=8) following auto-HSCT. The median age of patients with COVID-19 was 27 years (4-66). The median term for the COVID-19 onset was 68 days post-transplant (-1 to +2093). In most patients – 29 (74.3%) the HCT CI comorbidity index at the time of transplantation was 0. The stem cell source were either peripheral blood stem cells (n=22, 56.4%), or bone marrow (n=17, 43.6%). Most of the patients achieved complete remission of the underlying disease at the time of HSCT (n=30, 76.9%). The overall 100-day survival rate among HSCT recipients since the diagnosis of the COVID-19 was 79.5% (95% CI 0.609 – 0.884). The mortality rate was 20.5% (n=8). The causes of death were as follows: COVID-19 – 50% (n=4);secondary infectious complications, 25% (n=2);relapse of the underlying disease, 12.5% (n=1);hemorrhagic complications, 12.5% (n=1). The 100-day cumulative incidence of transplant-related mortality (TRM) among all HSCT recipients was 7% (95% CI 0.9 – 0.95) and 8.7% (95% CI 0.88 – 0.93) in 2019 and 2020, respectively (p=0.35). Conclusions Due to preventive measures, regular PCR screening, as well as the use of donors from the Russian Registry or haploidentical donors, we managed to maintain HSCT activity at the same level. The COVID-19 morbidity of HSCT recipients was 7.3%, their mortality rate – 20.5%. In summary, the pandemic did not affect transplant-related mortality among the HSCT recipients in our center. © Universitatsklinikum Hamburg - Eppendorf. All rights reserved.