Bone Marrow-Suppressive Treatment in Children Is Associated with Diminished IFN-γ Response from T Cells upon Polyclonal and Varicella Zoster Virus Peptide Stimulation.

Severe haematological diseases and lymphoid malignancies require bone marrow (BM)-suppressive treatments. Knowledge regarding the impact of BM-suppressive treatments on children's memory T cells is very limited. Memory T cells play a crucial role in defending against herpesviruses, which is particularly relevant in paediatric cancer care. We studied 53 children in total; 34 with cancer and 2 with severe haematological disorders, with some receiving BM-suppressive treatment with or without allogeneic-haematopoietic stem cell transplantation (allo-HSCT), alongside 17 healthy controls. We focused on peripheral blood proportions of memory T-cell subsets using flow cytometry and analysed cytokine-secreting T cells with a four-parameter FluoroSpot assay in response to T-cell mitogen and varicella zoster virus (VZV) peptides. Patients on BM-suppressive treatment showed increased clusters of differentiation (CD)4+ and CD8+ effector memory (TEM)/terminally differentiated effector (TEFF) T cells compared to the healthy controls. They also exhibited, amongst other things, when compared to the healthy controls, a reduced total number of cytokine-secreting cells, by means of interferon (IFN)-γ, interleukin (IL)-17A, IL-10, and IL-22, following mitogen activation. A diminished IFN-γ response among the children with BM-suppressive treatment was observed upon VZV-peptide stimulation, compared to the healthy children. Collectively, the findings herein indicate that the children who are undergoing or have finished BM-suppressive treatment display qualitative differences in their T-cell memory compartment, potentially increasing their susceptibility to severe viral infections and impacting their immunotherapy, which relies on the functional ability of autologous T cells.

COVID-19 seroprevalence and clinical picture in Swedish pediatric oncology and hematology patients.

BACKGROUND: Children develop symptomatic coronavirus disease 2019 (COVID-19) more rarely than adults upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pediatric oncology and hematology patients may be at increased risk of severe COVID-19 due to their underlying disease or treatment. We investigated COVID-19 and seroprevalence of anti-SARS-CoV-2 antibodies, respectively, in a Swedish cohort of pediatric oncology and hematology patients. PROCEDURE: Patients (n = 136) were recruited between June 2020 and September 2021 at Uppsala University Children's Hospital, Sweden. Up to six consecutive blood samples per patient were analyzed for wild-type anti-S1 IgM and IgG antibodies (including after vaccination, n = 4). Clinical data on COVID-19 (including polymerase chain reaction [PCR] test results) were collected from electronic medical records. A questionnaire was completed at recruitment. RESULTS: A cumulative seroprevalence (IgM and IgG) of 33% (45/136 patients, 95% confidence interval: 25%-41%) was observed in this patient cohort, of whom 66% (90/136 patients) were under severe immunosuppressive treatment during the study period. Increasing patient age (p = .037) and PCR test results (p < .002) were associated with seropositivity in nonvaccinated cases. Most seropositive, nonvaccinated cases (32/43, 74%) were never PCR-verified for SARS-CoV-2 infection. Of the 13 patients with PCR-verified infection, nine (69%) reported mild disease. A majority (63%) reported continued school attendance during the pandemic. CONCLUSIONS: Swedish pediatric oncology and hematology patients developed antibodies against SARS-CoV-2, despite their diagnosis and/or treatment, and the observed seroprevalence was similar to that in national pediatric outpatients. PCR-verified cases underestimate the true incidence of COVID-19 in this patient cohort.

Low numbers of COVID-19 in Swedish pediatric oncology patients during the first pandemic year despite an open society.

BACKGROUND: Sweden adopted a different strategy than many other countries to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and kept most schools open. Initial reports from China suggested that coronavirus disease 2019 (COVID-19) was milder in children compared to adults, but there was a lack of data from immunocompromised children. Therefore, we investigated the rate of verified SARS-CoV-2 infections in our Swedish pediatric oncology patients. PROCEDURE: This was a multicenter retrospective study. A questionnaire including patient data as well as SARS-CoV-2 data was sent to the six Swedish childhood cancer centers in May 2021. RESULTS: During the first pandemic year, 49 patients were identified as SARS-CoV-2 positive, and 22 (45%) children were hospitalized with COVID-19. Two children needed intensive care, but no COVID-19-related deaths were reported. Most patients (n = 36, 73%) were on active chemotherapy treatment and 23 children (49%) attended school or daycare at least part-time. Half of the SARS-CoV-2-positive patients experienced a delay in cancer treatment. CONCLUSIONS: Despite the rapid spread of SARS-CoV-2 in Sweden, without a strict lockdown of the society, the number of nationally reported pediatric oncology patients with polymerase chain reaction (PCR)-verified infection was low, and the majority of children had mild disease. Our data show that treatment interruptions occurred frequently and this should clearly be avoided for the coming years.