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.Funding Agencies|Swedish Childhood Cancer Fund [KP2021-0034, 2020-0008]</p

Reference standards for follicle density in ovarian cortex from birth to sexual maturity

Peer reviewe

Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation

Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions

Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation

Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions

Decreased spermatogonial numbers in boys with severe haematological diseases

This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose chemotherapy and/or radiation during HSCT can impact spermatogenesis requiring fertility preservation. Results show that 49% of patients have decreased and 19% severely depleted spermatogonial pool prior to HSCT. Patients with Fanconi anaemia exhibit significantly reduced spermatogonial numbers. Patients with immunodeficiency or aplastic anaemia generally present within the normal range, while results in patients with myelodysplastic syndrome or myeloproliferative neoplasm vary. The study emphasizes the importance of assessing spermatogonial numbers in patients with severe haematological diseases for informed fertility preservation decisions

Comparison Of Primary Human Cytotoxic T-Cell And Natural Killer Cell Responses Reveal Similar Molecular Requirements For Lytic Granule Exocytosis But Differences In Cytokine Production

Cytotoxic lymphocytes, encompassing cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, kill pathogen-infected, neoplastic, or certain hematopoietic cells through the release of perforin-containing lytic granules. In the present study, we first performed probability-state modeling of differentiation and lytic granule markers on CD8(+) T cells to enable the comparison of bona fide CTLs with NK cells. Analysis identified CD57(bright) expression as a reliable phenotype of granule marker-containing CTLs. We then compared CD3(+)CD8(+)CD57(bright) CTLs with NK cells. Healthy adult peripheral blood CD3(+)CD8(+)CD57(bright) CTLs expressed more granzyme B but less perforin than CD3(-)CD56(dim) NK cells. On stimulation, such CTLs degranulated more readily than other T-cell subsets, but had a propensity to degranulate that was similar to NK cells. Remarkably, the CTLs produced cytokines more rapidly and with greater frequency than NK cells. In patients with biallelic mutations in UNC13D, STX11, or STXBP2 associated with familial hemophagocytic lymphohistiocytosis, CTL and NK cell degranulation were similarly impaired. Therefore, cytotoxic lymphocyte subsets have similar requirements for Munc13-4, syntaxin-11, and Munc18-2 in lytic granule exocytosis. The present results provide a detailed comparison of human CD3(+)CD8(+)CD57(bright) CTLs and NK cells and suggest that analysis of CD57(bright) CTL function may prove useful in the diagnosis of primary immunodeficiencies including familial hemophagocytic lymphohistiocytosis.WoSScopu