The present and future of blood virome in allogeneic hematopoietic cell transplant recipients.

PURPOSE OF REVIEW: Allogeneic hematopoietic cell transplantation (allogeneic HCT) is a highly effective therapy for a broad range of hematological diseases and its use is increasing worldwide. Despite advances in antiviral prophylaxis and treatment, viral infections are still one of the leading causes of post-HCT morbidity and mortality. In this patient population, metagenomic next-generation sequencing (mNGS) revealed a much larger diversity of viruses than previously suspected via the targeted screening approach. In the context of profound immunosuppression, these viral infections may cause transient viremia or protracted replication and potentially be associated with yet unrecognized or unspecific clinical manifestations. On the contrary, by constantly interacting with the immune system, viral infections may have a significant impact on posttransplant outcomes. Here, we review the latest advances in research assessing the role of the blood virome in the development of post-HCT complications. RECENT FINDINGS: Research efforts are under way to uncover the potential role of several previously undetected viruses in the development of allogeneic HCT complications and their impact on transplant outcomes. SUMMARY: The identification of viral actors impacting post-HCT morbidity and survival is key to optimize monitoring and infection prevention/treatment strategies.

SARS-CoV-2 convalescence and hybrid immunity elicits mucosal immune responses.

BACKGROUND: Mucosal antibodies play a key role in the protection against SARS-CoV-2 infection in the upper respiratory tract, and potentially in limiting virus replication and therefore onward transmission. While systemic immunity to SARS-CoV-2 is well understood, we have a limited understanding about the antibodies present on the nasal mucosal surfaces. METHODS: In this study, we evaluated SARS-CoV-2 mucosal antibodies following previous infection, vaccination, or a combination of both. Paired nasal fluid and serum samples were collected from 143 individuals, which include convalescent, vaccinated, or breakthrough infections. FINDINGS: We detected a high correlation between IgG responses in serum and nasal fluids, which were higher in both compartments in vaccinated compared to convalescent participants. Contrary, nasal and systemic SARS-CoV-2 IgA responses were weakly correlated, indicating a compartmentalization between the local and systemic IgA responses. SARS-CoV-2 secretory component IgA (s-IgA) antibodies, present exclusively on mucosal surfaces, were detected in the nasal fluid only in a minority of vaccinated subjects and were significantly higher in previously infected individuals. Depletion of IgA antibodies in nasal fluids resulted in a tremendous reduction of neutralization activity against SARS-CoV-2, indicating that IgA is the crucial contributor to neutralization in the nasal mucosa. Neutralization against SARS-CoV-2 was higher in the mucosa of subjects with previous SARS-CoV-2 infections compared to vaccinated participants. INTERPRETATION: In summary, we demonstrate that currently available vaccines elicit strong systemic antibody responses, but SARS-CoV-2 infection generates higher titers of binding and neutralizing mucosal antibodies. Our results support the importance to develop SARS-CoV-2 vaccines that elicit mucosal antibodies. FUNDING: The work was funded by the COVID-19 National Research Program 78 (grant number 198412) of the Swiss National Science Foundation.

Longitudinal Detection of Twenty DNA and RNA Viruses in Allogeneic Hematopoietic Stem Cell Transplant Recipients Plasma.

Metagenomics revealed novel and routinely overlooked viruses, representing sources of unrecognized infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aim to describe DNA and RNA virus prevalence and kinetics in allo-HSCT recipients' plasma for one year post HSCT. We included 109 adult patients with first allo-HSCT from 1 March 2017 to 31 January 2019 in this observational cohort study. Seventeen DNA and three RNA viral species were screened with qualitative and/or quantitative r(RT)-PCR assays using plasma samples collected at 0, 1, 3, 6, and 12 months post HSCT. TTV infected 97% of patients, followed by HPgV-1 (prevalence: 26-36%). TTV (median 3.29 × 105 copies/mL) and HPgV-1 (median 1.18 × 106 copies/mL) viral loads peaked at month 3. At least one Polyomaviridae virus (BKPyV, JCPyV, MCPyV, HPyV6/7) was detected in >10% of patients. HPyV6 and HPyV7 prevalence reached 27% and 12% at month 3; CMV prevalence reached 27%. HSV, VZV, EBV, HHV-7, HAdV and B19V prevalence remained <5%. HPyV9, TSPyV, HBoV, EV and HPg-V2 were never detected. At month 3, 72% of patients had co-infections. TTV and HPgV-1 infections were highly prevalent. BKPyV, MCPyV and HPyV6/7 were frequently detected relative to classical culprits. Further investigation is needed into associations between these viral infections and immune reconstitution or clinical outcomes.

Neutralization capacity of antibodies elicited through homologous or heterologous infection or vaccination against SARS-CoV-2 VOCs.

Emerging SARS-CoV-2 variants raise questions about escape from previous immunity. As the population immunity to SARS-CoV-2 has become more complex due to prior infections with different variants, vaccinations or the combination of both, understanding the antigenic relationship between variants is needed. Here, we have assessed neutralizing capacity of 120 blood specimens from convalescent individuals infected with ancestral SARS-CoV-2, Alpha, Beta, Gamma or Delta, double vaccinated individuals and patients after breakthrough infections with Delta or Omicron-BA.1. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta and Omicron-BA.1) determined by plaque-reduction neutralization assay allowed us to map the antigenic relationship of SARS-CoV-2 variants. Highest neutralization titers were observed against the homologous variant. Antigenic cartography identified Zeta and Omicron-BA.1 as separate antigenic clusters. Substantial immune escape in vaccinated individuals was detected for Omicron-BA.1 but not Zeta. Combined infection/vaccination derived immunity results in less Omicron-BA.1 immune escape. Last, breakthrough infections with Omicron-BA.1 lead to broadly neutralizing sera.