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Background Human mastadenoviruses (HAdV) are associated with significant morbidity and mortality amongst the immunocompromised population. A recent surge in HAdV cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate. Methods To gain a complete transmission picture, we compared outbreak and non-outbreak sequences (54 sequences from 37 patients) with GenBank sequences and our own database of previously sequenced HAdVs (132 sequences from 37 patients). An improved bait set for WGS was used. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships paired with epidemiological data from routine Infection, Prevention and Control (IPC) activity. Results Nine monophyletic clusters were identified, seven of which were corroborated by epidemiological evidence and by comparison of single nucleotide polymorphisms. Two incomplete patient clusters were identified by IPC over the same time period. Of the five patients who died, one had a mixed HAdV infection and two were the source of transmission events. Conclusions The clinical consequences of unmitigated HAdV transmission events are high. Focusing on two high risk wards using WGS we identified six transmission events, over prolonged periods, that would have gone unnoticed using traditional polymerase chain reaction and epidemiology. Mixed infection is frequent (10% of patients), providing a sentinel source of recombination and superinfection. Immunosuppressed patients harbouring a high rate of HAdV positivity require comprehensive surveillance. As a consequence of these findings, HAdV WGS is being incorporated routinely into a clinical algorithm to prevent transmission and influence IPC policy in real-time. Summary Whole genome sequencing of adenovirus, direct from clinical samples, can be used to identify cryptic health care associated transmission events, and to resolve transmission suspected by traditional epidemiology. It can also identify mixed genotype infections in immunocompromised patient populations.

OBJECTIVES: Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. We sought to determine whether this also resulted in increased transmission within hospitals. METHODS: We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences. RESULTS: Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages. CONCLUSIONS: We find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern.

Chronic active Epstein Barr Virus (CAEBV) is a rare condition occurring in previously healthy individuals associated with persistent EBV viraemia, fever, lymphadenopathy and hepatosplenomegaly. Viral deletions have been found in CAEBV and other lymphomas. However, it is unclear how stable these deletions are, whether they are present in different sites and how they evolve overtime. We sequenced fourteen longitudinal blood samples from three European CAEBV patients and compared with CAEBV saliva samples and other sequences from EBV-related conditions. We observed large EBV deletions in blood, but not saliva from CAEBV patients. Deletions were stable over time but were lost following successful treatment. Our results are consistent with the likelihood that certain deletions in the virus from CAEBV patients are associated with the evolution and persistence of haematological clones. We propose that the loss of deletions following successful treatment should be investigated as a potential biomarker to aid CAEBV management.