Evaluating the cost implications of integrating SARS-CoV-2 genome sequencing for infection prevention and control investigation of nosocomial transmission within hospitals.

BACKGROUND: The COG-UK hospital-onset COVID-19 infection (HOCI) trial evaluated the impact of SARS-CoV-2 whole-genome sequencing (WGS) on acute infection, prevention, and control (IPC) investigation of nosocomial transmission within hospitals. AIM: To estimate the cost implications of using the information from the sequencing reporting tool (SRT), used to determine likelihood of nosocomial infection in IPC practice. METHODS: A micro-costing approach for SARS-CoV-2 WGS was conducted. Data on IPC management resource use and costs were collected from interviews with IPC teams from 14 participating sites and used to assign cost estimates for IPC activities as collected in the trial. Activities included IPC-specific actions following a suspicion of healthcare-associated infection (HAI) or outbreak, as well as changes to practice following the return of data via SRT. FINDINGS: The mean per-sample costs of SARS-CoV-2 sequencing were estimated at £77.10 for rapid and £66.94 for longer turnaround phases. Over the three-month interventional phases, the total management costs of IPC-defined HAIs and outbreak events across the sites were estimated at £225,070 and £416,447, respectively. The main cost drivers were bed-days lost due to ward closures because of outbreaks, followed by outbreak meetings and bed-days lost due to cohorting contacts. Actioning SRTs, the cost of HAIs increased by £5,178 due to unidentified cases and the cost of outbreaks decreased by £11,246 as SRTs excluded hospital outbreaks. CONCLUSION: Although SARS-CoV-2 WGS adds to the total IPC management cost, additional information provided could balance out the additional cost, depending on identified design improvements and effective deployment.

Joint consensus statement on the vaccination of adult and paediatric haematopoietic stem cell transplant recipients: Prepared on behalf of the British society of blood and marrow transplantation and cellular therapy (BSBMTCT), the Children's cancer and Leukaemia Group (CCLG), and British Infection Association (BIA).

Haematopoietic stem cell transplant (HSCT) recipients have deficiencies in their adaptive immunity against vaccine preventable diseases. National and International guidance recommends that HSCT recipients are considered 'never vaccinated' and offered a comprehensive course of revaccination. This position statement aims to draw upon the current evidence base and existing guidelines, and align this with national vaccine availability and licensing considerations in order to recommend a pragmatic and standardised re-vaccination schedule for adult and paediatric HSCT recipients in the UK.

Factors affecting turnaround time of SARS-CoV-2 sequencing for inpatient infection prevention and control decision making: analysis of data from the COG-UK HOCI study.

BACKGROUND: Barriers to rapid return of sequencing results can affect the utility of sequence data for infection prevention and control decisions. AIM: To undertake a mixed-methods analysis to identify challenges that sites faced in achieving a rapid turnaround time (TAT) in the COVID-19 Genomics UK Hospital-Onset COVID-19 Infection (COG-UK HOCI) study. METHODS: For the quantitative analysis, timepoints relating to different stages of the sequencing process were extracted from both the COG-UK HOCI study dataset and surveys of study sites. Qualitative data relating to the barriers and facilitators to achieving rapid TATs were included from thematic analysis. FINDINGS: The overall TAT, from sample collection to receipt of sequence report by infection control teams, varied between sites (median 5.1 days, range 3.0-29.0 days). Most variation was seen between reporting of a positive COVID-19 polymerase chain reaction (PCR) result to sequence report generation (median 4.0 days, range 2.3-27.0 days). On deeper analysis, most of this variability was accounted for by differences in the delay between the COVID-19 PCR result and arrival of the sample at the sequencing laboratory (median 20.8 h, range 16.0-88.7 h). Qualitative analyses suggest that closer proximity of sequencing laboratories to diagnostic laboratories, increased staff flexibility and regular transport times facilitated a shorter TAT. CONCLUSION: Integration of pathogen sequencing into diagnostic laboratories may help to improve sequencing TAT to allow sequence data to be of tangible value to infection control practice. Adding a quality control step upstream to increase capacity further down the workflow may also optimize TAT if lower quality samples are removed at an earlier stage.

Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS.

HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors - synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.

A bundle of infection control measures reduces postoperative sternal wound infection due to Staphylococcus aureus but not Gram-negative bacteria: a retrospective analysis of 6903 patient episodes.

BACKGROUND: Prevention of cardiac surgical site infection has largely focused on reducing infection due to Staphylococcus aureus, although other bacteria also play an important role in this complication. AIM: To assess the impact of an evolving infection control programme on the incidence of sternal wound infection (SWI), and the changing incidence of non-staphylococcal infections. METHODS: A retrospective cohort study of all patients who underwent primary sternotomy at a single UK centre between September 2010 and May 2018 was undertaken. Data were collated from the 2 years preceding the stepwise introduction of a broad-ranging infection control programme, including S. aureus decolonization. FINDINGS: In total, 6903 primary sternotomies were performed, of which 2.6% (N=178) were complicated by SWI. Gram-negative bacteria (GNB) and S. aureus were most commonly identified as causative pathogens (45.5% and 30.3%, respectively). Following programme introduction, there was a reduction in the rate of SWI from 3.9 to 1.8 cases/100 patients/month. This was mainly due to a sustained reduction in cases of S. aureus infection, with no discernible impact on GNB. Multi-variable logistic regression analysis identified coronary artery bypass grafting, procedural urgency, and procedures performed in the third quarter of the calendar year (July to September) as independent risk factors for postoperative infection. CONCLUSION: A multi-faceted infection control programme was successful at reducing the rate of SWI, primarily due to a reduction in S. aureus infections. GNB also play an important role in SWI, and traditional preventative measures fail to address these. Future intervention and impact assessments should consider GNB infections when measuring effectiveness.

Evaluation of procalcitonin as a contribution to antimicrobial stewardship in SARS-CoV-2 infection: a retrospective cohort study.

It can be a diagnostic challenge to identify patients with coronavirus disease 2019 in whom antibiotics can be safely withheld. This study evaluated the effectiveness of a guideline implemented at Sheffield Teaching Hospitals NHS Foundation Trust that recommends withholding antibiotics in patients with low serum procalcitonin (PCT), defined as ≤0.25 ng/mL. Results showed reduced antibiotic consumption in patients with PCT ≤0.25 ng/mL with no increase in mortality, alongside a reduction in subsequent carbapenem prescriptions during admission. The results support the effectiveness of this guideline, and further research is recommended to identify the optimal cut-off value for PCT in this setting.

Routine vaccination practice after adult and paediatric allogeneic haematopoietic stem cell transplant: a survey of UK NHS programmes.

This corrects the article DOI: 10.1038/bmt.2016.362.

Full-length sequence of KIR3DL1*0310102 detected in DNA samples from West Africa.

KIR3DL1*0310102 differs from KIR3DL1*0150101 with 11 nucleotide substitutions.

KIR3DL1*0040102 ­ a novel three-domain KIR subtype isolated from donors of African descent.

KIR3DL1*0040102 allele differs from KIR3DL1*0040101 by a single-nucleotide change at position 12356 (intron 6).

KIR3DL1*0250103: a novel three-domain KIR allele isolated in West African samples.

The full length sequence of KIR3DL1*0250103 differs from that of KIR3DL1*0150101 with nine single-nucleotide polymorphisms.

A novel KIR3DL1*0150103 subtype identified in West Africa.

A novel KIR3DL1*0150103 found in West Africa with five single nucleotide polymorphisms compared to KIR3DL1*0150101.

KIR3DL1*0250102: a novel three-domain KIR subtype identified in West Africa.

KIR3DL1*0250102 differs from the common West African KIR3DL1*0150101 by 11 single nucleotide polymorphisms (SNPs).

Identification of a novel three-domain KIR allele: KIR3DL1*087 using high-resolution molecular techniques.

KIR3DL1*087 is significantly different from KIR3DL1*0010101 with multiple non-synonymous changes and insertion/deletion sites.

Description of a novel KIR3DL1*0150211 allele isolated using molecular techniques.

KIR3DL1*0150211 differs from KIR3DL1*0150201 with six single nucleotide polymorphisms in introns 3, 4, 5, and 6.

Isolation of full-length genomic sequences of the KIR3DL1*0040103 allele from African donors using sequence-based techniques.

The full-length genomic sequence of KIR3DL1*0040103 differs from KIR3DL1*0040101 at three nucleotide positions.

Complete genomic sequence of KIR3DL1*0150102.

Full-length sequence of KIR3DL1*0150102 differs from that of KIR3DL1*0150101 in intron 6.

A new variant of killer-cell immunoglobulin-like receptor KIR3DL1*03101 isolated using sequence-based techniques.

The complete length genomic sequence of KIR3DL1*03101 differs from KIR3DL1*0010101 at multiple intronic and exonic sites.

Genomic full length sequence of a novel killer-cell immunoglobulin-like receptor, KIR3DL1*0010103 identified by sequencing.

KIR3DL1*0010103 differs from KIR3DL1*0010101 with four single nucleotide polymorphisms.

Full-length KIR3DL1*022 detected in an African donor.

KIR3DL1*022 is significantly different from the most common West African allele - KIR3DL1*01501.