Immunotherapy for infectious diseases in haematological immunocompromise.

Opportunistic infections remain a major problem across a broad spectrum of immunocompromised haematological patient groups, with viruses, bacteria, fungi and protozoa all presenting significant challenges. Given the major difficulties in treating many of these infections with the currently available antimicrobial chemotherapeutic arsenal, and the rapid emergence of antimicrobial resistance amongst all of the microbial kingdoms, novel strategies that enable host control or elimination of infection are urgently required. Recently, major progress has been made in our understanding of host immunocompromise in the haematological patient. In addition, a wide range of novel immunomodulatory strategies for infectious diseases have been developed. Here we discuss the major and wide-ranging areas of progress that have been made for host-directed immunotherapies in the context of infectious diseases, with relevance to haematological immunocompromise.

Efficacy of three antimicrobial mouthwashes in reducing SARS-CoV-2 viral load in the saliva of hospitalized patients: a randomized controlled pilot study.

This study aimed to evaluate the efficacy of 3 mouthwashes in reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in the saliva of coronavirus disease 2019 (COVID-19) patients at 30 min, 1, 2 and 3 h after rinsing. This pilot study included 40 admitted COVID-19 positive patients (10 in each group). Saliva samples were collected before rinsing and at 30 min, 1, 2 and 3 h after rinsing with: Group 1-0.2% Chlorhexidine digluconate (CHX); Group 2-1.5% Hydrogen peroxide (H2O2); Group 3-Cetylpyridinium chloride (CPC) or Group 4 (control group)-No rinsing. Viral load analysis of saliva samples was assessed by Reverse Transcription quantitative PCR. Mean log10 viral load at different time points was compared to that at baseline in all groups using a random effects linear regression analysis while for comparison between groups linear regression analysis was used. The results showed that all groups had a significantly reduced mean log10 viral load both at 2 (p = 0.036) and 3 (p = 0.041) hours compared to baseline. However, there was no difference in mean log10 viral load between any of the investigated mouthwashes and the control group (non-rinsing) at the evaluated time points. Although a reduction in the SARS-CoV-2 viral load in the saliva of COVID-19 patients was observed after rinsing with mouthwashes containing 0.2% CHX, 1.5% H2O2, or CPC, the reduction detected was similar to that achieved by the control group at the investigated time points. The findings of this study may suggest that the mechanical action of rinsing/spitting results in reduction of SARS-CoV-2 salivary load.

Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.

Background: Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings. Methods: We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital-onset COVID-19 infections (HOCIs; detected ≥48 hr from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on the incidence of probable/definite hospital-acquired infections (HAIs), was evaluated. Results: A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95% CI 0.85-3.01; p=0.14) or rapid (0.85, 0.48-1.50; p=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8 and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2 and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis, there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources. Conclusions: While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days. Funding: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute. Clinical trial number: NCT04405934.

SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men: multicentre cohort study.

BACKGROUND: SARS-CoV-2 lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented. METHODS: We collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16 November 2020 to 10 January 2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity. FINDINGS: Sequences were obtained from 2341 inpatients (HOCI cases=786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The HR for mortality of B.1.1.7 compared with other lineages was 1.01 (95% CI 0.79 to 1.28, p=0.94) and for ITU admission was 1.01 (95% CI 0.75 to 1.37, p=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95 to 1.78, p=0.096) and ITU admission (HR 1.82, 95% CI 1.15 to 2.90, p=0.011) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61 to 1.10, p=0.177; ITU HR 0.74, 95% CI 0.52 to 1.04, p=0.086). INTERPRETATION: In common with smaller studies of patients hospitalised with SARS-CoV-2, we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared with other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.

Universal screening for SARS-CoV-2 in pregnant women at term admitted to an East London maternity unit.

OBJECTIVE: To explore the prevalence of asymptomatic SARS-CoV-2 in the maternity population. STUDY DESIGN: Newham University Hospital based in East London serving a population with the highest death rate secondary to SARS-CoV-2 in the UK, commenced universal screening of all admissions to the Maternity Unit from 22nd April to 5th May, 2020. A proforma was created to capture key patient demographics, indication for admission and presence of SARS-CoV-2 related symptoms at the point of presentation. RESULTS: A total of 180 women with a mean age of 29.9 (SD 7.4) years, at a median gestation of 39 (IQR 37 + 1-40 + 3) weeks underwent universal screening with nasopharyngeal PCR swabs during the two-week period of the study. BAME identity or parity was not associated with the likelihood of a positive result. Seven women (3.9 %, 1.6-7.8) were tested positive for SARS-CoV-2, of whom 6 (3.3 %, 1.2-7.1) were asymptomatic; 85.7 % (42.1-99.6) of the SARS-CoV-2 positive women were asymptomatic. The sensitivity of symptom-driven testing was 14.3 % (0.36-57.87) and specificity was 91.86 % (86.72-95.48) with a positive predictive value of 6.67 % (1.08-31.95) and a negative predictive value of 96.34 % (95.10-97.28). CONCLUSION: The prevalence of SARS-CoV-2 in the maternity population served by Newham University Hospital was 3.9 %, four weeks after lockdown. Of the women who were found to be SARS-CoV-2 positive, a high proportion (87.9 %) were asymptomatic. These findings support the need for universal testing to enable targeted isolation and robust infectious control measures to mitigate outbreaks of SARS-CoV-2 in maternity units.