Genomic epidemiology of SARS-CoV-2 in a university outbreak setting and implications for public health planning.

Whole genome sequencing of SARS-CoV-2 has occurred at an unprecedented scale, and can be exploited for characterising outbreak risks at the fine-scale needed to inform control strategies. One setting at continued risk of COVID-19 outbreaks are higher education institutions, associated with student movements at the start of term, close living conditions within residential halls, and high social contact rates. Here we analysed SARS-CoV-2 whole genome sequences in combination with epidemiological data to investigate a large cluster of student cases associated with University of Glasgow accommodation in autumn 2020, Scotland. We identified 519 student cases of SARS-CoV-2 infection associated with this large cluster through contact tracing data, with 30% sequencing coverage for further analysis. We estimated at least 11 independent introductions of SARS-CoV-2 into the student population, with four comprising the majority of detected cases and consistent with separate outbreaks. These four outbreaks were curtailed within a week following implementation of control measures. The impact of student infections on the local community was short-term despite an underlying increase in community infections. Our study highlights the need for context-specific information in the formation of public health policy for higher educational settings.

Increased risk of HIV and other drug-related harms associated with injecting in public places: national bio-behavioural survey of people who inject drugs.

BACKGROUND: Whilst injecting drugs in public places is considered a proxy for high risk behaviour among people who inject drugs (PWID), studies quantifying its relationship with multiple drug-related harms are lacking and none have examined this in the context of an ongoing HIV outbreak (located in Glasgow, Scotland). We aimed to: 1) estimate the prevalence of public injecting in Scotland and associated risk factors; and 2) estimate the association between public injecting and HIV, current HCV, overdose, and skin and soft tissue infections (SSTI). METHODS: Cross-sectional, bio-behavioural survey (including dried blood spot testing to determine HIV and HCV infection) of 1469 current PWID (injected in last 6 months) recruited by independent interviewers from 139 harm reduction services across Scotland during 2017-18. Primary outcomes were: injecting in a public place (yes/no); HIV infection; current HCV infection; self-reported overdose in the last year (yes/no) and SSTI the last year (yes/no). Multi-variable logistic regression was used to determine factors associated with public injecting and to estimate the association between public injecting and drug-related harms (HIV, current HCV, overdose and SSTI). RESULTS: Prevalence of public injecting was 16% overall in Scotland and 47% in Glasgow city centre. Factors associated with increased odds of public injecting were: recruitment in Glasgow city centre (aOR=5.45, 95% CI 3.48-8.54, p<0.001), homelessness (aOR=3.68, 95% CI 2.61-5.19, p<0.001), high alcohol consumption (aOR=2.42, 95% CI 1.69-3.44, p<0.001), high injection frequency (≥4 per day) (aOR=3.16, 95% CI 1.93-5.18, p<0.001) and cocaine injecting (aOR=1.46, 95% CI 1.00 to 2.13, p = 0.046). Odds were lower for those receiving opiate substitution therapy (OST) (aOR=0.37, 95% CI 0.24 to 0.56, p<0.001) and older age (per year increase) (aOR=0.97, 95% CI 0.95 to 0.99, p = 0.013). Public injecting was associated with an increased risk of HIV infection (aOR=2.11, 95% CI 1.13-3.92, p = 0.019), current HCV infection (aOR=1.49, 95% CI 1.01-2.19, p = 0.043), overdose (aOR=1.59, 95% CI 1.27-2.01, p<0.001) and SSTI (aOR=1.42, 95% CI 1.17-1.73, p<0.001). CONCLUSIONS: These findings highlight the need to address the additional harms observed among people who inject in public places and provide evidence to inform proposals in the UK and elsewhere to introduce facilities that offer safer drug consumption environments.

Re-emergence of HIV related to injecting drug use despite a comprehensive harm reduction environment: a cross-sectional analysis.

BACKGROUND: In 2015, an outbreak of HIV was identified among people who inject drugs (PWID) in the Greater Glasgow and Clyde (GGC) area of Scotland, an area which distributes more than 1 million needles and syringes per year. This is the largest such incident in the UK for 30 years. Here, we provide an epidemiological analysis of the impact of the outbreak on HIV prevalence trends in the population and the individual and environmental risk factors associated with infection. METHODS: Four cross-sectional, anonymous, bio-behavioural surveys of almost 4000 PWID attending services providing injecting equipment across GGC between 2011 and 2018 were analysed. Participants were recruited by trained independent interviewers and eligible if they had a history of injecting drug use, either current (within the past 6 months) or historical. Interviewers asked participants questions about demographics, behaviours, and service use and to give a dried blood spot sample that was tested anonymously for the presence of blood-borne viruses. Our primary outcome measure was HIV infection status, as determined by the dried blood spot sample. We removed duplicates and participants with missing data and used all remaining participants to examine trends in prevalence of HIV infection, risk behaviours, and intervention coverage. We then did multivariate analysis with adjusted and unadjusted logistic regression to determine individual and environmental factors associated with HIV infection. FINDINGS: The overall GGC sample comprised 3641 PWID; data from 2712 PWID were available for multivariate analysis after further removal of duplicate participants and missing data. Between 2011 and 2018, HIV prevalence in GGC rose from 0·1% (95% CI 0·0-0·6) to 4·8% (3·4-6·2) overall, and from 1·1% (0·2-6·2) to 10·8% (7·4-15·5) in Glasgow city centre. Over the same period, the prevalence of cocaine injecting in all individuals in GGC in our sample rose from 16% (129/805) to 50% (291/583) overall, and from 37% (26/70) to 77% (117/153) in Glasgow city centre. HIV infection was more likely among PWID who had participated in surveys after the start of the outbreak in 2014 (adjusted odds ratio 3·4, 95% CI 1·7-6·7; p=0·00052), been homeless in the past 6 months (3·0, 1·7-5·0; p<0·0001), had had more than five incarcerations since they first began injecting (2·1, 1·2-3·7; p=0·0098); and had injected cocaine within the past 6 months (6·7, 3·8-12·1; p<0·0001). Age (per 1-year increase) was also a significant factor (1·1, 1·0-1·1; p=0·0016) but sex was not (1·7, 0·9-3·2; p=0·083). INTERPRETATION: Despite high coverage of harm reduction interventions, Glasgow has experienced a rapid rise in prevalence of HIV among its PWID population, associated with homelessness, incarceration, and a major shift to injection of cocaine. Robust surveillance through regular HIV testing of high-risk populations is crucial to ensure outbreaks are detected and rapid responses are informed by the best available evidence. FUNDING: Health Protection Scotland.

Recent and Rapid Transmission of HIV Among People Who Inject Drugs in Scotland Revealed Through Phylogenetic Analysis.

Background: Harm reduction has dramatically reduced HIV incidence among people who inject drugs (PWID). In Glasgow, Scotland, <10 infections/year have been diagnosed among PWID since the mid-1990s. However, in 2015 a sharp rise in diagnoses was noted among PWID; many were subtype C with 2 identical drug-resistant mutations and some displayed low avidity, suggesting the infections were linked and recent. Methods: We collected Scottish pol sequences and identified closely related sequences from public databases. Genetic linkage was ascertained among 228 Scottish, 1820 UK, and 524 global sequences. The outbreak cluster was extracted to estimate epidemic parameters. Results: All 104 outbreak sequences originated from Scotland and contained E138A and V179E. Mean genetic distance was <1% and mean time between transmissions was 6.7 months. The average number of onward transmissions consistently exceeded 1, indicating that spread was ongoing. Conclusions: In contrast to other recent HIV outbreaks among PWID, harm reduction services were not clearly reduced in Scotland. Nonetheless, the high proportion of individuals with a history of homelessness (45%) suggests that services were inadequate for those in precarious living situations. The high prevalence of hepatitis C (>90%) is indicative of sharing of injecting equipment. Monitoring the epidemic phylogenetically in real time may accelerate public health action.

HIV diagnosis in older adults.

It is recognised that those diagnosed with HIV infection over the age of 50 have higher rates of morbidity and mortality. Little is known about how clinical presentation at diagnosis of HIV varies within this group. We sought to compare clinical presentation and markers of outcome among those diagnosed with HIV aged 60 and over vs. those diagnosed aged 50-59, over a ten-year period. The results showed that 84/111 were diagnosed with HIV aged 50-59 and 27/111 aged ≥60. Ethnicity and HIV risk factors were similar between groups, and most infections were sexually acquired with 7.4% of those aged ≥60 suspected to have a recent infection. Median CD4 cell count at presentation was significantly lower in the ≥60 age group (111 vs. 249; p < 0.001), and the proportion with a CD4 cell count <50 was also significantly lower in this population (33% vs. 15%; p = 0.04). In keeping with this, the frequency of AIDS-defining illness at diagnosis was higher in the ≥60 group (38% vs. 4%; p < 0.001). Co-morbidities were found in both groups, and 38% of those aged ≥60 at diagnosis were known to have since died compared to 4% of those aged 50-59 at diagnosis ( p ≤ 0.01). Those aged ≥60 had lower CD4 cell counts at diagnosis and more AIDS-defining illnesses, highlighting the increased risk of poor outcomes in this group. The majority of infections were sexually acquired. More work is needed to understand survival in adults diagnosed with HIV at an older age and to consider those over 60 as a specific population worthy of further research.