A new outbreak of HIV infection among people who inject drugs during the COVID-19 pandemic in Greece.

BACKGROUND: Multiple HIV outbreaks have been recorded among people who inject drugs (PWID) since 2010. During an intervention for PWID in 2019-2021 in Thessaloniki, Greece, an increasing number of HIV cases was documented. Here, we provide an analysis of this new outbreak. METHODS: ALEXANDROS was a community-based program and participation included interviewing, rapid HIV/HCV tests, counselling and linkage to care. PWID were recruited through Respondent-Driven Sampling (RDS) in five sampling rounds. Crude and RDS-weighted HIV prevalence estimates were obtained. HIV incidence was estimated from data on 380 initially seronegative PWID with at least two tests. Multivariable Cox proportional hazards model was used to assess risk factors for HIV seroconversion. RESULTS: In total, 1,101 PWID were recruited. At first participation, 53.7% were current PWID, 20.1% homeless, 20.3% on opioid substitution treatment and 4.8% had received syringes in the past 12 months. HIV prevalence (95% CI) was 7.0% (5.6-8.7%) and an increasing trend was observed over 2019-2021 (p = 0.002). Two-thirds of the cases (67.5%) were new diagnoses. HIV incidence was 7.0 new infections/100 person-years (95% CI:4.8-10.2). Homelessness in the past 12 months (HR:2.68; 95% CI:1.24-5.81) and receptive syringe sharing (HR:3.86; 95% CI:1.75-8.51) were independently associated with increased risk of seroconversion. By the end of the program, 67.3% of the newly diagnosed cases initiated antiretroviral treatment. CONCLUSIONS: A new HIV outbreak among PWID was documented in Greece during the COVID-19 pandemic with homelessness and syringe sharing being associated with increased risk of HIV acquisition. Peer-driven programs targeting the population of high-risk underserved PWID can be used to early identify emerging outbreaks and to improve linkage to HIV care.

Securing Wider EU Commitment to the Elimination of HCV.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programs - from the municipality level to the EU level - were launched, resulting in an overall decrease of viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the 3rd EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and report the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

Evaluating the effects of second-dose vaccine-delay policies in European countries: A simulation study based on data from Greece.

The results of a simulation-based evaluation of several policies for vaccine rollout are reported, particularly focusing on the effects of delaying the second dose of two-dose vaccines. In the presence of limited vaccine supply, the specific policy choice is a pressing issue for several countries worldwide, and the adopted course of action will affect the extension or easing of non-pharmaceutical interventions in the next months. We employ a suitably generalised, age-structure, stochastic SEIR (Susceptible → Exposed → Infectious → Removed) epidemic model that can accommodate quantitative descriptions of the major effects resulting from distinct vaccination strategies. The different rates of social contacts among distinct age-groups (as well as some other model parameters) are informed by a recent survey conducted in Greece, but the conclusions are much more widely applicable. The results are summarised and evaluated in terms of the total number of deaths and infections as well as life years lost. The optimal strategy is found to be one based on fully vaccinating the elderly/at risk as quickly as possible, while extending the time-interval between the two vaccine doses to 12 weeks for all individuals below 75 years old, in agreement with epidemic theory which suggests targeting a combination of susceptibility and infectivity. This policy, which is similar to the approaches adopted in the UK and in Canada, is found to be effective in reducing deaths and life years lost in the period while vaccination is still being carried out.

Trends in COVID-19 Vaccination Intent, Determinants and Reasons for Vaccine Hesitancy: Results from Repeated Cross-Sectional Surveys in the Adult General Population of Greece during November 2020-June 2021.

Vaccine hesitancy is a major barrier to achieving large-scale COVID-19 vaccination. We report trends in vaccination intention and associated determinants from surveys in the adult general population in Greece. Four cross-sectional phone surveys were conducted in November 2020 and February, April and May 2021 on nationally representative samples of adults in Greece. Multinomial logistic regression was used on the combined data of the surveys to evaluate independent predictors of vaccination unwillingness/uncertainty. Vaccination intention increased from 67.6% in November 2020 to 84.8% in May 2021. Individuals aged 65 years or older were more willing to be vaccinated (May 2021: 92.9% vs. 79.5% in 18-39 years, p < 0.001) but between age-groups differences decreased over time. Vaccination intention increased substantially in both men and women, though earlier among men, and was higher in individuals with prograduate education (May 2021: 91.3% vs. 84.0% up to junior high). From multivariable analysis, unwillingness and/or uncertainty to be vaccinated was associated with younger age, female gender (in particular in the April 2021 survey), lower educational level and living with a child ≤12 years old. Among those with vaccine hesitancy, concerns about vaccine effectiveness declined over time (21.6% in November 2020 vs. 9.6% in May 2021, p = 0.014) and were reported more often by men; safety concerns remained stable over time (66.3% in November 2020 vs. 62.1% in May 2021, p = 0.658) and were reported more often by women. In conclusion, vaccination intention increased substantially over time. Tailored communication is needed to address vaccine hesitancy and concerns regarding vaccine safety.

Identifying Country-Level Risk Factors for the Spread of COVID-19 in Europe Using Machine Learning.

Coronavirus disease 2019 (COVID-19) has resulted in approximately 5 million deaths around the world with unprecedented consequences in people's daily routines and in the global economy. Despite vast increases in time and money spent on COVID-19-related research, there is still limited information about the factors at the country level that affected COVID-19 transmission and fatality in EU. The paper focuses on the identification of these risk factors using a machine learning (ML) predictive pipeline and an associated explainability analysis. To achieve this, a hybrid dataset was created employing publicly available sources comprising heterogeneous parameters from the majority of EU countries, e.g., mobility measures, policy responses, vaccinations, and demographics/generic country-level parameters. Data pre-processing and data exploration techniques were initially applied to normalize the available data and decrease the feature dimensionality of the data problem considered. Then, a linear ε-Support Vector Machine (ε-SVM) model was employed to implement the regression task of predicting the number of deaths for each one of the three first pandemic waves (with mean square error of 0.027 for wave 1 and less than 0.02 for waves 2 and 3). Post hoc explainability analysis was finally applied to uncover the rationale behind the decision-making mechanisms of the ML pipeline and thus enhance our understanding with respect to the contribution of the selected country-level parameters to the prediction of COVID-19 deaths in EU.

Is Mandatory Vaccination in Population over 60 Adequate to Control the COVID-19 Pandemic in E.U.?

Vaccine hesitancy, which potentially leads to the refusal or delayed acceptance of COVID-19 vaccines, is considered a key driver of the increasing death toll from the pandemic in the EU. The European Commission and several member states' governments are either planning or have already directly or indirectly announced mandatory vaccination for individuals aged over 60, the group which has repeatedly proved to be the most vulnerable. In this paper, an assessment of this strategy's benefits is attempted by deriving a metric for the potential gains of vaccination mandates that can be used to compare EU member states. This is completed by examining the reduction in Standard Expected Years of Life Lost (SEYLL) per person for the EU population over 60 as a function of the member states' vaccination percentage in these ages. The publicly available data and results of the second iteration of the SHARE COVID-19 survey on the acceptance of COVID-19 vaccines, conducted during the summer of 2021, are used as inputs.

Head-to-Head Comparison of Response Rates to the Two mRNA SARS-CοV-2 Vaccines in a Large Cohort of Solid Organ Transplant (SOT) Recipients.

Due to their higher risk of developing life-threatening COVID-19 disease, solid organ transplant (SOT) recipients have been prioritized in the vaccination programs of many countries. However, there is increasing evidence of reduced immunogenicity to SARS-CοV-2 vaccination. The present study investigated humoral response, safety, and effectiveness after the two mRNA vaccines in 455 SOT recipients. Overall, the antibody response rate was low, at 39.6%. Higher immunogenicity was detected among individuals vaccinated with the mRNA1273 compared to those with the BNT162b2 vaccine (47% vs. 36%, respectively, p = 0.025) as well as higher median antibody levels of 31 (7, 372) (AU/mL) vs. 11 (7, 215) AU/mL, respectively. Among the covariates assessed, vaccination with the BNT162b2 vaccine, antimetabolite- and steroid-containing immunosuppression, female gender, the type of transplanted organ and older age were factors that negatively influenced immune response. Only mild adverse effects were observed. Our findings confirm poor immunogenicity after vaccination, implicating a reevaluation of vaccination policy in SOT recipients.

Modelling SARS-CoV-2 Binding Antibody Waning 8 Months after BNT162b2 Vaccination.

Several lines of evidence suggest that binding SARS-CoV-2 antibodies such as anti-SARS-CoV-2 RBD IgG (anti-RBD) and neutralising antibodies (NA) are correlates of protection against SARS-CoV-2, and the correlation of anti-RBD and NA is very high. The effectiveness (VE) of BNT162b2 in preventing SARS-CoV-2 infection wanes over time, and this reduction is mainly associated with waning immunity, suggesting that the kinetics of antibodies reduction might be of interest to predict VE. In a study of 97 health care workers (HCWs) vaccinated with the BNT162b2 vaccine, we assessed the kinetics of anti-RBD 30-250 days after vaccination using 388 individually matched plasma samples. Anti-RBD levels declined by 85%, 92%, and 95% at the 4th, 6th, and 8th month from the peak, respectively. The kinetics were estimated using the trajectories of anti-RBD by various models. The restricted cubic splines model had a better fit to the observed data. The trajectories of anti-RBD declines were statistically significantly lower for risk factors of severe COVID-19 and the absence of vaccination side effects. Moreover, previous SARS-CoV-2 infection was associated with divergent trajectories consistent with a slower anti-RBD decline over time. These results suggest that anti-RBD may serve as a harbinger for vaccine effectiveness (VE), and it should be explored as a predictor of breakthrough infections and VE.

Age-dependent effects on infectivity and susceptibility to SARS-CoV-2 infection: results from nationwide contact tracing data in Greece.

BACKGROUND: Understanding the factors that affect the transmissibility of SARS-CoV-2 remains important to keep transmission low and maximize the health benefits of vaccination. We assessed the factors associated with the transmissibility of SARS-CoV-2 based on contact tracing data. METHODS: From 1 October to 9 December 2020, 29,385 laboratory-confirmed SARS-CoV-2 cases (index cases, i.e. the first identified laboratory-confirmed cases or with the earliest symptom onset in a setting) and 64,608 traced contacts were identified in Greece. We assessed the prevalence of symptoms in cases, calculated secondary attack rates and assessed factors associated with infectivity and susceptibility to infection. RESULTS: There were 11,232 contacts secondarily infected (secondary attack rate: 17.4%, 95% CI:17.0-17.8). Contacts aged 0-11 and 12-17 years were less susceptible to infection than adults 65 years or older (odds ratio (OR) [95% CI]: 0.28 [0.26-0.32] and 0.44 [0.40-0.49], respectively). Index cases aged 65 years or older were more likely to infect their contacts than other adults or children/adolescents. The odds of infection [95% CI] were higher in contacts exposed within the household (1.71 [1.59-1.85] vs. other) and in cases with cough (1.17 [1.11-1.25] vs. no cough). There was an interaction between the age of the index and the age of the contact with contacts 65 years or older having a higher probability of infection when exposed to cases of similar age than to children. CONCLUSIONS: Our findings highlight the role of age and age mixing in infectivity and susceptibility to SARS-CoV-2 infection. Precautions are necessary for individuals 65 or older as they have higher infectivity and susceptibility in contact with their peers.

Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection.

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1-2 weeks after vaccination or 15-59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651-5583), 6228 (3254-9203) and 7651 (4479-10,823) AU/mL in 35-44, 45-54, 55-70 yrs, respectively, compared with the 18-34 yrs group. In females, the median levels were higher by 2823 (859-4787), 5024 (3122-6926) in individuals with VSE, and 9971 (5158-14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.

Outbreaks of SARS-CoV-2 in naturally infected mink farms: Impact, transmission dynamics, genetic patterns, and environmental contamination.

SARS-CoV-2 infection outbreaks in minks have serious implications associated with animal health and welfare, and public health. In two naturally infected mink farms (A and B) located in Greece, we investigated the outbreaks and assessed parameters associated with virus transmission, immunity, pathology, and environmental contamination. Symptoms ranged from anorexia and mild depression to respiratory signs of varying intensity. Although the farms were at different breeding stages, mortality was similarly high (8.4% and 10.0%). The viral strains belonged to lineages B.1.1.218 and B.1.1.305, possessing the mink-specific S-Y453F substitution. Lung histopathology identified necrosis of smooth muscle and connective tissue elements of vascular walls, and vasculitis as the main early key events of the acute SARS-CoV-2-induced broncho-interstitial pneumonia. Molecular investigation in two dead minks indicated a consistently higher (0.3-1.3 log10 RNA copies/g) viral load in organs of the male mink compared to the female. In farm A, the infected farmers were responsible for the significant initial infection of 229 out of 1,000 handled minks, suggesting a very efficient human-to-mink transmission. Subsequent infections across the sheds wherein animals were being housed occurred due to airborne transmission. Based on a R0 of 2.90 and a growth rate equal to 0.293, the generation time was estimated to be 3.6 days, indicative of the massive SARS-CoV-2 dispersal among minks. After the end of the outbreaks, a similar percentage of animals were immune in the two farms (93.0% and 93.3%), preventing further virus transmission whereas, viral RNA was detected in samples collected from shed surfaces and air. Consequently, strict biosecurity is imperative during the occurrence of clinical signs. Environmental viral load monitoring, in conjunction with NGS should be adopted in mink farm surveillance. The minimum proportion of minks that need to be immunized to avoid outbreaks in farms was calculated at 65.5%, which is important for future vaccination campaigns.

Molecular Epidemiology of SARS-CoV-2 in Greece Reveals Low Rates of Onward Virus Transmission after Lifting of Travel Restrictions Based on Risk Assessment during Summer 2020.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly during the first months of 2020 and continues to expand in multiple areas across the globe. Molecular epidemiology has provided an added value to traditional public health tools by identifying SARS-CoV-2 clusters or providing evidence that clusters based on virus sequences and contact tracing are highly concordant. Our aim was to infer the levels of virus importation and to estimate the impact of public health measures related to travel restrictions to local transmission in Greece. Our phylogenetic and phylogeographic analyses included 389 full-genome SARS-CoV-2 sequences collected during the first 7 months of the pandemic in Greece and a random collection in five replicates of 3,000 sequences sampled globally, as well as the best hits to our data set identified by BLAST. Phylogenetic trees were reconstructed by the maximum likelihood method, and the putative source of SARS-CoV-2 infections was inferred by phylogeographic analysis. Phylogenetic analyses revealed the presence of 89 genetically distinct viruses identified as independent introductions into Greece. The proportion of imported strains was 41%, 11.5%, and 8.8% during the three periods of sampling, namely, March (no travel restrictions), April to June (strict travel restrictions), and July to September (lifting of travel restrictions based on thorough risk assessment), respectively. The results of phylogeographic analysis were confirmed by a Bayesian approach. Our findings reveal low levels of onward transmission from imported cases during summer and underscore the importance of targeted public health measures that can increase the safety of international travel during a pandemic. IMPORTANCE Our study based on current state-of-the-art molecular epidemiology methods suggests that virus screening and public health measures after the lifting of travel restrictions prevented SARS-CoV-2 onward transmission from imported cases during summer 2020 in Greece. These findings provide important data on the efficacy of targeted public health measures and have important implications regarding the safety of international travel during a pandemic. Our results can provide a roadmap about prevention policy in the future regarding the reopening of borders in the presence of differences in vaccination coverage, the circulation of the virus, and the presence of newly emergent variants across the globe.

Effects of Social Distancing Measures during the First Epidemic Wave of Severe Acute Respiratory Syndrome Infection, Greece.

Greece imposed a nationwide lockdown in March 2020 to mitigate transmission of severe acute respiratory syndrome coronavirus 2 during the first epidemic wave. We conducted a survey on age-specific social contact patterns to assess effects of physical distancing measures and used a susceptible-exposed-infectious-recovered model to simulate the epidemic. Because multiple distancing measures were implemented simultaneously, we assessed their overall effects and the contribution of each measure. Before measures were implemented, the estimated basic reproduction number (R0) was 2.38 (95% CI 2.01-2.80). During lockdown, daily contacts decreased by 86.9% and R0 decreased by 81.0% (95% credible interval [CrI] 71.8%-86.0%); each distancing measure decreased R0 by 10%-24%. By April 26, the attack rate in Greece was 0.12% (95% CrI 0.06%-0.26%), one of the lowest in Europe, and the infection fatality ratio was 1.12% (95% CrI 0.55%-2.31%). Multiple social distancing measures contained the first epidemic wave in Greece.

Antibodies against SARS-CoV-2 among health care workers in a country with low burden of COVID-19.

INTRODUCTION: Greece is a country with limited spread of SARS-CoV-2 and cumulative infection attack rate of 0.12% (95% CI 0.06-0.26). Health care workers (HCWs) are a well-recognized risk group for COVID-19. The study aimed to estimate the seroprevalence of antibodies to SARS-CoV-2 in a nosocomial setting and assess potential risk factors. METHODS: HCWs from two hospitals participated in the study. Hospital-1 was a tertiary university affiliated center, involved in the care of COVID-19 patients while hospital-2 was a tertiary specialized cardiac surgery center not involved in the care of these patients. A validated, CE, rapid, IgM/IgG antibody point-of-care test was used. Comparative performance with a reference globally available assay was assessed. RESULTS: 1,495 individuals consented to participate (response rate 77%). The anti-SARS-CoV-2 weighted prevalence was 1.26% (95% CI 0.43, 3.26) overall and 0.53% (95% CI 0.06, 2.78) and 2.70% (95% CI 0.57, 9.19) in hospital-1 and hospital-2, respectively although the study was underpowered to detect statistically significant differences. The overall, hospital-1, and hospital-2 seroprevalence was 10, 4 and 22 times higher than the estimated infection attack rate in general population, respectively. Suboptimal use of personal protective equipment was noted in both hospitals. CONCLUSIONS: These data have implications for the preparedness of a second wave of COVID-19 epidemic, given the low burden of SARS-CoV-2 infection rate, in concordance with national projections.