Efficacy of Tocilizumab in Severely Ill COVID-19 Patients With Rapid Respiratory Deterioration: A Single Center Experience During the Third Pandemic Wave in Greece.

BACKGROUND/AIM: Immunomodulatory therapy with Tocilizumab (TCZ), a monoclonal antibody against interleukin-6 receptor-alpha, has been endorsed by the World Health Organization and other major regulatory bodies, as part of the standard-of-care therapy for severe or critical COVID-19 cases despite discordant trial outcomes. The aim of the present study was to report the experience of our center regarding TCZ routine use in severely ill COVID-19 patients who were hospitalized during the third pandemic wave in Greece. PATIENTS AND METHODS: From March 2021 to December 2021, we retrospectively analyzed COVID-19 patients with radiological findings of pneumonia and signs of rapid respiratory deterioration that were treated with TCZ. The primary outcome included the risk of intubation or/and death in TCZ-treated patients compared to matched controls. RESULTS: TCZ administration was neither predictive of intubation and/or death [OR=17.5 (95% CI=0.47-652.2; p=0.12)] or associated with fewer events (p=0.92) in multivariate analysis. CONCLUSION: Our single-center real-life experience is in line with recently published research, revealing no benefit from TCZ routine use in severely or critically ill patients with COVID-19.

Prolonged SARS-CoV-2 Infection With Common Features in Two Patients Receiving Anti-CD20 Therapy.

BACKGROUND/AIM: Anti-CD20-depleting monoclonal antibodies predispose patients to the development of severe disease of SARS-CoV-2 infection. These antibodies are given as backbone or maintenance therapy in patients with hematological malignancies and rheumatology diseases, inducing effective B-cell depletion along with antibody-dependent cell-mediated cytotoxicity (ADCC) and disrupting infection-protective antibody responses. CASE REPORT: We describe two cases of prolonged SARS-CoV-2 infection with common features, in two patients receiving anti-CD20 therapies, the first for chronic lymphocytic leukemia (CLL) and the second for rheumatoid arthritis (RA). For CLL patient, despite administration of antiviral therapy, signs and symptoms of SARS-CoV-2 infection persisted for 43 days, with resolution and lymphocyte recovery from day 33. For RA patient, despite administration of two courses of antiviral therapy, signs and symptoms of SARS-CoV-2 infection persisted for 47 days, without resolution and lymphocyte recovery, leading to a fatal outcome due to acute respiratory distress syndrome (ARDS) and unspecified sepsis. CONCLUSION: These two cases highlight the risk for persistent SARS-CoV-2 infection in patients treated with anti-CD20 monoclonal antibodies and support a role for cellular immunity recovery for disease control.

Dating the Origin and Estimating the Transmission Rates of the Major HIV-1 Clusters in Greece: Evidence about the Earliest Subtype A1 Epidemic in Europe.

Our aim was to estimate the date of the origin and the transmission rates of the major local clusters of subtypes A1 and B in Greece. Phylodynamic analyses were conducted in 14 subtype A1 and 31 subtype B clusters. The earliest dates of origin for subtypes A1 and B were in 1982.6 and in 1985.5, respectively. The transmission rate for the subtype A1 clusters ranged between 7.54 and 39.61 infections/100 person years (IQR: 9.39, 15.88), and for subtype B clusters between 4.42 and 36.44 infections/100 person years (IQR: 7.38, 15.04). Statistical analysis revealed that the average difference in the transmission rate between the PWID and the MSM clusters was 6.73 (95% CI: 0.86 to 12.60; p = 0.026). Our study provides evidence that the date of introduction of subtype A1 in Greece was the earliest in Europe. Transmission rates were significantly higher for PWID than MSM clusters due to the conditions that gave rise to an extensive PWID HIV-1 outbreak ten years ago in Athens, Greece. Transmission rate can be considered as a valuable measure for public health since it provides a proxy of the rate of epidemic growth within a cluster and, therefore, it can be useful for targeted HIV prevention programs.

Appraisal of a Contact Tracing Training Program for COVID-19 in Greece Focusing on Vulnerable Populations.

BACKGROUND: Contact tracing as an epidemiological strategy has repeatedly contributed to the containment of various past epidemics and succeeded in controlling the spread of disease in the community. Systematic training of contact tracers is crucial in ensuring the effectiveness of epidemic containment. METHODS: An intensive training course was offered to 216 health and other professionals who work with vulnerable population groups, such as Roma, refugees, and migrants in Greece, by the scientific team of the postgraduate programme "Global Health-Disaster Medicine" of the Medical School, National and Kapodistrian University of Athens, with the support of the Swiss embassy in Greece. The course was delivered online due to the pandemic restriction measures and was comprised of 16 h over 2 days. The course curriculum was adapted in Greek using, upon agreement, a similar training course to what was developed by the Johns Hopkins University Bloomberg School of Public Health. Evaluation of the course was conducted in order to determine the short term satisfaction from participating in this training course. RESULTS: A total of 70% of the course participants completed the evaluation questionnaires and all trainers gave feedback on the course. The training modules were ranked as extremely useful by the majority of the participants and over 50% of the participants specifically stated that the course content was directly related to their work with vulnerable groups. Content about the ethics of contact tracing and the effective communication skills presented were deemed most useful. CONCLUSION: The course was well organised and provided the required skills for effective contact tracing. Many course participants intend to use some components in their work with vulnerable populations groups. Contact tracing efforts work best in a systematic and coordinated way and the provision of systematic and organised training can greatly increase its effectiveness.

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.

Beneficial Effects of Intermediate Dosage of Anticoagulation Treatment on the Prognosis of Hospitalized COVID-19 Patients: The ETHRA Study.

BACKGROUND/AIM: To investigate the efficacy (prognosis, coagulation/inflammation biomarkers) and safety (bleeding events) of different anticoagulation dosages in COVID-19 inpatients. PATIENTS AND METHODS: COVID-19 inpatients (Athens, Greece) were included. The "Enhanced dose THRomboprophylaxis in Admissions (ETHRA)" protocol was applied in certain Departments, suggesting the use of intermediate anticoagulation dosage. The primary endpoint was a composite of intubation/venous thromboembolism/death. Inflammation/coagulation parameters were assessed. RESULTS: Among 127 admissions, 95 fulfilled the inclusion criteria. Twenty-one events (4 deaths, 17 intubations) were observed. Regression analysis demonstrated significant reduction of events with intermediate or therapeutic dosage [HR=0.16 (95%CI=0.05-0.52) p=0.002; HR=0.17 (0.04-0.71) p=0.015, respectively]. D-Dimer values were higher in those who met the composite endpoint. Intermediate dosage treatment was associated with decreased values of ferritin. Three patients (3%) had minor hemorrhagic complications. CONCLUSION: Anticoagulation treatment (particularly intermediate dosage) appears to have positive impact on COVID-19 inpatients' prognosis by inhibiting both coagulation and inflammatory cascades.

A Nationwide Study about the Dispersal Patterns of the Predominant HIV-1 Subtypes A1 and B in Greece: Inference of the Molecular Transmission Clusters.

Our aim was to investigate the dispersal patterns and parameters associated with local molecular transmission clusters (MTCs) of subtypes A1 and B in Greece (predominant HIV-1 subtypes). The analysis focused on 1751 (28.4%) and 2575 (41.8%) sequences of subtype A1 and B, respectively. Identification of MTCs was based on phylogenetic analysis. The analyses identified 38 MTCs including 2-1518 subtype A1 sequences and 168 MTCs in the range of 2-218 subtype B sequences. The proportion of sequences within MTCs was 93.8% (1642/1751) and 77.0% (1982/2575) for subtype A1 and B, respectively. Transmissions within MTCs for subtype A1 were associated with risk group (Men having Sex with Men vs. heterosexuals, OR = 5.34, p < 0.001) and Greek origin (Greek vs. non-Greek origin, OR = 6.05, p < 0.001) and for subtype B, they were associated with Greek origin (Greek vs. non-Greek origin, OR = 1.57, p = 0.019), younger age (OR = 0.96, p < 0.001), and more recent sampling (time period: 2011-2015 vs. 1999-2005, OR = 3.83, p < 0.001). Our findings about the patterns of across and within country dispersal as well as the parameters associated with transmission within MTCs provide a framework for the application of the study of molecular clusters for HIV prevention.

In the midst of the perfect storm: Swift public health actions needed in order to increase societal safety during the COVID-19 pandemic.

The phenomenal speed of COVID-19 has subjected the public health professionals worldwide to struggle to subdue the spread of the disease and its impact of the affected societies. The limited biomedical and epidemiological understanding of COVID-19 along with the lack of vaccines and therapeutics have led to the reception of draconian measures from the societal safety domain, limiting human interaction through social distancing. Grounded on the adopted approaches, interventions in sero-prevalence studies, mobilisation of the primary health care (PHC) sector, as well as target socially vulnerable groups should be taken into consideration by heath authorities.

Reflecting upon the humanitarian use of unmanned aerial vehicles (drones).

Nine years after the earthquake in Haiti and the appearance of the concept of “humanitarian drones”, it remains a poorly discussed yet highly controversial issue. Emergency mapping and light cargo deliveries to inaccessible areas are only some of the most popular ways in which drones are currently used for post-disaster relief and health crisis management by first responders around the world. On the other hand, every single successful use for drones is always followed by controversy about the problems caused by that very same, initially successful, use. However, examples of good practices will contribute to the investigation, study and analysis of the ways in which new, cutting-edge technologies such as drones can be implemented and adapted to meet the needs and requirements of humanitarian organisations and local communities affected by disasters. The issue is how and under what circumstances drone use can potentially fulfil humanitarian functions, particularly in the aftermath of a disaster, and how this type of technology could be deployed in non-violent, ethically desirable ways as part of the humanitarian response. In conclusion, it is questionable whether the benefits of using drones outnumber the moral obstacles they raise, and whether they will eventually be considered an inseparable part of humanitarian aid as well as a cutting-edge technological toy.

Identifying, linking, and treating people who inject drugs and were recently infected with HIV in the context of a network-based intervention.

Identifying and linking people to care soon after HIV infection could limit viral transmission and protect their health. This work aims at describing the continuum of care among recently HIV-infected people who inject drugs (PWID) and participated in an intervention in the context of an HIV outbreak in Athens, Greece. The Transmission Reduction Intervention Project (TRIP) conducted risk network-based contact tracing and screened people for recent HIV infection. A comprehensive approach with a case management component that aimed to remove barriers to accessing care was adopted. Follow-up data on antiretroviral treatment (ART) and HIV-RNA levels were obtained from HIV clinics. TRIP enrolled 45 recently HIV-infected PWID (80% male) with a median viral load at recruitment of 5.43 log10 copies/mL. Of the recently infected persons in TRIP, 87% were linked to care; of these, 77% started ART; and of those on ART, 89% achieved viral load <200 copies/mL. TRIP and its public health allies managed to get most of the recently HIV-infected PWID who were identified by the program into care and many of them onto ART. This resulted in very low HIV-RNA levels. Treatment as prevention can work if individuals are aided in overcoming difficulties in entry to, or attrition from care.

Time to Rethink Refugee and Migrant Health in Europe: Moving from Emergency Response to Integrated and Individualized Health Care Provision for Migrants and Refugees.

In the last three years, the European Union (EU) is being confronted with the most significant influx of migrants and refugees since World War II. Although the dimensions of this influx-taking the global scale into account-might be regarded as modest, the institutional response to that phenomenon so far has been suboptimal, including the health sector. While inherent challenges of refugee and migrant (R&M) health are well established, it seems that the EU health response oversees, to a large extend, these aspects. A whole range of emergency-driven health measures have been implemented throughout Europe, yet they are failing to address adequately the changing health needs and specific vulnerabilities of the target population. With the gradual containment of the migratory and refugee waves, three years after the outbreak of the so-called 'refugee crisis', we are, more than ever, in need of a sustainable and comprehensive health approach that is aimed at the integration of all of migrants and refugees-that is, both the new and old population groups that are already residing in Europe-in the respective national health systems.

Early HIV diagnosis through use of rapid diagnosis test (RDT) in the community and direct link to HIV care: a pilot project for vulnerable populations in Athens, Greece.

INTRODUCTION: An increase in the incidence of HIV new infections among intravenous drug users (IDUs) by 1500%, was noted in the center of Athens in 2011. Increasing problematic drug use, homelessness, health cuts amidst the economic crisis, have contributed to the epidemic. New cases doubled within a year, challenging the HIV care delivery system (1). MATERIALS AND METHODS: A pilot project funded by the National Strategic Reference Framework (NSRF) 2007-2013 of the European Union (EU), was launched from August 2012 to March 2014. It was a partnership between the HIV Clinic of Evangelismos Hospital and the NGO PRAKSIS. The project is aimed at offering early diagnosis and comprehensive care to hard to reach populations. RDT diagnosis through mobile units, direct linkage to care, elimination of waiting times, flexibility, psychosocial support and link to harm reduction services for active IDUs were offered to the beneficiaries. RESULTS: A total of 117 people enrolled in the program following HIV RDT offered by mobile units of the NGO PRAKSIS in community sites. Sixty-eight percent were IDUs, 12% were men who have sex with men (MSM) and 19.5% were heterosexuals. Men were 74.3% and women were 25.6%. Country born patients were 43.5% and non-country born patients were 56.4%. Nine people were HIV negative but needed post-exposure prophylaxis (PEP), treatment for Hepatitis C and one test was false positive. Two deaths occurred and six people were deported. Of the remaining 100 patients, 84 enrolled in the care program. Of those 77% (65/84) remain in care for three months after the end of the project. Care retention was 73.5% (39/53) for IDUs, 91% (10/11) for MSM, 80% (16/20) for heterosexuals, 73% (25/35) for country born and 82% (40/49) for non-country born individuals. Among those that remain in care, 77.7% (42/54) with <350 CD4 are on antiretroviral therapy (ART). Among those on ART >90% have undetectable viral load. Mean value of CD4 cells at enrollment was 298 cells/mm(3). At follow up, three months after the end of the program, the mean value of CD4 cells was 464 cells/mm(3). CONCLUSIONS: The project has proven the feasibility of a novel approach of active case finding in the community with direct link to care. Retention to care was satisfactory as most of those patients would not have been able to access care through the normal ART delivery mode of the Public Health System. However, more obstacles to care remain. Being homeless, poor nutrition, complicated access to harm reduction services, lack of One Stop Shop services and police operations in the city center impede further progress [2,3].