Publications by authors named "Sotirios Tsiodras"

209 Publications

The benefits, costs and feasibility of a low incidence COVID-19 strategy.

Lancet Reg Health Eur 2022 Feb 2;13:100294. Epub 2022 Jan 2.

University of Luxembourg, Esch-sur-Alzette, Luxembourg.

In the summer of 2021, European governments removed most NPIs after experiencing prolonged second and third waves of the COVID-19 pandemic. Most countries failed to achieve immunization rates high enough to avoid resurgence of the virus. Public health strategies for autumn and winter 2021 have ranged from countries aiming at low incidence by re-introducing NPIs to accepting high incidence levels. However, such high incidence strategies almost certainly lead to the very consequences that they seek to avoid: restrictions that harm people and economies. At high incidence, the important pandemic containment measure 'test-trace-isolate-support' becomes inefficient. At that point, the spread of SARS-CoV-2 and its numerous harmful consequences can likely only be controlled through restrictions. We argue that all European countries need to pursue a low incidence strategy in a coordinated manner. Such an endeavour can only be successful if it is built on open communication and trust.
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http://dx.doi.org/10.1016/j.lanepe.2021.100294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720492PMC
February 2022

Real-Life Effectiveness and Safety of Baricitinib as Adjunctive to Standard-of-Care Treatment in Hospitalized Patients With Severe Coronavirus Disease 2019.

Open Forum Infect Dis 2022 Jan 22;9(1):ofab588. Epub 2021 Nov 22.

4th Department of Internal Medicine, National and Kapodistrian University of Athens School of Medicine, Attikon University General Hospital, Chaidari, Greece.

Background: Therapeutic options for hospitalized patients with severe coronavirus disease 2019 (sCOVID-19) are limited. Preliminary data have shown promising results with baricitinib, but real-life experience is lacking. We assessed the safety and effectiveness of add-on baricitinib to standard-of-care (SOC) including dexamethasone in hospitalized patients with sCOVID-19.

Methods: This study is a 2-center, observational, retrospective cohort study of patients with sCOVID-19, comparing outcomes and serious events between patients treated with SOC versus those treated with SOC and baricitinib combination.

Results: We included 369 patients with sCOVID-19 (males 66.1%; mean age 65.2 years; median symptom duration 6 days). The SOC was administered in 47.7% and combination in 52.3%. Patients treated with the combination reached the composite outcome (intensive care unit [ICU] admission or death) less frequently compared with SOC (22.3% vs 36.9%,  = .002). Mortality rate was lower with the combination in the total cohort (14.7% vs 26.6%,  = .005), and ICU admission was lower in patients with severe acute respiratory distress syndrome (29.7% vs 44.8%,  = .03). By multivariable analysis, age (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.36-2.44, per 10-year increase), partial pressure of oxygen/fraction of inspired oxygen ratio (OR = 0.60, 95% CI = .52-0.68, per 10 units increase), and use of high-flow nasal cannula (OR = 0.34; 95% CI, .16-0.74) were associated with the composite outcome, whereas baricitinib use was marginally not associated with the composite outcome (OR = 0.52; 95% CI, .26-1.03). However, baricitinib use was found to be significant after inverse-probability weighted regression (OR = 0.93; 95% CI, .87-0.99). No difference in serious events was noted between treatment groups.

Conclusions: In real-life settings, addition of baricitinib to SOC in patients hospitalized with sCOVID-19 is associated with decreased mortality without concerning safety signals.
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http://dx.doi.org/10.1093/ofid/ofab588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8711791PMC
January 2022

Total patient load, regional disparities and in-hospital mortality of intubated COVID-19 patients in Greece, from September 2020 to May 2021.

Scand J Public Health 2021 Dec 13:14034948211059968. Epub 2021 Dec 13.

National Public Health Organization, Athens, Greece.

Aims: While healthcare services have been expanding capacity during the COVID-19 pandemic, quality of care under increasing patient loads has received less attention. We examined in-hospital mortality of intubated COVID-19 patients in Greece, in relation to total intubated patient load, intensive care unit (ICU) availability and hospital region.

Methods: Anonymized surveillance data were analyzed from all intubated COVID-19 patients in Greece between 1 September 2020 and 6 May 2021. Poisson regression was used to estimate the hazard of dying as a function of fixed and time-varying covariates.

Results: Mortality was significantly increased above 400 patients, with an adjusted hazard ratio of 1.25 (95% confidence interval (CI): 1.03-1.51), rising progressively up to 1.57 (95% CI: 1.22-2.02) for 800+ patients. Hospitalization outside an ICU or away from the capital region of Attica were also independently associated with significantly increased mortality.

Conclusions:
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http://dx.doi.org/10.1177/14034948211059968DOI Listing
December 2021

ESCMID COVID-19 living guidelines: drug treatment and clinical management.

Clin Microbiol Infect 2021 Nov 22. Epub 2021 Nov 22.

Clinical Unit of Infectious Diseases and Microbiology Virgen Macarena University Hospital and Department of Medicine, University of Seville, Institute of Biomedicine of Seville, Seville, Spain.

Scope: In January 2021, the ESCMID Executive Committee decided to launch a new initiative to develop ESCMID guidelines on several COVID-19-related issues, including treatment of COVID-19.

Methods: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panellist involved in case of inconsistent results. Voting was based on the GRADE approach.

Questions Addressed By The Guideline And Recommendations: A synthesis of the available evidence and recommendations is provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab and interferon β-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine and interferon β-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild-moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids were recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19.

Scope: The aim of the present guidance is to provide evidence-based recommendations for management of adults with coronavirus disease 2019 (COVID-19). More specifically, the goal is to aid clinicians managing patients with COVID-19 at various levels of severity including outpatients, hospitalized patients, and those admitted to intensive care unit. Considering the composition of the panel, mostly clinical microbiologists or infectious disease specialists with no pulmonology or intensive care background, we focus only on pharmacological treatment and do not give recommendations on oxygen supplement/support. Similarly, as no paediatricians were included in the panel; the recommendations are only for adult patients with COVID-19. Considering the current literature, no guidance was given for special populations such as the immunocompromised.
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http://dx.doi.org/10.1016/j.cmi.2021.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606314PMC
November 2021

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

Infect Dis (Lond) 2022 03 7;54(3):186-195. Epub 2021 Nov 7.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, 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.
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http://dx.doi.org/10.1080/23744235.2021.1995627DOI Listing
March 2022

Angiotensin-converting-enzyme insertion/deletion polymorphism, ACE activity, and COVID-19: A rather controversial hypothesis. A case-control study.

J Med Virol 2021 Oct 28. Epub 2021 Oct 28.

Department of Clinical Biochemistry, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Accumulating data has shown a contribution of the renin-angiotensin system in COVID-19 pathogenesis. The role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism as a risk factor in developing COVID-19 disease comes from epidemiological data and is controversially discussed. We conducted a retrospective case-control study and assessed the impact of ACE I/D genotype in COVID-19 disease prevalence and severity. In 81 COVID-19 patients explicitly characterized and 316 controls, recruited during the first wave of COVID-19 pandemic, ACE I/D genotype, and ACE activity were determined. A generalized linear model was used and Poisson regression analysis estimated the risk ratios (RRs) of alleles and genotypes for disease severity. DD patients had almost 2.0-fold increased risk (RR: 1.886, confidence limit [CL] 95%: 1.266-2.810, p = 0.0018) of developing a more severe disease when contrasted to ID and II individuals, as did D allele carriers compared to I carriers (RR: 1.372; CL 95%: 1.051-1.791; p = 0.0201). ACE activity (expressed as arbitrary units, AU/L) was lower in patients (3.62 ± 0.26) than in controls (4.65 ± 0.13) (p < 0.0001), and this reduction was observed mainly among DD patients compared to DD controls (3.97 ± 0.29 vs. 5.38 ± 0.21; p = 0.0014). Our results demonstrate that ACE DD genotype may predispose to COVID-19 increased disease severity via a mechanism associated, at least in part, with the significant fall in their ACE activity. Our findings suggest a more complex pattern of synergy between this polymorphism and ACE activity in COVID-19 patients compared to healthy individuals and set the grounds for large-scale studies assessing ACE genotype-based optimized therapies with ACE inhibitors and angiotensin receptor blockers.
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http://dx.doi.org/10.1002/jmv.27417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661574PMC
October 2021

SARS-CoV-2 wastewater surveillance data can predict hospitalizations and ICU admissions.

Sci Total Environ 2022 Jan 7;804:150151. Epub 2021 Sep 7.

Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, University Campus, Zografou, 15771, Athens, Greece. Electronic address:

We measured SARS-CoV-2 RNA load in raw wastewater in Attica, Greece, by RT-qPCR for the environmental surveillance of COVID-19 for 6 months. The lag between RNA load and pandemic indicators (COVID-19 hospital and intensive care unit (ICU) admissions) was calculated using a grid search. Our results showed that RNA load in raw wastewater is a leading indicator of positive COVID-19 cases, new hospitalization and admission into ICUs by 5, 8 and 9 days, respectively. Modelling techniques based on distributed/fixed lag modelling, linear regression and artificial neural networks were utilized to build relationships between SARS-CoV-2 RNA load in wastewater and pandemic health indicators. SARS-CoV-2 mutation analysis in wastewater during the third pandemic wave revealed that the alpha-variant was dominant. Our results demonstrate that clinical and environmental surveillance data can be combined to create robust models to study the on-going COVID-19 infection dynamics and provide an early warning for increased hospital admissions.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421077PMC
January 2022

Upregulation of Human Endogenous Retroviruses in Bronchoalveolar Lavage Fluid of COVID-19 Patients.

Microbiol Spectr 2021 10 6;9(2):e0126021. Epub 2021 Oct 6.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Severe COVID-19 pneumonia has been associated with the development of intense inflammatory responses during the course of infections with SARS-CoV-2. Given that human endogenous retroviruses (HERVs) are known to be activated during and participate in inflammatory processes, we examined whether HERV dysregulation signatures are present in COVID-19 patients. By comparing transcriptomes of bronchoalveolar lavage fluid (BALF) of COVID-19 patients and healthy controls, and peripheral blood monocytes (PBMCs) from patients and controls, we have shown that HERVs are intensely dysregulated in BALF of COVID-19 patients compared to those in BALF of healthy control patients but not in PBMCs. In particular, upregulation in the expression of specific HERV families was detected in BALF samples of COVID-19 patients, with HERV-FRD being the most highly upregulated family among the families analyzed. In addition, we compared the expression of HERVs in human bronchial epithelial cells (HBECs) without and after senescence induction in an oncogene-induced senescence model in order to quantitatively measure changes in the expression of HERVs in bronchial cells during the process of cellular senescence. This apparent difference of HERV dysregulation between PBMCs and BALF warrants further studies in the involvement of HERVs in inflammatory pathogenetic mechanisms as well as exploration of HERVs as potential biomarkers for disease progression. Furthermore, the increase in the expression of HERVs in senescent HBECs in comparison to that in noninduced HBECs provides a potential link for increased COVID-19 severity and mortality in aged populations. SARS-CoV-2 emerged in late 2019 in China, causing a global pandemic. Severe COVID-19 is characterized by intensive inflammatory responses, and older age is an important risk factor for unfavorable outcomes. HERVs are remnants of ancient infections whose expression is upregulated in multiple conditions, including cancer and inflammation, and their expression is increased with increasing age. The significance of this work is that we were able to recognize dysregulated expression of endogenous retroviral elements in BALF samples but not in PBMCs of COVID-19 patients. At the same time, we were able to identify upregulated expression of multiple HERV families in senescence-induced HBECs in comparison to that in noninduced HBECs, a fact that could possibly explain the differences in disease severity among age groups. These results indicate that HERV expression might play a pathophysiological role in local inflammatory pathways in lungs afflicted by SARS-CoV-2 and their expression could be a potential therapeutic target.
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http://dx.doi.org/10.1128/Spectrum.01260-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510252PMC
October 2021

Cerebral Venous Sinus Thrombosis and Thrombotic Events After Vector-Based COVID-19 Vaccines: A Systematic Review and Meta-analysis.

Neurology 2021 11 5;97(21):e2136-e2147. Epub 2021 Oct 5.

From the Second Department of Neurology (L.P., M.-I.S., A.H.K., S.G., K.I.V., G.T.), Second Department of Psychiatry (I.M.), and Fourth Department of Internal Medicine (S.T.), "Attikon" University Hospital, Department of Hygiene, Epidemiology and Medical Statistics (P.L., A.N.), School of Medicine, and Third Department of Critical Care Medicine, Evgenideio Hospital, Medical School (T.I.V.), and Third Department of Pediatrics (V.P.), National and Kapodistrian University of Athens, Greece; Division of Neurology (A.H.K.), McMaster University/Population Health Research Institute, Hamilton, Canada; Department of Neurosciences and Mental Health (D.A.d.S.), Hospital de Santa Maria, CHULN, University of Lisbon, Portugal; Department of Neurology (J.M.C.), Amsterdam UMC, University of Amsterdam, the Netherlands; Department of Epidemiology (P.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Neurology (K.V.), University Hospital of Alexandroupolis, Democritus University of Thrace; Hellenic Centre for Disease Control and Prevention (S.T.), Athens, Greece; and Department of Neurology (G.T.), University of Tennessee Health Science Center, Memphis.

Background And Objectives: There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes.

Methods: We performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal.

Results: Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval [CI] 36%-66%; = 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0-97.3; = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%-36%) and 38% (95% CI 27%-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8-12) and affected predominantly women (69%; 95% CI 60%-77%) under age 45, even in the absence of prothrombotic risk factors.

Discussion: Approximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination.

Registration Information: The prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).
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http://dx.doi.org/10.1212/WNL.0000000000012896DOI Listing
November 2021

Diagnostic Value of IL-1β, IL-17A, and IL-17F Serum Levels in Patients with Upper Extremity Infections.

J Long Term Eff Med Implants 2021 ;31(4):39-44

Third Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.

We prospectively studied 51 patients (38 men and 13 women; mean age, 52 years) with upper extremity infections. Body mass index (BMI), smoking habits, and comorbidities such as diabetes mellitus, hypertension, hyperlipidemia, thyroid disease, and the site and type of infection were recorded. The 0-10 point Visual Analogue Scale (VAS) was used to evaluate the pain of the affected limb, and the Quick DASH Score was used to assess the severity of upper limb injury. ESR, CRP, and WBC, as well as serum levels of IL-1β, IL-17A, and IL-17F were measured. The serum levels of IL-1β and IL-17F were not elevated in the majority of the patients. In contrast, 14 patients (27.4%) had elevated levels of IL-17A. However, serum levels of IL-17A were not correlated with sex, age, BMI, comorbidities, fever, VAS score, WBC, CRP, ESR, and IL-17F. A trend to significance was observed between IL-17A and DASH score, and a strong association was observed between IL-17A and IL-1β. No correlation was detected between serum levels of IL-17A and type of isolated bacteria, Gram stain, site and type of infection. After controlling the impact of sex, age, and BMI, a trend to significance was observed between IL-17A and VAS score, and a marginal significance was observed between IL-17A and DASH score.
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http://dx.doi.org/10.1615/JLongTermEffMedImplants.2021038760DOI Listing
November 2021

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

Vaccines (Basel) 2021 Sep 13;9(9). Epub 2021 Sep 13.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.

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.
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http://dx.doi.org/10.3390/vaccines9091017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471735PMC
September 2021

Kinetics of Nucleocapsid, Spike and Neutralizing Antibodies, and Viral Load in Patients with Severe COVID-19 Treated with Convalescent Plasma.

Viruses 2021 09 15;13(9). Epub 2021 Sep 15.

Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.

COVID-19 is an ongoing pandemic with high morbidity and mortality. Despite meticulous research, only dexamethasone has shown consistent mortality reduction. Convalescent plasma (CP) infusion might also develop into a safe and effective treatment modality on the basis of recent studies and meta-analyses; however, little is known regarding the kinetics of antibodies in CP recipients. To evaluate the kinetics, we followed 31 CP recipients longitudinally enrolled at a median of 3 days post symptom onset for changes in binding and neutralizing antibody titers and viral loads. Antibodies against the complete trimeric Spike protein and the receptor-binding domain (Spike-RBD), as well as against the complete Nucleocapsid protein and the RNA binding domain (N-RBD) were determined at baseline and weekly following CP infusion. Neutralizing antibody (pseudotype NAb) titers were determined at the same time points. Viral loads were determined semi-quantitatively by SARS-CoV-2 PCR. Patients with low humoral responses at entry showed a robust increase of antibodies to all SARS-CoV-2 proteins and Nab, reaching peak levels within 2 weeks. The rapid increase in binding and neutralizing antibodies was paralleled by a concomitant clearance of the virus within the same timeframe. Patients with high humoral responses at entry demonstrated low or no further increases; however, virus clearance followed the same trajectory as in patients with low antibody response at baseline. Together, the sequential immunological and virological analysis of this well-defined cohort of patients early in infection shows the presence of high levels of binding and neutralizing antibodies and potent clearance of the virus.
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http://dx.doi.org/10.3390/v13091844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473255PMC
September 2021

Efficient and targeted COVID-19 border testing via reinforcement learning.

Nature 2021 11 22;599(7883):108-113. Epub 2021 Sep 22.

Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Throughout the coronavirus disease 2019 (COVID-19) pandemic, countries have relied on a variety of ad hoc border control protocols to allow for non-essential travel while safeguarding public health, from quarantining all travellers to restricting entry from select nations on the basis of population-level epidemiological metrics such as cases, deaths or testing positivity rates. Here we report the design and performance of a reinforcement learning system, nicknamed Eva. In the summer of 2020, Eva was deployed across all Greek borders to limit the influx of asymptomatic travellers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and to inform border policies through real-time estimates of COVID-19 prevalence. In contrast to country-wide protocols, Eva allocated Greece's limited testing resources on the basis of incoming travellers' demographic information and testing results from previous travellers. By comparing Eva's performance against modelled counterfactual scenarios, we show that Eva identified 1.85 times as many asymptomatic, infected travellers as random surveillance testing, with up to 2-4 times as many during peak travel, and 1.25-1.45 times as many asymptomatic, infected travellers as testing policies that utilize only epidemiological metrics. We demonstrate that this latter benefit arises, at least partially, because population-level epidemiological metrics had limited predictive value for the actual prevalence of SARS-CoV-2 among asymptomatic travellers and exhibited strong country-specific idiosyncrasies in the summer of 2020. Our results raise serious concerns on the effectiveness of country-agnostic internationally proposed border control policies that are based on population-level epidemiological metrics. Instead, our work represents a successful example of the potential of reinforcement learning and real-time data for safeguarding public health.
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http://dx.doi.org/10.1038/s41586-021-04014-zDOI Listing
November 2021

A look into the future of the COVID-19 pandemic in Europe: an expert consultation.

Lancet Reg Health Eur 2021 Sep 30;8:100185. Epub 2021 Jul 30.

Dublin City University, Dublin, Ireland.

How will the coronavirus disease 2019 (COVID-19) pandemic develop in the coming months and years? Based on an expert survey, we examine key aspects that are likely to influence the COVID-19 pandemic in Europe. The challenges and developments will strongly depend on the progress of national and global vaccination programs, the emergence and spread of variants of concern (VOCs), and public responses to non-pharmaceutical interventions (NPIs). In the short term, many people remain unvaccinated, VOCs continue to emerge and spread, and mobility and population mixing are expected to increase. Therefore, lifting restrictions too much and too early risk another damaging wave. This challenge remains despite the reduced opportunities for transmission given vaccination progress and reduced indoor mixing in summer 2021. In autumn 2021, increased indoor activity might accelerate the spread again, whilst a necessary reintroduction of NPIs might be too slow. The incidence may strongly rise again, possibly filling intensive care units, if vaccination levels are not high enough. A moderate, adaptive level of NPIs will thus remain necessary. These epidemiological aspects combined with economic, social, and health-related consequences provide a more holistic perspective on the future of the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.lanepe.2021.100185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321710PMC
September 2021

Transmission of Infections during Cardiopulmonary Resuscitation.

Clin Microbiol Rev 2021 12 28;34(4):e0001821. Epub 2021 Jul 28.

Fourth Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece.

Cardiopulmonary resuscitation (CPR) is an emergency lifesaving endeavor, performed in either the hospital or outpatient settings, that significantly improves outcomes and survival rates when performed in a timely fashion. As with any other medical procedure, CPR can bear potential risks not only for the patient but also for the rescuer. Among those risks, transmission of an infectious agent has been one of the most compelling triggers of reluctance to perform CPR among providers. The concern for transmission of an infection from the resuscitated subject may impede prompt initiation and implementation of CPR, compromising survival rates and neurological outcomes of the patients. Infections during CPR can be potentially acquired through airborne, droplet, contact, or hematogenous transmission. However, only a few cases of infection transmission have been actually reported globally. In this review, we present the available epidemiological findings on transmission of different pathogens during CPR and data on reluctance of health care workers to perform CPR. We also outline the levels of personal protective equipment and other protective measures according to potential infectious hazards that providers are potentially exposed to during CPR and summarize current guidelines on protection of CPR providers from international societies and stakeholders.
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http://dx.doi.org/10.1128/CMR.00018-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404692PMC
December 2021

Wastewater monitoring as a supplementary surveillance tool for capturing SARS-COV-2 community spread. A case study in two Greek municipalities.

Environ Res 2021 09 24;200:111749. Epub 2021 Jul 24.

Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 22 Papakyriazi str, Larissa, Greece. Electronic address:

A pilot study was conducted from late October 2020 until mid-April 2021, aiming to examine the association between SARS-CoV-2 RNA concentrations in untreated wastewater and recorded COVID-19 cases in two Greek municipalities. A population of Random Forest and Linear Regression Machine Learning models was trained and evaluated incorporating the concentrations of SARS-CoV-2 RNA in 111 wastewater samples collected from the inlets of two Wastewater Treatment Plants, along with physicochemical parameters of the wastewater influent. The model's predictions were adequately associated with the 7-day cumulative cases with the correlation coefficients (after 5-fold cross validation) ranging from 0.754 to 0.960 while the mean relative errors ranged from 30.42% to 59.46%. Our results provide indications that wastewater-based predictions can be applied in diverse settings and in prolonged time periods, although the accuracy of these predictions may be mitigated. Wastewater-based epidemiology can support and strengthen epidemiological surveillance.
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http://dx.doi.org/10.1016/j.envres.2021.111749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302483PMC
September 2021

Combining Minimally Invasive Techniques in Managing a Frail Patient with Postpneumonectomy Bronchopleural Fistula.

Case Rep Pulmonol 2021 7;2021:5513136. Epub 2021 Apr 7.

Thoracic Surgery Department, Attikon University Hospital of Athens, Greece.

A postpneumonectomy bronchopleural fistula is a life-threatening complication requiring aggressive treatment and early repair. Reoperations are common due to initial treatment failure. Advanced bronchoscopic techniques are rapidly evolving, but permanent results are questionable. We report the minimally invasive management of a frail 79-year-old patient with postpneumonectomy fistula in respiratory failure due to repeated infections. Previous bronchoscopic closure attempts with fibrin failed. The multistep interdisciplinary management included airway surveillance by virtual bronchoscopy, percutaneous fibrin glue instillation under computed tomography, and awake thoracoscopic surgery to achieve temporary closure. This provided an acceptable long period of symptomatic and physical improvement. The bronchial stump failed again four months later, and the patient succumbed to pneumonia. Pneumonectomy has to be avoided unless strongly indicated. Complications are best managed with surgery for definite treatment. We emphasize our approach only when a patient declines surgery or is medically unfit as a temporary time-buying strategy in view of definite surgery in a high-volume center.
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http://dx.doi.org/10.1155/2021/5513136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221083PMC
April 2021

SARS-CoV-2 Antigenemia as a Confounding Factor in Immunodiagnostic Assays: A Case Study.

Viruses 2021 06 14;13(6). Epub 2021 Jun 14.

Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, GR-11527 Athens, Greece.

Humoral immunity has emerged as a vital immune component against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, a subset of recovered Coronavirus Disease-2019 (COVID-19) paucisymptomatic/asymptomatic individuals do not generate an antibody response, constituting a paradox. We assumed that immunodiagnostic assays may operate under a competitive format within the context of antigenemia, potentially explaining this phenomenon. We present a case where persistent antigenemia/viremia was documented for at least 73 days post-symptom onset using 'in-house' methodology, and as it progressively declined, seroconversion took place late, around day 55, supporting our hypothesis. Thus, prolonged SARS-CoV-2 antigenemia/viremia could mask humoral responses, rendering, in certain cases, the phenomenon of 'non-responders' a misnomer.
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http://dx.doi.org/10.3390/v13061143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232125PMC
June 2021

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.

mSphere 2021 Jun 30:e0018021. Epub 2021 Jun 30.

Center of New Biotechnologies & Precision Medicine, Medical School, National and Kapodistrian University of Athensgrid.5216.0, Athens, Greece.

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. 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.
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http://dx.doi.org/10.1128/mSphere.00180-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265632PMC
June 2021

Repeated Leftover Serosurvey of SARS-CoV-2 IgG Antibodies in Greece, May to August 2020.

Vaccines (Basel) 2021 May 13;9(5). Epub 2021 May 13.

Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larissa, Greece.

A serosurvey of IgG antibodies against SARS-CoV-2 was conducted in Greece between May and August 2020. It was designed as a cross-sectional survey and was repeated at monthly intervals. The leftover sampling methodology was used and a geographically stratified sampling plan was applied. Of 20,110 serum samples collected, 89 (0.44%) were found to be positive for anti-SARS-CoV-2 antibodies, with higher seroprevalence (0.35%) observed in May 2020. The highest seroprevalence was primarily observed in the "30-49" year age group. Females presented higher seroprevalence compared to males in May 2020 (females: 0.58% VS males: 0.10%). This difference reversed during the study period and males presented a higher proportion in August 2020 (females: 0.12% VS males: 0.58%). Differences in the rate of seropositivity between urban areas and the rest of the country were also observed during the study period. The four-month infection fatality rate (IFR) was estimated to be 0.47%, while the respective case fatality rate (CFR) was at 1.89%. Our findings confirm low seroprevalence of COVID-19 in Greece during the study period. The young adults are presented as the most affected age group. The loss of the cumulative effect of seropositivity in a proportion of previous SARS-CoV-2 infections was indicated.
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http://dx.doi.org/10.3390/vaccines9050504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152765PMC
May 2021

Circulation of pertussis and poor protection against diphtheria among middle-aged adults in 18 European countries.

Nat Commun 2021 05 17;12(1):2871. Epub 2021 May 17.

University of Turku, Turku, Finland.

Reported incidence of pertussis in the European Union (EU) and the European Economic Area (EEA) varies and may not reflect the real situation, while vaccine-induced protection against diphtheria and tetanus seems sufficient. We aimed to determine the seroprevalence of DTP antibodies in EU/EEA countries within the age groups of 40-49 and 50-59 years. Eighteen countries collected around 500 samples between 2015 and 2018 (N = 10,302) which were analysed for IgG-DTP specific antibodies. The proportion of sera with pertussis toxin antibody levels ≥100 IU/mL, indicative of recent exposure to pertussis was comparable for 13/18 countries, ranging between 2.7-5.8%. For diphtheria the proportion of sera lacking the protective level (<0.1 IU/mL) varied between 22.8-82.0%. For tetanus the protection was sufficient. Here, we report that the seroprevalence of pertussis in these age groups indicates circulation of B. pertussis across EU/EEA while the lack of vaccine-induced seroprotection against diphtheria is of concern and deserves further attention.
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http://dx.doi.org/10.1038/s41467-021-23114-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128873PMC
May 2021

Active case finding of pulmonary TB in a European refugee camp: lessons learnt from Oinofyta hosting site in Greece.

Trop Med Int Health 2021 09 1;26(9):1068-1074. Epub 2021 Jun 1.

Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Objectives: To report on an active case finding (ACF) intervention that took place in the migrant camp of Oinofyta, Greece, upon suspicion of active TB transmission.

Methods: Upon diagnosis of 3 TB cases among camp residents, an ACF intervention among contacts was implemented. All camp residents were offered two-step screening, that is tuberculin skin testing (TST) followed by chest X-ray in case of positive TST (defined as ≥5 mm).

Results: 336 of 379 (89%) camp residents underwent TST testing, of whom 110 (33%) exhibited a positive skin reaction. The rate of positive TST results was particularly high in the elderly and significantly higher in adults than in children. Differences by sex or nationality were not observed. Of the 110 cases with positive TST, only 75 underwent chest X-ray, resulting in the detection of one pulmonary TB case in an adult woman.

Conclusions: In the given intervention context, two-step ACF proved to be operationally cumbersome, with many residents lost to follow-up and a high Number Needed to Screen. Simpler ACF designs should be pilot-tested in similar settings in the future, and blanket screening of all camp residents should be reconsidered. Conclusions drawn by these exercises should pave the way for adopting a comprehensive, context-specific and evidence-based national strategy on TB in migrants.
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http://dx.doi.org/10.1111/tmi.13626DOI Listing
September 2021

COVID-19 Outbreak on a Passenger Ship and Assessment of Response Measures, Greece, 2020.

Emerg Infect Dis 2021 07 12;27(7):1927-1930. Epub 2021 May 12.

We describe response measures to an outbreak involving 128 (33.4%) coronavirus disease cases (46.1% asymptomatic) among 383 persons onboard a passenger ship. Multivariate analysis indicated that dining in certain rooms and bar areas, nationality, working department (for crew members), and quarantining onboard the ship were significantly associated with infection.
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http://dx.doi.org/10.3201/eid2707.210398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237900PMC
July 2021

Temporal Dominance of B.1.1.7 over B.1.354 SARS-CoV-2 Variant: A Hypothesis Based on Areas of Variant Co-Circulation.

Life (Basel) 2021 Apr 22;11(5). Epub 2021 Apr 22.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Some emergent SARS-CoV-2 variants raise concerns due to their altered biological properties. For both B.1.1.7 and B.1351 variants, named as variants of concern (VOC), increased transmissibility was reported, whereas B.1.351 was more resistant to multiple monoclonal antibodies (mAbs), as well as convalescent and vaccination sera. To test this hypothesis, we examined the proportion of VOC over time across different geographic areas where the two VOC, B.1.1.7 and B.1.351, co-circulate. Our comparative analysis was based on the number of SARS-CoV-2 sequences on GISAID database. We report that B.1.1.7 dominates over B.1.351 in geographic areas where both variants co-circulate and the B.1.1.7 was the first variant introduced in the population. The only areas where B.1.351 was detected at higher proportion were South Africa and Mayotte in Africa, where this strain was associated with increased community transmission before the detection of B.1.1.7. The dominance of B.1.1.7 over B.1.351 could be important since B.1.351 was more resistant to certain mAbs, as well as heterologous convalescent and vaccination sera, thus suggesting that it may be transmitted more effectively in people with pre-existing immunity to other VOC. This scenario would lessen the effectiveness of vaccine and urge the need to update them with new strains.
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http://dx.doi.org/10.3390/life11050375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143446PMC
April 2021

A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis.

Microorganisms 2021 Apr 11;9(4). Epub 2021 Apr 11.

Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.

COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention ( = 59) to a control group ( = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004-0.36), : 0.005], significantly better overall survival by Kaplan-Meir analysis ( < 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64-348.9), : 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209).
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http://dx.doi.org/10.3390/microorganisms9040806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069820PMC
April 2021

A case of encapsulating peritoneal sclerosis in a patient with chronic schistosomiasis.

IDCases 2021 12;24:e01123. Epub 2021 Apr 12.

4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Attikon" University Hospital, 1 Rimini Str, Chaidari, Athens, 12462, Greece.

Encapsulating peritoneal sclerosis (EPS) is a debilitating condition, mainly associated with long-term peritoneal dialysis, where up-regulation of intra-abdominal inflammatory pathways leads to a fibrocollagenous peritoneal membrane formation resembling a cocoon. EPS causes intestinal encapsulation leading to bowel obstruction and dilatation. Chronic schistosomiasis is characterized by dysregulation of pro-inflammatory and anti-inflammatory cytokines. EPS has never been reported before in patients with chronic schistosomiasis. We report the first, to our knowledge, case of a 57-year-old male originated from Burkina Faso with chronic intestinal and urogenital schistosomiasis and EPS. Although causality cannot be established solely by this case, we hypothesize that EPS may be the result of chronic inflammatory activation, due to immune dysregulation driven by chronic schistosomiasis. The potential pathogenetic linkage between these two conditions should be further explored.
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http://dx.doi.org/10.1016/j.idcr.2021.e01123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065271PMC
April 2021
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