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1.
Trends in Molecular Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-1799776

ABSTRACT

Vaccination is a major tool for mitigating the COVID-19 pandemic and mRNA vaccines are central to the ongoing vaccination campaign that is undoubtedly saving thousands of lives. However, adverse effects (AEs) following vaccination have been noted which may relate to a pro-inflammatory action of the employed lipid nanoparticles or the delivered mRNA (i.e., vaccines formulation) as well as to the herein discussed unique nature, expression pattern, binding profile and pro-inflammatory effects of the produced antigens (S protein and/or its subunits-peptide fragments) in human tissues/organs. Current knowledge on this topic mostly originates from cell-based assays or from model organisms, therefore further research on the cellular-molecular basis of the mRNA vaccines induced AEs, will guarantee safety, maintain trust, and direct health policies.

2.
Vaccines (Basel) ; 10(3)2022 Mar 18.
Article in English | MEDLINE | ID: covidwho-1760857

ABSTRACT

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.

3.
Viruses ; 14(3)2022 03 17.
Article in English | MEDLINE | ID: covidwho-1753689

ABSTRACT

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.


Subject(s)
COVID-19 , COVID-19/epidemiology , Europe/epidemiology , Humans , Machine Learning , Risk Factors , Support Vector Machine
4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330080

ABSTRACT

Background Nationwide data at a country level on Covid-19 in unvaccinated patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are scarce. Methods By interlinking data from national electronic registries, covering nearly 99% of the Greek population (approximately 11,000,000), between March 2020 and February 2021, when vaccination became available, we recorded confirmed infections and Covid-19-associated hospitalizations and deaths in essentially all adult patients with RA, AS, PsA, SLE, and SSc under treatment (n=74,970, median age of 67.5, 51.2, 58.1, 56.2, 62.2 years, respectively) and in individually matched (1:5) on age, sex, and region of domicile random comparators from the general population. Results Binary logistic regression analysis after adjusting for age, sex and biologic agents, revealed that RA, PsA, SLE and SSc, but not AS patients, had significantly higher risk of infection (by 43%, 25%, 20% and 49%, respectively), and hospitalization for Covid-19 (by 81%, 56%, 94%, and 111%, respectively), possibly due, at least in part, to increased testing and lower threshold for admission. Patients with RA and SSc had indeed higher Covid-19 associated mortality rates [OR:1.86 (95% CI 1.37 to 2.52) and OR:2.90 (95% CI 0.97 to 8.67), respectively] compared to the general population. Each additional year of age increased the risk of hospitalization for Covid-19 by 3% (OR 1.030, 95% CI: 1.028 to 1.034) and the risk of Covid-19 related death by 8% (OR 1.08, 95% CI: 1.07 to 1.09), independently of gender, systemic rheumatic disease, and biologic agents. A further analysis using AS patients as the reference category, adjusting again for age, sex and use of biologic agents showed that patients with SSc had increased mortality (OR: 6.90, 95% CI: 1.41 to 33.72), followed by SLE (OR: 4.05 95% CI: 0.96 to 17.12) and RA patients (OR: 3.65, 95% CI: 1.06 to 12.54), whereas PsA patients had comparable mortality risk with AS patients. Conclusion Comparing to the general population, Covid-19 may have a more severe impact in real-world patients with systemic rheumatic disease. Covid-19 related mortality is increased in subgroups of patients with specific rheumatic diseases, especially in older ones, underscoring the need for priority vaccination policies and access to targeted treatments.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-329444

ABSTRACT

Numerous studies covering some aspects of SARS-CoV-2 data analyses are being published on a daily basis, including a regularly updated phylogeny on nextstrain.org . Here, we review the difficulties of inferring reliable phylogenies by example of a data snapshot comprising all virus sequences available on May 5, 2020 from gisaid.org . We find that it is difficult to infer a reliable phylogeny on these data due to the large number of sequences in conjunction with the low number of mutations. We further find that rooting the inferred phylogeny with some degree of confidence either via the bat and pangolin outgroups or by applying novel computational methods on the ingroup phylogeny does not appear to be possible. Finally, an automatic classification of the current sequences into sub-classes based on statistical criteria is also not possible, as the sequences are too closely related. We conclude that, although the application of phylogenetic methods to disentangle the evolution and spread of COVID-19 provides some insight, results of phylogenetic analyses, in particular those conducted under the default settings of current phylogenetic inference tools, as well as downstream analyses on the inferred phylogenies, should be considered and interpreted with extreme caution.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314454

ABSTRACT

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.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306454

ABSTRACT

Throughout the COVID-19 pandemic, countries relied on a variety of ad-hoc border control protocols to allow for non-essential travel while safeguarding public health: from quarantining all travelers to restricting entry from select nations based on 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 travelers infected with 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 based upon incoming travelers’ demographic information and testing results from previous travelers. By comparing Eva’s performance against modeled counterfactual scenarios, we show that Eva identified 1.85 times as many asymptomatic, infected travelers 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 travelers as testing policies that only utilize 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 travelers 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.

8.
Vaccines (Basel) ; 10(2)2022 Feb 13.
Article in English | MEDLINE | ID: covidwho-1687069

ABSTRACT

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.

9.
Endocrine ; 75(2): 317-327, 2022 02.
Article in English | MEDLINE | ID: covidwho-1639291

ABSTRACT

PURPOSE: The beneficial effect of glucocorticoids in coronavirus disease (COVID-19) is established, but whether adrenal cortisol secretion is impaired in COVID-19 is not fully elucidated. In this case-control study, we investigated the diurnal free bioavailable salivary cortisol secretion in COVID-19 patients. METHODS: Fifty-two consecutive COVID-19 patients-before dexamethasone treatment in cases required-recruited between April 15 to June 15, 2021, (NCT04988269) at Laikon Athens University-Hospital, and 33 healthy age- and sex-matched controls were included. Diurnal salivary cortisol (8 a.m., 12, 6, and 10 p.m.), plasma adrenocorticotropin (ACTH) and aldosterone, and serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels were assessed. Diurnal salivary dehydroepiandrosterone (DHEA) and IL-6 were also assessed in subgroups of patients. RESULTS: Median CRP and IL-6 measurements were about sixfold higher in patients than controls (both p < 0.001) Morning salivary cortisol levels did not differ between the two groups, but patients exhibited higher median levels of evening and nocturnal salivary cortisol compared to controls [0.391 (0.054, 0663) vs. 0.081 (0.054, 0.243) µg/dl, p < 0.001 and 0.183 (0.090, 0.834) vs. 0.054 (0.054, 0.332) µg/dl, p < 0.001, respectively], resulting in higher time-integrated area under the curve (AUC) (4.81 ± 2.46 vs. 2.75 ± 0.810, respectively, p < 0.001). Circulating ACTH, DHEA, and aldosterone levels were similar in patients and controls. Serum IL-6, but not ACTH levels, was strongly correlated with nocturnal cortisol salivary levels (ρ = 0.555, p < 0.001) in patients. CONCLUSIONS: Increased evening and nocturnal but not morning cortisol secretion may occur in even clinically mild COVID-19. In the context of acute viral infection (COVID-19), IL-6 may partially replace ACTH as a stimulus of the glucocorticoid-secreting adrenal zona-fasciculata without influencing the secretion of DHEA and aldosterone. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04988269?term=yavropoulou&draw=2&rank=3 (NCT04988269).


Subject(s)
COVID-19 , Interleukin-6 , Case-Control Studies , Humans , Hydrocortisone , SARS-CoV-2
10.
Viruses ; 14(1)2021 12 24.
Article in English | MEDLINE | ID: covidwho-1580409

ABSTRACT

Health-Care-Workers (HCWs) are considered at high risk for SARS-CoV-2 infection. We sought to compare rates and severity of Coronavirus disease 2019 (COVID-19) among vaccinated and unvaccinated HCWs conducting a retrospective cohort study in two tertiary Academic Hospitals, namely Laiko and Attikon, in Athens, Greece. Vaccinated by BNT162b2 Pfizer-BioNTech COVID-19 mRNA vaccine and unvaccinated HCWs were included and data were collected between 1 January 2021 and 15 September 2021. Overall, 2921 of 3219 HCWs without a history of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection were fully vaccinated during the study period (90.7% at each Hospital). Demographic characteristics were comparable between 102/2921 (3.5%) vaccinated and 88/298 (29.5%) unvaccinated HCWs with COVID-19, although age and occupation differed significantly. None were in need of hospital admission in the vaccinated Group, whereas in the unvaccinated Group 4/88 (4.5%) were hospitalized and one (1.1%) died. Multivariable logistic regression analysis revealed that lack of vaccination was an independent risk factor for COVID-19 with an odds ratio 11.54 (95% CI: 10.75-12.40). Vaccination hesitancy among HCWs resulted to highly increased COVID-19 rates; almost one in three unvaccinated HCWs was SARS-CoV-2 infected during the 9-month period. The absolute need of vaccination of HCWs, including boosting dose, is highlighted. Evidence should be used appropriately to overcome any hesitancy.


Subject(s)
COVID-19/epidemiology , Health Personnel/statistics & numerical data , /statistics & numerical data , Adult , COVID-19/prevention & control , Female , Greece/epidemiology , Humans , Male , Middle Aged , Retrospective Studies , Risk , SARS-CoV-2/immunology , Severity of Illness Index , Tertiary Care Centers , Vaccination/statistics & numerical data
11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292387

ABSTRACT

Purpose: The beneficial effect of glucocorticoids in coronavirus disease (COVID-19) is established, but whether adrenal cortisol secretion is impaired in COVID-19 is not fully elucidated. In this case-control study we investigated the diurnal free bioavailable salivary cortisol secretion in COVID-19 patients. Methods: : Fifty-two consecutive COVID-19 patients -before dexamethasone treatment- recruited between April 15 th -June15 th -2021, (NCT04988269) at Laikon Athens University-Hospital, and 33 healthy age- and sex-matched controls were included. Diurnal salivary cortisol (8am, 12, 6, and 10pm), plasma adrenocorticotropin (ACTH) and aldosterone, and serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels were assessed. Diurnal salivary dehydroepiandrosterone (DHEA) and IL-6 were also assessed in subgroups of patients. Results: Median CRP and IL-6 measurements were about 6-fold higher in patients than controls (both p<0.001) Morning salivary cortisol levels did not differ between the two groups, but patients exhibited higher median levels of evening and nocturnal salivary cortisol compared to controls [0.391(0.054, 0,663) vs. 0.081(0.054, 0.243)μg/dl, p<0.001 and 0.183(0.090, 0.834) vs. 0.054(0.054, 0.332)μg/dl, p<0.001, respectively], resulting in higher time-integrated area under the curve (AUC) (4.81±2.46 vs. 2.75±0.810, respectively, p<0.001 ). Circulating ACTH, DHEA, and aldosterone levels were similar in patients and controls. Serum IL-6, but not ACTH levels, WAS strongly correlated with nocturnal cortisol salivary levels (rho=0.555, p<0.001 ) in patients. Conclusion: Increased evening and nocturnal but not morning cortisol secretion occur in even clinically mild COVID-19. In the context of acute viral infection (Covid-19), IL-6 may partially replace ACTH as a stimulus of the glucocorticoid-secreting adrenal zona-fasciculata without influencing the secretion of DHEA and aldosterone.

12.
RMD Open ; 7(3)2021 11.
Article in English | MEDLINE | ID: covidwho-1504941

ABSTRACT

OBJECTIVES: To compare current all-cause mortality rates in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) versus general population. METHODS: In this population-based, retrospective cohort study, anonymised data on 11 186 586 citizens, including all patients with RA (42 735, 79% female), AS (9707, 43% female), PsA (13 779, 55% female), SLE (10 440, 89% female) and SSc (2277, 88% female), (median age of 64/47/54/53/59 years at study entry, respectively), under prescribed treatment between 2015 and 2019, were extracted from the electronic database covering nearly 99% of the Greek population. RESULTS: After 1:5 (patients:general population) matching for gender/age, we found that survival was worse in SSc, followed by SLE and inflammatory arthritis. Compared with the general population HRs for death increased from the first 3 years to 5 years of observation possibly due to increases in disease duration: RA (from 0.63 to 1.13 (95% CI: 1.05 to 1.22), AS (from 0.62 to 1.01, (95% CI: 0.76 to 1.33)), PsA (from 0.68 to 1.06, (95% CI: 0.88 to 1.28)), SLE (from 1.52 to 1.98, (95% CI: 1.67 to 2.33)) and SSc (from 2.27 to 4.24, (95% CI: 3.19 to 5.63)). In both SLE and SSc mortality was increased in men than women and in patients younger than 50 years. CONCLUSIONS: Survival rates over 5 years in inflammatory arthritis under treatment are currently becoming comparable (AS/PsA) or slightly higher (RA) than those of the general population. However, all-cause mortality is almost twofold and fourfold higher in SLE and SSc, respectively, being even higher for male and younger patients.


Subject(s)
Arthritis, Psoriatic , Arthritis, Rheumatoid , Lupus Erythematosus, Systemic , Rheumatic Diseases , Arthritis, Psoriatic/drug therapy , Female , Humans , Lupus Erythematosus, Systemic/drug therapy , Male , Middle Aged , Retrospective Studies , Rheumatic Diseases/drug therapy
13.
Front Immunol ; 12: 746203, 2021.
Article in English | MEDLINE | ID: covidwho-1477828

ABSTRACT

The reasons behind the clinical variability of SARS-CoV-2 infection, ranging from asymptomatic infection to lethal disease, are still unclear. We performed genome-wide transcriptional whole-blood RNA sequencing, bioinformatics analysis and PCR validation to test the hypothesis that immune response-related gene signatures reflecting baseline may differ between healthy individuals, with an equally robust antibody response, who experienced an entirely asymptomatic (n=17) versus clinical SARS-CoV-2 infection (n=15) in the past months (mean of 14 weeks). Among 12.789 protein-coding genes analysed, we identified six and nine genes with significantly decreased or increased expression, respectively, in those with prior asymptomatic infection relatively to those with clinical infection. All six genes with decreased expression (IFIT3, IFI44L, RSAD2, FOLR3, PI3, ALOX15), are involved in innate immune response while the first two are interferon-induced proteins. Among genes with increased expression six are involved in immune response (GZMH, CLEC1B, CLEC12A), viral mRNA translation (GCAT), energy metabolism (CACNA2D2) and oxidative stress response (ENC1). Notably, 8/15 differentially expressed genes are regulated by interferons. Our results suggest that subtle differences at baseline expression of innate immunity-related genes may be associated with an asymptomatic disease course in SARS-CoV-2 infection. Whether a certain gene signature predicts, or not, those who will develop a more efficient immune response upon exposure to SARS-CoV-2, with implications for prioritization for vaccination, warrant further study.


Subject(s)
Antibodies, Viral/blood , Asymptomatic Infections , Immunity, Innate/genetics , SARS-CoV-2/immunology , Transcriptome/genetics , Adult , COVID-19/pathology , Female , Gene Expression Profiling , Humans , Immunity, Innate/immunology , Male , RNA, Messenger/genetics , Sequence Analysis, RNA , Severity of Illness Index
14.
Microbiol Spectr ; 9(2): e0126021, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1455683

ABSTRACT

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. IMPORTANCE 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.


Subject(s)
Bronchioles/virology , Bronchoalveolar Lavage Fluid/virology , COVID-19/pathology , Endogenous Retroviruses/growth & development , Respiratory Mucosa/virology , Bronchioles/cytology , Endogenous Retroviruses/isolation & purification , Epithelial Cells/virology , Humans , Inflammation/virology , Leukocytes, Mononuclear/virology , Respiratory Mucosa/cytology , SARS-CoV-2 , Transcriptome/genetics , Up-Regulation
15.
Vaccines (Basel) ; 9(9)2021 Sep 13.
Article in English | MEDLINE | ID: covidwho-1438752

ABSTRACT

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.

16.
Nature ; 599(7883): 108-113, 2021 11.
Article in English | MEDLINE | ID: covidwho-1434121

ABSTRACT

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 rates1,2. 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 policies3 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.


Subject(s)
COVID-19/diagnosis , COVID-19/prevention & control , Carrier State/diagnosis , Carrier State/prevention & control , Machine Learning , Travel Medicine , Travel , COVID-19/epidemiology , COVID-19/transmission , Carrier State/epidemiology , Carrier State/transmission , Greece , Humans , Prevalence , Public Health
17.
Sci Total Environ ; 804: 150151, 2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1401851

ABSTRACT

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Hospitalization , Humans , Intensive Care Units , RNA, Viral , Waste Water , Wastewater-Based Epidemiological Monitoring
18.
PLoS Pathog ; 17(9): e1009883, 2021 09.
Article in English | MEDLINE | ID: covidwho-1398940

ABSTRACT

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.


Subject(s)
COVID-19/veterinary , Mink/virology , Animals , COVID-19/epidemiology , COVID-19/genetics , COVID-19/transmission , Disease Outbreaks/veterinary , Environmental Microbiology , Farms , Female , Greece/epidemiology , Humans , Male , Mink/genetics , Occupational Exposure , Viral Zoonoses/transmission , Viral Zoonoses/virology
19.
mSphere ; : e0018021, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1288358

ABSTRACT

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.

20.
Life (Basel) ; 11(5)2021 Apr 22.
Article in English | MEDLINE | ID: covidwho-1202314

ABSTRACT

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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