Systematic review of seroprevalence of SARS-CoV-2 antibodies and appraisal of evidence, prior to the widespread introduction of vaccine programmes in the WHO European Region, January-December 2020.

OBJECTIVES: Systematic review of SARS-CoV-2 seroprevalence studies undertaken in the WHO European Region to measure pre-existing and cumulative seropositivity prior to the roll out of vaccination programmes. DESIGN: A systematic review of the literature. DATA SOURCES: We searched MEDLINE, EMBASE and the preprint servers MedRxiv and BioRxiv in the WHO 'COVID-19 Global literature on coronavirus disease' database using a predefined search strategy. Articles were supplemented with unpublished WHO-supported Unity-aligned seroprevalence studies and other studies reported directly to WHO Regional Office for Europe and European Centre for Disease Prevention and Control. ELIGIBILITY CRITERIA: Studies published before the widespread implementation of COVID-19 vaccination programmes in January 2021 among the general population and blood donors, at national and regional levels. DATA EXTRACTION AND SYNTHESIS: At least two independent researchers extracted the eligible studies; a third researcher resolved any disagreements. Study risk of bias was assessed using a quality scoring system based on sample size, sampling and testing methodologies. RESULTS: In total, 111 studies from 26 countries published or conducted between 1 January 2020 and 31 December 2020 across the WHO European Region were included. A significant heterogeneity in implementation was noted across the studies, with a paucity of studies from the east of the Region. Sixty-four (58%) studies were assessed to be of medium to high risk of bias. Overall, SARS-CoV-2 seropositivity prior to widespread community circulation was very low. National seroprevalence estimates after circulation started ranged from 0% to 51.3% (median 2.2% (IQR 0.7-5.2%); n=124), while subnational estimates ranged from 0% to 52% (median 5.8% (IQR 2.3%-12%); n=101), with the highest estimates in areas following widespread local transmission. CONCLUSIONS: The low levels of SARS-CoV-2 antibody in most populations prior to the start of vaccine programmes underlines the critical importance of targeted vaccination of priority groups at risk of severe disease, while maintaining reduced levels of transmission to minimise population morbidity and mortality.

Comparative study between virus neutralisation testing and other serological methods detecting anti-SARS-CoV-2 antibodies in Europe, 2021.

One consequence of the ongoing coronavirus disease pandemic was the rapid development of both in-house and commercial serological assays detecting anti-SARS-CoV-2 antibodies, in an effort to reliably detect acute and past SARS-CoV-2 infections. It is crucial to evaluate the quality of these serological tests and consequently the sero-epidemiological studies that are performed with the respective tests. Here, we describe the set-up and results of a comparative study, in which a laboratory contracted by the European Centre for Disease Prevention and Control offered a centralised service to EU/EEA Member and pre-accession Member States to test representative serum specimens with known serological results, with the gold standard technique (virus neutralisation tests) to determine the presence of neutralising antibodies. Laboratories from 12 European countries shared 719 serum specimens with the contractor laboratory. We found that in-house serological tests detecting neutralising antibodies showed the highest percent agreement, both positive and negative, with the virus neutralisation test results. Despite extensive differences in virus neutralisation protocols neutralisation titres showed a strong correlation. From the commercial assays, the best positive percent agreement was found for SARS-CoV-2 IgG (sCOVG) (Siemens - Atellica IM Analyzer). Despite lower positive percent agreement of LIAISON SARS-CoV-2 TrimericS IgG kit (Diasorin Inc.), the obtained results showed relatively good correlation with neutralisation titres. The set-up of this study allowed for high comparability between laboratories and enabled laboratories that do not have the capacity or capability to perform VNTs themselves. Given the variety of in-house protocols detecting SARS-CoV-2 specific neutralising antibodies, including the virus strain, it could be of interest to select reference isolates for SARS-CoV-2 diagnostic to be made available for interested EU Member States and pre-accession countries.

External quality assessment of SARS-CoV-2 serology in European expert laboratories, April 2021.

BackgroundCountries worldwide are focusing to mitigate the ongoing SARS-CoV-2 pandemic by employing public health measures. Laboratories have a key role in the control of SARS-CoV-2 transmission. Serology for SARS-CoV-2 is of critical importance to support diagnosis, define the epidemiological framework and evaluate immune responses to natural infection and vaccine administration.AimThe aim of this study was the assessment of the actual capability among laboratories involved in sero-epidemiological studies on COVID-19 in EU/EEA and EU enlargement countries to detect SARS-CoV-2 antibodies through an external quality assessment (EQA) based on proficiency testing.MethodsThe EQA panels were composed of eight different, pooled human serum samples (all collected in 2020 before the vaccine roll-out), addressing sensitivity and specificity of detection. The panels and two EU human SARS-CoV-2 serological standards were sent to 56 laboratories in 30 countries.ResultsThe overall performance of laboratories within this EQA indicated a robust ability to establish past SARS-CoV-2 infections via detection of anti-SARS-CoV-2 antibodies, with 53 of 55 laboratories using at least one test that characterised all EQA samples correctly. IgM-specific test methods provided most incorrect sample characterisations (24/208), while test methods detecting total immunoglobulin (0/119) and neutralising antibodies (2/230) performed the best. The semiquantitative assays used by the EQA participants also showed a robust performance in relation to the standards.ConclusionOur EQA showed a high capability across European reference laboratories for reliable diagnostics for SARS-CoV-2 antibody responses. Serological tests that provide robust and reliable detection of anti-SARS-CoV-2 antibodies are available.

Legionella spp. Risk Assessment in Recreational and Garden Areas of Hotels.

Several Travel-associated Legionnaires' disease (TALD) cases occur annually in Europe. Except from the most obvious sites (cooling towers and hot water systems), infections can also be associated with recreational, water feature, and garden areas of hotels. This argument is of great interest to better comprehend the colonization and to calculate the risk to human health of these sites. From July 2000-November 2017, the public health authorities of the Island of Crete (Greece) inspected 119 hotels associated with TALD, as reported through the European Legionnaires' Disease Surveillance Network. Five hundred and eighteen samples were collected from decorative fountain ponds, showers near pools and spas, swimming pools, spa pools, garden sprinklers, drip irrigation systems (reclaimed water) and soil. Of those, 67 (12.93%), originating from 43 (35.83%) hotels, tested positive for Legionella (Legionella pneumophila serogroups 1, 2, 3, 6, 7, 8, 13, 14, 15 and non-pneumophila species (L. anisa, L. erythra, L. taurinensis, L. birminghamensis, L. rubrilucens). A Relative Risk (R.R.) > 1 (p < 0.0001) was calculated for chlorine concentrations of less than 0.2 mg/L (R.R.: 54.78), star classification (<4) (R.R.: 4.75) and absence of Water Safety Plan implementation (R.R.: 3.96). High risk (≥104 CFU/L) was estimated for pool showers (16.42%), garden sprinklers (7.46%) and pool water (5.97%).

Legionellosis: a Walk-through to Identification of the Source of Infection.

OBJECTIVES: Although a number of human Legionnaires' disease in tourists are recorded annually in Europe, there are few cases where a direct link can be made between the infected person and the source of infection (hotel or other accommodation). We present a scheme followed in order to track down and identify the source of infection in a tourist suffering from L. pneumophila sg 5 infection, who was accommodated in seven different hotels during his holidays in the island of Crete, and we comment on various difficulties and draw-backs of the process. METHOD: Water samples were collected from the seven hotels where the patient had resided and analyzed at the regional public health laboratory using cultivation and molecular tests. RESULTS: Of 103 water samples analyzed, 19 (18.4%) were positive for Legionella non-pneumophila and 8 (7.8%) were positive for L. pneumophila. A successful L. pneumophila sg 5 match was found between the clinical and environmental sample, which led us to the final identification of the liable hotel. CONCLUSION: Timely notification of the case, within the the European Legionnaires' Disease Surveillance Network (ELDSNet) of the partners involved, is crucial during a course of travel associated with Legionella case investigation. Moreover, the urinary antigen test alone cannot provide sufficient information for the source identification. However, acquiring clinical as well as environmental isolates for serogroup and SBT identification is highly important for the successful matching.

Factors associated with severe preeclampsia and eclampsia in Jahun, Nigeria.

OBJECTIVE: To explore traditional herbal medicines as potential risk factors of severe preeclampsia and eclampsia in Nigeria. METHODS: We conducted a retrospective case-control study from October 2010 to May 2011. The cases were all pregnant women admitted to the Jahun Hospital during the study period with severe preeclampsia or eclampsia and women presenting with normal pregnancy after 22 weeks. RESULTS: During the study period, a total of 1,257 women (44%) were recorded as having normal pregnancy, and 419 (16%) women had severe preeclampsia/eclampsia (175 with severe preeclampsia and 244 with eclampsia). The risk factors found to be associated with a greater risk of severe preeclampsia/eclampsia included personal history of preeclampsia (odds ratio [OR] = 21.5; P < 0.001), personal history of preexisting hypertension (OR = 10.5; P < 0.001), primiparity (OR = 2.5; P = 0.001), occupation as housewife (OR = 1.9; P = 0.008), and fewer than four antenatal care visits (OR = 1.6; P = 0.02). Use of traditional treatments during pregnancy was associated with a higher risk of developing severe preeclampsia/eclampsia (OR = 1.6 95%; confidence interval [CI]: 1.2-2.1) by univariate analysis only. CONCLUSION: Use of traditional treatment, which increases delays before consulting the official health sector, might be a marker for harmful behavior. Community-based studies could provide additional information on the practice of herbal therapy in this population.

High maternal and neonatal mortality rates in northern Nigeria: an 8-month observational study.

BACKGROUND: Despite considerable efforts to reduce the maternal mortality ratio, numerous pregnant women continue to die in many developing countries, including Nigeria. We conducted a study to determine the incidence and causes of maternal mortality over an 8-month period in a rural-based secondary health facility located in Jahun, northern Nigeria. METHODS: A retrospective observational study was performed in a 41-bed obstetric ward. From October 2010 to May 2011, demographic data, obstetric characteristics, and outcome were collected from all pregnant women admitted. The total number of live births during the study period was recorded in order to calculate the maternal mortality ratio. RESULTS: There were 2,177 deliveries and 39 maternal deaths during the study period, with a maternal mortality ratio of 1,791/100,000 live births. The most common causes of maternal mortality were hemorrhage (26%), puerperal sepsis (19%), and obstructed labor (5%). No significant difference (P = 0.07) in mean time to reach the hospital was noted between fatal cases (1.9 hours, 95% confidence interval [CI] 1.1-2.6) and nonfatal cases (1.4 hours, 95% CI 1.4-1.5). Two hundred and sixty-six women were admitted presenting with stillbirth. Maternal mortality was higher for unbooked patients than for booked patients (odds ratio 5.1, 95% CI 3.5-6.2, P < 0.0001). The neonatal mortality rate was calculated at 46/1,000 live births. The main primary causes of neonatal deaths were prematurity (44%) and birth asphyxia (22%). CONCLUSION: Maternal and neonatal mortality remains unacceptably high in this setting. Reducing unbooked emergencies should be a priority with continuous programs including orthodox practices in order to meet the fifth Millennium Development Goal.

Cigarette smoke-induced transgenerational alterations in genome stability in cord blood of human F1 offspring.

The relevance of preconceptional and prenatal toxicant exposures for genomic stability in offspring is difficult to analyze in human populations, because gestational exposures usually cannot be separated from preconceptional exposures. To analyze the roles of exposures during gestation and conception on genomic stability in the offspring, stability was assessed via the Comet assay and highly sensitive, semiautomated confocal laser scans of γH2AX foci in cord, maternal, and paternal blood as well as spermatozoa from 39 families in Crete, Greece, and the United Kingdom. With use of multivariate linear regression analysis with backward selection, preconceptional paternal smoking (% tail DNA: P>0.032; γH2AX foci: P>0.018) and gestational maternal (% tail DNA: P>0.033) smoking were found to statistically significantly predict DNA damage in the cord blood of F1 offspring. Maternal passive smoke exposure was not identified as a predictor of DNA damage in cord blood, indicating that the effect of paternal smoking may be transmitted via the spermatozoal genome. Taken together, these studies reveal a role for cigarette smoke in the induction of DNA alterations in human F1 offspring via exposures of the fetus in utero or the paternal germline. Moreover, the identification of transgenerational DNA alterations in the unexposed F1 offspring of smoking-exposed fathers supports the claim that cigarette smoke is a human germ cell mutagen.

Completeness of infectious disease notification in the United Kingdom: A systematic review.

OBJECTIVES: Infectious disease legislation in the United Kingdom has recently changed. Our aim was to provide a baseline against which to assess the impact of these changes by synthesising current knowledge on completeness of notification and on factors associated with better reporting rates. METHODS: We systematically reviewed the literature for studies reporting completeness of reporting of notifiable infectious diseases in the United Kingdom over the past 35 years. RESULTS: Altogether, 46 studies met our search criteria. Reporting completeness varied from 3% to 95% and was most strongly correlated with the disease being reported. Median reporting completeness was 73% (range 6%-93%) for tuberculosis, 65% (range 40%-95%) for meningococcal disease, and 40% (range 3%-87%) for other diseases (Kruskal-Wallis test, p < 0.05). Reporting completeness did not change for either tuberculosis or meningococcal disease over the period studied. In multivariate analysis, none of the factors examined (study size, study time period, number of data sources used to assess completeness, uncorrected or corrected study design) were significantly associated with reporting completeness. CONCLUSION: Reporting completeness has not improved over the past three decades. It remains sub-optimal even for diseases which are under enhanced surveillance or are of significant public health importance.

Maternal and gestational factors and micronucleus frequencies in umbilical blood: the NewGeneris Rhea cohort in Crete.

BACKGROUND: The use of cancer-related biomarkers in newborns has been very limited. OBJECTIVE: We investigated the formation of micronuclei (MN) in full-term and preterm newborns and their mothers from the Rhea cohort (Crete), applying for the first time in cord blood a validated semiautomated analysis system, in both mono- and binucleated T lymphocytes. METHODS: We assessed MN frequencies in peripheral blood samples from the mothers and in umbilical cord blood samples. We calculated MN in mononucleated (MNMONO) and binucleated (MNBN) T lymphocytes and the cytokinesis block proliferation index (CBPI) in 251 newborns (224 full term) and 223 mothers, including 182 mother-child pairs. Demographic and lifestyle characteristics were collected. RESULTS: We observed significantly higher MNBN and CBPI levels in mothers than in newborns. In newborns, MNMONO and MNBN were correlated (r = 0.35, p < 0.001), and we found a moderate correlation between MNMONO in mothers and newborns (r = 0.26, p < 0.001). MNMONO frequencies in newborns were positively associated with the mother's body mass index and inversely associated with gestational age and mother's age, but we found no significant predictors of MNBN or CBPI in newborns. CONCLUSIONS: Although confirmation is needed by a larger study population, the results indicate the importance of taking into account both mono- and binucleated T lymphocytes for biomonitoring of newborns, because the first reflects damage expressed during in vivo cell division and accumulated in utero, and the latter includes additional damage expressed as MN during the in vitro culture step.