Comparison of SARS-CoV-2 infections in healthcare workers with high and low exposures to Covid-19 patients in a Norwegian University Hospital.

INTRODUCTION: A year into the pandemic, the knowledge of SARS-CoV-2 infection risks among healthcare workers remains limited. In this cross-sectional study, we examined whether healthcare workers with high exposure to Covid-19 patients had a higher risk of SARS-CoV-2 infection than other healthcare workers in a Norwegian University Hospital. We also investigated the prevalence of asymptomatic healthcare workers in a ward with a SARS-CoV-2 outbreak. METHODS: Healthcare workers from five wards at Akershus University Hospital were included between May 11 and June 11, 2020. Blood samples were analyzed for SARS-CoV-2 antibodies and seroprevalences compared between participants with high and low exposure to Covid-19 patients. Demographic data and SARS-CoV-2 infection risk factors were recorded in a questionnaire. Naso-/oropharyngeal swabs from participants from the outbreak ward were analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: 360/436 (82.6%) healthcare workers participated. 9/262 (3.4%) participants from wards with high exposure to Covid-19 patients were SARS-CoV-2 seropositive versus 3/98 (3.1%) from wards with low exposure (OR 1.13; 95%CI 0.3-4.26, p = .861). SARS-CoV-2 antibodies were found in 11/263 (4.2%) participants who had worked one or more shifts caring for Covid-19 patients versus in 1/85 (1.2%) without any known occupational Covid-19 exposure (OR 3.67; 95%CI 0.46-29.06, p = .187). SARS-CoV-2 was detected in naso-/oropharyngeal swabs from 2/78 (2.6%) participants. CONCLUSION: We found no significantly increased risk of SARS-CoV-2 infection in healthcare workers with high exposure to COVID-19 patients. Five healthcare workers had either serologic or molecular evidence of past or present unrecognized SARS-CoV-2 infection

Exploring the evolution and epidemiology of European CC1-MRSA-IV: tracking a multidrug-resistant community-associated meticillin-resistant Staphylococcus aureus clone

This study investigated the evolution and epidemiology of the community-associated and multidrug-resistant Staphylococcus aureus clone European CC1-MRSA-IV. Whole-genome sequences were obtained for 194 European CC1-MRSA-IV isolates (189 of human and 5 of animal origin) from 12 countries, and 10 meticillin-susceptible precursors (from North-Eastern Romania; all of human origin) of the clone. Phylogenetic analysis was performed using a maximum-likelihood approach, a time-measured phylogeny was reconstructed using Bayesian analysis, and in silico microarray genotyping was performed to identify resistance, virulence-associated and SCCmec (staphylococcal cassette chromosome mec) genes. Isolates were typically sequence type 1 (190/204) and spa type t127 (183/204). Bayesian analysis indicated that European CC1-MRSA-IV emerged in approximately 1995 before undergoing rapid expansion in the late 1990s and 2000s, while spreading throughout Europe and into the Middle East. Phylogenetic analysis revealed an unstructured meticillin-resistant S. aureus (MRSA) population, lacking significant geographical or temporal clusters. The MRSA were genotypically multidrug-resistant, consistently encoded seh, and intermittently (34/194) encoded an undisrupted hlb gene with concomitant absence of the lysogenic phage-encoded genes sak and scn. All MRSA also harboured a characteristic ~5350 nt insertion in SCCmec adjacent to orfX. Detailed demographic data from Denmark showed that there, the clone is typically (25/35) found in the community, and often (10/35) among individuals with links to South-Eastern Europe. This study elucidated the evolution and epidemiology of European CC1-MRSA-IV, which emerged from a meticillin-susceptible lineage prevalent in North-Eastern Romania before disseminating rapidly throughout Europe

Phylodynamic signatures in the emergence of community-associated MRSA

Community-associated, methicillin-resistant Staphylococcus aureus (MRSA) lineages have emerged in many geographically distinct regions around the world during the past 30 y. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast their patterns of emergence and dissemination. We generated whole-genome sequencing data for the Australian sequence type (ST) ST93-MRSA-IV from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from metropolitan communities in Pakistan. Increases in the effective reproduction number (Re) and sustained transmission (Re > 1) coincided with spread of progenitor methicillin-susceptible S. aureus (MSSA) in remote northern Australian populations, dissemination of the ST93-MRSA-IV genotype into population centers on the Australian East Coast, and subsequent importation into the highlands of Papua New Guinea and Far North Queensland. Applying the same phylodynamic methods to existing lineage datasets, we identified common signatures of epidemic growth in the emergence and epidemiological trajectory of community-associated S. aureus lineages from America, Asia, Australasia, and Europe. Surges in Re were observed at the divergence of antibiotic-resistant strains, coinciding with their establishment in regional population centers. Epidemic growth was also observed among drug-resistant MSSA clades in Africa and northern Australia. Our data suggest that the emergence of community-associated MRSA in the late 20th century was driven by a combination of antibiotic-resistant genotypes and host epidemiology, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional population centers

Phylodynamic signatures in the emergence of community-associated MRSA

Community-associated, methicillin-resistant Staphylococcus aureus (MRSA) lineages have emerged in many geographically distinct regions around the world during the past 30 y. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast their patterns of emergence and dissemination. We generated whole-genome sequencing data for the Australian sequence type (ST) ST93-MRSA-IV from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from metropolitan communities in Pakistan. Increases in the effective reproduction number (Re) and sustained transmission (Re > 1) coincided with spread of progenitor methicillin-susceptible S. aureus (MSSA) in remote northern Australian populations, dissemination of the ST93-MRSA-IV genotype into population centers on the Australian East Coast, and subsequent importation into the highlands of Papua New Guinea and Far North Queensland. Applying the same phylodynamic methods to existing lineage datasets, we identified common signatures of epidemic growth in the emergence and epidemiological trajectory of community-associated S. aureus lineages from America, Asia, Australasia, and Europe. Surges in Re were observed at the divergence of antibiotic-resistant strains, coinciding with their establishment in regional population centers. Epidemic growth was also observed among drug-resistant MSSA clades in Africa and northern Australia. Our data suggest that the emergence of community-associated MRSA in the late 20th century was driven by a combination of antibiotic-resistant genotypes and host epidemiology, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional population centers

nfeksjonssykdommer og fattigdom : hva vet vi og hva kan vi gjøre?

Combating infectious diseases and poverty are hot topics on the world development agenda. The vicious cycle of ill health and poverty is reinforced by a “medical poverty trap” relating to households being impoverished due to escalating illness-related out-of-pocket costs, especially in combination with loss of income due to incapacity to work. Evidence-based knowledge on the impacts of ill health on household welfare is essential to design adequate interventions and evaluate their efficiency. This thesis presents the findings of a critical review of studies assessing the impacts of infectious diseases on households’ ability to utilize their resources and generate income in rural Sub-Saharan Africa. The review revealed a dearth of relevant studies (merely 15), poor methodological quality in short-term geographically limited surveys, and large diversity in study design obstructing comparison of results and extraction of general conclusions. Major research obstacles are discussed and recommendations for coordination, standardization and scaling up of data collection that allows adequate impact assessment are suggested. Experimental intervention studies are recommended to improve quality and efficiency of interventions and guide prioritizing processes prior to large scale implementations to avoid waste of time and resources. The linkages between infectious diseases and poverty are complex and multifaceted and thus imply multi- and interdisciplinary research approaches. Collaboration between various disciplines like health sciences, economics, geography and sociology give opportunities of linking data in innovative ways to provide new insights and perspectives that have the potential to analyse the impacts of infectious diseases on poverty in a more comprehensive manner. Methodological standardisation and consensus will enable us to accumulate comparable results and scale up research and thereby contribute to foundation of efficient interventions to accomplish sustainable improvements in health and significant reductions in poverty.Kampen mot infeksjonssykdommer og fattigdom er høyt prioritert på den globale agenda. Dårlig helse og fattigdom utgjør en ond sirkel som forsterkes av en ”medisinsk fattigdomsfelle” grunnet økende sykdomsrelaterte utgifter kombinert med tap av inntekt fordi sykdom hindrer en i å arbeide. Evidensbasert kunnskap om sykdommenes konsekvenser for husholdenes velferd er påkrevet for å utarbeide adekvate intervensjoner og evaluere deres effektivitet. Denne masteroppgaven presenterer resultatene av en kritisk gjennomgang av publiserte studier som analyserer effekter av infeksjonssykdommer på rurale husholds evne til å nyttiggjøre seg av sine ressurser og generere inntekt i afrikanske land sør for Sahara. Litteraturgjennomgangen avdekket få relevante studier (bare 15), svak metodologisk kvalitet i geografisk begrensede studier og stor diversitet i studiedesign. Diversiteten gjorde det nesten umulig å sammenlige resultater og sammenfatte generelle konklusjoner. De viktigste forskningsmessige hindringene diskuteres og det foreslås anbefalinger for koordinering, standardisering og oppskalering av datainnsamling som muliggjør adekvat konsekvensanalyse. Eksperimentelle intervensjonsstudier anbefales både som ledd i prioriteringsprosesser, for å bedre intervensjoners kvalitet og effektivitet og for å unngå sløsing med tid og ressurser før stor-skala implementeringer. Sammenhengen mellom infeksjonssykdommer og fattigdom er kompleks og mangesidig og innbyr dermed til flerfaglige og tverrfaglige tilnærminger. Samarbeid mellom ulike fagområder som medisin, økonomi, sosiologi og geografi åpner for muligheter til å kombinere data på innovative måter for å frembringe nye perspektiver og innsikter med potensiale til å analysere infeksjonssykdommers effekt på hushold mer omfattende og helhetlig. Metodologisk standardisering og konsensus åpner for oppskalering av forskningen og for akkumulering av sammenlignbare resultater. Slik kan investeringer i forskning bidra til å få kontroll med infeksjonssykdommer og legge forholdene bedre tilrette for økonomisk vekst i utviklingslandISBN 978-91-85721-07-8</p

Can MLVA differentiate among endemic-like MRSA isolates with identical spa-type in a low-prevalence region?

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Norway is low, but an endemic-like MRSA clone with Staphylococcal protein A (spa)-type t304 has been established especially in nursing homes in the Oslo region causing several large outbreaks. The challenge was that spa-typing and the gold standard Pulsed-Field Gel Electrophoresis (PFGE) were inadequate in discriminating isolates in outbreak investigations. Additional higher resolution genotyping methods were needed. The aims of this study were a) to evaluate whether Multiple-Locus Variable number of tandem repeat Analysis (MLVA) could differentiate within the PFGE clusters between epidemiologically related and unrelated endemic-like ST8-MRSA-IV-t304-PVL-neg (MRSA-t304) isolates and b) investigate the evolution of the endemic-like MRSA-t304 clone over a 15-year time period. All MRSA-t304 isolates detected in the region from 1998 through April 2013 were included. In total, 194 of 197 isolates were available for PFGE and MLVA analyses. PFGE results on isolates from 1998–2010 have been published previously. Two PFGE clusters subdivided into eight MLVA types were detected. One major outbreak clone (PFGE cluster C2/ MLVA type MT5045) appeared from 2004 to 2011 causing long-lasting and large outbreaks in seven nursing homes and one hospital. Five new MLVA types (N = 9 isolates) differing in only one VNTR compared to the outbreak clone C2/MT5045 were detected, but only one (C2/MT5044) was seen after 2011. We suggest that MLVA can replace PFGE analysis, but MLVA may not be the optimal method in this setting as it did not discriminate between all epidemiologically unrelated isolates. The results may indicate that all eight outbreaks in different locations within the PFGE C2 cluster may be branches of one large regional outbreak. The major outbreak strain C2/MT5045 may now, however, be under control, extinguished or has moved geographically

Can MLVA differentiate among endemic-like MRSA isolates with identical spa-type in a low-prevalence region?

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Norway is low, but an endemic-like MRSA clone with Staphylococcal protein A (spa)-type t304 has been established especially in nursing homes in the Oslo region causing several large outbreaks. The challenge was that spa-typing and the gold standard Pulsed-Field Gel Electrophoresis (PFGE) were inadequate in discriminating isolates in outbreak investigations. Additional higher resolution genotyping methods were needed. The aims of this study were a) to evaluate whether Multiple-Locus Variable number of tandem repeat Analysis (MLVA) could differentiate within the PFGE clusters between epidemiologically related and unrelated endemic-like ST8-MRSA-IV-t304-PVL-neg (MRSA-t304) isolates and b) investigate the evolution of the endemic-like MRSA-t304 clone over a 15-year time period. All MRSA-t304 isolates detected in the region from 1998 through April 2013 were included. In total, 194 of 197 isolates were available for PFGE and MLVA analyses. PFGE results on isolates from 1998–2010 have been published previously. Two PFGE clusters subdivided into eight MLVA types were detected. One major outbreak clone (PFGE cluster C2/ MLVA type MT5045) appeared from 2004 to 2011 causing long-lasting and large outbreaks in seven nursing homes and one hospital. Five new MLVA types (N = 9 isolates) differing in only one VNTR compared to the outbreak clone C2/MT5045 were detected, but only one (C2/MT5044) was seen after 2011. We suggest that MLVA can replace PFGE analysis, but MLVA may not be the optimal method in this setting as it did not discriminate between all epidemiologically unrelated isolates. The results may indicate that all eight outbreaks in different locations within the PFGE C2 cluster may be branches of one large regional outbreak. The major outbreak strain C2/MT5045 may now, however, be under control, extinguished or has moved geographically

No associations established between single nucleotide polymorphisms in human Toll-like receptor 2 and Toll-interacting protein and Staphylococcus aureus bloodstream infections

Staphylococcus aureus bloodstream infections (SABSI) are associated with high morbidity and mortality. The Toll‐like receptor 2 (TLR2) and Toll‐interacting protein (TOLLIP) are important in recognition and regulation of human innate immunity response to S. aureus. Single nucleotide polymorphisms (SNPs) in the TLR2 and TOLLIP encoding genes have been associated with disease, including BSI. The aim of this study was to examine potential associations between a selection of SNPs in the genes encoding TLR2 and TOLLIP, and predisposition, severity, and outcome of SABSI. All patients ≥18 years of age with at least one S. aureus positive blood culture collected from March 2011 through February 2014 at Akershus University Hospital, Lørenskog, Norway, were considered for inclusion. Patients attending elective orthopaedic surgery (total hip and knee replacements, lumbar surgery) served as a control group. The TLR2 Arg753Gln, TLR2 Pro631His, TOLLIP rs5743942, and rs5743867 polymorphisms were analysed using TaqMan SNP Genotyping Assays. A total of 209 SABSI patients and 295 controls were included. The TLR2 Arg753Gln and TLR2 Pro631His polymorphisms were infrequent with no homozygotes and <10% heterozygotes. The included TLR2 and TOLLIP polymorphisms were not associated with susceptibility to SABSI, severity, 30‐day all‐cause mortality, or SABSI caused by the clonal complex 30 (CC30) genotype

Minimum spanning tree of the 8 different MLVA types found in 194 ST8-MRSA-IV-t304-PVL-negative isolates from 1998–2013.

<p>Short lines indicate difference in one VNTR, whereas long lines indicate difference in two VNTRs. The size of the circles corresponds to the number of isolates. MLVA types within PFGE cluster 1 (C1) is marked in grey, whereas MLVA types within PFGE C2 are white.</p

Longitudinal whole blood transcriptomic analysis characterizes neutrophil activation and interferon signaling in moderate and severe COVID-19

Abstract A maladaptive inflammatory response has been implicated in the pathogenesis of severe COVID-19. This study aimed to characterize the temporal dynamics of this response and investigate whether severe disease is associated with distinct gene expression patterns. We performed microarray analysis of serial whole blood RNA samples from 17 patients with severe COVID-19, 15 patients with moderate disease and 11 healthy controls. All study subjects were unvaccinated. We assessed whole blood gene expression patterns by differential gene expression analysis, gene set enrichment, two clustering methods and estimated relative leukocyte abundance using CIBERSORT. Neutrophils, platelets, cytokine signaling, and the coagulation system were activated in COVID-19, and this broad immune activation was more pronounced in severe vs. moderate disease. We observed two different trajectories of neutrophil-associated genes, indicating the emergence of a more immature neutrophil phenotype over time. Interferon-associated genes were strongly enriched in early COVID-19 before falling markedly, with modest severity-associated differences in trajectory. In conclusion, COVID-19 necessitating hospitalization is associated with a broad inflammatory response, which is more pronounced in severe disease. Our data suggest a progressively more immature circulating neutrophil phenotype over time. Interferon signaling is enriched in COVID-19 but does not seem to drive severe disease