SARS-CoV-2 variants of concern and spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencing

From Springer Nature via Jisc Publications RouterHistory: received 2022-04-21, rev-recd 2022-09-08, accepted 2022-10-05, registration 2022-10-10, pub-electronic 2022-10-18, online 2022-10-18, collection 2022-12Acknowledgements: Acknowledgements: We are immensely grateful to all our co-workers at the Section for Clinical Microbiology and Hospital Hygiene at Uppsala University Hospital, who PCR tested all the COVID-19 samples and consequently extracted the viral RNA for us from the positive samples. Secondly, we are deeply thankful to Tor-Elesh Albrigtsen for the remarkable assistance with data science, analysis and programming in Python.Publication status: PublishedFunder: Science for Life Laboratory; doi: http://dx.doi.org/10.13039/501100009252; Grant(s): ZSC – National core facility for pandemic preparednessFunder: Scandinavian Society for Antimicrobial Chemotherapy Foundation; doi: http://dx.doi.org/10.13039/501100011777; Grant(s): SLS-961049Funder: Erik, Karin and Gösta Selander Foundation; Grant(s): 2022Funder: Regionala Forskningsrådet Uppsala/Örebro; doi: http://dx.doi.org/10.13039/100019032; Grant(s): RFR-930984Funder: Uppsala UniversityAbstract: Background: Since the beginning of the COVID-19 pandemic, new variants of significance to public health have emerged. Consequently, early detection of new mutations and variants through whole-genome sequencing remains crucial to assist health officials in employing appropriate public health measures. Methods: We utilized the ARTIC Network SARS-CoV-2 tiled amplicon approach and Nanopore sequencing to sequence 4,674 COVID-19 positive patient samples from Uppsala County, Sweden, between week 15 and 52 in 2021. Using this data, we mapped the circulating variants of concern (VOC) in the county over time and analysed the Spike (S) protein mutational dynamics in the Delta variant throughout 2021. Results: The distribution of the SARS-CoV-2 VOC matched the national VOC distribution in Sweden, in 2021. In the S protein of the Delta variant, we detected mutations attributable to variants under monitoring and variants of interest (e.g., E484Q, Q613H, Q677H, A222V and Y145H) and future VOC (e.g., T95I and Y144 deletion, which are signature mutations in the Omicron variant). We also frequently detected some less well-described S protein mutations in our Delta sequences, that might play a role in shaping future emerging variants. These include A262S, Q675K, I850L, Q1201H, V1228L and M1237I. Lastly, we observed that some of the Delta variant’s signature mutations were underrepresented in our study due to artifacts of the used bioinformatics tools, approach and sequencing method. We therefore discuss some pitfalls and considerations when sequencing SARS-CoV-2 genomes. Conclusion: Our results suggest that genomic surveillance in a small, representative cohort can be used to make predictions about the circulating variants nationally. Moreover, we show that detection of transient mutations in currently circulating variants can give valuable clues to signature mutations of future VOC. Here we suggest six such mutations, that we detected frequently in the Delta variant during 2021. Lastly, we report multiple systematic errors that occurred when following the ARTIC Network SARS-CoV-2 tiled amplicon approach using the V3 primers and Nanopore sequencing, which led to the masking of some of the important signature mutations in the Delta sequences

Yrityksen x ulkomaalaisten työntekijöiden näkemyksiä perehdyttämisestä

Tämän opinnäytetyön tavoitteena on selvittää, miten kansainväliset työntekijät kokevat yrityksen perehdyttämisen organisaatioon sekä yhteiskuntaan. Opinnäytetyö rajataan käsittelemään suomalaiseen työyhteisöön ja yhteiskuntaan perehdyttämistä sekä työ- hönopastusta. Tarkoituksena on selvittää, miten kansainväliset työntekijät itse kokevat saamansa perehdytyksen, onko siitä ollut iso apu henkilöiden integroitumisessa yritykseen ja uuteen maahan sekä voisiko sitä jotenkin kehittää. Työ tehdään toimeksiantona ja toimeksiantajayritys on suomalainen matkailualan orga- nisaatio, jossa työskentelee useiden maiden kansalaisia palvelutyössä. Opinnäytetyön kohderyhmä rajautuu EU-maista muuttaneihin Helsingissä työskenteleviin henkilöihin. EU:n sisältä muuttavia rekrytoitavia henkilöitä on viime vuosina ollut huomattavasti isompi määrä, koska yrityksen haut avattiin EU tasoisesti. Tämän vuoksi haluttiinkin selvittää, miten ulkomaalaiset työntekijät kokevat yrityksen perehdyttämisen sekä voitaisiinko sitä jotenkin kehittää tulevaisuuden kasvavassa monikulttuurisessa työyhteisössä. Opinnäytetyö muodostuu teoriaosasta ja siihen liittyvästä empiirisestä tutkimuksesta. Teoria rakentuu perehdyttämisen ja monikulttuurisen työyhteisön termeihin. Tutkimusongelmat johdatetaan teoriaosasta ja perustellaan siellä osoitetulla tiedolla. Teoriaosa laadittiin helmi-maaliskuussa 2020. Tutkimuksessa hyödynnettiin sekä kvantitatiivista eli määrällistä tutkimusta että kvalita- tiivista eli laadullista tutkimusta. Kahden tutkimustavan avulla saatiin luotettavampia tut- kimustuloksia ja niitä pystyttiin vertailemaan toisiinsa. Tutkimuksessa verrattiin juuri aloittaneiden ja jo yli vuoden työsuhteessa olleiden näkemyksiä. Määrällinen tutkimus toteutettiin internetin kautta tehtävällä kyselytutkimuksella 24.4.-8.5.2020. Laadullinen tutkimus suoritettiin teemahaastatteluina eli puolistrukturoituna haastatteluna 4.-8.5.2020 välillä. Tutkimustulokset analysoitiin toukokuussa 2020. Määrällisen tutkimuksen heikon otannan vuoksi, tulokset ovat sattumanvaraisia eikä niitä voi yleistää. Molemmat tutkimustulokset antavat suuntaa siitä, että kielimuurilla on iso vaikutus ulkomaalaisten työyhteisöön ja maahan sopeutumisessa. Lisäksi tutkimukset osoittavat, että perehdytyksen osalta henkilöt kaipaisivat enemmän tukea ja aikaa käytännön asioiden hoitamiseen sekä yrityksen sisäisten toimintatapojen ymmärtämiseen. He ovat sitä mieltä, että mentoritoiminta voisi auttaa erilaisissa sopeutumiseen ja kotoutumiseen liittyvissä asioissa

Enkätbaserad utvärdering av farmakogenetisk kunskap bland finska läkare, farmaceuter och studerande i respektive område

Over 90 percent of the population has a genetic variation in any of the significant genes that metabolize drugs in the body (David, et al., 2021). These variants can be detected with a pharmacogenetic (PGx) test and, hence, avoid any adverse drug reactions or side effects that may occur due to abnormal drug metabolism. A PGx test alone is not enough for improved drug treatment. The physician needs to understand the results and know what changes need to be implemented based on the results, either by discontinuing the treatment, dose adjustment or choosing another drug. PGx testing has previously been perceived as something that is relevant only in the future. The fact is that PGx testing has lately received much more attention and it has become an important tool for personalized medicine (Edris, et al., 2021). However, its clinical implementation still remains limited. In this study, a 28-question survey was distributed online to Finnish physicians and pharmacists, including students in respective professions, working in either/both the municipal and/or private sector in Finland. The survey aimed to evaluate the current knowledge and perceptions among Finnish physicians and pharmacists of pharmacogenetics. The first eighteen questions and/or statements examine participants´ characteristics and general knowledge about pharmacogenetics. The following ten questions and/or statements examine participants´ deeper knowledge about pharmacogenetics. Altogether, 151 answers were submitted, of which 88 by pharmacists, 46 by physicians, and 17 by students. Forty-six percent strongly agreed, and forty-two percent agreed to the statement: “I believe that pharmacogenetic testing is helpful for predicting the risk of side effects for the patient”. However, only 6.5% (n=3) of all physicians stated that they have used PGx testing in their clinical practice more frequently. Even though twenty-six percent either strongly disagreed or disagreed with the statement: “I have basic knowledge of pharmacogenetics”, the results showed that the majority were nevertheless interested in receiving PGx education

SARS-CoV-2 variants of concern and spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencing.

From PubMed via Jisc Publications RouterHistory: received 2022-04-21, revised 2022-09-08, accepted 2022-10-05Publication status: epublishFunder: Science for Life Laboratory; Grant(s): ZSC - National core facility for pandemic preparednessFunder: Scandinavian Society for Antimicrobial Chemotherapy Foundation; Grant(s): SLS-961049Funder: Erik, Karin and Gösta Selander Foundation; Grant(s): 2022Funder: Regionala Forskningsrådet Uppsala/Örebro; Grant(s): RFR-930984Since the beginning of the COVID-19 pandemic, new variants of significance to public health have emerged. Consequently, early detection of new mutations and variants through whole-genome sequencing remains crucial to assist health officials in employing appropriate public health measures. We utilized the ARTIC Network SARS-CoV-2 tiled amplicon approach and Nanopore sequencing to sequence 4,674 COVID-19 positive patient samples from Uppsala County, Sweden, between week 15 and 52 in 2021. Using this data, we mapped the circulating variants of concern (VOC) in the county over time and analysed the Spike (S) protein mutational dynamics in the Delta variant throughout 2021. The distribution of the SARS-CoV-2 VOC matched the national VOC distribution in Sweden, in 2021. In the S protein of the Delta variant, we detected mutations attributable to variants under monitoring and variants of interest (e.g., E484Q, Q613H, Q677H, A222V and Y145H) and future VOC (e.g., T95I and Y144 deletion, which are signature mutations in the Omicron variant). We also frequently detected some less well-described S protein mutations in our Delta sequences, that might play a role in shaping future emerging variants. These include A262S, Q675K, I850L, Q1201H, V1228L and M1237I. Lastly, we observed that some of the Delta variant's signature mutations were underrepresented in our study due to artifacts of the used bioinformatics tools, approach and sequencing method. We therefore discuss some pitfalls and considerations when sequencing SARS-CoV-2 genomes. Our results suggest that genomic surveillance in a small, representative cohort can be used to make predictions about the circulating variants nationally. Moreover, we show that detection of transient mutations in currently circulating variants can give valuable clues to signature mutations of future VOC. Here we suggest six such mutations, that we detected frequently in the Delta variant during 2021. Lastly, we report multiple systematic errors that occurred when following the ARTIC Network SARS-CoV-2 tiled amplicon approach using the V3 primers and Nanopore sequencing, which led to the masking of some of the important signature mutations in the Delta sequences. [Abstract copyright: © 2022. The Author(s).

In-Flight Transmission of a SARS-CoV-2 Lineage B.1.617.2 Harbouring the Rare S:E484Q Immune Escape Mutation

We describe a flight-associated infection scenario of seven individuals with a B.1.617.2 (Delta) lineage, harbouring an S:E484Q point mutation. In Sweden, at least 10% of all positive SARS-CoV-2 samples were sequenced in each county; the B.1.717.2 + S:E484Q combination was not detected in Sweden before and was imported within the scenario described in this report. The high transmission rate of the delta lineage combined with the S:E484Q mutation, associated with immune escape in other lineages, makes this specific genetic combination a possible threat to the global fight against the COVID-19 pandemic. Even within the Omicron wave, the B.1.617.2 + S:E484Q variant appeared in community samples in Sweden, as it seems that this combination has an evolutionary gain compared to other B.1.617.2 lineages. The here described genomic combination was not detectable with the common fasta file-based Pango-lineage analysis, hence increasing the probability of the true global prevalence to be higher

Assessing compatibility and viral fitness between poultry-adapted H9N2 and wild bird-derived neuraminidases

Exchange of viral segments between one or more influenza virus subtypes can contribute to a shift in virulence and adaptation to new hosts. Among several influenza subtypes, H9N2 is widely circulating in poultry populations worldwide and has the ability to infect humans. Here, we studied the reassortant compatibility between chicken H9N2 with N1-N9 gene segments of wild bird origin, either with an intact or truncated stalk. Naturally occurring amino acid deletions in the NA stalk of the influenza virus can lead to increased virulence in both mallard ducks and chickens. Our findings show extended genetic compatibility between chicken H9Nx gene segments and the wild-bird NA with and without 20 amino acid stalk deletion. Replication kinetics in avian, mammalian and human cell lines revealed that parental chH9N2 and rH9N6 viruses with intact NA-stalk replicated significantly better in avian DF1 cells compared to human A549 cells. After introducing a stalk deletion, an enhanced preference for replication in mammalian and human cell lines could be observed for rH9N2(Delta)(H6), rH9N6(Delta) and rH9N9(Delta) compared to the parental chH9N2 virus. This highlights the potential emergence of novel viruses with variable phenotypic traits, warranting the continuous monitoring of H9N2 and co-circulating subtypes in avian hosts