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1.
Nat Commun ; 15(1): 7123, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164246

RESUMEN

Vast amounts of pathogen genomic, demographic and spatial data are transforming our understanding of SARS-CoV-2 emergence and spread. We examined the drivers of molecular evolution and spread of 291,791 SARS-CoV-2 genomes from Denmark in 2021. With a sequencing rate consistently exceeding 60%, and up to 80% of PCR-positive samples between March and November, the viral genome set is broadly whole-epidemic representative. We identify a consistent rise in viral diversity over time, with notable spikes upon the importation of novel variants (e.g., Delta and Omicron). By linking genomic data with rich individual-level demographic data from national registers, we find that individuals aged  < 15 and  > 75 years had a lower contribution to molecular change (i.e., branch lengths) compared to other age groups, but similar molecular evolutionary rates, suggesting a lower likelihood of introducing novel variants. Similarly, we find greater molecular change among vaccinated individuals, suggestive of immune evasion. We also observe evidence of transmission in rural areas to follow predictable diffusion processes. Conversely, urban areas are expectedly more complex due to their high mobility, emphasising the role of population structure in driving virus spread. Our analyses highlight the added value of integrating genomic data with detailed demographic and spatial information, particularly in the absence of structured infection surveys.


Asunto(s)
COVID-19 , Genoma Viral , SARS-CoV-2 , Humanos , Dinamarca/epidemiología , COVID-19/epidemiología , COVID-19/virología , COVID-19/transmisión , SARS-CoV-2/genética , SARS-CoV-2/clasificación , Genoma Viral/genética , Adulto , Persona de Mediana Edad , Anciano , Adolescente , Adulto Joven , Evolución Molecular , Masculino , Femenino , Preescolar , Niño , Filogenia , Lactante
2.
APMIS ; 132(10): 734-740, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38961316

RESUMEN

SARS-CoV-2 variants of concern (VOC), such as Delta and Omicron have harbored mutations, which increased viral infectivity or ability to evade neutralizing antibodies. Immunocompromised patients might be a source of some of these emerging variants. In this study, we sequenced 17 consecutive samples from an immunocompromised patient with a long-term SARS-CoV-2 infection with the pre-VOC era lineage B.1.177.35. We here describe the emergence of 73 nonsynonymous minority variants in this patient and show that 10 of these mutations became dominant in the viral population during the treatment period. Four of these were seen throughout the infection period and had a very low global prevalence, although three of them were also observed later in the Alpha, Delta, and Omicron lineages. We also found that two adjacent nsp12 variants (M785I and S786P) belonged to different quasi-species and competed during the early stages of infection and remdesivir administration. This emphasizes the importance of ongoing genome surveillance of SARS-CoV-2 among immunocpromised patients.


Asunto(s)
COVID-19 , Huésped Inmunocomprometido , Mutación , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , COVID-19/virología , Dinamarca/epidemiología , Tratamiento Farmacológico de COVID-19 , Antivirales/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Masculino , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Glicoproteína de la Espiga del Coronavirus/genética , Femenino , Genoma Viral/genética , Persona de Mediana Edad , Enfermedad Crónica , ARN Polimerasa Dependiente de ARN de Coronavirus
3.
PLoS Pathog ; 20(7): e1012039, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38950065

RESUMEN

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) not only caused the COVID-19 pandemic but also had a major impact on farmed mink production in several European countries. In Denmark, the entire population of farmed mink (over 15 million animals) was culled in late 2020. During the period of June to November 2020, mink on 290 farms (out of about 1100 in the country) were shown to be infected with SARS-CoV-2. Genome sequencing identified changes in the virus within the mink and it is estimated that about 4000 people in Denmark became infected with these mink virus variants. However, the routes of transmission of the virus to, and from, the mink have been unclear. Phylogenetic analysis revealed the generation of multiple clusters of the virus within the mink. Detailed analysis of changes in the virus during replication in mink and, in parallel, in the human population in Denmark, during the same time period, has been performed here. The majority of cases in mink involved variants with the Y453F substitution and the H69/V70 deletion within the Spike (S) protein; these changes emerged early in the outbreak. However, further introductions of the virus, by variants lacking these changes, from the human population into mink also occurred. Based on phylogenetic analysis of viral genome data, we estimate, using a conservative approach, that about 17 separate examples of mink to human transmission occurred in Denmark but up to 59 such events (90% credible interval: (39-77)) were identified using parsimony to count cross-species jumps on transmission trees inferred using Bayesian methods. Using the latter approach, 136 jumps (90% credible interval: (117-164)) from humans to mink were found, which may underlie the farm-to-farm spread. Thus, transmission of SARS-CoV-2 from humans to mink, mink to mink, from mink to humans and between humans were all observed.


Asunto(s)
COVID-19 , Visón , Filogenia , SARS-CoV-2 , Visón/virología , COVID-19/transmisión , COVID-19/virología , COVID-19/epidemiología , COVID-19/veterinaria , SARS-CoV-2/genética , Animales , Dinamarca/epidemiología , Humanos , Pandemias , Granjas , Betacoronavirus/genética , Betacoronavirus/clasificación , Genoma Viral , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/transmisión , Glicoproteína de la Espiga del Coronavirus/genética
5.
Euro Surveill ; 28(29)2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37470739

RESUMEN

BackgroundThe COVID-19 pandemic was of major concern in Greenland. There was a high possibility of rapid transmission in settlements, and an increased risk of morbidity and mortality because of comorbidities in the population and limited access to specialised healthcare in remote areas.AimTo describe the epidemiology of the COVID-19 pandemic in Greenland and evaluate the effects of a strict COVID-19 strategy until risk groups were immunised.MethodsWe studied the epidemiology during March 2020 to June 2022. We describe the non-pharmaceutical interventions (NPIs), PCR-confirmed COVID-19 cases and vaccination coverage with data from the registries of the Greenlandic health authority.ResultsWe found 21,419 confirmed cases per 100,000 inhabitants (54% female, 46% male), 342 per 100,000 were hospitalised and 16 per 100,000 were admitted to the intensive care unit. The COVID-19 mortality rate was 39 per 100,000, all those affected were aged above 65 years. No excess overall mortality was observed. The vaccination coverage by June 2022 was 71.67 and 41% for one, two and three doses, respectively.ConclusionSARS-CoV-2 circulation in Greenland was low, given strict restrictions until all eligible inhabitants had been offered immunisation. The main impact of the pandemic was from May 2021 onwards with increasing numbers of confirmed cases. This occurred after introduction of the vaccine programme, which may have had an influence on the severity of the associated morbidity and mortality experienced. Halting community transmission of SARS-CoV-2 with NPIs until the majority of the population had been immunised was a successful strategy in Greenland.


Asunto(s)
COVID-19 , Masculino , Humanos , Femenino , Anciano , COVID-19/epidemiología , Pandemias/prevención & control , SARS-CoV-2 , Groenlandia/epidemiología , Factores de Riesgo
6.
Viruses ; 15(6)2023 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-37376698

RESUMEN

Metagenomic next-generation sequencing (mNGS) is receiving increased attention for the detection of new viruses and infections occurring at the human-animal interface. The ability to actively transport and relocate this technology enables in situ virus identification, which could reduce response time and enhance disease management. In a previous study, we developed a straightforward mNGS procedure that greatly enhances the detection of RNA and DNA viruses in human clinical samples. In this study, we improved the mNGS protocol with transportable battery-driven equipment for the portable, non-targeted detection of RNA and DNA viruses in animals from a large zoological facility, to simulate a field setting for point-of-incidence virus detection. From the resulting metagenomic data, we detected 13 vertebrate viruses from four major virus groups: (+)ssRNA, (+)ssRNA-RT, dsDNA and (+)ssDNA, including avian leukosis virus in domestic chickens (Gallus gallus), enzootic nasal tumour virus in goats (Capra hircus) and several small, circular, Rep-encoding, ssDNA (CRESS DNA) viruses in several mammal species. More significantly, we demonstrate that the mNGS method is able to detect potentially lethal animal viruses, such as elephant endotheliotropic herpesvirus in Asian elephants (Elephas maximus) and the newly described human-associated gemykibivirus 2, a human-to-animal cross-species virus, in a Linnaeus two-toed sloth (Choloepus didactylus) and its enclosure, for the first time.


Asunto(s)
Pollos , Herpesviridae , Animales , Humanos , Pollos/genética , Herpesviridae/genética , Virus ADN/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , ARN , Dinamarca , Metagenómica/métodos , Mamíferos
7.
Microbiol Spectr ; 11(1): e0359122, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36625603

RESUMEN

Multiple mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) increase transmission, disease severity, and immune evasion and facilitate zoonotic or anthropozoonotic infections. Four such mutations, ΔH69/V70, L452R, E484K, and N501Y, occurred in the SARS-CoV-2 spike glycoprotein in combinations that allow the simultaneous detection of VOCs. Here, we present two flexible reverse transcription-quantitative PCR (RT-qPCR) platforms for small- and large-scale screening (also known as variant PCR) to detect these mutations and schemes for adapting the platforms to future mutations. The large-scale RT-qPCR platform was validated by pairwise matching of RT-qPCR results with whole-genome sequencing (WGS) consensus genomes, showing high specificity and sensitivity. Both platforms are valuable examples of complementing WGS to support the rapid detection of VOCs. Our mutational signature approach served as an important intervention measure for the Danish public health system to detect and delay the emergence of new VOCs. IMPORTANCE Denmark weathered the SARS-CoV-2 crisis with relatively low rates of infection and death. Intensive testing strategies with the aim of detecting SARS-CoV-2 in symptomatic and nonsymptomatic individuals were available by establishing a national test system called TestCenter Denmark. This testing regime included the detection of SARS-CoV-2 signature mutations, with referral to the national health system, thereby delaying outbreaks of variants of concern. Our study describes the design of the large-scale RT-qPCR platform established at TestCenter Denmark in conjunction with whole-genome sequencing to report mutations of concern to the national health system. Validation of the large-scale RT-qPCR platform using paired WGS consensus genomes showed high sensitivity and specificity. For smaller laboratories with limited infrastructure, we developed a flexible small-scale RT-qPCR platform to detect three signature mutations in a single run. The RT-qPCR platforms are important tools to support the control of the SARS-CoV-2 endemic in Denmark.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Transcripción Reversa , COVID-19/diagnóstico , Reacción en Cadena de la Polimerasa , Mutación
8.
Lancet Infect Dis ; 23(2): 167-176, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36270311

RESUMEN

BACKGROUND: Estimates of immunity and severity for the SARS-CoV-2 omicron subvariant BA.5 are important to assess the public health impact associated with its rapid global spread despite vaccination. We estimated natural and vaccine immunity and severity of BA.5 relative to BA.2 in Denmark, a country with high mRNA-vaccination coverage and free-of-charge RT-PCR testing. METHODS: This nation-wide population-based study in Denmark included residents aged 18 years or older who had taken an RT-PCR test between 10 April and 30 June, 2022 (ie, the outcome period), and who the national COVID-19 surveillance system identified as having information since February 2020 on RT-PCR tests, whole-genome sequencing, vaccinations, and hospitalisation with a positive RT-PCR test and COVID-19 as the main diagnosis. First, we used a case-control design, in which cases were people infected with BA.5 or BA.2 during the outcome period and controls were people who tested negative for SARS-CoV-2 infection during the outcome period. We calculated the protection provided by a previous PCR-confirmed omicron infection against BA.5 and BA.2 infection and hospitalisation among triple-vaccinated individuals. Second, we compared vaccination status in people infected with BA.5 versus BA.2 and estimated relative vaccine protection against each subvariant. Third, we compared rates of hospitalisation for COVID-19 among people infected with BA.5 versus BA.2. We estimated effects using logistic regression with adjustment for sex, age, region, PCR-test date, comorbidity and, as appropriate, vaccination and previous infection status. FINDINGS: A total of 210 (2·4%) of 8678 of BA.5 cases, 192 (0·7%) of 29 292 of BA.2 cases, and 33 972 (19·0%) of 178 669 PCR-negative controls previously had an omicron infection, which was estimated in the adjusted analyses to offer 92·7% (95% CI 91·6-93·7) protection against BA.5 infection and 97·1% (96·6-97·5) protection against BA.2 infection. We found similarly high amounts of protection against hospitalisation owing to infection with BA.5 (96·4% [95% CI 74·2-99·5]) and BA.2 (91·2% [76·3-96·7]). Vaccine coverage (three mRNA doses vs none) was 9307 (94·2%) of 9878 among BA.5 cases and 30 581 (94·8%) of 32 272 among BA.2 cases, although in the adjusted analysis, there was a trend towards slightly higher vaccination coverage among BA.5 cases than BA.2 cases (OR 1·18 [95% CI 0·99-1·42]; p=0·064), possibly suggesting marginally poorer vaccine protection against BA.5. The rate of hospitalisation due to COVID-19 was higher among the BA.5 cases (210 [1·9%] of 11 314) than among the BA.2 cases (514 [1·4%] of 36 805), with an OR of 1·34 (95% CI 1·14-1·57) and an adjusted OR of 1·69 (95% CI 1·22-2·33), despite low and stable COVID-19 hospitalisation numbers during the study period. INTERPRETATION: The study provides evidence that a previous omicron infection in triple-vaccinated individuals provides high amounts of protection against BA.5 and BA.2 infections. However, protection estimates greater than 90% might be too high if individuals with a previous infection were more likely than those without one to come forward for a test for reasons other than suspicion of COVID-19. Our analysis also showed that vaccine protection against BA.5 infection was similar to, or slightly weaker than, protection against BA.2 infection. Finally, there was evidence that BA.5 infections were associated with an increased risk of hospitalisation compared with BA.2 infections. FUNDING: There was no funding source for this study.


Asunto(s)
COVID-19 , Vacunas , Humanos , Reinfección , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2/genética , ARN Mensajero , Dinamarca/epidemiología
9.
PLoS Med ; 19(9): e1003992, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36048766

RESUMEN

BACKGROUND: The continued occurrence of more contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants and waning immunity over time require ongoing reevaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in 2 age groups (12 to 59 and 60 years or above) of 2 or 3 vaccine doses (BNT162b2 mRNA or mRNA-1273) by time since vaccination against SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) hospitalization in an Alpha-, Delta-, or Omicron-dominated period. METHODS AND FINDINGS: A Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha, Delta, or Omicron variant. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all previously uninfected residents in Denmark aged 12 years or above (18 years or above for the analysis of 3 doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021), and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated (1-hazard ratio∙100) using Cox proportional hazard regression models with underlying calendar time and adjustments for age, sex, comorbidity, and geographical region. Vaccination status was included as a time-varying exposure. In the oldest age group, VE against infection after 2 doses was 90.7% (95% CI: 88.2; 92.7) for the Alpha variant, 82.3% (95% CI: 75.5; 87.2) for the Delta variant, and 39.9% (95% CI: 26.3; 50.9) for the Omicron variant 14 to 30 days since vaccination. The VE waned over time and was 73.2% (Alpha, 95% CI: 57.1; 83.3), 50.0% (Delta, 95% CI: 46.7; 53.0), and 4.4% (Omicron, 95% CI: -0.1; 8.7) >120 days since vaccination. Higher estimates were observed after the third dose with VE estimates against infection of 86.1% (Delta, 95% CI: 83.3; 88.4) and 57.7% (Omicron, 95% CI: 55.9; 59.5) 14 to 30 days since vaccination. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 98.1% or above for the Alpha and Delta variants. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 95.5% or above for the Omicron variant. The main limitation of this study is the nonrandomized study design including potential differences between the unvaccinated (reference group) and vaccinated individuals. CONCLUSIONS: Two vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha and Delta variants with protection, notably against infection, waning over time. Two vaccine doses provided only limited and short-lived protection against SARS-CoV-2 infection with Omicron. However, the protection against COVID-19 hospitalization following Omicron SARS-CoV-2 infection was higher. The third vaccine dose substantially increased the level and duration of protection against infection with the Omicron variant and provided a high level of sustained protection against COVID-19 hospitalization among the +60-year-olds.


Asunto(s)
COVID-19 , Vacunas Virales , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , Estudios de Cohortes , Dinamarca/epidemiología , Hospitalización , Humanos , SARS-CoV-2/genética , Eficacia de las Vacunas
10.
Nat Commun ; 13(1): 5760, 2022 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-36180438

RESUMEN

SARS coronavirus 2 (SARS-CoV-2) continues to evolve and new variants emerge. Using nationwide Danish data, we estimate the transmission dynamics of SARS-CoV-2 Omicron subvariants BA.1 and BA.2 within households. Among 22,678 primary cases, we identified 17,319 secondary infections among 50,588 household contacts during a 1-7 day follow-up. The secondary attack rate (SAR) was 29% and 39% in households infected with Omicron BA.1 and BA.2, respectively. BA.2 was associated with increased susceptibility of infection for unvaccinated household contacts (Odds Ratio (OR) 1.99; 95%-CI 1.72-2.31), fully vaccinated contacts (OR 2.26; 95%-CI 1.95-2.62) and booster-vaccinated contacts (OR 2.65; 95%-CI 2.29-3.08), compared to BA.1. We also found increased infectiousness from unvaccinated primary cases infected with BA.2 compared to BA.1 (OR 2.47; 95%-CI 2.15-2.84), but not for fully vaccinated (OR 0.66; 95%-CI 0.57-0.78) or booster-vaccinated primary cases (OR 0.69; 95%-CI 0.59-0.82). Omicron BA.2 is inherently more transmissible than BA.1. Its immune-evasive properties also reduce the protective effect of vaccination against infection, but do not increase infectiousness of breakthrough infections from vaccinated individuals.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/prevención & control , Dinamarca/epidemiología , Composición Familiar , Humanos , SARS-CoV-2/genética
11.
Euro Surveill ; 27(36)2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36082686

RESUMEN

Following the report of a non-travel-associated cluster of monkeypox cases by the United Kingdom in May 2022, 41 countries across the WHO European Region have reported 21,098 cases and two deaths by 23 August 2022. Nowcasting suggests a plateauing in case notifications. Most cases (97%) are MSM, with atypical rash-illness presentation. Spread is mainly through close contact during sexual activities. Few cases are reported among women and children. Targeted interventions of at-risk groups are needed to stop further transmission.


Asunto(s)
Exantema , Mpox , Animales , Niño , Brotes de Enfermedades , Femenino , Humanos , Mpox/diagnóstico , Mpox/epidemiología , Monkeypox virus , Organización Mundial de la Salud
12.
Infect Dis Rep ; 14(4): 501-504, 2022 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-35893472

RESUMEN

HIV-1 resistance towards integrase inhibitors is a potential threat of the success of HIV-1 combination treatment. G118R is a rare drug resistance mutation conferring pan-integrase resistance. Here, we describe the occurrence of G118R in a HIV-1 subtype-B-positive individual with major compliance problems, detected while the patient was on dolutegravir-based cART. We speculate the pre-selection of M184I/V aided the occurrence of G118R in this case, and discuss the robustness of dolutegravir-based therapies.

13.
Nat Commun ; 13(1): 3764, 2022 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-35773247

RESUMEN

Effective vaccines protect individuals by not only reducing the susceptibility to infection, but also reducing the infectiousness of breakthrough infections in vaccinated cases. To disentangle the vaccine effectiveness against susceptibility to infection (VES) and vaccine effectiveness against infectiousness (VEI), we took advantage of Danish national data comprising 24,693 households with a primary case of SARS-CoV-2 infection (Delta Variant of Concern, 2021) including 53,584 household contacts. In this setting, we estimated VES as 61% (95%-CI: 59-63), when the primary case was unvaccinated, and VEI as 31% (95%-CI: 26-36), when the household contact was unvaccinated. Furthermore, unvaccinated secondary cases with an infection exhibited a three-fold higher viral load compared to fully vaccinated secondary cases with a breakthrough infection. Our results demonstrate that vaccinations reduce susceptibility to infection as well as infectiousness, which should be considered by policy makers when seeking to understand the public health impact of vaccination against transmission of SARS-CoV-2.


Asunto(s)
COVID-19 , Vacunas , COVID-19/prevención & control , Humanos , SARS-CoV-2 , Vacunación
14.
Genome Med ; 14(1): 47, 2022 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-35505393

RESUMEN

BACKGROUND: In early 2021, the SARS-CoV-2 lineage B.1.1.7 (Alpha variant) became dominant across large parts of the world. In Denmark, comprehensive and real-time test, contact-tracing, and sequencing efforts were applied to sustain epidemic control. Here, we use these data to investigate the transmissibility, introduction, and onward transmission of B.1.1.7 in Denmark. METHODS: We analyzed a comprehensive set of 60,178 SARS-CoV-2 genomes generated from high-throughput sequencing by the Danish COVID-19 Genome Consortium, representing 34% of all positive cases in the period 14 November 2020 to 7 February 2021. We calculated the transmissibility of B.1.1.7 relative to other lineages using Poisson regression. Including all 1976 high-quality B.1.1.7 genomes collected in the study period, we constructed a time-scaled phylogeny, which was coupled with detailed travel history and register data to outline the introduction and onward transmission of B.1.1.7 in Denmark. RESULTS: In a period with unchanged restrictions, we estimated an increased B.1.1.7 transmissibility of 58% (95% CI: [56%, 60%]) relative to other lineages. Epidemiological and phylogenetic analyses revealed that 37% of B.1.1.7 cases were related to the initial introduction in November 2020. The relative number of cases directly linked to introductions varied between 10 and 50% throughout the study period. CONCLUSIONS: Our findings corroborate early estimates of increased transmissibility of B.1.1.7. Both substantial early expansion when B.1.1.7 was still unmonitored and continuous foreign introductions contributed considerably to case numbers. Finally, our study highlights the benefit of balanced travel restrictions and self-isolation procedures coupled with comprehensive surveillance efforts, to sustain epidemic control in the face of emerging variants.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Dinamarca/epidemiología , Humanos , Filogenia , SARS-CoV-2/genética
15.
Epidemiol Infect ; 150: e123, 2022 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-35317884

RESUMEN

Denmark hosted four games during the 2020 UEFA European championships (EC2020). After declining positive SARS-CoV-2 test rates in Denmark, a rise occurred during and after the tournament, concomitant with the replacement of the dominant Alpha lineage (B.1.1.7) by the Delta lineage (B.1.617.2), increasing vaccination rates and cessation of several restrictions. A cohort study including 33 227 cases was conducted from 30 May to 25 July 2021, 14 days before and after the EC2020. Included was a nested cohort with event information from big-screen events and matches at the Danish national stadium, Parken (DNSP) in Copenhagen, held from 12 June to 28 June 2021. Information from whole-genome sequencing, contact tracing and Danish registries was collected. Case-case connections were used to establish transmission trees. Cases infected on match days were compared to cases not infected on match days as a reference. The crude incidence rate ratio (IRR) of transmissions was 1.55, corresponding to 584 (1.76%) cases attributable to EC2020 celebrations. The IRR adjusted for covariates was lower (IRR 1.41) but still significant, and also pointed to a reduced number of transmissions from fully vaccinated cases (IRR 0.59). These data support the hypothesis that the EC2020 celebrations contributed to the rise of cases in Denmark in the early summer of 2021.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Estudios de Cohortes , Dinamarca/epidemiología , Humanos
16.
Euro Surveill ; 27(10)2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35272746

RESUMEN

Following emergence of the SARS-CoV-2 variant Omicron in November 2021, the dominant BA.1 sub-lineage was replaced by the BA.2 sub-lineage in Denmark. We analysed the first 2,623 BA.2 cases from 29 November 2021 to 2 January 2022. No epidemiological or clinical differences were found between individuals infected with BA.1 versus BA.2. Phylogenetic analyses showed a geographic east-to-west transmission of BA.2 from the Capital Region with clusters expanding after the Christmas holidays. Mutational analysis shows distinct differences between BA.1 and BA.2.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Dinamarca/epidemiología , Humanos , Epidemiología Molecular , Filogenia , SARS-CoV-2/genética
17.
J Med Case Rep ; 16(1): 62, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-35164871

RESUMEN

BACKGROUND: Human immunodeficiency virus-1-associated neurocognitive disorder is a known complication in individuals treated with antiretroviral therapy. Cerebrospinal fluid escape, which is defined as discordant higher cerebrospinal fluid viremia than plasma, may occur in antiretroviral therapy-experienced individuals. Different cerebrospinal fluid versus plasma mutation patterns have been observed in individuals with cerebrospinal fluid escape. CASE PRESENTATION: A 46-year-old adult African male with human immunodeficiency virus-1 infection and acquired immunodeficiency syndrome based on cerebral toxoplasmosis and a chronic hepatitis B virus infection developed cerebrospinal fluid escape. A different human immunodeficiency virus-1 genotypic drug resistance profile was observed in plasma compared with cerebrospinal fluid. Brain biopsy and cerebral magnetic resonance imaging indicated the development of human immunodeficiency virus encephalopathy. A discordant protease inhibitor mutation/wild-type T74PT in plasma but not in cerebrospinal fluid indicated poor central nervous system penetration due to the selective pressure of drug therapy. An intensified antiretroviral therapy regimen including dolutegravir with good central nervous system penetration improved conditions. CONCLUSIONS: This case shows the importance of measuring human immunodeficiency virus drug resistance in cerebrospinal fluid, which might differ from resistance detected in plasma samples and target effective antiretroviral therapy treatment accordingly.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Hepatitis B Crónica , Adulto , Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Plasma , Carga Viral
18.
J Clin Virol Plus ; 2(4): 100120, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36945677

RESUMEN

Early detection of pathogens at the point of care helps reduce the threats to human and animal health from emerging pathogens. Initially, the disease-causing agent will be unknown and needs to be identified; this often requires specific laboratory facilities. Here we describe the development of an unbiased detection assay for RNA and DNA viruses using metagenomic Nanopore sequencing and simple methods that can be transferred into a field setting. Human clinical samples containing the RNA virus SARS-CoV-2 or the DNA viruses human papillomavirus (HPV) and molluscum contagiosum virus (MCV) were used as a test of concept. Firstly, the virus detection potential was optimized by investigating different pretreatments for reducing non-viral nucleic acid components. DNase I pretreatment followed by filtration increased the proportion of SARS-CoV-2 sequenced reads > 500-fold compared with no pretreatments. This was sufficient to achieve virus detection with high confidence and allowed variant identification. Next, we tested individual SARS-CoV-2 samples with various viral loads (measured as CT-values determined by RT-qPCR). Lastly, we tested the assay on clinical samples containing the DNA virus HPV and co-infection with MCV to show the assay's detection potential for DNA viruses. This protocol is fast (same day results). We hope to apply this method in other settings for point of care detection of virus pathogens, thus eliminating the need for transport of infectious samples, cold storage and a specialized laboratory.

19.
Nat Commun ; 12(1): 7251, 2021 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-34903718

RESUMEN

New lineages of SARS-CoV-2 are of potential concern due to higher transmissibility, risk of severe outcomes, and/or escape from neutralizing antibodies. Lineage B.1.1.7 (the Alpha variant) became dominant in early 2021, but the association between transmissibility and risk factors, such as age of primary case and viral load remains poorly understood. Here, we used comprehensive administrative data from Denmark, comprising the full population (January 11 to February 7, 2021), to estimate household transmissibility. This study included 5,241 households with primary cases; 808 were infected with lineage B.1.1.7 and 4,433 with other lineages. Here, we report an attack rate of 38% in households with a primary case infected with B.1.1.7 and 27% in households with other lineages. Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load.


Asunto(s)
Factores de Edad , COVID-19/transmisión , SARS-CoV-2 , Carga Viral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , Niño , Preescolar , Dinamarca/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Adulto Joven
20.
Euro Surveill ; 26(50)2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34915977

RESUMEN

By 9 December 2021, 785 SARS-CoV-2 Omicron variant cases have been identified in Denmark. Most cases were fully (76%) or booster-vaccinated (7.1%); 34 (4.3%) had a previous SARS-CoV-2 infection. The majority of cases with available information reported symptoms (509/666; 76%) and most were infected in Denmark (588/644; 91%). One in five cases cannot be linked to previous cases, indicating widespread community transmission. Nine cases have been hospitalised, one required intensive care and no deaths have been registered.


Asunto(s)
COVID-19 , SARS-CoV-2 , Dinamarca/epidemiología , Humanos
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