Project description:BackgroundEstimates of the severity of the SARS-CoV-2 omicron variant (B.1.1.529) are crucial to assess the public health impact associated with its rapid global dissemination. We estimated the risk of SARS-CoV-2-related hospitalisations after infection with omicron compared with the delta variant (B.1.617.2) in Denmark, a country with high mRNA vaccination coverage and extensive free-of-charge PCR testing capacity.MethodsIn this observational cohort study, we included all RT-PCR-confirmed cases of SARS-CoV-2 infection in Denmark, with samples taken between Nov 21 (date of first omicron-positive sample) and Dec 19, 2021. Individuals were identified in the national COVID-19 surveillance system database, which included results of a variant-specific RT-PCR that detected omicron cases, and data on SARS-CoV-2-related hospitalisations (primary outcome of the study). We calculated the risk ratio (RR) of hospitalisation after infection with omicron compared with delta, overall and stratified by vaccination status, in a Poisson regression model with robust SEs, adjusted a priori for reinfection status, sex, age, region, comorbidities, and time period.FindingsBetween Nov 21 and Dec 19, 2021, among the 188 980 individuals with SARS-CoV-2 infection, 38 669 (20·5%) had the omicron variant. SARS-CoV-2-related hospitalisations and omicron cases increased during the study period. Overall, 124 313 (65·8%) of 188 980 individuals were vaccinated, and vaccination was associated with a lower risk of hospitalisation (adjusted RR 0·24, 95% CI 0·22-0·26) compared with cases with no doses or only one dose of vaccine. Compared with delta infection, omicron infection was associated with an adjusted RR of hospitalisation of 0·64 (95% CI 0·56-0·75; 222 [0·6%] of 38 669 omicron cases admitted to hospital vs 2213 [1·5%] of 150 311 delta cases). For a similar comparison by vaccination status, the RR of hospitalisation was 0·57 (0·44-0·75) among cases with no or only one dose of vaccine, 0·71 (0·60-0·86) among those who received two doses, and 0·50 (0·32-0·76) among those who received three doses.InterpretationWe found a significantly lower risk of hospitalisation with omicron infection compared with delta infection among both vaccinated and unvaccinated individuals, suggesting an inherent reduced severity of omicron. Our results could guide modelling of the effect of the ongoing global omicron wave and thus health-care system preparedness.FundingNone.
Project description:The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become widespread across the world in a flashing manner. As of December 7, 2021, a total of 758 Omicron cases were confirmed in Denmark. Using the nucleotide sequences of the Delta and Omicron variants registered from Denmark in the GISAID database, we found that the effective (instantaneous) reproduction number of Omicron is 3.19 (95% confidence interval [CI]: 2.82-3.61) times greater than that of Delta under the same epidemiological conditions. The proportion of Omicron infections among all SARS-CoV-2 infections in Denmark was expected to exceed 95% on December 28, 2021, with a 95% CI from December 25 to December 31, 2021. Given that the Delta variant or variants less transmissible than Delta are dominant in most countries, the rapid increase in Omicron in the virus population may be observed as soon as the Omicron is introduced. Preparing proactive control measures is vital, assuming the substantial advantage of the transmission by Omicron.
Project description:BackgroundThe more infectious SARS-CoV-2 lineage B.1.1.7 rapidly spread in Europe after December, 2020, and a concern that B.1.1.7 could cause more severe disease has been raised. Taking advantage of Denmark's high RT-PCR testing and whole genome sequencing capacities, we used national health register data to assess the risk of COVID-19 hospitalisation in individuals infected with B.1.1.7 compared with those with other SARS-CoV-2 lineages.MethodsWe did an observational cohort study of all SARS-CoV-2-positive cases confirmed by RT-PCR in Denmark, sampled between Jan 1 and March 24, 2021, with 14 days of follow-up for COVID-19 hospitalisation. Cases were identified in the national COVID-19 surveillance system database, which includes data from the Danish Microbiology Database (RT-PCR test results), the Danish COVID-19 Genome Consortium, the National Patient Registry, the Civil Registration System, as well as other nationwide registers. Among all cases, COVID-19 hospitalisation was defined as first admission lasting longer than 12 h within 14 days of a sample with a positive RT-PCR result. The study population and main analysis were restricted to the proportion of cases with viral genome data. We calculated the risk ratio (RR) of admission according to infection with B.1.1.7 versus other co-existing lineages with a Poisson regression model with robust SEs, adjusted a priori for sex, age, calendar time, region, and comorbidities. The contribution of each covariate to confounding of the crude RR was evaluated afterwards by a stepwise forward inclusion.FindingsBetween Jan 1 and March 24, 2021, 50 958 individuals with a positive SARS-CoV-2 test and at least 14 days of follow-up for hospitalisation were identified; 30 572 (60·0%) had genome data, of whom 10 544 (34·5%) were infected with B.1.1.7. 1944 (6·4%) individuals had a COVID-19 hospitalisation and of these, 571 (29·4%) had a B.1.1.7 infection and 1373 (70·6%) had an infection with other SARS-CoV-2 lineages. Although the overall number of hospitalisations decreased during the study period, the proportion of individuals infected with B.1.1.7 increased from 3·5% to 92·1% per week. B.1.1.7 was associated with a crude RR of hospital admission of 0·79 (95% CI 0·72-0·87; p<0·0001) and an adjusted RR of 1·42 (95% CI 1·25-1·60; p<0·0001). The adjusted RR was increased in all strata of age and calendar period-the two covariates with the largest contribution to confounding of the crude RR.InterpretationInfection with SARS-CoV-2 lineage B.1.1.7 was associated with an increased risk of hospitalisation compared with that of other lineages in an analysis adjusted for covariates. The overall effect on hospitalisations in Denmark was lessened due to a strict lockdown, but our findings could support hospital preparedness and modelling of the projected impact of the epidemic in countries with uncontrolled spread of B.1.1.7.FundingNone.
Project description:The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on long term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We here have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma and Epsilon, at picomolar ranges of IC50 in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by co-treatment in K18-hACE2-transgenic mice, accompanying with a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggests that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic.
Project description:In late 2021, the Omicron SARS-CoV-2 variant overtook the previously dominant Delta variant, but the extent to which this transition was driven by immune evasion or a change in the inherent transmissibility is currently unclear. We estimate SARS-CoV-2 transmission within Danish households during December 2021. Among 26,675 households (8,568 with the Omicron VOC), we identified 14,140 secondary infections within a 1-7-day follow-up period. The secondary attack rate was 29% and 21% in households infected with Omicron and Delta, respectively. For Omicron, the odds of infection were 1.10 (95%-CI: 1.00-1.21) times higher for unvaccinated, 2.38 (95%-CI: 2.23-2.54) times higher for fully vaccinated and 3.20 (95%-CI: 2.67-3.83) times higher for booster-vaccinated contacts compared to Delta. We conclude that the transition from Delta to Omicron VOC was primarily driven by immune evasiveness and to a lesser extent an inherent increase in the basic transmissibility of the Omicron variant.
Project description:BackgroundThe SARS-CoV-2 Delta variant was first identified in the U.S. in March 2021 and has rapidly become the predominant lineage across the U.S. due to increased transmissibility, immune evasion and vaccine breakthrough. The aim of this study was to better understand the genetic diversity and the potential impact of mutations observed in SARS-CoV-2 viruses circulating in the U.S. in vaccinated individuals.ResultsWhole genome sequencing was performed on thirty-four SARS-CoV-2 positive samples using the Oxford Nanopore MinION. Evolutionary genomic analysis revealed two novel mutations, ORF1b:V2354F and a premature stop codon, ORF7a:Q94*, identified in a cluster of SARS-CoV-2 Delta isolates collected from vaccinated individuals in Colorado. The ORF1b:V2354F mutation, corresponding to NSP15:V303F, may induce a conformational change and result in a disruption to a flanking beta-sheet structure. The premature stop codon, ORF7a:Q94*, truncates the transmembrane protein and cytosolic tail used to mediate protein transport. This may affect protein localization to the ER-Golgi. In addition to these novel mutations, the cluster of vaccinated isolates contain an additional mutation in the spike protein, at position 112, compared to the Delta variant defining mutations. This mutation, S112L, exists in isolates previously obtained in the U.S. The S112L mutation substitutes a bulky hydrophobic side chain for a polar side chain, which results in a non-conservative substitution within the protein that may affect antibody-binding affinity. Additionally, the vaccinated cluster of isolates contains non-synonymous mutations within ORF8 and NSPs which further distinguish this cluster from the respective ancestral Delta variant.ConclusionsThese results show there is an emerging sub-lineage of the ancestral Delta variant circulating in the U.S. As mutations emerge in constellations, those with a potentially beneficial advantage to the virus may continue to circulate while others will cease.
Project description:In May 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in Asiatic lions in a zoological park in India. Sequence and phylogenetic analyses showed the SARS-CoV-2 strains were the B.1.617.2 (Delta) variant. To reduce transmission of variants of concern, surveillance of SARS-CoV-2 in wild animal populations should be increased.
Project description:COVID-19 infection is a global pandemic health emergency. This contagious disease was caused by the Severe Acute Respiratory Syndrome Coronavirus‑2 (SARS‑CoV-2) which is mutating over time. In 2021, the Delta variant became the most dominant transmissible form. During the crisis, human practice and knowledge were critical in the overall efforts to encompass the outbreak. A cross-sectional, web-based approach was conducted among adults in Jordan to quantify knowledge, attitude, and practices towards SARS-CoV-2 (Delta variant). This research was carried out between 15th April and 15th of May 2021. The study questionnaire consisted of four sections including the participant's demographics, knowledge, practices and attitude. Comparative evaluation of responses was accomplished using a scoring system. Respondents who scored above the mean score (60%) on the item measured were categorized as knowledgeable, having a positive attitude, and good practices. Participants were allocated to one of the three groups; medical, non-medical and others (unemployed and housewives). Data collected was analyzed using Statistical Package for Social Sciences (SPSS) version 23.0 software. A variance test to assess the statistical difference between groups was used. Pearson's chi-squared test was applied to compare the variables and identify significant predictors. Of the participants, 308 (66%) were in the age group of 18-25yrs, 392 (84.1%) females, 120 (25.8%) employed and 346 (74.2%) unemployed. The principle source of knowledge was social media (291, 62.4%). Interestingly, participants had adequate overall knowledge. The mean knowledge score was 22.6 (± 0.19), 20.6 (± 0.19), and 21.3 (± 0.18) for the medical, the non-medical and the others group, respectively. Also, participants showed a positive attitude and good practices towards SARS-CoV-2 (Delta variant). The mean practice score for medical, the non-medical and the others groups was 7.35 (± 0.25), 7.38 (± 0.24), 7.35 (± 0.24) and the mean attitude score was 10.8 (± 0.16), 9.4 (± 0.21), 9.5 (± 0.22), respectively. The studied groups generally had good knowledge, positive attitudes and good practices about SARS-CoV-2 (Delta variant). This was expected due to the authorities' successful management of the pandemic and the high educational level of the Jordanian society, bearing in mind the economic and social impact of COVID-19 disease.
Project description:BackgroundSARS-CoV-2 is described to cause mild to moderate symptoms in children. To date, clinical data and symptoms of the Delta variant in pediatric patients are lacking.AimTo describe clinical characteristics and outcomes of infants admitted in the pediatric intensive care unit (PICU) during the period of Delta variant predominance.MethodsWe performed a retrospective study, between June 23, 2021 and August 16, 2021. We included children aged under 15 years, admitted to PICU with severe and critical form of SARS-CoV-2 infection as confirmed by RT-PCR. We reviewed medical records for all patients.ResultsDuring the study period, 20 infants were included. The median age was 47 days (IQR: 26.5-77). The sex ratio was 0.8 (9 males). No underlying medical conditions were noted. Parents were not vaccinated. Respiratory involvement was the main feature to be observed in our cohort. Eleven patients had pediatric acute respiratory distress (PARDS) with a median oxygen saturation index (OSI) of 9 (IQR: 7-11). PARDS was mild in 4 cases, moderate in 5 cases and severe in 2 cases. Hemodynamic instability was observed in 4 cases. The main radiological finding was ground glass opacities in 11 cases. Seventeen patients were mechanically ventilated and 3 of them were escalated to high-frequency oscillatory ventilation. The median duration of mechanical ventilation was 6 days (IQR 2.5-12.5). The remaining patients were managed with high flow nasal cannula. Four patients died.ConclusionWe report herein a case series of very young infants, with no comorbidities, and with a life-threatening illness due to SARS-CoV-2 Delta variant.