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1.
Preprint in English | medRxiv | ID: ppmedrxiv-22270044

ABSTRACT

1The Omicron SARS-CoV-2 variant of concern (VOC lineage B.1.1.529), which became dominant in many countries during early 2022, includes several subvariants with strikingly different genetic characteristics. Several countries, including Denmark, have observed the two Omicron subvariants: BA.1 and BA.2. In Denmark the latter has rapidly replaced the former as the dominant subvariant. Based on nationwide Danish data, we estimate the transmission dynamics of BA.1 and BA.2 following the spread of Omicron VOC within Danish households in late December 2021 and early January 2022. Among 8,541 primary household cases, of which 2,122 were BA.2, we identified a total of 5,702 secondary infections among 17,945 potential secondary cases during a 1-7 day follow-up period. The secondary attack rate (SAR) was estimated as 29% and 39% in households infected with Omicron BA.1 and BA.2, respectively. We found BA.2 to be associated with an increased susceptibility of infection for unvaccinated individuals (Odds Ratio (OR) 2.19; 95%-CI 1.58-3.04), fully vaccinated individuals (OR 2.45; 95%-CI 1.77-3.40) and booster-vaccinated individuals (OR 2.99; 95%-CI 2.11-4.24), compared to BA.1. We also found an increased transmissibility from unvaccinated primary cases in BA.2 households when compared to BA.1 households, with an OR of 2.62 (95%-CI 1.96-3.52). The pattern of increased transmissibility in BA.2 households was not observed for fully vaccinated and booster-vaccinated primary cases, where the OR of transmission was below 1 for BA.2 compared to BA.1. We conclude that Omicron BA.2 is inherently substantially more transmissible than BA.1, and that it also possesses immune-evasive properties that further reduce the protective effect of vaccination against infection, but do not increase its transmissibility from vaccinated individuals with breakthrough infections.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-22268841

ABSTRACT

1The SARS-CoV-2 Delta variant of concern (VOC), which has shown increased transmission compared with previous variants, emerged rapidly globally during the first half of 2021, and became one of the most widespread SARS-CoV-2 variants worldwide. We utilized total population data from 24,693 Danish households with 53,584 potential secondary cases to estimate household transmission of the Delta VOC in relation to vaccination status. We found that the vaccine effectiveness against susceptibility (VES) was 61% (95%-CI: 59-63) and that the vaccine effectiveness against transmissibility (VET) was 42% (95%-CI: 39-45). We also found that unvaccinated individuals with an infection exhibited a higher viral load (one third of a standard deviation) compared to fully vaccinated individuals with a breakthrough infection. Our results imply that vaccinations reduce susceptibility as well as transmissibility. The results are important for policy makers to select strategies for reducing transmission of SARS-CoV-2.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-21268278

ABSTRACT

1The Omicron variant of concern (VOC) is a rapidly spreading variant of SARS-CoV-2 that is likely to overtake the previously dominant Delta VOC in many countries by the end of 2021. We estimated the transmission dynamics following the spread of Omicron VOC within Danish households during December 2021. We used data from Danish registers to estimate the household secondary attack rate (SAR). Among 11,937 households (2,225 with the Omicron VOC), we identified 6,397 secondary infections during a 1-7 day follow-up period. The SAR was 31% and 21% in households with the Omicron and Delta VOC, respectively. We found an increased transmission for unvaccinated individuals, and a reduced transmission for booster-vaccinated individuals, compared to fully vaccinated individuals. Comparing households infected with the Omicron to Delta VOC, we found an 1.17 (95%-CI: 0.99-1.38) times higher SAR for unvaccinated, 2.61 times (95%-CI: 2.34-2.90) higher for fully vaccinated and 3.66 (95%-CI: 2.65-5.05) times higher for booster-vaccinated individuals, demonstrating strong evidence of immune evasiveness of the Omicron VOC. Our findings confirm that the rapid spread of the Omicron VOC primarily can be ascribed to the immune evasiveness rather than an inherent increase in the basic transmissibility.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-21267966

ABSTRACT

In this brief communication we are showing original research results with early estimates from Danish nationwide databases of vaccine effectiveness (VE) against the novel SARS-CoV-2 Omicron variant (B.1.1.529) up to five months after a primary vaccination series with the BNT162b2 or mRNA-1273 vaccines. Our study provides evidence of protection against infection with the Omicron variant after completion of a primary vaccination series with the BNT162b2 or mRNA-1273 vaccines; in particular, we found a VE against the Omicron variant of 55.2% (95% confidence interval (CI): 23.5 to 73.7%) and 36.7% (95% CI: -69.9 to 76.4%) for the BNT162b2 and mRNA-1273 vaccines, respectively, in the first month after primary vaccination. However, the VE is significantly lower than that against Delta infection and declines rapidly over just a few months. The VE is re-established upon revaccination with the BNT162b2 vaccine (54.6%, 95% CI: 30.4 to 70.4%).

5.
Preprint in English | medRxiv | ID: ppmedrxiv-21255459

ABSTRACT

1AimThe aim of this study was to estimate the household transmissibility of SARS-CoV-2 for lineage B.1.1.7 compared with other lineages, by age and viral load. Further-more, we wanted to estimate whether there is a multiplicative or additive effect of the increased transmissibility of B.1.1.7 compared with other lineages. BackgroundNew 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 has been estimated to be more transmissible than other previously known lineages, but the association between transmissibility and risk factors, such as age of primary case and viral load is still unknown. MethodsWe used comprehensive administrative data from Denmark, comprising the full population, all SARS-CoV-2 RT-PCR tests, and all WGS lineage data (January 11 to February 7, 2021), to estimate household transmissibility stratified by lineage B.1.1.7 and other lineages. ResultsWe included 5,241 households with primary cases; 808 were infected with SARS-CoV-2 lineage B.1.1.7 and 4,433 were infected with other lineages. The attack rate was 38% in households with a primary case infected with B.1.1.7 and 27% in households with a primary case infected 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. ConclusionsThe results found in this study add new knowledge that can be used to mitigate the further spread of SARS-CoV-2 lineage B.1.1.7, which is becoming increasingly widespread in numerous countries. Our results clarify that the transmissibility of B.1.1.7 should be included as a multiplicative effect in mathematical models used as a tool for decision makers. The results may have important public health implications, as household transmission may serve as a bridge between otherwise separate transmission domains, such as schools and physical workplaces, despite implemented non-pharmaceutical interventions.

6.
Preprint in English | medRxiv | ID: ppmedrxiv-21252608

ABSTRACT

AimThe objective of this nationwide study was to investigate the association between SARS-CoV-2 transmissibility, viral load, and age of primary cases in Danish households. BackgroundSpread in households represents a major mode of transmission of SARS-CoV-2. In order to take proper action against the spread of the disease, it is important to have a better understanding of transmission in the household domain--including the role of viral load of primary cases. MethodsThe study was designed as an observational cohort study, using detailed administrative register data. We included the full population of Denmark and all SARS-CoV-2 tests (August 25, 2020 to February 10, 2021) to estimate transmissibility in house-holds comprising 2-6 people. RT-PCR Cycle threshold (Ct) values were used as a proxy for viral load. ResultsWe identified 63,657 primary cases and 139,882 household members of which 21% tested positive by RT-PCR within a 1-14 day period after the primary case. There was an approximately linear association between Ct value of the sample and transmissibility, implying that cases with samples having a higher viral load were more transmissible than cases with samples having a lower viral load. However, even for primary cases with relatively high sample Ct values, the transmissibility was not negligible, e.g., for primary cases with a sample Ct value of 38, we found that 13% of the primary cases had at least one secondary household case. Moreover, 34% of all secondary cases were found in households with primary cases having sample Ct values >30. An increasing transmissibility with age of the primary cases for adults ([≥]20 years) and a decreasing transmissibility with age for children (<20 years) were found. ConclusionsAlthough primary cases with sample high viral loads (low Ct values) were associated with higher SARS-CoV-2 transmissibility, we found no obvious cut-off for sample Ct values to eliminate transmissibility and a substantial amount of household transmission occurred in households where the primary cases had high sample Ct values (low viral load), The study further showed that transmissibility increases with age. These results have important public health implications, as they suggest that contact tracing should prioritize cases according to Ct values and age, and underline the importance of quick identification and isolation of cases. Furthermore, the study highlights that households can serve as a transmission bridge by creating connections between otherwise separate domains.

7.
Preprint in English | medRxiv | ID: ppmedrxiv-20191239

ABSTRACT

BackgroundThe Covid-19 pandemic is one of the most serious global public health threats in recent times. Understanding transmission of SARS-CoV-2 is of utmost importance to be able to respond to outbreaks and take action against spread of the disease. Transmission within the household is a concern, especially because infection control is difficult to apply within the household domain. MethodsWe used comprehensive administrative register data from Denmark, comprising the full population and all COVID-19 tests, to estimate household transmission risk and attack rate. ResultsWe studied the testing dynamics for COVID-19 and found that the day after receiving a positive test result within the household, 35% of potential secondary cases were tested and 13% of these were positive. After a primary case in 6,782 households, 82% of potential secondary cases were tested within 14 days, of which 17% tested positive as secondary cases, implying an attack rate of 17%. Among primary cases, those aged 0-24 were underrepresented when compared with the total population. We found an approximately linearly increasing relationship between attack rate and age. We investigated the transmission risk from primary cases by age, and found an increasing risk with age of primary cases for adults, while the risk seems to decrease with age for children. ConclusionsAlthough there is an increasing attack rate and transmission risk of SARS-CoV-2 with age, children are also able to transmit SARS-CoV-2 within the household.

8.
Preprint in English | medRxiv | ID: ppmedrxiv-20075291

ABSTRACT

BackgroundThe pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has tremendous consequences for our societies. Knowledge of the seroprevalence of SARS-CoV-2 is needed to accurately monitor the spread of the epidemic and also to calculate the infection fatality rate (IFR). These measures may help the authorities to make informed decisions and adjust the current societal interventions. Blood donors comprise approximately 4.7% of the similarly aged population of Denmark and blood is donated in all areas of the country. The objective of this study was to perform real-time seroprevalence surveying among blood donors as a tool to estimate previous SARS-CoV-2 infections and the population based IFR. MethodsAll Danish blood donors aged 17-69 years giving blood April 6 to 17 were tested for SARS-CoV-2 immunoglobulin M and G antibodies using a commercial lateral flow test. Antibody status was compared between areas and an estimate of the IFR was calculated. The seroprevalence was adjusted for assay sensitivity and specificity taking the uncertainties of the test validation into account when reporting the 95% confidence intervals (CI). ResultsThe first 9,496 blood donors were tested and a combined adjusted seroprevalence of 1.7% (CI: 0.9-2.3) was calculated. The seroprevalence differed across areas. Using available data on fatalities and population numbers a combined IFR in patients younger than 70 is estimated at 82 per 100,000 (CI: 59-154) infections. ConclusionsThe IFR was estimated to be slightly lower than previously reported from other countries not using seroprevalence data. The IFR, including only individuals with no comorbidity, is likely several fold lower than the current estimate. This may have implications for risk mitigation. We have initiated real-time nationwide anti-SARS-CoV-2 seroprevalence surveying of blood donations as a tool in monitoring the epidemic.

9.
Pediatrics ; 114(3): 782-5, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15342854

ABSTRACT

OBJECTIVE: To describe incidence and temporal trends of intussusceptions in Danish children during 1980 to 2001. METHODS: A population-based cohort study was conducted of 1.67 million children who were younger than 5 years during 1980 to 2001 and were followed up for 6.66 million person-years. The Danish National Patient Registry was used to identify cases of intussusception in the cohort. Age-specific incidence rates were main outcome measure. RESULTS: A total of 1814 cases of intussusception among children who were younger than 5 years were reported from 1980 to 2001. The incidence rate remained fairly constant during 1980 to 1990 but decreased by 55% (95% confidence interval: 43%-65%) from 1990 to 2001. The reduction was most pronounced among children aged 3 to 5 months. CONCLUSIONS: The incidence of intussusception among Danish children declined significantly during the 1990s, particularly among infants 3 to 5 months of age.


Subject(s)
Intussusception/epidemiology , Age Distribution , Child, Preschool , Cohort Studies , Denmark/epidemiology , Female , Hospitalization/statistics & numerical data , Hospitalization/trends , Humans , Incidence , Infant , Infant, Newborn , Male , Poisson Distribution , Regression Analysis , Sex Distribution
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