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The spreading of a disease largely occurs in buildings or in collective transport. The microenvironment flow processes around people contribute to the cross-infection risk, for example when two persons are standing close to each other. The cross-infection risk is also dependent on the macro-environment e.g. distribution of velocity and turbulence in the room, particularly when the background airflow is strong. The surrounding temperature and the presence of a vertical temperature gradient can also modify airflows in the microenvironment and subsequently influence the cross-infection risk. This work is based on a fully mixed flow in a room without a vertical temperature gradient, considering different room temperatures.Exhalation flow and aerosol distribution are studied by smoke experiments and the cross-infection risk is expressed as concentration in the susceptible breathing zone normalized by the concentration in the room.

More than half of the human population lives in cities meaning that most people predominantly experience nature in urban greenspace. Nature exposure is an important contributor to social, mental and physical health. As the world faces a pandemic which threatens the physical and mental health of billions of people, it is crucial to understand that all have the possibility to access nature exposure to alleviate some of these challenges. Here, for the first time, we integrate data from Facebook, Twitter, and Google Search users to show that people looked for greenspace during COVID-19 mobility restrictions but may not have always managed to reach it. People spent more time in areas with greenspace when they could and that depended on the level of multiple deprivation in the neighbourhood where the greenspace was embedded. Importantly, while people sought greenspace throughout the first 20 months of the pandemic, this preference intensified through the waves of lockdown. Living in an affluent area conferred a greenspace advantage in London and Paris but we find that in Berlin more deprived neighbourhoods sought greenspace more, including outside their neighbourhood. This highlights the need to understand how greenspace access and deprivation interact to create more sustainable communities. 32 pages, 4 main figures, 13 additional figures, and 10 additional tables. submitted

Background:Denmark was one of the few countries where it was politically decided to continue cancer screening during the COVID-19 pandemic. We assessed the actual population uptake of mammography and cervical screening during this period.Methods:The first COVID-19 lockdown in Denmark was announced on 11 March 2020. To investigate possible changes in cancer screening activity due to the COVID-19 pandemic, we analysed data from the beginning of 2017 until the end of 2021. A time series analysis was carried out to discover possible trends and outliers in the screening activities in the period 2017–2021. Data on mammography screening and cervical screening were retrieved from governmental pandemic-specific monitoring of health care activities.Results:A brief drop was seen in screening activity right after the first COVID-19 lockdown, but the activity quickly returned to its previous level. A short-term deficit of 43% [CI –49 to –37] was found for mammography screening. A short-term deficit of 62% [CI –65 to –58] was found for cervical screening. Furthermore, a slight, statistically significant downward trend in cervical screening from 2018 to 2021 was probably unrelated to the pandemic. Other changes, for example, a marked drop in mammography screening towards the end of 2021, also seem unrelated to the pandemic.Conclusions:Denmark continued cancer screening during the pandemic, but following the first lockdown a temporary drop was seen in breast and cervical screening activity.Funding:Region Zealand (R22-A597).

BACKGROUND: New-onset chronic pain has been acknowledged as part of the post-COVID-19 condition. However, available fine-grained data about its clinical phenotype, trajectories and main associated characteristics remain scarce. We described the distinct temporal evolutions of post-COVID-19 pain, their epidemiological and phenotypical features.METHODS: A prospective cross-sectional study enrolled post-COVID-19 condition patients (i.e. who had persisting COVID-19-related symptoms over 30 days since their first positive laboratorial test), whose COVID-19 diagnosis had been supported by RT-PCR of oral/nasopharyngeal swab or serology. They underwent in-person evaluations with structured interview, pain and quality-of-life-related questionnaires and thorough physical examination. Chronic pain (CP) and probable neuropathic pain (NP) were defined according to IASP criteria.RESULTS: The present study included 226 individuals, 177 (78.3%) of whom presented over 3 months since their first COVID-19 symptom. New-onset pain occurred in 170 (75.2%) participants and was chronic in 116 (68.2%). A chronic course was associated with COVID-19-related hospitalization, new-onset fatigue, lower cognitive performance, motor and thermal sensory deficits, mood and sleep impairments, and overall lower quality of life levels. Probable NP occurred in only 7.6% new-onset pain patients, and was associated with pain chronification, new-onset fatigue, motor and thermal sensory deficits, mechanical allodynia, and lower rates of SARS-CoV-2 vaccination. Previous CP was reported by 86 (38.1%) individuals and had aggravated after the infection in 66 (76.7%) of them, which was associated with orthostatic hypotension.CONCLUSIONS: Post-COVID pain phenomena follow different paths, which are associated with specific clinical and epidemiological features, and possibly distinct underlying mechanisms, prognostic, and therapeutic implications.

In light of the negative consequences caused by the COVID-19 pandemic, countries around the world have initiated negotiations to create an international instrument to strengthen pandemic prevention, preparedness, and response.(1) The latest outline of this international pandemic instrument, which includes antimicrobial resistance (AMR) within its scope, also contains various references to increasing research and development (R&D) mechanisms to address future pandemics.(2) The inclusion of this feature is not only a welcome addition to better mitigate the threat of future global health crises, but it also presents an opportunity to revamp the current pharmaceutical R&D system, as it has historically disfavoured antimicrobial innovation. Correspondingly, this paper argues that the World Health Organization’s (WHO) upcoming international pandemic instrument presents a unique opportunity to support stronger R&D mechanisms for antimicrobials in its framework. We focus on some of the promising R&D incentive models that have been previously proposed to increase antimicrobial innovation, while calling attention to how they could be incorporated into an international pandemic instrument given the fast pace of collaborative medical advancements during the COVID-19 pandemic. With 1.27 million deaths directly attributable to bacterial AMR in 2019,(3) it is clear that the timing is right for countries to capitalize on the opportunity presented by this international instrument in order to promote innovation for new – and potentially lifesaving – antimicrobials.

Recent estimates have reiterated that non-fatal causes of disease, such as low back pain, headaches and depressive disorders, are amongst the leading causes of disability-adjusted life years (DALYs). For these causes, the contribution of years lived with disability (YLD) – put simply, ill-health – is what drives DALYs, not mortality. Being able to monitor trends in YLD closely is particularly relevant for countries that sit high on the socio-demographic spectrum of development, as it contributes more than half of all DALYs. There is a paucity of data on how the population-level occurrence of disease is distributed according to severity, and as such, the majority of global and national efforts in monitoring YLD lack the ability to differentiate changes in severity across time and location. This raises uncertainties in interpreting these findings without triangulation with other relevant data sources. Our commentary aims to bring this issue to the forefront for users of burden of disease estimates, as its impact is often easily overlooked as part of the fundamental process of generating DALY estimates. Moreover, the wider health harms of the COVID-19 pandemic have underlined the likelihood of latent and delayed demand in accessing vital health and care services that will ultimately lead to exacerbated disease severity and health outcomes. This places increased importance on attempts to be able to differentiate by both the occurrence and severity of disease.

BACKGROUND: The incidence of respiratory syncytial virus (RSV) increased in several countries after the relaxation of COVID-19 restrictions. We aimed to investigate the age-related risk of RSV-associated hospital admissions and need for mechanical ventilation during the RSV resurgence in summer and autumn 2021 compared with the four RSV seasons preceding the COVID-19 pandemic. We also aimed to describe the clinical complications necessitating mechanical ventilation.METHODS: This population-based cohort study included patients aged 0-17 years admitted to hospital with RSV in Denmark during the RSV resurgence in summer and autumn 2021, and the four pre-COVID-19 RSV seasons (2016-17, 2017-18, 2018-19, and 2019-20). We retrieved data on RSV-associated hospital admissions from the Danish National Patient Registry and demographic and clinical details of children who received mechanical ventilation through prospective real-time data collection in 2021-22 and retrospective data collection for the 2016-17 to 2019-20 RSV seasons from all eight paediatric and neonatal intensive care units in Denmark. Risk factors for severe RSV disease were as defined as age younger than 3 months or severe comorbidities. We calculated the risk of RSV-associated hospital admissions per 100 000 population in each RSV season from week 21 to week 20 of the following year. We also calculated the risk rate of receiving mechanical ventilation per 100 000 population and 1000 RSV-associated hospital admissions during each RSV season from week 21 to week 20 of the following year. We calculated risk ratios (RRs) for hospital admission and mechanical ventilation by dividing the risk rate of hospital admission and mechanical ventilation in 2021-22 by annual mean risk rates in the four pre-COVID-19 RSV epidemics (2016-17 to 2019-20). We compared RRs using Fisher's exact test. We compared complications leading to intubation between children with and without risk factors for severe RSV disease. The study is registered at ClinicalTrials.gov, NCT05186597.FINDINGS: Among 310 423 Danish children aged younger than 5 years, the mean number of RSV-associated hospital admissions increased from 1477 (SD 226) in the 2016-17 to 2019-20 RSV seasons to 3000 in the 2021-22 RSV season (RR 2·0 [95% CI 1·9-2·1]). 54 children with RSV received mechanical ventilation in 2021-22 compared with 15-28 annually in the 2016-17 to 2019-20 RSV seasons (2·3 [1·6-3·3]). The highest increase in hospital admissions and need for mechanical ventilation occurred among children aged 24-59 months (4·1 [3·6-4·7] for hospital admission; 4·6 [1·7-12·6] for mechanical ventilation). Among children admitted to hospital, the risk of mechanical ventilation was similar in 2021-22 and the four pre-COVID-19 seasons (risk rate 14·3 per 1000 RSV-associated hospital admissions [95% CI 10·4-19·3] vs 12·9 [10·1-16·1]; RR 1·1 [95% CI 0·8-1·6]). Across all RSV seasons studied, among children younger than 3 months or those with severe comorbidities, respiratory failure due to bronchiolitis led to mechanical ventilation in 69 (79%) of 87 children. Of 46 children with no risk factors for severe RSV, 40 (87%) received mechanical ventilation due to additional complications, including neurological (n=16; 35%), cardiac (n=1; 2%), and pulmonary complications (n=23; 50%; eg, wheeze responsive to bronchodilator therapy, severe bacterial co-infections, and pneumothorax).INTERPRETATION: In Denmark, RSV disease did not seem to be more severe for the individual child during the RSV resurgence in 2021 following relaxation of COVID-19 restrictions. However, hospital admissions were higher among older children, possibly due to a postponed first RSV infection or no recent reinfection. Older children without risk factors for severe RSV disease had atypical complications that led to intubation. If new RSV-preventive interventions for healthy infants delay first RSV infection, a higher number of older children might be admitted to hospital due to atypical clinical phenotypes, rather than classical bronchiolitis.FUNDING: National Ministry of Higher Education and Science and the Innovation Fund Denmark.

Aim: The COVID-19 pandemic resulted in a significant decrease in the number of hospital admissions for severe emergent cardiovascular diseases during lockdowns worldwide. This study aimed to determine the impact of both the first and the second Danish nationwide lockdown on the implantation rate of cardiac implantable electronic devices (CIEDs). Methods: We retrospectively analysed the number of CIED implantations performed in Denmark and stratified them into 3-week intervals. Results: The total number of de novo CIED implantations decreased during the first lockdown by 15.5% and during the second by 5.1%. Comparing each 3-week interval using rate ratios, a significant decrease in the daily rates of the total number of de novo and replacement CIEDs (0.82, 95% CI [0.70, 0.96]), de novo CIEDs only (0.82, 95% CI [0.69, 0.98]), and non-acute pacemaker implantations (0.80, 95% CI [0.63, 0.99]) was observed during the first interval of the first lockdown. During the second lockdown (third interval), a significant decrease was seen in the daily rates of de novo CIEDs (0.73, 95% CI [0.55, 0.97]), and of pacemakers in total during both the second (0.78, 95% CI [0.62, 0.97]) and the third (0.60, 95% CI [0.42, 0.85]) intervals. Additionally, the daily rates of acute pacemaker implantation decreased during the second interval (0.47, 95% CI [0.27, 0.79]) and of non-acute implantation during the third interval (0.57, 95% CI [0.38, 0.84]). A significant increase was observed in the number of replacement procedures during the first interval of the second lockdown (1.70, 95% CI [1.04, 2.85]). Conclusions: Our study found only modest changes in CIED implantations in Denmark during two national lockdowns.

BACKGROUND: Capsid virus-like particles (cVLP) have proven safe and immunogenic and can be a versatile platform to counter pandemics. We aimed to clinically test a modular cVLP COVID-19 vaccine in individuals who were naive to SARS-CoV-2.METHODS: In this phase 1, single-centre, dose-escalation, adjuvant-selection, open-label clinical trial, we recruited participants at the Radboud University Medical Center in Nijmegen, Netherlands, and sequentially assigned them to seven groups. Eligible participants were healthy, aged 18-55 years, and tested negative for SARS-CoV-2 and anti-SARS-CoV-2 antibodies. Participants were vaccinated intramuscularly on days 0 and 28 with 6 μg, 12 μg, 25 μg, 50 μg, or 70 μg of the cVLP-based COVID-19 vaccine (ABNCoV2). A subgroup received MF59-adjuvanted ABNCoV2. Follow-up was for 24 weeks after second vaccination. The primary objectives were to assess the safety and tolerability of ABNCoV2 and to identify a dose that optimises the tolerability-immunogenicity ratio 14 days after the first vaccination. The primary safety endpoint was the number of related grade 3 adverse events and serious adverse events in the intention-to-treat population. The primary immunogenicity endpoint was the concentration of ABNCoV2-specific antibodies. The trial is registered with ClinicalTrials.gov, NCT04839146.FINDINGS: 45 participants (six to nine per group) were enrolled between March 15 and July 15, 2021. Participants had a total of 249 at least possibly related solicited adverse events (185 grade 1, 63 grade 2, and one grade 3) within a week after vaccination. Two serious adverse events occurred; one was classified as a possible adverse reaction. Antibody titres were dose-dependent with levels plateauing at a vaccination dose of 25-70 μg ABNCoV2. After second vaccination, live virus neutralisation activity against major SARS-CoV-2 variants was high but was lower with an omicron (BA.1) variant. Vaccine-specific IFNγ+ CD4+ T cells were induced.INTERPRETATION: Immunisation with ABNCoV2 was well tolerated, safe, and resulted in a functional immune response. The data support the need for additional clinical development of ABNCoV2 as a second-generation SARS-CoV-2 vaccine. The modular cVLP platform will accelerate vaccine development, beyond SARS-CoV-2.FUNDING: EU, Carlsberg Foundation, and the Novo Nordisk Foundation.