Exploring the dynamics of COVID-19 in a Greenlandic cohort: Mild acute illness and moderate risk of long COVID.

Objectives: This study aimed to explore how the Greenlandic population experienced the course of both acute and long-term COVID-19. It was motivated by the unique epidemiologic situation in Greenland, with delayed community transmission of SARS-CoV-2 relative to the rest of the world. Methods: In a survey among 310 Greenlandic adults, we assessed the association between previous SARS-CoV-2 infection and overall health outcomes by administering three repeated questionnaires over 12 months after infection, with a response rate of 41% at the 12-month follow-up. The study included 128 individuals with confirmed SARS-CoV-2 infection from January/February 2022 and 182 test-negative controls. Participants were recruited through personal approaches, phone calls, and social media platforms. Results: A total of 53.7% of 162 participants who were test-positive recovered within 4 weeks and 2.5% were hospitalized due to SARS-CoV-2. The most common symptoms were fatigue and signs of mild upper respiratory tract infection. Less than 5% reported sick leave above 2 weeks after infection. Compared with participants who were test-negative, there was an increased risk of reporting fatigue (risk differences 25.4%, 95% confidence interval 8.8-44.0) and mental exhaustion (risk differences 23.4%, 95% confidence interval 4.8-42.2) up to 12 months after a positive test. Conclusions: Our results indicate that during a period dominated by the Omicron variant, Greenlanders experienced a mild acute course of COVID-19, with quick recovery, minimizing the impact on sick leave. Long COVID may be present in Greenlanders, with symptoms persisting up to 12 months after infection. However, it is important to consider the small sample size and modest response rate as limitations when interpreting the results.

Cohort profile: EFTER-COVID - a Danish nationwide cohort for assessing the long-term health effects of the COVID-19 pandemic.

PURPOSE: To follow SARS-CoV-2-infected persons up to 18 months after a positive test in order to assess the burden and nature of post acute symptoms and health problems. PARTICIPANTS: Persons in Denmark above 15 years of age, who were tested positive for SARS-CoV-2 during 1 September 2020 to 21 February 2023 using a RT-PCR test. As a reference group, three test-negative individuals were selected for every two test-positive individuals by matching on test date. FINDINGS TO DATE: In total, 2 427 913 invitations to baseline questionnaires have been sent out and 839 528 baseline questionnaires (34.5%) have been completed. Females, the age group 50-69 years, Danish-born and persons, who had received at least one SARS-CoV-2 vaccination booster dose were more likely to participate. Follow-up questionnaires were sent at 2, 4, 6, 9, 12 and 18 months after the test, with response rates at 42%-54%. FUTURE PLANS: New participants have been recruited on a daily basis from 1 August 2021 to 23 March 2023. Data collection will continue until the last follow-up questionnaires (at 18 months after test) have been distributed in August 2024.

A register and questionnaire study of long-term general health symptoms following SARS-CoV-2 vaccination in Denmark.

Many individuals who refuse COVID-19 vaccination have concerns about long-term side effects. Here, we report findings on self-reported symptoms from a Danish survey- and register study. The study included 34,868 vaccinated primary course recipients, 95.8% of whom received mRNA vaccines, and 1,568 unvaccinated individuals. Participants had no known history of SARS-CoV-2 infection. Using g-computation on logistic regression, risk differences (RDs) for symptoms between vaccinated and unvaccinated persons were estimated with adjustments for possible confounders. Within six weeks after vaccination, higher risks were observed for physical exhaustion (RD 4.9%, 95% CI 1.1% to 8.4%), fever or chills (RD 4.4%, 95% CI 2.1% to 6.7%), and muscle/joint pain (RD 7.0%, 95% CI 3.1% to 10.7%), compared to unvaccinated individuals. Beyond twenty-six weeks, risks were higher among the vaccinated for sleeping problems (RD 3.0, 95% 0.2 to 5.8), fever or chills (RD 2.0, 95% CI 0.4 to 3.6), reduced/altered taste (RD 1.2, 95% CI 0.2 to 2.3) and shortness of breath (RD 2.6, 95% CI 0.9 to 4.0). However, when examining pre-omicron responses only, the difference for reduced/altered taste was significant. As expected, the risk of experiencing physical exhaustion, fever or chills, and muscle/joint pain was higher among persons who responded within six weeks of completing the primary course. No significant differences were observed for the 7-25-week period after vaccination. Associations for the period beyond 26 weeks must be interpreted with caution and in the context of undetected SARS-CoV-2 infection, wide confidence intervals, and multiple testing. Overall, we observe no concerning signs of long-term self-reported physical, cognitive, or fatigue symptoms after vaccination.

A Danish questionnaire study of acute symptoms of SARS-CoV-2 infection by variant, vaccination status, sex and age.

It is not well-described how the acute symptoms of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ by variant, vaccination, sex and age. A cross-sectional questionnaire study linked to national testing- and registry data was conducted among 148,874 SARS-CoV-2 first time reverse transcription polymerase chain reaction (RT-PCR) test-positive individuals and corresponding date-matched symptomatic test-negative controls. Major SARS-CoV-2 variants (Index/wild type, Alpha, Delta and Omicron) were defined using periods of predominance. Risk differences (RDs) were estimated for each of 21 predefined acute symptoms comparing: (1) test-positive and -negative individuals, by variant period, (2) vaccinated and unvaccinated test-positives, by variant period, (3) individuals tested positive during the Omicron and Delta periods, by vaccination status, and (4) vaccinated Omicron test-positive and -negative individuals, by age and sex. Compared to pre-Omicron, RDs between test-positive and test-negative individuals during the Omicron period were lower for most symptoms. RDs for altered sense of smell (dysosmia) and taste (dysgeusia) were highest for Delta (RD = 50.8 (49.4-52.0) and RD = 54.7 (53.4-56.0), respectively) and lowest for Omicron (RD = 12.8 (12.1-13.5) and RD = 11.8 (11.1-12.4), respectively). Across variants, vaccinated individuals reported fewer symptoms. During Omicron, females and 30-59 year-old participants reported more symptoms.

Post-acute symptoms 4 months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study.

Post-acute symptoms are not uncommon after SARS-CoV-2 infection with pre-Omicron variants. How Omicron and COVID-19 booster vaccination influence the risk of post-acute symptoms is less clear. We analyzed data from the nationwide Danish questionnaire study EFTER-COVID comprising 44,553 individuals ≥15 years old, tested between July 2021 and January 2022, in order to evaluate the association of the Omicron variant and COVID-19 booster vaccination with post-acute symptoms and new-onset general health problems, four months after infection with SARS-CoV-2. Risk differences (RDs) were estimated by comparing Omicron -cases to controls, Omicron to Delta -cases, and Omicron vaccinated cases with three to -two doses, adjusted for age, sex, BMI, self-reported chronic diseases, Charlson comorbidity index, healthcare occupation, and vaccination status. Four months after testing for SARS-CoV-2 during the Omicron period, cases experienced substantial post-acute symptoms and new-onset health problems compared to controls; the largest RD was observed for memory issues (RD=7.2%, 95%CI: 6.4 to 8.1). However, risks were generally lower than in the Delta period, particularly for dysosmia (RD=-15.0%, 95%CI: -17.0 to -13.2) and dysgeusia (RD=-11.2%, 95%CI: -13.2 to -9.5). Booster vaccination was associated with fewer post-acute symptoms and new-onset health problems, four months after Omicron infection, compared to two COVID-19 vaccine doses.

A hybrid register and questionnaire study of Covid-19 and post-acute sick leave in Denmark.

Post-acute sick leave is an underexplored indicator of the societal burden of SARS-CoV-2. Here,  we report findings about self-reported sick leave and risk factors thereof from a hybrid survey and register study, which include 37,482 RT-PCR confirmed SARS-CoV-2 cases and 51,336 test-negative controls who were tested during the index- and alpha-dominant waves. We observe that an additional 33 individuals per 1000 took substantial sick leave following acute infection compared to persons with no known history of infection, where substantial sick leave is defined as >1 month of sick leave within the period 1-9 months after the RT-PCR test date. Being female, 50-65 years, or having certain pre-existing health conditions such as obesity, chronic lung diseases, and fibromyalgia each increase risk for taking substantial sick leave. Altogether, these results may help motivate improved diagnostic and treatment options for persons living with post-Covid conditions.

Persistent Symptoms and Sequelae After Severe Acute Respiratory Syndrome Coronavirus 2 Infection Not Requiring Hospitalization: Results From Testing Denmark, a Danish Cross-sectional Survey.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with persistent symptoms ("long COVID"). We assessed the burden of long COVID among nonhospitalized adults with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Methods: In the fall of 2020, a cross-sectional survey was performed in the adult Danish general population. This included a self-administered point-of-care test for SARS-CoV-2 antibodies, the Short Form Health Survey (SF-12), and coronavirus disease 2019 (COVID-19)-associated symptom questions. Nonhospitalized respondents with a positive SARS-CoV-2 PCR test ≥12 weeks before the survey (cases) were matched (1:10) to seronegative controls on age, sex, and body mass index. Propensity score-weighted odds ratios (ORs) and ORs for risk factors were estimated for each health outcome. Results: In total, 742 cases and 7420 controls were included. The attributable risk of at least 1 long-COVID symptom was 25.0 per 100 cases (95% confidence interval [CI], 22.2-27.4). Compared to controls, cases reported worse general health (OR, 5.9 [95% CI, 5.0-7.0]) and had higher odds for a broad range of symptoms, particularly loss of taste (OR, 11.8 [95% CI, 9.5-14.6]) and smell (OR, 11.2 [95% CI, 9.1-13.9]). Physical and Mental Component Summary scores were also significantly reduced with differences of -2.5 (95% CI, -3.1 to -1.8) and -2.0 (95% CI, -2.7 to -1.2), respectively. Female sex and severity of initial infection were major risk factors for long COVID. Conclusions: Nonhospitalized SARS-CoV-2 PCR-positive individuals had significantly reduced physical and mental health, and 1 in 4 reported persistence of at least 1 long-COVID symptom.

A nationwide questionnaire study of post-acute symptoms and health problems after SARS-CoV-2 infection in Denmark.

A considerable number of individuals infected with SARS-CoV-2 continue to experience symptoms after the acute phase. Here, we report findings from a nationwide questionnaire study in Denmark including 61,002 RT-PCR confirmed SARS-CoV-2 cases and 91,878 test-negative controls aged 15-years or older. Six to twelve months after the test, the risks of 18 out of 21 symptoms were elevated among test-positives. The largest adjusted risk differences (RD) were observed for dysosmia (RD = 10.92%, 95% CI 10.68-11.21%), dysgeusia (RD = 8.68%, 95% CI 8.43-8.93%), fatigue/exhaustion (RD = 8.43%, 95%CI 8.14-8.74%), dyspnea (RD = 4.87%, 95% CI 4.65-5.09%) and reduced strength in arms/legs (RD = 4.68%, 95% CI 4.45-4.89%). During the period from the test and until completion of the questionnaire, new diagnoses of anxiety (RD = 1.15%, 95% CI 0.95-1.34%) or depression (RD = 1.00%, 95% CI 0.81-1.19%) were also more common among test-positives. Even in a population where the majority of test-positives were not hospitalized, a considerable proportion experiences symptoms up to 12 months after infection. Being female or middle-aged increases risks.

A dynamic model for spread of livestock-associated methicillin-resistant Staphylococcus aureus on a pig farm, incorporating bacterial load and human exposure through air.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is widely distributed in the pig population in many countries, where its presence is undesirable, because as an opportunistic human pathogen, it poses a threat to human health. At present, there is a lack of knowledge regarding successful methods for eradication of LA-MRSA on a pig farm, which does not involve emptying the farm and culling all pigs. Some studies have reported an association between levels of LA-MRSA in the barn air and LA-MRSA carriage among humans entering or working in the pig barns. Therefore, interventions that are able to reduce the amount of LA-MRSA carried by the pigs and/or the concentration of LA-MRSA in the barn air, might be highly relevant if aiming for reducing the spread of LA-MRSA into the general human population. In the present study, an existing agent-based simulation model for spread of LA-MRSA within a pig herd was extended to also include LA-MRSA load and spread through air. This makes it possible to use the model for studying the air exposure to LA-MRSA for humans entering the pig barns. The model was used for simulating various types of interventions in contaminated herds. At present quantitative data for nasal carriage of LA-MRSA in pigs are sparse, and many knowledge gaps regarding spread of LA-MRSA remain. Thus, our goal of building this model was not to provide exact values for risk reduction, but to avail a model that can be used for studying the effect of various types of interventions mechanistically, once more relevant data become available. Collection of more data on the influence of load is crucial for getting a better understanding of which possible interventions strategies, that might still have some potential in countries, where LA-MRSA has already spread to the majority of the pig population.

Risk factors for the occurrence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in Danish pig herds.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is widespread in many European countries including Denmark, where 88% of randomly selected production herds tested positive in 2016. In the present study, we investigated herd-level risk factors for farms being classified as LA-MRSA positive (study 1), in addition to herd-level risk factors for farms changing status from LA-MRSA negative to LA-MRSA positive during a 2-year period (study 2). Risk factors previously identified in other studies were confirmed in study 1: large herd size, herd type (lower risk in herds with sows) and number of pig suppliers. Due to the effect of herd type, data from sow herds (N = 41) and herds without sows (N = 166) were analysed separately. A univariable analysis found that the variables significantly associated with LA-MRSA status for sow herds were: use of wet feed in the sow units; higher weights of piglets at weaning; availability of a delivery room on the farm; cleaning of aisles after pigs were moved; number of pigs per weaner section; number of pigs purchased in the past year, and factors related to rodent control and human traffic in the herd. In herds without sows, the univariable analysis showed that the presence of other species of animal on the farm; negative pressure ventilation; full sectioning; frequent visits from the veterinarian; peroral use of tetracyclines for weaners; number of pigs purchased in the past year, and factors related to rodent control and human traffic in the herd were significantly associated with LA-MRSA status. For herds that changed from LA-MRSA negative to positive (study 2), having a company contract for mouse control, having more than one pig supplier and using group medication in the drinking water were the variables associated with LA-MRSA status in the univariable analysis. We did not succeed in building a biologically meaningful multivariable model based on any of the datasets and, as observed in similar studies, many of the risk factors identified in the univariable analysis were related to herd size. It was therefore not possible to determine whether it was the size of the herd or related factors that were the causal risk factors for being LA-MRSA positive.

Mechanistic modelling of interventions against spread of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) within a Danish farrow-to-finish pig herd.

Knowledge on successful interventions against livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) within pig herds is sparse. In situations like this, a mechanistic simulation model can be a valuable tool for assessing the effect of potential intervention strategies, and prioritising which should be tested in the field. We have simulated on-farm interventions in a farrow-to-finish pig herd, with a previously published LA-MRSA spread model, within four different areas: 1) Reduced antimicrobial consumption, 2) Reduced number of pigs within each section, 3) Reduced mixing of pigs, and 4) Improved internal biosecurity. To model a decrease in the selective pressure, the transmission rates were reduced after LA-MRSA had become fully established within a herd, which resulted in a marked decrease in the prevalence within all stable units. However, LA-MRSA rarely disappeared completely from the herd; this was only observed in scenarios where the transmission rates were reduced to ≤ 30% of the original level. While changes in antimicrobial consumption patterns might be a very important step towards reducing the spread of LA-MRSA, the simulation results indicate that it may need to be paired with other preventive or intervention measures. Reducing the number of pigs within each section, reducing mixing of pigs, or improving internal biosecurity after LA-MRSA had become established within the herd only resulted in marginal changes in the median prevalence within the herd. However, these factors might be important in relation to being able to achieve or maintain a low level of antimicrobial consumption, and thus still indirectly influence the LA-MRSA prevalence within the herd. The results of a sensitivity analysis indicated the assumptions regarding the existence of pigs persistently shedding MRSA have a noticeable influence on the model results. The assumptions regarding transmission from sow to offspring at the day of birth also had a considerable influence on the MRSA prevalence within the farrowing unit but did not cause any marked changes in the simulated effect of interventions. Effects might differ between different farm types contaminated in different levels and this simulation study highlights a strong need for more knowledge from on-farm trials.

A mechanistic model for spread of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) within a pig herd.

Before an efficient control strategy for livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA) in pigs can be decided upon, it is necessary to obtain a better understanding of how LA-MRSA spreads and persists within a pig herd, once it is introduced. We here present a mechanistic stochastic discrete-event simulation model for spread of LA-MRSA within a farrow-to-finish sow herd to aid in this. The model was individual-based and included three different disease compartments: susceptible, intermittent or persistent shedder of MRSA. The model was used for studying transmission dynamics and within-farm prevalence after different introductions of LA-MRSA into a farm. The spread of LA-MRSA throughout the farm mainly followed the movement of pigs. After spread of LA-MRSA had reached equilibrium, the prevalence of LA-MRSA shedders was predicted to be highest in the farrowing unit, independent of how LA-MRSA was introduced. LA-MRSA took longer to spread to the whole herd if introduced in the finisher stable, rather than by gilts in the mating stable. The more LA-MRSA positive animals introduced, the shorter time before the prevalence in the herd stabilised. Introduction of a low number of intermittently shedding pigs was predicted to frequently result in LA-MRSA fading out. The model is a potential decision support tool for assessments of short and long term consequences of proposed intervention strategies or surveillance options for LA-MRSA within pig herds.