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Limited data have been published on the epidemiology and outcomes of breakthrough COVID-19 in patients with hematological malignancy (HM) after anti-SARS-CoV-2 vaccination. Adult HM who received at least one dose of anti-SARS-CoV-2 vaccine and diagnosed with breakthrough COVID-19 between January 2021 and March 2022 and registered in EPICOVIDEHA were included in this analysis. A total of 1548 cases were included, mainly with lymphoid malignancies (1181 cases, 76%). After viral genome sequencing in 753 cases (49%), Omicron variant was prevalent (517, 68.7%). Most of the patients received at least two vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received specific treatment for COVID-19. After 30-days follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with Omicron variant was of 7.9%, comparable to that reported for the other variants. The 30-day mortality rate was significantly lower than in the pre-vaccine era (31%). In the univariable analysis, older age (p<0.001), active HM (p<0.001), severe and critical COVID-19 (p=0.007 and p<0.001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (p<0.001). In the multivariable model, older age, active disease, critical COVID-19 and at least 2-3 comorbidities were correlated with a higher mortality, whereas the administration of monoclonal antibodies, alone (p<0.001) or combined with antivirals (p=0.009), was observed protective. While mortality is significantly lower than in the pre-vaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals. EPICOVIDEHA (www.clinicaltrials.gov; National Clinical Trials identifier NCT04733729) is an international open web-based registry for patients with HMs infected with SARS-CoV-2.

BackgroundSevere 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.MethodsIn 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.ResultsIn 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.ConclusionsNonhospitalized 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 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.In this national cross-sectional survey, long-COVID symptoms after SARS-CoV-2 infection are common compared to seronegative controls, affecting both physical and mental health. Female sex and severity of infection are dominant risk factors. Informed interdisciplinary management strategies for long COVID are needed.

Porcine epidemic diarrhea virus (PEDV), belonging to the genus Alphacoronavirus, can cause serious disease in pigs of all ages, especially in suckling pigs. Differences in virulence have been observed between various strains of this virus. In this study, four pigs were inoculated with PEDV from Germany (intestine/intestinal content collected from pigs in 2016) and four pigs with PEDV from Italy (intestine/intestinal material collected from pigs in 2016). The pigs were re-inoculated with the same virus on multiple occasions to create a more robust infection and enhance the antibody responses. The clinical signs and pathological changes observed were generally mild. Two distinct peaks of virus excretion were seen in the group of pigs inoculated with the PEDV from Germany, while only one strong peak was seen for the group of pigs that received the virus from Italy. Seroconversion was seen by days 18 and 10 post-inoculation with PEDV in all surviving pigs from the groups that received the inoculums from Germany and Italy, respectively. Attempts to infect pigs with a swine enteric coronavirus (SeCoV) from Slovakia were unsuccessful, and no signs of infection were observed in the inoculated animals.

Abstract Background Physical activity (PA) at moderate intensity is recommended for healthy pregnant women. The three-arm FitMum randomised controlled trial showed that it was possible to increase PA level during pregnancy with structured supervised exercise training (EXE) compared to standard care. Motivational counselling on PA (MOT) did not increase PA. This process evaluation aims to understand the implementation and mechanisms of impact of EXE and MOT. Methods A mixed methods process evaluation was conducted using the UK Medical Research Council’s process evaluation framework by assessing implementation (reach, fidelity, and dose) and mechanisms of impact of the two interventions provided to pregnant women in FitMum. Data was collected both quantitatively (n = 220) and qualitatively (n = 20). Results The FitMum trial reached educated pregnant women (80% having an educational level ≥ bachelor’s degree) with high autonomy of everyday life. Most participants (58%) were recruited at their first-trimester ultrasonic scan. Reasons to participate were personal (91%) and altruistic (56%). The intervention dose was delivered as intended with high fidelity in the original physical intervention setup and in the altered online setup during the COVID-19 restrictions. A low dose received in EXE (1.3 [95% CI, 1.1; 1.5] sessions/week) was partly explained by the pre-scheduled EXE sessions favouring participants with a flexible everyday life and a supportive social network. Dose received in EXE increased during online intervention delivery. Participants in MOT received 5.2 [4.7; 5.7] of 7 sessions. Mechanisms of impact comprised a perception of intervention commitment among participants in EXE due to the scheduled EXE sessions, whereas participants in MOT considered themselves as PA self-determined. PA was considered as constrained activities in EXE and included in daily activities in MOT. Conclusion The FitMum interventions was delivered with high fidelity. During COVID-19, the dose received in EXE increased compared to the previous physical setup. Mechanisms of impact as commitment, perception of empowerment and perception of PA as well as the paradox between prioritising PA and family and the need of a flexible everyday life need to be considered when offering pregnant women PA interventions. Future interventions should consider a combination of physical and online exercise training for pregnant women.

AbstractSpatial resolution in existing chest x-ray (CXR)-based scoring systems for coronavirus disease 2019 (COVID-19) pneumonia is low, and should be increased for better representation of anatomy, and severity of lung involvement. An existing CXR-based system, the Brixia score, was modified to increase the spatial resolution, creating the MBrixia score. The MBrixia score is the sum, of a rule-based quantification of CXR severity on a scale of 0 to 3 in 12 anatomical zones in the lungs. The MBrixia score was applied to CXR images from COVID-19 patients at a single tertiary hospital in the period May 4th–June 5th, 2020. The relationship between MBrixia score, and level of respiratory support at the time of performed CXR imaging was investigated. 37 hospitalized COVID-19 patients with 290 CXRs were identified, 22 (59.5%) were admitted to the intensive care unit and 10 (27%) died during follow-up. In a Poisson regression using all 290 MBrixia scored CXRs, a higher MBrixia score was associated with a higher level of respiratory support at the time of performed CXR. The MBrixia score could potentially be valuable as a quantitative surrogate measurement of COVID-19 pneumonia severity, and future studies should investigate the score’s validity and capabilities of predicting clinical outcomes.

Abstract Southern Madagascar recently experienced a severe food security crisis, made significantly worse by well below average rainfall from July 2019 to June 2021. This exceptional drought has affected a region with high pre-existing levels of vulnerability to food insecurity (subsistence agriculture and pastoralism in the region is rain-fed only), while impacts have been compounded further by COVID-19 restrictions and pest infestations. The rainy seasons of both 2019/20 and 2020/21 saw just 60% of normal rainfall across the Grand South region and was estimated as a 1-in-135 year dry event, only surpassed in severity by the devastating drought of 1990–92. Based on a combination of observations and climate modelling, the likelihood of experiencing such poor rains in the region was not significantly increased due to human-caused climate change: while the observations and models combine to indicate a small shift toward more droughts like the 2019–2021 event as a consequence of climate change, these trends remain overwhelmed by natural variability. This result is consistent with previous research, with the Intergovernmental Panel on Climate Change (IPCC)’s Sixth Assessment Report concluding that any perceptible changes in drought will only emerge in this region if global mean temperatures exceed 2 °C above pre-industrial levels.

When the COVID-19 pandemic reached Norway, primary health care had to reorganize to ensure safe patient treatment and maintain infection control. General practitioners (GPs) are key health care providers in the municipalities. Our aim was to explore the experiences and management strategies of Norwegian GPs during the COVID-19 pandemic - over time, and in the context of a sudden organizational change.Longitudinal qualitative interview study with two interview rounds. The first round of interviews was conducted from September-December 2020, the second round from January-April 2021. In the first interview round, we performed eight semi-structured interviews with GPs from eight municipalities in Norway. In the second round, five of the GPs were re-interviewed. Consecutive interviews were performed 2-4 months apart. To analyze the data, we used thematic analysis.The COVID-19 pandemic required GPs to balance several concerns, such as continuity of care and their own professional efforts. Several GPs experienced challenges in the collaboration with the municipality and in relation to defining their own professional position. Guided by The Norwegian Association of General practitioners, The Norwegian College of General Practice and collegial support, they found viable solutions and ended up with a feeling of having adapted to a new normal.Although our study demonstrates that the GPs adapted to the changing conditions, the current municipal health care models are not ideal. There is a need for clarification of responsibilities between GPs and the municipality to facilitate a more coordinated future pandemic response.Key PointsFacing the COVID-19 pandemic, the primary health care service in Norway had to reorganize to ensure safe patient treatment and maintain infection control.Several GPs experienced challenges in collaboration with the municipalities.There is a need for clarification of responsibilities between GPs and the municipality.

AbstractBoth the USA and Europe experienced substantial excess mortality in 2020 and 2021 related to the COVID-19 pandemic. Methods used to estimate excess mortality vary, making comparisons difficult. This retrospective observational study included data on deaths from all causes occurring in the USA and 25 European countries or subnational areas participating in the network for European monitoring of excess mortality for public health action (EuroMOMO). We applied the EuroMOMO algorithm to estimate excess all-cause mortality in the USA and Europe during the first two years of the COVID-19 pandemic, 2020–2021, and compared excess mortality by age group and time periods reflecting three primary waves. During 2020–2021, the USA experienced 154.5 (95% Uncertainty Interval [UI]: 154.2–154.9) cumulative age-standardized excess all-cause deaths per 100,000 person years, compared with 110.4 (95% UI: 109.9–111.0) for the European countries. Excess all-cause mortality in the USA was higher than in Europe for nearly all age groups, with an additional 44.1 excess deaths per 100,000 person years overall from 2020–2021. If the USA had experienced an excess mortality rate similar to Europe, there would have been approximately 391 thousand (36%) fewer excess deaths in the USA.

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.