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In the context of severe coronavirus disease 2019 (COVID-19) illness, we examined endogenous glucocorticoid concentrations, steroidogenic enzyme activity, and their correlation with inflammation and patient outcomes. This observational study included 125 hospitalized COVID-19 patients and 101 healthy individuals as a reference group. We utilized LC-MS to assess serum concentrations of 11-deoxycortisol, cortisol, and cortisone, as well as activities of steroidogenic enzymes (11β-hydroxylase and 11β-hydroxysteroid-dehydrogenase type 1). Cox proportional hazards regression analysis and competing risk analysis were employed to analyze associations between glucocorticoid concentrations and outcomes, adjusting for relevant factors. In patients with COVID-19, cortisol concentrations were higher and cortisone concentrations were lower compared to the reference group, while 11-deoxycortisol concentrations were similar. Steroidogenic enzyme activity favored cortisol production. Correlations between glucocorticoid concentrations and inflammatory markers were low. A doubling in concentrations cortisol, was associated with increased 90-day mortality and mechanical ventilation (HR: 2.40 95% CI: (1.03–5.59) , P = 0.042 and HR: 3.83 (1.19–12.31), P = 0.024). A doubling in concentrations of 11-deoxycortisol was also associated to mortality (HR: 1.32 (1.05–1.67), P = 0.018), whereas concentrations of cortisone were associated with mechanical ventilation (HR: 5.09 (1.49–17.40), P = 0.009). In conclusion, serum concentrations of glucocorticoid metabolites were altered in patients hospitalized with severe COVID-19, and steroidogenic enzyme activity resulting in the conversion of cortisone to biologically active cortisol was preserved, thus not favoring critical-illness-related corticosteroid insufficiency at the enzymatic level. Glucocorticoid release did not counterbalance the hyperinflammatory state in patients with severe COVID-19. High serum concentrations of 11-deoxycortisol and cortisol were associated with 90-day mortality, and high serum concentrations of cortisol and cortisone were associated with mechanical ventilation.

Objectives: This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity. Methods: Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day 0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day 90, Day 180, 28 days after 3rd vaccination (Day 251), Day 365, and prior to 4th vaccination (Day 535). SARS-CoV-2 PCR results were extracted from the national microbiology database. Mixed-effect multivariable linear regression investigated the impact of hybrid-immunity (stratified into 4 groups: no hybrid immunity, PCR+ prior to 3rd dose, PCR+ after 3rd dose and before Day 365, PCR+ after Day 365) on anti-spike IgG trajectories. Results: A total of 4,936 individuals were included, 47% developed hybrid-immunity. Anti-spike IgG increases were observed in all groups at Day 251, with the highest levels in those PCR+ prior to 3rd dose (Geometric Mean; 535,647AU/mL vs. 374,665AU/mL with no hybrid-immunity, P

ObjectivesEndothelial injury may promote declining lung function. We aimed to investigate in well-treated persons living with HIV (PLWH) whether elevated levels of thrombomodulin (TM) and syndecan-1 (SDC1) are associated with excess lung function decline and worsening dyspnea.MethodsA prospective cohort study comprising patients from the Copenhagen municipality. We included 698 PLWH with undetectable viral load. Biomarkers and demographics were measured at baseline, spirometry [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)] and dyspnea score both at baseline and 2-year follow-up.Both biomarkers were dichotomized at the 3rd quartile. Decline in lung function was estimated using a linear mixed model with patient-specific random effect. Increase in dyspnea score was estimated using a general mixed logistic regression model.ResultsWe did not find an association between elevated SDC1 or TM and an excess decline in neither FEV1: SDC1: 4.5 mL/year (95% CI: −3.9–12.9, p = 0.30), TM: 2.2 mL/year (95% CI: −6.0–10.4, p = 0.60) nor FVC: SDC1: 4.1 mL/year (95% CI: −6.0–14.2, p = 0.42), TM: 1.4 mL/year (95% CI: −8.3–11.1, p = 0.78). A subgroup analysis of never-smokers was consistent with the main analysis.Likewise, we did not find any association between elevated SDC1 and TM and increase in dyspnea score: SDC1: OR 1.43 (95% CI: 0.89–2.30, p = 0.14), TM: OR 1.05 (95% CI: 0.65–1.71, p = 0.26).ConclusionWe did not find a significant association between elevated biomarkers of endothelial injury and decline in lung function nor dyspnea.

BackgroundTesting for SARS-CoV-2 is essential to provide early COVID-19 treatment for people at high risk of severe illness and to limit the spread of infection in society. Proper upper respiratory specimen collection is the most critical step in the diagnosis of the SARS-CoV-2 virus in public settings, and throat swabs were the preferred specimens used for mass testing in many countries during the COVID-19 pandemic. However, there is still a discussion about whether throat swabs have a high enough sensitivity for SARS-CoV-2 diagnostic testing, as previous studies have reported a large variability in the sensitivity from 52% to 100%. Many previous studies exploring the diagnostic accuracy of throat swabs lack a detailed description of the sampling technique, which makes it difficult to compare the different diagnostic accuracy results. Some studies perform a throat swab by only collecting specimens from the posterior oropharyngeal wall, while others also include a swab of the palatine tonsils for SARS-CoV-2 testing. However, studies suggest that the palatine tonsils could have a tissue tropism for SARS-CoV-2 that may improve the SARS-CoV-2 detection during sampling. This may explain the variation of sensitivity reported, but no clinical studies have yet explored the differences in sensitivity and patient discomfort whether the palatine tonsils are included during the throat swab or not. ObjectiveThe objective of this study is to examine the sensitivity and patient discomfort of a throat swab including the palatine tonsils compared to only swabbing the posterior oropharyngeal wall in molecular testing for SARS-CoV-2. MethodsWe will conduct a randomized controlled study to compare the molecular detection rate of SARS-CoV-2 by a throat swab performed from the posterior oropharyngeal wall and the palatine tonsils (intervention group) or the posterior oropharyngeal wall only (control group). Participants will be randomized in a 1:1 ratio. All participants fill out a baseline questionnaire upon enrollment in the trial, examining their reason for being tested, symptoms, and previous tonsillectomy. A follow-up questionnaire will be sent to participants to explore the development of symptoms after testing. ResultsA total of 2315 participants were enrolled in this study between November 10, 2022, and December 22, 2022. The results from the follow-up questionnaire are expected to be completed at the beginning of 2024. ConclusionsThis randomized clinical trial will provide us with information about whether throat swabs including specimens from the palatine tonsils will improve the diagnostic sensitivity for SARS-CoV-2 molecular detection. These results can, therefore, be used to improve future testing recommendations and provide additional information about tissue tropism for SARS-CoV-2. Trial RegistrationClinicalTrials.gov NCT05611203; https://clinicaltrials.gov/study/NCT05611203 International Registered Report Identifier (IRRID)DERR1-10.2196/47446

Abstract Introduction The Neutrophil-Lymphocyte Ratio (NLR) in blood has demonstrated its capability to predict bacteremia in emergency departments, and its association with mortality has been established in patients with sepsis in intensive care units. However, its potential concerning mortality and readmission in patients with Gram-negative bacteremia (GNB) is unexplored. Methods This retrospective cohort study included patients with GNB between 2018 and 2022 from six hospitals in the Capital Region of Denmark. Patients who were immunosuppressed or had missing NLR values on the day of blood culture were excluded. Logistic regression models were used to analyze the association between NLR levels and 90-day all-cause mortality, while the logit link interpretation of the cumulative incidence function was used to assess the association between NLR levels and 60-day readmission. Associations were quantified as odds ratios (OR) with corresponding 95% confidence intervals (CI). Results The study included 1763 patients with a median age was 76.8 years and 51.3% were female. The median NLR was 17.3 and 15.8% of patients had a quick sequential organ failure assessment score of two or three. Urinary tract infection (UTI) was the most frequent focus and Escherichia coli the most frequent pathogen. Statistically significant differences in median NLR were found by age group and pathogen, and for patients with or without hypertension, liver disease, chronic obstructive pulmonary disease, dementia, and alcohol abuse. 378 patients (21.4%) died before 90 days. 526 (29.8%) patients were readmitted to the hospital within 60 days. For each doubling of the NLR, the OR for all-cause 90-day mortality was 1.15 (95% CI, 1.04–1.27) and 1.12 (95% CI, 1.02–1.24) for 60-day readmission. Analysis of subgroups did not show statistically significant differences between groups in relation to the association between NLR and mortality. The discriminatory ability of NLR for mortality was limited and comparable to blood neutrophil or lymphocyte count, producing receiver operating characteristic curves with an area under the curve of 0.59 (95% CI, 0.56–0.63), 0.60 (95% CI, 0.56–0.65) and 0.53 (95% CI, 0.49–0.56), respectively. Conclusion Blood neutrophil-lymphocyte ratio was associated with 90-day all-cause mortality and 60-day readmission in patients with GNB. However, the ratio has limited ability in predicting mortality or readmission.

Objectives: We aimed to determine the incidence rate, pathogen composition, and risk factors, particularly airflow limitation, associated with bacterial respiratory infection and pneumonia in a prospective cohort of well-treated people with HIV (PWH) between 2015-2021. Methods: We included 1007 PWH from the Copenhagen Comorbidity in HIV infection (COCOMO) study. Spirometry was performed at inclusion. Microbiology samples were collected prospectively. Cumulative incidence was determined by the Aalen-Johansen estimator. Cox proportional hazard models were used to calculate risk factors, adjusted for traditional and HIV-specific variables. Results: The incidence rates of first bacterial respiratory infection and pneumonia were 12.4 (95% CI 9.7-15.5) and 5.5 (95% CI: 3.8-7.7) per 1000 person-years, respectively. The cumulative incidence of pneumonia was four times higher in PWH with airflow limitation (11.8% vs 3.2%, P

Abstract Community acquired bacterial meningitis (CABM) is a medical emergency requiring timely appropriate action. More knowledge about pre-hospital symptoms is needed. Retrospective observational study of pre-hospital management in patients with CABM between 2016 and 2021 admitted to a hospital in the Capital Region of Denmark. Reported symptoms were extracted from archived audio files of the initial phone call to emergency medical service. The majority of the 209 patients (82%) were adults. The most common symptoms were altered mental state (58%) and fever (57%), while neck stiffness was less common (9%). Children more often presented with fever, fatigue, rashes, and neck stiffness, while adults more often presented with altered mental state, and leg pain. Most patients (85%) reported at least 1 of the 3 symptoms in the classical triad of meningitis, while 3% reported all 3. Children more often presented at least 2 of 3 symptoms in the triad. One child (3%) and 7 adults (4%) received antibiotics pre-admission. Patients with CABM reported a variety of symptoms that differed significantly in children and adults. The classic triad was rare. Very few patients received antibiotics pre-admission. We suggest that questioning relevant symptoms should be done in febrile or mentally altered patients.

BackgroundEthnic minorities living in high-income countries have been disproportionately affected by Coronavirus Disease 2019 (COVID-19) in terms of infection rates, hospitalisations, and deaths; however, less is known about long COVID in these populations. Our aim was to examine the risk of long COVID and associated symptoms among ethnic minorities.Methods and findingsWe used nationwide register-based cohort data on individuals diagnosed with COVID-19 aged ≥18 years (n = 2,287,175) between January 2020 and August 2022 in Denmark. We calculated the risk of long COVID diagnosis and long COVID symptoms among ethnic minorities compared with native Danes using multivariable Cox proportional hazard regression and logistic regression, respectively. Among individuals who were first time diagnosed with COVID-19 during the study period, 39,876 (1.7%) were hospitalised and 2,247,299 (98.3%) were nonhospitalised individuals. Of the diagnosed COVID-19 cases, 1,952,021 (85.3%) were native Danes and 335,154 (14.7%) were ethnic minorities. After adjustment for age, sex, civil status, education, family income, and Charlson comorbidity index, ethnic minorities from North Africa (adjusted hazard ratio [aHR] 1.41, 95% confidence interval [CI] [1.12,1.79], p = 0.003), Middle East (aHR 1.38, 95% CI [1.24,1.55], p < 0.001), Eastern Europe (aHR 1.35, 95% CI [1.22,1.49], p < 0.001), and Asia (aHR 1.23, 95% CI [1.09,1.40], p = 0.001) had significantly greater risk of long COVID diagnosis than native Danes. In the analysis by largest countries of origin, the greater risks of long COVID diagnosis were found in people of Iraqi origin (aHR 1.56, 95% CI [1.30,1.88], p < 0.001), people of Turkish origin (aHR 1.42, 95% CI [1.24,1.63], p < 0.001), and people of Somali origin (aHR 1.42, 95% CI [1.07,1.91], p = 0.016). A significant factor associated with an increased risk of long COVID diagnosis was COVID-19 hospitalisation. The risk of long COVID diagnosis among ethnic minorities was more pronounced between January 2020 and June 2021. Furthermore, the odds of reporting cardiopulmonary symptoms (including dyspnoea, cough, and chest pain) and any long COVID symptoms were higher among people of North African, Middle Eastern, Eastern European, and Asian origins than among native Danes in both unadjusted and adjusted models. Despite including the nationwide sample of individuals diagnosed with COVID-19, the precision of our estimates on long COVID was limited to the sample of patients with symptoms who had contacted the hospital.ConclusionsBelonging to an ethnic minority group was significantly associated with an increased risk of long COVID, indicating the need to better understand long COVID drivers and address care and treatment strategies in these populations.

INTRODUCTION The UN General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to tackle the global environmental crisis. They will meet again at the biodiversity summit in Kunming, China and the climate conference (COP26) in Glasgow, UK. Ahead of these pivotal meetings, we – the editors of health journals worldwide – call for urgent action to keep average global temperature increases below 1.5°C, halt the destruction of nature, and protect health. Health is already being harmed by global temperature increases and the destruction of the natural world, a state of affairs health professionals have been bringing attention to for decades.1 The science is unequivocal; a global increase of 1.5°C above the pre-industrial average and the continued loss of biodiversity risk catastrophic harm to health pulmonary morbidity and mortality.5,6 Harms disproportionately affect the most vulnerable, including among children, older populations, ethnic minorities, poorer communities and those with underlying health problems.2,4 Global heating is also contributing to the decline in global yield potential for major crops, falling by 1.8-5.6% since 1981; this, together with the effects of extreme weather and soil depletion, is hampering efforts to reduce undernutrition.4 Thriving ecosystems are essential to human health, and the widespread destruction of nature, including habitats and species, is eroding water and food security and increasing the chance of pandemics.3,7,8 The consequences of the environmental crisis fall disproportionately on those countries and communities that have contributed least to the problem and are least able to mitigate the harms. Yet no country, no matter how wealthy, can shield itself from these impacts. Allowing the consequences to fall disproportionately on the most vulnerable will breed more conflict, food insecurity, forced displacement and zoonotic disease – with severe implications for all countries and communities. As with the covid-19 pandemic, we are globally as strong as our weakest member. Rises above 1.5°C increase the chance of reaching tipping points in natural systems that could lock the world into an acutely unstable state. This would critically impair our ability to mitigate harms and to prevent catastrophic, runaway environmental change.9,10

IntroductionImmune dysregulation with an excessive release of cytokines has been identified as a key driver in the development of severe COVID-19. The aim of this study was to evaluate the initial cytokine profile associated with 90-day mortality and respiratory failure in a cohort of patients hospitalized with COVID 19 that did not receive immunomodulatory therapy.MethodsLevels of 45 cytokines were measured in blood samples obtained at admission from patients with confirmed COVID-19. Logistic regression analysis was utilized to determine the association between cytokine levels and outcomes. The primary outcome was death within 90 days from admission and the secondary outcome was need for mechanical ventilation.ResultsA total of 132 patients were included during the spring of 2020. We found that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with the odds of 90-day mortality, specifically: interleukin-1 receptor antagonist, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-3α, macrophage inflammatory protein-3β, and fractalkine. All but fractalkine were also associated with the odds of respiratory failure during admission. Monocyte chemoattractant protein-1 showed the strongest estimate of association with both outcomes.ConclusionWe showed that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with 90-day mortality in patients hospitalized with COVID-19 that did not receive immunomodulatory therapy.

Abstract Background Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood. Methods In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51–72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections. Results We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified. Conclusions SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.

Summary: SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron breakthrough infection.The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR [95% CI] for BA.2: 0.83 [0.73–0.95], p = 0.006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of infection (aOR [95% CI] for BA.2 spike-specific IgG: 0.65 [0.48–0.88], p = 0.006 and BA.2 ACE2-blocking antibodies: 0.46 [0.30–0.69], p = 0.0002). A sex-stratified analysis showed more pronounced associations for females than males.High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new variants and to estimate the necessity and timing of booster vaccination.

Aim: To explore pituitary–gonadal hormone concentrations and assess their association with inflammation, severe respiratory failure, and mortality in hospitalized men and women with COVID-19, and compare these to hormone concentration s in hospitalized patients with bacterial community-acquired pneumonia (CAP) and influenza virus CAP and to concentrations in a reference group of healthy individuals. Methods: Serum concentrations of testosterone, estrone sulfate, luteini zing hormone (LH), follicle-stimulating hormone (FSH), and interleukin-6 (IL-6) were measured within 4 days of admission. Associations were assessed by logistic regression analysis in patients with COVID-19, and results were reported as odds ratio with 95% CI per two-fold reduction after adjustment for age, comorbidities, days to sample collection, and IL-6 concentrations. Results: In total, 278 patients with COVID-19, 21 with influenza virus CA P, and 76 with bacterial CAP were included. Testosterone concentrations were suppressed in men hospitalized with COVID-19, bacterial and influenza virus CA P, and moderately suppressed in women. Reductions in testosterone (OR: 3.43 (1.14–10.30), P = 0.028) and LH (OR: 2.51 (1.28–4.92), P = 0.008) were associated with higher odds of mehanical ventilation (MV) in men with COVID-19. In women with COVID-19, reductions in LH (OR: 3.34 (1.02–10-90), P = 0.046) and FSH (OR: 2.52 (1.01–6.27), P = 0.047) were associated with higher odds of MV. Conclusion: Low testosterone and LH concentrations were predictive of severe respiratory failure in men with COVID-19, whereas low concentrations of LH and FSH were predictive of severe respiratory failure in women with COVID-19.

Abstract Passive immunotherapy with convalescent plasma may be the only available agent during the early phases of a pandemic. Here, we report safety and efficacy of high-titer convalescent plasma for COVID-19 pneumonia. Double-blinded randomized multicenter placebo-controlled trial of adult patients hospitalized with COVID-19 pneumonia. The intervention was COVID-19 convalescent plasma and placebo was saline allocated 2:1. The primary outcome was clinical status 14 days after the intervention evaluated on a clinical ordinal scale. The trial was registered at ClinicalTrials.Gov, NCT04345289, 14/04/2020. The CCAP-2 trial was terminated prematurely due to futility. Of 147 patients randomized, we included 144 patients in the modified intention-to-treat population. The ordinal clinical status 14 days post-intervention was comparable between treatment groups (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.72–2.09). Results were consistent when evaluating clinical progression on an individual level 14 days after intervention (OR 1.09; 95% CI 0.46–1.73). No significant differences in length of hospital stay, admission to ICU, frequency of severe adverse events or all-cause mortality during follow-up were found between the intervention and the placebo group. Infusion of convalescent plasma did not influence clinical progression, survival or length of hospitalization in patients with COVID-19 pneumonia.

Introduction With longer life expectancy in people living with HIV (PLWH) on antiretroviral therapy, cardiovascular disease (CVD) has become a common cause of mortality among them. Abacavir has been associated with an increased risk of myocardial infarction, but the mechanism is unknown. Additionally, abacavir may be obesogenic which could mediate an additional risk factor of CVD. We aim to investigate if discontinuation of abacavir will have a favourable impact on body weight and cardiac parameters in PLWH.Methods and analysis Randomised, controlled, superiority trial of virologically suppressed PLWH on dolutegravir, abacavir and lamivudine (DTG/ABC/3TC) for ≥6 months. In total, 70 PLWH will be randomised 1:2 to either continue DTG/ABC/3TC or to switch to dolutegravir and lamivudine (DTG/3TC) providing the power of 80% at alpha 5% to detect a mean difference in weight change of 2 kg (Δ) given an SD of 2.7 kg. Follow-up will be 48 weeks. Data will be collected at baseline and week 48. Primary outcome will be change in mean body weight from baseline to week 24 and 48 evaluated in a linear mixed model. Secondary outcomes will be changes in cardiac, inflammatory and metabolic parameters, fat distribution, coagulation, endothelial, platelet function, quality of life and virological control from baseline to week 48. Measurements include CT of thorax and abdomen, external carotid artery ultrasound, liver elastography and dual energy X-ray absorptiometry and blood analysis. Plasma HIV RNA will be measured at baseline, week 4, 24 and 48. Forty participants (20 from each arm) will be included in a substudy involving cardiac MRI at baseline and week 48. Twenty non-HIV-infected controls will be included with a single scan to compare with baseline scan data.Ethics and dissemination Result from this study will lead to a better understanding of the association between antiretroviral therapy and the impact on weight and risk of CVD. Findings will be useful for both clinicians and PLWH in the guidance of a more individualised HIV treatment. Results from the main study and the substudies will be submitted for publication in a peer-reviewed journal(s). The AVERTAS study is approved by the Ethics Committee of the Capital Region, Denmark (H-20011433), Danish Medicines Agency (EudraCT no. 2019-004999-19) and Regional Data Protection Centre (P-2020–207).Trial registration number Pre-results registration at ClinicalTrials.gov Identifier: NCT04904406, registered 27 May 2021. Protocol version: Protocol version 9.0, 4 April 2023, approved 10-05-2023 by Ethics Committee of the Capital Region, Denmark (H-20011433). Danish Medicines Agency (EudraCT no. 2019-004999-19). Regional Data Protection Centre (P-2020–207) ClinicalTrials.gov.

Introduction The optimal duration of antibiotic therapy for community-acquired pneumonia (CAP) is unsettled. Short-course therapy has proved successful in clinical trials but is not yet implemented in everyday clinical practice. Validation of results from randomised controlled trials is crucial to evaluate existing evidence and provide clinicians with assurance of using new treatment strategies. In a pragmatic framework, we aim to assess the use of short-course antibiotic therapy guided by the onset of clinical stability in patients hospitalised with CAP.Methods and analysis This study is a randomised controlled trial with a non-inferiority design that will examine the efficacy of short-course antibiotic therapy in patients hospitalised with CAP. From six hospitals across Denmark, we plan to enrol 564 patients between 2019 and 2024. Within 3–5 days after initiating antibiotic therapy, participants will be randomised 1:1 to parallel treatment arms: (1) short-course antibiotic therapy of 5 days or (2) antibiotic therapy of at least 7 days. The primary outcome will be 90-day readmission-free survival and will be estimated as an absolute risk difference with a predefined non-inferiority margin of −6%. Secondary outcomes will comprise other safety measures including new antibiotics, adverse events, length of hospital stay and postdischarge outpatient visits. Both intention-to-treat and per-protocol analyses will be performed.Ethics and dissemination This study has been approved by the Health Research Ethics Committee of the Capital Region of Denmark (identifier number: H-19014479). Trial data will be made available in anonymous form when the trial has ended.Trial registration number NCT04089787, ClinicalTrials.Gov.

The SARS-CoV-2 Omicron variant is associated with high rates of vaccine breakthrough infections, but the immunological basis for this is not well characterised. Here, the authors show that increased anti-Spike IgG antibody levels are associated with a reduced risk of infection with the Delta variant, but not with Omicron.

Abstract The diagnosis of COVID-19 is based on detection of SARS-CoV-2 in oro-/nasopharyngel swabs, but due to discomfort and minor risk during the swab procedure, detection of SARS-CoV-2 has been investigated in other biological matrixes. In this proof-of-concept study, individuals with confirmed SARS-CoV-2 infection performed a daily air sample for five days. Air samples were obtained through a non-invasive electrostatic air sampler. Detection of SARS-CoV-2 RNA was determined with qRT-PCR. The association of positive samples with different exposures was evaluated through mixed-effect models. We obtained 665 air samples from 111 included participants with confirmed SARS-CoV-2 infection. Overall, 52 individuals (46.8%) had at least one positive air sample, and 129 (19.4%) air samples were positive for SARS-CoV-2. Participants with symptoms or a symptom duration ≤ four days had significantly higher odds of having a positive air sample. Cycle threshold values were significantly lower in samples obtained ≤ 4 days from symptom onset. Neither variant of SARS-CoV-2 nor method of air sampling were associated with a positive air sample. We demonstrate that SARS-CoV-2 is detectable in human breath by electrostatic air sampling with the highest detection rate closest to symptom onset. We suggest further evaluation of the air sampling technique to increase sensitivity.

Mannose-binding lectin-associated serine protease 2 (MASP-2) is the main activator of the lectin complement pathway and has been suggested to be involved in the pathophysiology of coronavirus disease 2019 (COVID-19). To study a possible association between MASP-2 and COVID-19, we aimed at developing a sensitive and reliable MASP-2 ELISA. From an array of novel mouse-monoclonal antibodies using recombinant MASP-2 as antigen, two clones were selected to create a sandwich ELISA. Plasma samples were obtained from 216 healthy controls, 347 convalescent COVID-19 patients, and 147 prospectively followed COVID-19 patients. The assay was specific towards MASP-2 and did not recognize the truncated MASP2 splice variant MAP-2 (MAp19). The limit of quantification was shown to be 0.1 ng/mL. MASP-2 concentration was found to be stable after multiple freeze-thaw cycles. In healthy controls, the mean MASP-2 concentration was 524 ng/mL (95% CI: 496.5–551.6). No significant difference was found in the MASP-2 concentrations between COVID-19 convalescent samples and controls. However, a significant increase was observed in prospectively followed COVID-19 patients (mean: 834 ng/mL [95% CI: 765.3–902.7, p < 0.0001]). In these patients, MASP-2 concentration correlated significantly with the concentrations of the terminal complement complex (ρ = 0.3596, p < 0.0001), with the lectin pathway pattern recognition molecules ficolin-2 (ρ = 0.2906, p = 0.0004) and ficolin-3 (ρ = 0.3952, p < 0.0001) and with C-reactive protein (ρ = 0.3292, p = 0.0002). Overall, we developed a specific quantitative MASP-2 sandwich ELISA. MASP-2 correlated with complement activation and inflammatory markers in COVID-19 patients, underscoring a possible role of MASP-2 in COVID-19 pathophysiology.

Introduction Prolonged use of antibiotics is closely related to antibiotic-associated infections, antimicrobial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract source of infection is poorly defined.Methods and analysis Investigator-initiated multicentre, non-blinded, non-inferiority randomised controlled trial with two parallel treatment arms. One arm will receive shortened antibiotic treatment of 5 days and the other arm will receive antibiotic treatment of 7 days or longer. Randomisation will occur in equal proportion (1:1) no later than day 5 of effective antibiotic treatment as determined by antibiogram. Immunosuppressed patients and those with GNB due to non-fermenting bacilli (Acinetobacter spp, Pseudomonas spp), Brucella spp, Fusobacterium spp or polymicrobial growth are ineligible.The primary endpoint is 90-day survival without clinical or microbiological failure to treatment. Secondary endpoints include all-cause mortality, total duration of antibiotic treatment, hospital readmission and Clostridioides difficile infection. Interim safety analysis will be performed after the recruitment of every 100 patients. Given an event rate of 12%, a non-inferiority margin of 10%, and 90% power, the required sample size to determine non-inferiority is 380 patients. Analyses will be performed on both intention-to-treat and per-protocol populations.Ethics and dissemination The study is approved by the Danish Regional Committee on Health Research (H-19085920) and the Danish Medicines Agency (2019-003282-17). The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.Trial registration number ClinicalTrials.Gov:NCT04291768.

Abstract Background As people living with HIV (PLWH) are growing older, there is increased incidence of metabolic diseases, including type 2 diabetes mellitus, for which insulin resistance is a key determinant. In this study, we aimed to investigate risk factors associated with insulin resistance in PLWH. Methods We included well-treated PLWH without hepatitis co-infection, and with available fasting serum insulin and plasma glucose (n = 643) from the Copenhagen Comorbidity in HIV Infection Study. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). We investigated the association between risk factors and high HOMA-IR in a logistic regression model adjusted for age, sex, abdominal obesity, smoking status, and origin. When including use of thymidine analogues and/or didanosine in the model, we also adjusted for time with HIV. Results Median (IQR) age of PLWH was 52 years (46–61), and 87% (n = 557) were male. Median (IQR) HOMA-IR was 1.86 (1.23–3.14) mmol/L × mU/L. Risk factors significantly associated with high HOMA-IR included older age, BMI ≥ 25, abdominal obesity, waist circumference, use of thymidine analogues and/or didanosine, time with HIV, and CD4+ nadir

Abstract Background Monocytes play an important role in inflammation, and monocytosis and monocyte activation are features of chronic inflammation. We aimed to investigate if HIV status was associated with monocyte count and monocyte activation and to assess the relationship between monocyte count and monocyte activation markers and HIV-related factors. Methods Persons living with HIV (PLWH) with measured monocyte count and sCD14 and sCD163 were included from the Copenhagen Comorbidity in HIV infection (COCOMO) study and matched 1:5 on sex and age with uninfected controls. In addition, 74 uninfected individuals from COCOMO with measured sCD14 and sCD163 were included. Identical protocols and equipment were used to determine monocyte counts and monocyte activation in PLWH and uninfected controls. Linear regression adjusted for age, sex, smoking and waist-to-hip-ratio was used to analyze the association between possible risk factors and monocyte outcomes. Results We included 871 PLWH and 4355 uninfected controls. PLWH had − 0.021 [− 0.031 − 0.011] × 109/L) lower monocyte count than uninfected controls, and in adjusted analyses HIV status was independently associated with − 0.035 [− 0.045, − 0.025] × 109/L lower monocyte count. In contrast, PLWH had higher sCD163 and sCD14 concentrations than uninfected controls. After adjustment, HIV-status was associated with higher sCD14 and sCD163 concentrations (588 [325, 851] ng/ml, and 194 [57, 330] ng/ml, respectively). Conclusion PLWH had lower monocyte counts than controls, but the absolute difference was small, and any clinical impact is likely limited. In contrast, concentrations of monocyte activation markers, previously implicated as drivers of non-AIDS comorbidity, were higher in PLWH than in controls.

Abstract To provide novel data on surfactant levels in adult COVID-19 patients, we collected bronchoalveolar lavage fluid less than 72 h after intubation and used Fourier Transform Infrared Spectroscopy to measure levels of dipalmitoylphosphatidylcholine (DPPC). A total of eleven COVID-19 patients with moderate-to-severe ARDS (CARDS) and 15 healthy controls were included. CARDS patients had lower DPPC levels than healthy controls. Moreover, a principal component analysis was able to separate patient groups into distinguishable subgroups. Our findings indicate markedly impaired pulmonary surfactant levels in COVID-19 patients, justifying further studies and clinical trials of exogenous surfactant.

Objectives: Streptococcus pneumoniae is one of the most important causes of diseases leading to child mortality, especially in low- and lower-middle-income countries. This review aims to describe the prevalence of carriage of S. pneumoniae and the impact of vaccination among children aged under five years in low- and lower-middle-income countries since 2012. Method: The study is a systematic review of the literature. Relevant publications were searched in PubMed and screened systematically for information on the prevalence of carriage of S. pneumoniae among children aged under five years. 149 publications were identified, and 20 were included in the review. Results: The prevalence of S. pneumoniae ranged between 26.7% - 90.7%. The prevalence of vaccine-type carriage ranged between 4.4% - 57.6% but generally decreased in countries after the introduction of PCV, with a reduction of 15.6% - 65.7%. Half of the post- pneumococcal conjugate vaccine (PCV) studies reported a vaccine-type carriage rate below 15%. Conclusion: Vaccine-type-carriage has decreased in most countries with the introduction of PCV. Still, coverage is only moderate, and carriage rates of S. pneumoniae vary significantly between countries. Continuous monitoring of carriage is needed to evaluate the effect of the further introduction of PCV10 and PCV13.

The course of COVID-19 is unpredictable, ranging from asymptomatic to respiratory failure and death. Prognostic biomarkers are urgently needed. We hypothesized that long pentraxin PTX3 could be a valuable plasma biomarker due to its essential role in inflammatory processes. In a prospective hospitalized COVID-19 derivation cohort (n = 126) during the spring of 2020, we measured PTX3 within 4 days of admission. The predictive value of mechanical ventilation (MV) and 30-day mortality compared with clinical parameters and other markers of inflammation were assessed by logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Analyses were repeated in a prospective validation cohort (n = 112) of hospitalized patients with COVID-19 treated with remdesivir and dexamethasone. Thirty-day mortality in the derivation cohort was 26.2%. In patients who died, the median PTX3 concentration upon admission was 19.5 ng/mL (IQR: 12.5–33.3) versus 6.6 ng/mL (IQR 2.9–12.3) (p < 0.0001) for survivors. After adjustment for covariates, the odds of 30-day mortality increased two-fold for each doubling of PTX3 (OR 2.03 [95% CI: 1.23–3.34], p = 0.006), which was also observed in the validation cohort (OR 1.70 [95% CI: 1.09–2.67], p = 0.02). Similarly, PTX3 levels were associated with MV. After adjustment for covariates, OR of MV was 2.34 (95% CI: 1.33–4.12, p = 0.003) in the derivation cohort and 1.64 (95% CI: 1.03–2.62, p = 0.04) in the validation cohort. PTX3 appears to be a useful clinical biomarker to predict 30-day respiratory failure and mortality risk in COVID-19 patients treated with and without remdesivir and dexamethasone.

Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PWH). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, and fecal 16 S microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PWH. Through network analysis and similarity network fusion (SNF), we identified three groups of PWH (SNF-1–3): healthy (HC)-like (SNF-1), mild at-risk (SNF-3), and severe at-risk (SNF-2). The PWH in the SNF-2 (45%) had a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4+ T-cell counts than the other two clusters. However, the HC-like and the severe at-risk group had a similar metabolic profile differing from HIV-negative controls (HNC), with dysregulation of amino acid metabolism. At the microbiome profile, the HC-like group had a lower α-diversity, a lower proportion of men having sex with men (MSM) and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in Prevotella, with a high proportion of MSM, which could potentially lead to higher systemic inflammation and increased cardiometabolic risk profile. The multi-omics integrative analysis also revealed a complex microbial interplay of the microbiome-associated metabolites in PWH. Those severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their dysregulated metabolic traits, aiming to achieve healthier aging.

ABSTRACT The aim of this study was to provide information about immunity against COVID-19 along with risk factors and behavior among employees in day care facilities and preschools (DCS) in Denmark. In collaboration with the Danish Union of Pedagogues, during February and March 2021, 47,810 members were offered a point-of-care rapid SARS-CoV-2 antibody test (POCT) at work and were invited to fill in an electronic questionnaire covering COVID-19 exposure. Seroprevalence data from Danish blood donors (total Ig enzyme-linked immunosorbent assay [ELISA]) were used as a proxy for the Danish population. A total of 21,018 (45%) DCS employees completed the questionnaire and reported their POCT result {median age, 44.3 years (interquartile range [IQR], [32.7 to 53.6]); females, 84.1%}, of which 20,267 (96.4%) were unvaccinated and included in analysis. A total of 1,857 (9.2%) participants tested seropositive, significantly higher than a seroprevalence at 7.6% (risk ratio [RR], 1.2; 95% confidence interval [CI], 1.14 to 1.27) among 40,541 healthy blood donors (median age, 42 years [IQR, 28 to 53]; males, 51.3%). Exposure at work (RR, 2.9; 95% CI, 2.3 to 3.6) was less of a risk factor than exposure within the household (RR, 12.7; 95% CI, 10.2 to 15.8). Less than 25% of participants reported wearing face protection at work. Most of the participants expressed some degree of fear of contracting COVID-19 both at work and outside work. SARS-CoV-2 seroprevalence was slightly higher in DCS staff than in blood donors, but possible exposure at home was associated with a higher risk than at work. DCS staff expressed fear of contracting COVID-19, though there was limited use of face protection at work. IMPORTANCE Identifying at-risk groups and evaluating preventive interventions in at-risk groups is imperative for the ongoing pandemic as well as for the control of future epidemics. Although DCS staff have a much higher risk of being infected within their own household than at their workplace, most are fearful of being infected with COVID-19 or bringing COVID-19 to work. This represents an interesting dilemma and an important issue which should be addressed by public health authorities for risk communication and pandemic planning. This study design can be used in a strategy for ongoing surveillance of COVID-19 immunity or other infections in the population. The findings of this study can be used to assess the need for future preventive interventions in DCS, such as the use of personal protective equipment.

IntroductionPeople living with HIV (PLWH) are at twice the risk of developing cardiovascular diseases and have more than four times higher odds of aortic aneurysm (AA) than the uninfected population. However, biomarkers of AA in PLWH are yet to be discovered. We aimed to investigate whether circulating biomarkers reflecting platelet activation, hemostasis and endothelial disruption, i.e. sCD40L, D-dimer, syndecan-1, and thrombomodulin, were associated with AA in PLWH.MethodsFive hundred seventy one PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study ≥40 years of age with an available contrast-enhanced CT scan as well as available biomarker analyses were included. The biomarkers were analyzed on thawed plasma. For each biomarker, we defined high level as a concentration in the upper quartile and low level as a concentration below the upper quartile. For D-dimer, the cut-off was defined as the lower limit of detection. Using unadjusted and adjusted logistic and linear regression models, we analyzed associations between AA and sCD40L, D-dimer, syndecan-1, and thrombomodulin, respectively in PLWH.ResultsPLWH had median (IQR) age 52 years (47-60), 88% were male, median (IQR) time since HIV diagnosis was 15 years (8-23), and 565 (99%) were currently on antiretroviral treatment. High level of sCD40L was associated with lower odds of AA in both unadjusted (odds ratio, OR, 0.23 (95% CI 0.07-0.77; P=0.017)) and adjusted models (adjusted OR, aOR, 0.23 (95% CI 0.07-0.78; P=0.019)). Detectable level of D-dimer was associated with higher odds of AA in both unadjusted (OR 2.76 (95% CI 1.34-5.67; P=0.006)) and adjusted models (aOR 2.22 (95% CI 1.02-4.85; P=0.045)).ConclusionsSCD40L was associated with lower odds of AA whereas D-dimer was independently associated with higher odds of AA in PLWH. This calls for further investigations into specific biomarkers to aid early diagnosis of AA in PLWH.

Objective. We aimed to assess the association between low N-terminal pro-brain natriuretic peptide (NT-proBNP) and body mass index (BMI), adipose tissue distribution, adiponectin, and HIV-specific risk factors among people with HIV (PWH). Methods. We included 811 PWH with measurement of height, weight and waist circumference, blood samples analyzed for NT-proBNP, and visceral-(VAT) and subcutaneous (SAT) adipose tissue areas measured from CT-scans. Low concentrations of NT-proBNP were defined as concentrations below the limit of quantification (5.9 pmol/L). Associations were explored with multivariable logistic regression analyses adjusted for relevant confounders. Results. We identified 471 (58%) individuals with low concentrations of NT-proBNP. Increasing BMI was associated with higher odds of low NT-proBNP (adjusted OR (aOR) 1.06 (95% CI: 1.01–1.11) per 1 kg/m2). Central obesity and large areas of VAT were associated with higher odds of low NT-proBNP (aOR 1.66 (1.16–2.36) and aOR 1.69 (1.09–2.62), respectively). Higher adiponectin was associated with lower odds of low NT-proBNP (aOR 0.86 (0.79–0.95) per 10% increase). No associations were found between low NT-proBNP and HIV-specific risk factors. Conclusions. In PWH, low NT-proBNP is associated with an adverse adipose tissue profile with high BMI, central obesity, accumulation of VAT, and low adiponectin.

Background. Chronic low-grade inflammation associated with a dysregulated adipose tissue might contribute to amplifying the inflammatory response in severe COVID-19. The aim of this study was to examine the association between levels of circulating leptin and adiponectin and the severity and mortality of COVID-19. Methods. Serum levels of leptin and adiponectin were determined at admission in 123 individuals with confirmed COVID-19 and their association with 90-day mortality and respiratory failure was analyzed by logistic regression analysis and expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Results. The median values of circulating leptin and adiponectin were 7.2 ng/mL (IQR 3.8–13.4) and 9.0 μg/mL (IQR 5.7–14.6), respectively. After adjustment for age, sex, body mass index, hypertension, diabetes, chronic obstructive pulmonary disease, and oxygen saturation at admission, a doubling of circulating adiponectin was associated with a 38% reduction in odds of 90-day mortality (OR 0.62, CI 0.43–0.89) and a 40% reduction in odds of respiratory failure (OR 0.60, CI 0.42–0.86). The association tended to be strongest in individuals below the median age of 72 years. Circulating leptin was not associated with outcomes. Conclusions. Circulating adiponectin at admission was inversely associated with mortality and respiratory failure in SARS-CoV-2 infection. Further studies are needed to elucidate how exactly adipokines, especially adiponectin, are linked to the progression and prognosis of COVID-19.

Purpose The ENFORCE cohort is a national Danish prospective cohort of adults who received a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as part of the Danish National SARS-CoV-2 vaccination programme. It was designed to investigate the long-term effectiveness, safety and durability of SARS-CoV-2 vaccines used in Denmark.Participants A total of 6943 adults scheduled to receive a SARS-CoV-2 vaccine in the Danish COVID-19 vaccination programme were enrolled in the study prior to their first vaccination. Participants will be followed for a total of 2 years with five predetermined follow-up visits and additional visits in relation to any booster vaccination. Serology measurements are performed after each study visit. T-cell immunity is evaluated at each study visit for a subgroup of 699 participants. Safety information is collected from participants at visits following each vaccination. Data on hospital admissions, diagnoses, deaths and SARS-CoV-2 PCR results are collected from national registries throughout the study period. The median age of participants was 64 years (IQR 53–75), 56.6% were women and 23% were individuals with an increased risk of a serious course of COVID-19. A total of 340 (4.9%) participants tested positive for SARS-CoV-2 spike IgG at baseline.Findings to date Results have been published on risk factors for humoral hyporesponsiveness and non-durable response to SARS-CoV-2 vaccination, the risk of breakthrough infections at different levels of SARS-CoV-2 spike IgG by viral variant and on the antibody neutralising capacity against different SARS-CoV-2 variants following primary and booster vaccinations.Future plans The ENFORCE cohort will continuously generate studies investigating immunological response, effectiveness, safety and durability of the SARS-CoV-2 vaccines.Trial registration number NCT04760132.

Abstract Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Abstract Background An early appropriate response is the cornerstone of treatment for invasive meningococcal disease. Little evidence exists on how cases with invasive meningococcal disease present at first contact to emergency medical services. Methods Retrospective observational study of cases presenting with invasive meningococcal disease from January 1st of 2016 to December 31st of 2020 in the Capital Region of Denmark with a catchment area population of 1,800,000. A single medical emergency center provides services to the region. Data was collected from emergency medical services’ call audio files, data from the call receiver registrations, registrations from ambulance personal and electronic health record data from the hospitalization. Results Of 1527 cases suspected of meningitis, 38 had invasive meningococcal disease and had been in contact with the emergency service. Most contacts were to the medical helpline rather than the emergency call center at initial contact to emergency medical services. All were hospitalized within 12 h. At initial contact, fever was present in 28 (74%) of 38 cases, while specific symptoms such as headache (n=12 (32%)), a rash or petechiae (n=9 (23%)) and stiffness of the neck (n=4 (11%)) varied and were infrequent. Cases younger than 18 years of age were more often male and more often presented with fever and rash/petechiae. Only 4 (11%) received prehospital antibiotic treatment. Conclusions Cases with invasive meningococcal disease presented with fever and unspecific symptoms. Although few were acutely ill at their initial contact, all were admitted within 12 h. We suggest that all feverish cases should be systematically asked about specific symptoms and should be wary of symptom progression to optimize the early management if cases with invasive meningococcal disease.

Abstract Persons living with HIV (PLWH) may have increased incidence of cardiovascular events and longer QTc intervals than uninfected persons. We aimed to investigate the incidence and risk factors of de novo major electrocardiogram (ECG) abnormalities and QTc prolongation in well-treated PLWH. We included virologically suppressed PLWH without major ECG abnormalities, who attended the 2-year follow-up in the Copenhagen comorbidity in HIV infection (COCOMO) study. ECGs were categorized according to Minnesota Code Manual. We defined de novo major ECG abnormalities as new major Minnesota Code Manual abnormalities. Prolonged QTc was defined as QTc > 460 ms in females and QTc > 450 ms in males. Of 667 PLWH without major ECG abnormalities at baseline, 34 (5%) developed de novo major ECG abnormalities after a median of 2.3 years. After adjustment, age (RR: 1.57 [1.08–2.28] per decade older), being underweight (RR: 5.79 [1.70–19.71]), current smoking (RR: 2.34 [1.06–5.16]), diabetes (RR: 3.89 [1.72–8.80]) and protease inhibitor use (RR: 2.45 [1.27–4.74) were associated with higher risk of getting de novo major ECG abnormalities. Of PLWH without prolonged QTc at baseline, only 11 (1.6%) participants developed de novo prolonged QTc. Five percent of well-treated PLWH acquired de novo major ECG abnormalities and protease inhibitor use was associated with more than twice the risk of de novo major ECG abnormalities. De novo prolonged QTc was rare and did not seem to constitute a problem in well-treated PLWH.

La publicación de este artículo es una iniciativa organizada por la Alianza Global por el Clima y la Salud (GCHA, por sus siglas en inglés) a través de la Alianza de Salud del Reino Unido sobre el Cambio Climático (UKHACC, por sus siglas en inglés) y los miembros del Grupo de Trabajo Latinoamericano sobre Cambio Climático y Salud. La convocatoria tiene un doble objetivo: que los líderes mundiales acuerden los cambios necesarios para mantener el aumento de la temperatura global por debajo de 1,5°C y que los profesionales de la salud adquieran una mayor relevancia en el debate global sobre la crisis climática y la pérdida de la biodiversidad. La convocatoria se desarrolla en el contexto de la próxima celebración de la Asamblea General de Naciones Unidas que se iniciará el 14 de septiembre de 2021, así como también de la celebración de la conferencia climática COP26 que este año se realizará en Glasgow. Este artículo, cuya autoría pertenece principalmente a editores de 18 prestigiosas revistas científicas ampliamente representativas de los continentes y disciplinas de la salud del mundo, ya ha sido publicada simultáneamente en más de 200 revistas científicas internacionales (https://www.bmj.com/content/full-list-authors-and-signatories-climate-emergency-editorial-september-2021). En esta ocasión, la Revista Argentina de Salud Pública se suma a esta iniciativa conjunta a través de la publicación del artículo en español, con el fin de promover su difusión en los países de la Región. El editorial expresa también la necesidad de restablecer la diversidad biológica y proteger la salud, y de que los países de altos ingresos hagan mayores recortes en sus emisiones de carbono y transfieran fondos a los países de ingresos bajos y medianos. Además, exhorta a la intervención de los gobiernos en el rediseño de los sistemas de transporte, las ciudades, la producción y distribución de alimentos, los mercados para las inversiones financieras, los sistemas de salud, entre otros aspectos, lo que redundaría en amplios beneficios para la salud.

(1) Background: Here, we investigate the incidence of mpox and factors associated with vaccine uptake in mainly well-treated men who have sex with men and are living with HIV (MSMWH). (2) Methods: This study included 727 MSMWH from the Copenhagen co-morbidity in HIV infection (COCOMO) study from 1 May to 31 October 2022. Mpox infection and vaccination status were obtained from the Danish Microbiology Database and The Danish Vaccination Register. Vaccination willingness was assessed through an online survey. (3) Results: At a median follow-up of 180 days, 13 (1.8%) participants had laboratory-confirmed mpox infections. Furthermore, 238 (32.7%) had received the mpox vaccine. A sexually transmitted disease (STD) in the preceding two years was associated with a higher risk of mpox infection (hazard ratio 7.1; 95% confidence interval (CI) [1.9–26.9]) and with higher odds of vaccination (adjusted odds ratio 3.1; 95% CI [2.2–4.6]). 401 (55.2%) participants responded to the survey. 228 (57.0%) reported very high vaccination willingness. The self-perceived risk of infection was associated with vaccine uptake. (4) Conclusions: The incidence of mpox was low. A prior STD was associated with both a higher risk of mpox infection and higher odds of vaccination. Despite high-risk sexual behavior and high vaccination willingness, a sizable fraction of participants had not been vaccinated.

Objectives: Neisseria meningitidis serogroup W incidence has increased. Mortality associated with serogroup W has been higher than for other serogroups. Here we report epidemiological characteristics and risks of poor outcomes associated with invasive meningococcal disease in Denmark since 1980. Methods: All cases of invasive meningococcal disease reported from 1980–2018 were analyzed. Incidence rates by age, sex, manifestation, and serogroup were calculated. Poisson regression was used to analyze the rise in serogroup W, and multivariate logistic analysis was used to analyze risk factors for mortality. Results: A total of 5825 cases were analyzed. Risk of serogroup W infection increased after 2015 compared with all previous periods. Younger (

ABSTRACT Our objective was to examine whether empirical antimicrobial therapy (EAT) against methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) with piperacillin-tazobactam (TZP), cefuroxime or combination therapy with one of these was differentially associated with 7-, 30-, and 90- day all-cause mortality or MS-SAB relapse. A multicenter retrospective cohort study of adults with MS-SAB from 2009 through 2018 was used, and 7-, 30-, 90-day mortality and relapse within 90 days were assessed and expressed as hazard ratio (HR) with a 95% confidence interval (95% CI) using Cox proportional hazard regression analysis. Matching of the two monotherapy groups was performed using propensity score matching. In total, 1158 MS-SAB cases were included and received one of three EAT regimens: TZP (n = 429), cefuroxime (n = 337), or TZP or cefuroxime with one or more additional effective antimicrobial (n = 392). The overall 30-day mortality was 28.0% (25.5 to 30.3%). After adjustment and matching, there was no significant difference in 7-, 30-, or 90-day mortality between the therapy groups. The matched HR of death was 0.81 (95% CI, 0.38 to 1.76) at 7 days, 0.82 (95% CI, 0.47 to 1.46) at 30 days, and 0.81 (95% CI, 0.50 to 1.32) at 90 days for TZP compared with cefuroxime. Adjusted HR of 90-day relapse was insignificant between the three therapy groups: TZP: 1.55 (95% CI, 0.54 to 4.43); combination therapy: 1.73 (95% CI, 0.62 to 4.80) compared to cefuroxime. There was no significant difference in 7-, 30-, or 90-day mortality or relapse between MS-SAB patients treated with empirical TZP or cefuroxime after adjustment and matching of covariables. IMPORTANCE This multicenter retrospective matched cohort study evaluated the effect of empirical antimicrobial therapy on the clinical outcome of methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) in >1100 adult patients. To the best of our knowledge, this is the largest study to date evaluating the effect of empirical treatment on the MS-SAB outcome. Importantly, the study found no significant difference in either short- or long-term mortality nor relapse between patients with MS-SAB receiving empirical treatment with cefuroxime or piperacillin-tazobactam. As such, this study provides crucial contemporary data supporting the widespread clinical practice of initiating empirical antimicrobial therapy of sepsis with β-lactam-β-lactamase-inhibitor.

Introduction: Outbreaks of invasive meningococcal disease (IMD) among men who have sex with men (MSM) caused by a hypervirulent, non-encapsulated Neisseria meningitidis (Nm) clone belonging to genogroup C have been described. We aimed to determine the oral and anal carriage rates and genogroups of Nm among MSM living with HIV. Methods: Sexually active MSM living with HIV were included. A questionnaire, an oral wash sample and an anal swab were collected at baseline and 12 months follow-up. Identification of Nm and genogrouping was performed using real-time polymerase chain reaction analysis. Results: Among 82 MSM, the Nm carriage rate was 31.7% (95% CI 21.9–42.9) at baseline. The oral carriage rate was 24.4% (95% CI 15.6–35.1) and the anal rate was 11.0% (95% CI 5.1–19.8). Non-groupable Nm were most prevalent followed by genogroup B and genogroup Y. Rates were similar at follow-up. Conclusion: Strains of Nm were detected in both oral washes and anal samples in our study. Our results suggest that Nm may be transmitted sexually among MSM. Non-groupable Nm were predominant in our population and no genogroup C Nm were detected.

Abstract Background Congenital cytomegalovirus disease (cCMV) is common and can be fatal or cause severe sequelae. Circulating strains of cytomegalovirus carry a high number of variable or disrupted genes. One of these is UL146, a highly diverse gene with 14 distinct genotypes encoding a CXC-chemokine involved in viral dissemination. UL146 genotypes 5 and 6 lack the conserved ELR motif, potentially affecting strain virulence. Here, we investigate whether UL146 genotypes 5 and 6 were associated with congenital CMV infection. Methods Viral DNA was extracted and UL146 sequenced from 116 neonatal dried blood spots (DBS) stored in the Danish National Biobank since 1982 and linked to registered cCMV cases through a personal identifier. These sequences were compared to UL146 control sequences obtained from CMV DNA extracted from 83 urine samples from children with suspected bacterial urinary tract infections. Results Three non-ELR UL146 genotypes (5 and 6) were observed among the cases (2.6%) and two were observed among the controls (2.4%; P > 0.99). Additionally, no significant association with cCMV was found for the other 12 genotypes in a post-hoc analysis, although genotype 8 showed a tendency to be more frequent among cases with 12 observations against three (P = 0.10). All fourteen genotypes were found to have little intra-genotype variation. Viral load, gender, and sample age were not found to be associated with any particular UL146 genotype. Conclusions No particular UL146 genotype was associated with cCMV in this nationwide retrospective case-control study. Associations between CMV disease and disrupted or polymorph CMV genes among immunosuppressed people living with HIV/AIDS and transplant recipients should be investigated in future studies.