Immune cell populations and induced immune responses at admission in patients hospitalized with vaccine breakthrough SARS-CoV-2 infections.

Background: Vaccine breakthrough SARS-CoV-2 infections are common and of clinical and public health concern. However, little is known about the immunological characteristics of patients hospitalized due to these infections. We aimed to investigate and compare immune cell subpopulations and induced immune responses in vaccinated and non-vaccinated patients hospitalized with severe COVID-19. Methods: A nested case-control study on adults (≥ 18 years) who received at least two doses of a mRNA-COVID-19 vaccine and were hospitalized with SARS-CoV-2 breakthrough infections and severe COVID-19 between January 7, 2021, and February 1, 2022, were eligible for inclusion. Age- and sex-matched non-vaccinated controls were identified. Immunophenotyping was performed using a custom-designed 10-color flow cytometry prefabricated freeze-dried antibody panel (DuraClone, Beckman Coulter (BC), Brea, Calif). TruCulture (Myriad RBM, Austin, USA) was used to assess induced immune response in whole blood, revealing different critical signaling pathways as a proxy for immune function. All samples were obtained within 48 hours of admission. Results: In total, 20 hospitalized patients with severe COVID-19 and a breakthrough SARS-CoV-2 infection were included, ten vaccinated and ten non-vaccinated patients. Vaccinated patients had lower concentrations of CD19 B cells (p = 0.035), naïve CD4 T cells (p = 0.015), a higher proportion of γδ1 T cells (p = 0.019), and higher unstimulated immune cell release of IL-10 (p = 0.015). Conclusion: We observed immunological differences between vaccinated and non-vaccinated patients hospitalized due to severe COVID-19 that indicate that vaccinated patients had lower B cell concentrations, lower concentrations of CD4 naïve T cells, a skewed gamma-delta V1/V2 ratio, and an exaggerated IL-10 response at admission. These results could indicate a suboptimal immune response involved in SARS-CoV-2 breakthrough infections that cause severe COVID-19 in vaccinated adults. However, the sample size was small, and further research is needed to confirm these results.

Existing Data Sources in Clinical Epidemiology: Database of Community Acquired Infections Requiring Hospital Referral in Eastern Denmark (DCAIED) 2018-2021.

Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018-2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records. Adult patients (≥18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.

Inhalation devices and inhaled corticosteroids particle size influence on severe pneumonia in patients with chronic obstructive pulmonary disease: a nationwide cohort study.

BACKGROUND: Inhaled corticosteroids (ICSs) are associated with an increased risk of pneumonia among patients with chronic obstructive pulmonary disease (COPD). The introduction of extrafine particle ICS has aimed to improve the distribution of medicine in the airways by altering deposition within the lungs, potentially affecting efficacy and side effects. It remains unclear if extrafine particle ICS administration alters the risk of pneumonia compared with standard particle size ICS. METHODS: An observational cohort study including all Danish COPD outpatients receiving ICS from 2010 to 2017. The primary outcome was pneumonia hospitalisation in the different ICS particle dosing regimens. The primary analysis was an adjusted Cox proportional hazards model. For sensitivity analysis, a subgroup analysis of patients receiving spray devices was done. Further, we created a propensity score matched cohort, in which we matched for the same covariates as adjusted for in the main analysis. RESULTS: A total of 35 691 patients were included of whom 1471 received extrafine particle ICS. Among these patients, 4657 were hospitalised due to pneumonia. Patients with COPD receiving extrafine particle ICS had a lower risk of hospitalisation due to pneumonia compared with patients receiving standard particle size ICS in our primary analysis (HR 0.75; 95% CI 0.63 to 0.89; p=0.002), subgroup analysis (HR 0.54; 95% CI 0.45 to 0.65; p<0.0001) and the propensity-matched population (HR 0.72; 95% CI 0.60 to 0.87; p=0.0006). INTERPRETATION: The use of extrafine particle ICS administration was associated with a lower risk of pneumonia hospitalisation in patients with COPD compared with those who received standard size treatment.

Implementation of a vaccination clinic for adult solid organ transplant candidates: A single-center experience.

Vaccination is an evidence-based strategy to prevent or reduce the severity of infectious diseases (ID). Here, we aimed to describe the experience of implementing a vaccination clinic specifically targeting liver, heart, lung, and combined dual organ transplantation at a single transplantation center in Denmark. In this cohort of 242 solid organ transplant (SOT) candidates, we investigated seroprotection and the proportion of recommended vaccinations documented before transplantation. Furthermore, we registered completed vaccinations after ID consultations. The median age in our cohort was 53 years (IQR, 42-60), 60% were males (n = 135), and liver transplants (n = 138; 57%) were the most frequently planned organ transplants. Before the consultation to the vaccination clinic, influenza and pneumococcal vaccines had the highest proportion of documented vaccination (58% and 37%, respectively). Serological protection was more frequently observed for measles, mumps, or rubella (MMR, approximately 90% for each), while only 30% (n = 72) of SOT candidates showed seroprotection against pneumococcal disease. All SOT candidates required at least one of the recommended vaccines, and over 90% required three or more. At least 10% of patients in our cohort needed a live attenuated vaccine for either MMR or yellow fever. The most frequently administered vaccine was the tetanus-diphtheria-acelullar pertussis (Tdap) booster (n = 217; 90%), influenza vaccination was either administered (n = 16; 7%) or recommended (n = 226; 93%), PCV13 was administered (n = 155; 64%) or recommended (n = 27; 11%), and PPSV23 was either administered (n = 18; 7.4%) or recommended (n = 140; 58%). All SOT candidates adhered completely to their vaccination schedules. Based on our findings, we recommend prioritizing vaccination before transplantation by providing ID consultations for SOT candidates.

Positive Predictive Value of ICD-10 Diagnosis Codes for COVID-19.

PURPOSE: To examine the positive predictive value (PPV) of International Classification version 10 (ICD-10) diagnosis codes for Coronavirus disease 2019 (COVID-19). PATIENTS AND METHODS: Medical record review of all patients assigned a diagnosis code of COVID-19 (DB342A or DB972A) at six Danish departments of infectious diseases from February 27 through May 4, 2020. Confirmed COVID-19 diagnosis was defined as either: 1) definite, a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) on a respiratory sample combined with symptoms suggestive of COVID-19: 2) probable, clinical presentation of COVID-19 without detection of SARS-CoV-2 and no alternative diagnoses considered more likely; or 3) possible, clinical presentation of COVID-19 without detection of SARS-CoV-2, and the patient was discharged or deceased before further investigations were carried out. We computed the PPV with 95% confidence intervals (CI) as the number of patients with confirmed (i.e., definite, probable, and possible) COVID-19 divided by the number of patients assigned a diagnosis code for COVID-19. RESULTS: The study included 710 patients with a median age of 61 years (interquartile range [IQR] 47-74) and 285/710 (40%) were female. COVID-19 was confirmed in 706/710 (99%) with 705/710 (99%) categorized as definite, 1/710 (0.1%) as probable, and 0 patients as possible COVID-19. The diagnosis was disproven in 4/710 (0.6%) patients who were hospitalized due to bacterial pneumonia (n = 2), influenza (n = 1), and urinary tract infection (n = 1). The overall PPV for COVID-19 was 99% (95% CI 99-100) and remained consistently high among all subgroups including sex, age groups, calendar period, and stratified by diagnosis code and department of infectious diseases (range 97-100%). CONCLUSION: The overall PPV of diagnosis codes for COVID-19 in Denmark was high and may be suitable for future registry-based prognosis studies of COVID-19.

First wave of COVID-19 hospital admissions in Denmark: a Nationwide population-based cohort study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease coronavirus disease 2019 (COVID-19), is a worldwide emergency. Demographic, comorbidity and laboratory determinants of death and of ICU admission were explored in all Danish hospitalised patients. METHODS: National health registries were used to identify all hospitalized patients with a COVID-19 diagnosis. We obtained demographics, Charlson Comorbidity Index (CCI), and laboratory results on admission and explored prognostic factors for death using multivariate Cox proportional hazard regression and competing risk survival analysis. RESULTS: Among 2431 hospitalised patients with COVID-19 between February 27 and July 8 (median age 69 years [IQR 53-80], 54.1% males), 359 (14.8%) needed admission to an intensive care unit (ICU) and 455 (18.7%) died within 30 days of follow-up. The seven-day cumulative incidence of ICU admission was lower for females (7.9%) than for males (16.7%), (p < 0.001). Age, high CCI, elevated C-reactive protein (CRP), ferritin, D-dimer, lactate dehydrogenase (LDH), urea, creatinine, lymphopenia, neutrophilia and thrombocytopenia within ±24-h of admission were independently associated with death within the first week in the multivariate analysis. Conditional upon surviving the first week, male sex, age, high CCI, elevated CRP, LDH, creatinine, urea and neutrophil count were independently associated with death within 30 days. Males presented with more pronounced laboratory abnormalities on admission. CONCLUSIONS: Advanced age, male sex, comorbidity, higher levels of systemic inflammation and cell-turnover were independent factors for mortality. Age was the strongest predictor for death, moderate to high level of comorbidity were associated with a nearly two-fold increase in mortality. Mortality was significantly higher in males after surviving the first week.

Shock in the emergency department; a 12 year population based cohort study.

BACKGROUND: The knowledge of the frequency and associated mortality of shock in the emergency department (ED) is limited. The aim of this study was to describe the incidence, all-cause mortality and factors associated with death among patients suffering shock in the ED. METHODS: Population-based cohort study at an University Hospital ED in Denmark from January 1, 2000, to December 31, 2011. All patients aged ≥18 years living in the hospital catchment area with a first time ED presentation with shock (n = 1646) defined as hypotension (systolic blood pressure (SBP) ≤100 mmHg)) and ≥1 organ failures. Outcomes were annual incidence per 100,000 person-years at risk (pyar), all-cause mortality at 0-7, and 8-90 days and risk factors associated with death. RESULTS: We identified 1646 of 438,191 (0.4 %) ED patients with shock at arrival. Incidence of shock increased from 53.8 to 80.6 cases per 100,000 pyar. The 7-day, and 90-day mortality was 23.1 % (95 % CI: 21.1-25.1) and 40.7 % (95 % CI: 38.3-43.1), respectively. Independent predictors of 7-day mortality were: age (adjusted HR 1.03 (95 % CI: 1.03-1.04), and number of organ failures (≥3 organ failures; adjusted HR 3.13 95 % CI: 2.28-4.30). Age, comorbidity level and number of organ failure were associated with 90-day mortality. CONCLUSION: Shock is a frequent and critical finding in the ED, carrying a 7- and, 90- day mortality of 23.1 and 40.7 %, respectively. Age and number of organ failures are independent prognostic factors for death within 7 days, whereas age, comorbidity and organ failures are of significance within 8-90 days.

Systolic blood pressure and short-term mortality in the emergency department and prehospital setting: a hospital-based cohort study.

INTRODUCTION: Systolic blood pressure is a widely used tool to assess circulatory function in acutely ill patients. The systolic blood pressure limit where a given patient should be considered hypotensive is the subject of debate and recent studies have advocated higher systolic blood pressure thresholds than the traditional 90 mmHg. The aim of this study was to identify the best performing systolic blood pressure thresholds with regards to predicting 7-day mortality and to evaluate the applicability of these in the emergency department as well as in the prehospital setting. METHODS: A retrospective, hospital-based cohort study was performed at Odense University Hospital that included all adult patients in the emergency department between 1995 and 2011, all patients transported to the emergency department in ambulances in the period 2012 to 2013, and all patients serviced by the physician-staffed mobile emergency care unit (MECU) in Odense between 2007 and 2013. We used the first recorded systolic blood pressure and the main outcome was 7-day mortality. Best performing thresholds were identified with methods based on receiver operating characteristics (ROC) and multivariate regression. The performance of systolic blood pressure thresholds was evaluated with standard summary statistics for diagnostic tests. RESULTS: Seven-day mortality rates varied from 1.8% (95% CI (1.7, 1.9)) of 112,727 patients in the emergency department to 2.2% (95% CI (2.0, 2.5)) of 15,862 patients in the ambulance and 5.7% (95% CI (5.3, 6.2)) of 12,270 patients in the mobile emergency care units. Best performing thresholds ranged from 95 to 119 mmHg in the emergency department, 103 to 120 mmHg in the ambulance, and 101 to 115 mmHg in the MECU but area under the ROC curve indicated poor overall discriminatory performance of SBP thresholds in all cohorts. CONCLUSIONS: Systolic blood pressure alone is not sufficient to identify patients at risk regardless of the defined threshold for hypotension. If, however, a threshold is to be defined, a systolic blood pressure threshold of 100 to 110 mmHg is probably more relevant than the traditional 90 mmHg.

Lactate level, aetiology and mortality of adult patients in an emergency department: a cohort study.

BACKGROUND: Increased lactate is associated with high mortality among patients with suspected infection or trauma in the emergency department (ED), but the association with patients with other aetiologies is less well described. The aim of this study was to describe the relation between lactate, aetiology and 7-day mortality in adult ED patients. METHODS: A retrospective cohort study of all adult patients who had a lactate measured within 4 h after arrival to the ED at Odense University Hospital between June 2012 and May 2013. The categorisation of suspected aetiology was based on discharge diagnoses. RESULTS: 5360 patients were included; 51.7% were men, and the median age was 67 years (IQR 50-79). 77.2% had low lactate (0-1.9 mmol/L), 16.2% intermediate lactate (2-3.9 mmol/L), and 6.6% high lactate (≥4 mmol/L). 7-day mortality was 2.9% (95% CI 2.4% to 3.5%) for patients with low lactate, 7.8% (95% CI 6.1% to 9.8%) for patients with intermediate lactate, and 23.9% (95% CI 19.6% to 28.8%) for patients with high lactate. The association between lactate level and mortality varied across different diagnostic groups. Based on Area Under the Curve in receiver operating characteristic analysis, lactate level showed to be useful in patients with infection (0.78, 95% CI 0.73 to 0.84), trauma (0.78, 95% CI 0.65 to 0.92), cardiac diseases (0.83, 95% CI 0.75 to 0.91) and gastrointestinal diseases (0.83, 95% CI 0.68 to 0.98). Lactate level was not useful in neurological (0.58, 95% CI 0.50 to 0.67) and respiratory disease (0.64, 95% CI 0.55 to 0.74), and of uncertain value in the remaining diagnostic groups. CONCLUSIONS: Among adult ED patients, the prognostic value of lactate varies between diagnostic groups.

Nontraumatic hypotension and shock in the emergency department and the prehospital setting, prevalence, etiology, and mortality: a systematic review.

BACKGROUND: Acute patients presenting with hypotension in the prehospital or emergency department (ED) setting are in need of focused management and knowledge of the epidemiology characteristics might help the clinician. The aim of this review was to address prevalence, etiology and mortality of nontraumatic hypotension (SBP ≤ 90 mmHg) with or without the presence of shock in the prehospital and ED setting. METHODS: We performed a systematic literature search up to August 2013, using Medline, Embase, Cinahl, Dare and The Cochrane Library. The analysis and eligibility criteria were documented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-guidelines) and The Cochrane Collaboration. No restrictions on language, publication date, or status were imposed. We used the Newcastle-Ottawa quality assessment scale (NOS-scale) and the Strengthening the Reporting of Observational studies in Epidemiology (STROBE-statement) to assess the quality. RESULTS: Six observational studies were considered eligible for analysis based on the evaluation of 11,880 identified papers. Prehospital prevalence of hypotension was 19.5/1000 emergency medicine service (EMS) contacts, and the prevalence of hypotensive shock was 9.5-19/1000 EMS contacts with an inhospital mortality of shock between 33 to 52%. ED prevalence of hypotension was 4-13/1000 contacts with a mortality of 12%. Information on mortality, prevalence and etiology of shock in the ED was limited. A meta-analysis was not feasible due to substantial heterogeneity between studies. CONCLUSION: There is inadequate evidence to establish concise estimates of the characteristics of nontraumatic hypotension and shock in the ED or in the prehospital setting. The available studies suggest that 2% of EMS contacts present with nontraumatic hypotension while 1-2% present with shock. The inhospital mortality of prehospital shock is 33-52%. Prevalence of hypotension in the ED is 1% with an inhospital mortality of 12%. Prevalence, etiology and mortality of shock in the ED are not well described.

[Fatal Clostridium sordellii infection originated in an ovarian cyst]. / Fatal Clostridium sordellii-infektion udgået fra ovariecyste.

Clostridium sordellii is a Gram-positive bacterium which can cause a serious toxic shock syndrome with a mortality of up to 69%. C. sordellii is a part of the normal vaginal flora in up to 10% of all women. This case describes a fatal case of a healthy 49 year-old woman with a C. sordellii-infection originating from an ovarian cyst. Quick diagnosis is difficult because of the non-specific flu-like symptoms. Survival requires immediate source control and specific antibiotic therapy capable of suppressing toxin production. In rodents superantigen antibodies have shown neutralizing effects.

Using MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in infective endocarditis: a case report of a patient with mitral valve infective endocarditis caused by Abiotrophia defectiva.

A case of infective endocarditis caused by Abiotrophia defectiva is presented. The use of MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in infective endocarditis is discussed.