Post-COVID-19 Condition After SARS-CoV-2 Infections During the Omicron Surge vs the Delta, Alpha, and Wild Type Periods in Stockholm, Sweden.

Little is known about the post-COVID-19 condition (PCC) after infections with different SARS-CoV-2 variants. We investigated the risk of PCC diagnosis after primary omicron infections as compared with preceding variants in population-based cohorts in Stockholm, Sweden. When compared with omicron (n = 215 279, 0.2% receiving a PCC diagnosis), the adjusted hazard ratio (95% CI) was 3.26 (2.80-3.80) for delta (n = 52 182, 0.5% PCC diagnosis), 5.33 (4.73-5.99) for alpha (n = 97 978, 1.0% PCC diagnosis), and 6.31 (5.64-7.06) for the wild type (n = 107 920, 1.3% PCC diagnosis). These findings were consistent across all subgroup analyses except among those treated in the intensive care unit.

Outcomes of SARS-CoV-2 Omicron Variant Infections Compared With Seasonal Influenza and Respiratory Syncytial Virus Infections in Adults Attending the Emergency Department: A Multicenter Cohort Study.

BACKGROUND: There is a controversy over the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in an era of less virulent variants and an increasing population immunity. We compared outcomes in adults attending the emergency department (ED) with an Omicron, influenza, or respiratory syncytial virus (RSV) infection. METHODS: Retrospective multicenter cohort study including adults attending the ED in 6 acute care hospitals in Stockholm County, Sweden, with an Omicron, influenza, or RSV infection during 2021-2022 and 2015-2019. During 2021-2022, patients were tested for all 3 viruses by multiplex polymerase chain reaction (PCR) testing. The primary outcome was 30-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality, hospitalization, and intensive care unit (ICU) admission. RESULTS: A total of 6385 patients from 2021-2022 were included in the main analyses: 4833 Omicron, 1099 influenza, and 453 RSV. The 30-day mortality was 7.9% (n = 381) in the Omicron, 2.5% (n = 28) in the influenza, and 6.0% (n = 27) in the RSV cohort. Patients with Omicron had an adjusted 30-day mortality odds ratio (OR) of 2.36 (95% confidence interval [CI] 1.60-3.62) compared with influenza and 1.42 (95% CI .94-2.21) compared with RSV. Among unvaccinated Omicron patients, stronger associations were observed compared with both influenza (OR 5.51 [95% CI 3.41-9.18]) and RSV (OR 3.29 [95% CI 2.01-5.56]). Similar trends were observed for secondary outcomes. Findings were consistent in comparisons with 5709 pre-pandemic influenza 995 RSV patients. CONCLUSIONS: In patients attending the ED, infections with Omicron were both more common and associated with more severe outcomes compared with influenza and RSV, in particular among unvaccinated patients.

Scoring systems for prediction of malaria and dengue fever in non-endemic areas among travellers arriving from tropical and subtropical areas.

BACKGROUND: Fever is a common symptom among travellers returning from tropical/subtropical areas to Europe, and promptly distinguishing severe illnesses from self-limiting febrile syndromes is important but can be challenging due to non-specific clinical presentation. METHODS: A cross-sectional study enrolled adults and children who sought care during 2015-2020 at Karolinska University Hospital, Stockholm, Sweden with fever within 2 months after returning from travel to a tropical/subtropical area. Data on symptoms and laboratory parameters were prospectively and retrospectively collected. Two separate scoring systems for malaria and dengue were developed based on backward elimination regressions. RESULTS: In total, 2113 adults (18-94 years) and 202 children (1-17 years) were included, with 112 (4.8%) confirmed malaria by blood thick smear and 90 (3.9%) PCR/serology dengue-positive cases. Malaria was more likely in a patient who had visited sub-Saharan Africa and presented with combination of thrombocytopenia, anaemia and fever ≥39.5°C. Leucopenia, muscle pain and rash after travelling to Asia or South/Latin America indicated high probability of dengue. Two scoring systems with points between 0 and 7 for prediction of malaria or dengue were created based on the above predictors. Scores ≥3 indicated >80% sensitivity and specificity for malaria and >90% specificity for dengue in children and adults (area under the curve (AUC) for dengue: 0.92 in adults (95% CI 0.90 to 0.95) and 0.95 in children (95% CI 0.88 to 1.0); AUC for malaria: 0.93 in adults (95% CI 0.91 to 0.96) and 0.88 in children (95% CI 0.78 to 0.99)). Internal validation of optimism and overfitting was managed with bootstrap. CONCLUSION: The presented scoring systems provide novel tools for structured assessment of patients with tropical fever in a non-endemic area and highlight clinical signs associated with a potential severe aetiology to direct the need for microbial investigation.

Association Between Time to Appropriate Antimicrobial Treatment and 30-day Mortality in Patients With Bloodstream Infections: A Retrospective Cohort Study.

BACKGROUND: Effective antimicrobial treatment is key for survival in bloodstream infection (BSI), but the impact of timing of treatment remains unclear. Our aim was to assess the association between time to appropriate antimicrobial treatment and 30-day mortality in BSI patients. METHODS: This was a retrospective cohort study using electronic health record data from a large academic center in Sweden. Adult patients admitted between the years 2012 and 2019, with onset of BSI at the emergency department or general wards, were included. Pathogen-antimicrobial drug combinations were classified as appropriate or inappropriate based on reported in vitro susceptibilities. To avoid immortal time bias, the association between appropriate therapy and mortality was assessed with multivariable logistic regression analysis at pre-specified landmark times. RESULTS: We included 10 628 BSI-episodes, occurring in 9192 unique patients. The overall 30-day mortality was 11.8%. No association in favor of a protective effect between appropriate therapy and mortality was found at the 1, 3 and 6 hours landmark after blood culture collection. At 12 hours, the risk of death increased with inappropriate treatment (adjusted odds ratio 1.17 [95% confidence interval {CI}, 1.01-1.37]) and continued to increase gradually at 24, 48, and 72 hours. Stratifying by high or low SOFA score generated similar odds ratios, with wider confidence intervals. CONCLUSIONS: Delays in appropriate antimicrobial treatment were associated with increased 30-day mortality after 12 hours from blood culture collection, but not at 1, 3, and 6 hours, in BSI. These results indicate a benchmark for providing rapid microbiological diagnostics of blood cultures.

Sociodemographic disparities affect COVID-19 vaccine uptake in non-elderly adults with increased risk of severe COVID-19.

BACKGROUND: There is limited information about sociodemographic disparities in COVID-19 vaccine uptake among non-elderly adults with an increased risk of severe COVID-19. We investigated the COVID-19 vaccine uptake in individuals aged 18-64 years with an increased risk of severe COVID-19 (non-elderly risk group) in Stockholm County, Sweden. METHOD: We used population-based health and sociodemographic registries with high coverage to perform a cohort study of COVID-19 vaccine uptake of one to four doses up until 21 November 2022. The vaccine uptake in the non-elderly risk group was compared with non-risk groups aged 18-64 years (non-elderly non-risk group) and individuals aged ≥65 years (elderly). RESULTS: The uptake of ≥3 vaccine doses was 55%, 64% and 87% in the non-elderly non-risk group (n = 1,005,182), non-elderly risk group (n = 308,904) and elderly (n = 422,604), respectively. Among non-elderly risk group conditions, Down syndrome showed the strongest positive association with receiving three doses (adjusted risk ratio [aRR] 1.62, 95% confidence interval [CI] 1.54-1.71), whereas chronic liver disease showed the strongest negative association (aRR 0.90, 95% CI 0.88-0.92). Higher vaccine uptake among the non-elderly risk group was associated with increasing age, being born in Sweden, higher education, higher income and living in a household where other adults had been vaccinated. Similar trends were observed for the first, second, third and fourth doses. CONCLUSION: These results call for measures to tackle sociodemographic disparities in vaccination programmes during and beyond the COVID-19 pandemic.

Post COVID-19 condition diagnosis: A population-based cohort study of occurrence, associated factors, and healthcare use by severity of acute infection.

BACKGROUND: The occurrence and healthcare use trajectory of post COVID-19 condition (PCC) is poorly understood. Our aim was to investigate these aspects in SARS-CoV-2-positive individuals with and without a PCC diagnosis. METHODS: We conducted a population-based cohort study of adults in Stockholm, Sweden, with a verified infection from 1 March 2020 to 31 July 2021, stratified by the severity of the acute infection. The outcome was a PCC diagnosis registered any time 90-360 days after a positive test. We performed Cox regression models to assess baseline characteristics associated with the PCC diagnosis. Individuals diagnosed with PCC were then propensity-score matched to individuals without a diagnosis to assess healthcare use beyond the acute infection. RESULTS: Among 204,805 SARS-CoV-2-positive individuals, the proportion receiving a PCC diagnosis was 1% among individuals not hospitalized for their COVID-19 infection, 6% among hospitalized, and 32% among intensive care unit (ICU)-treated individuals. The most common new-onset symptom diagnosis codes among individuals with a PCC diagnosis were fatigue (29%) among nonhospitalized and dyspnea among both hospitalized (25%) and ICU-treated (41%) individuals. Female sex was associated with a PCC diagnosis among nonhospitalized and hospitalized individuals, with interactions between age and sex. Previous mental health disorders and asthma were associated with a PCC diagnosis among nonhospitalized and hospitalized individuals. Among individuals with a PCC diagnosis, the monthly proportion with outpatient care was substantially elevated up to 1 year after acute infection compared to before, with substantial proportions of this care attributed to PCC-related care. CONCLUSION: The differential association of age, sex, comorbidities, and healthcare use with the severity of the acute infection indicates different trajectories and phenotypes of PCC, with incomplete resolution 1 year after infection.

Outcomes of octogenarians and nonagenarians with Pseudomonas aeruginosa bacteremia: a multicenter retrospective study.

BACKGROUND: P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years). METHODS: We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults. RESULTS: Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65-79 years (n = 894) and 25% among patients < 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23-1.51, p < 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24-8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33-3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality. CONCLUSIONS: In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.

EuCARE-hospitalised study protocol: a cohort study of patients hospitalised with COVID-19 in the EuCARE project.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), can lead to hospitalisation, particularly in elderly, immunocompromised, and non-vaccinated or partially vaccinated individuals. Although vaccination provides protection, the duration of this protection wanes over time. Additional doses can restore immunity, but the influence of viral variants, specific sequences, and vaccine-induced immune responses on disease severity remains unclear. Moreover, the efficacy of therapeutic interventions during hospitalisation requires further investigation. The study aims to analyse the clinical course of COVID-19 in hospitalised patients, taking into account SARS-CoV-2 variants, viral sequences, and the impact of different vaccines. The primary outcome is all-cause in-hospital mortality, while secondary outcomes include admission to intensive care unit and length of stay, duration of hospitalisation, and the level of respiratory support required. METHODS: This ongoing multicentre study observes hospitalised adult patients with confirmed SARS-CoV-2 infection, utilising a combination of retrospective and prospective data collection. It aims to gather clinical and laboratory variables from around 35,000 patients, with potential for a larger sample size. Data analysis will involve biostatistical and machine-learning techniques. Selected patients will provide biological material. The study started on October 14, 2021 and is scheduled to end on October 13, 2026. DISCUSSION: The analysis of a large sample of retrospective and prospective data about the acute phase of SARS CoV-2 infection in hospitalised patients, viral variants and vaccination in several European and non-European countries will help us to better understand risk factors for disease severity and the interplay between SARS CoV-2 variants, immune responses and vaccine efficacy. The main strengths of this study are the large sample size, the long study duration covering different waves of COVID-19 and the collection of biological samples that allows future research. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov. The unique identifier assigned to this trial is NCT05463380.

Clinical outcomes during and beyond different COVID-19 critical illness variant periods compared with other lower respiratory tract infections.

BACKGROUND: It is yet to be better understood how outcomes during and after the critical illness potentially differ between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants from other lower respiratory tract infections (LRTIs). We aimed to compare outcomes in adults admitted to an intensive care unit (ICU) with coronavirus disease 2019 (COVID-19) during the Wild-type, Alpha, Delta, and Omicron periods with individuals admitted with other LRTI. METHODS: Population-based cohort study in Stockholm, Sweden, using health registries with high coverage, including ICU-admitted adults from 1 January 2016 to 15 September 2022. Outcomes were in-hospital mortality, 180-day post-discharge mortality, 180-day hospital readmission, 180-day days alive and at home (DAAH), and incident diagnoses registered during follow-up. RESULTS: The number of ICU admitted individuals were 1421 Wild-type, 551 Alpha, 190 Delta, 223 Omicron, and 2380 LRTI. In-hospital mortality ranged from 28% (n = 665) in the LRTI cohort to 35% (n = 77) in the Delta cohort. The adjusted cause-specific hazard ratio (CSHR) compared with the LRTI cohort was 1.33 (95% confidence interval [CI] 1.16-1.53) in the Wild-type cohort, 1.53 (1.28-1.82) in the Alpha cohort, 1.70 (1.30-2.24) in the Delta cohort, and 1.59 (1.24-2.02) in the Omicron cohort. Among patients discharged alive from their COVID-19 hospitalization, the post-discharge mortality rates were lower (1-3%) compared with the LRTI cohort (9%), and the risk of hospital readmission was lower (CSHRs ranging from 0.42 to 0.68). Moreover, all COVID-19 cohorts had compared with the LRTI cohort more DAAH after compared with before the critical illness. CONCLUSION: Overall, COVID-19 critical was associated with an increased hazard of in-hospital mortality, but among those discharged alive from the hospital, less severe long-term outcomes were observed compared with other LRTIs.

Influence of perioperative SARS-CoV-2 infection on mortality in orthopaedic inpatients with surgically treated traumatic fractures.

BACKGROUND: SARS-CoV-2 has had an extensive influence on orthopaedic surgery practice and has been associated with an increased risk of mortality. There is limited evidence of how this pertains to acute orthopaedic surgery with inpatient care. METHODS: A retrospective cohort study on traumatic fracture patients requiring inpatient care between February 25, 2020 and March 25, 2021 was conducted. Patients were grouped by perioperative SARS-CoV-2 infection, defined as a positive SARS-CoV-2 test from 7 days before to 7 days after orthopaedic surgery, and compared using linear regression and Cox proportional hazards model for primary outcome 30-day mortality and secondary outcome hospital length of stay. RESULTS: In total, 5174 adults with a length of stay ≥ 48 h and an orthopaedic procedure due to a registered traumatic fracture were admitted from February 25, 2020 and discharged before March 26, 2021. Among the 5174 patients, 65% (3340/5174) were female, 22% (1146/5174) were 60-74 years and 56% (2897/5174) were 75 years or older. In total, 144 (3%) had a perioperative SARS-CoV-2 infection. Perioperative SARS-CoV-2 infection was associated with an increased 30-day mortality (aOR 4.19 [95% CI 2.67-6.43], p < 0.001). The median (IQR) length of stay after surgery was 13 days (IQR 6-21) for patients with, and 7 days (IQR 2-13) for patients without, perioperative SARS-CoV-2 infection. CONCLUSIONS: Perioperative SARS-CoV-2 infection increased 30-day mortality risk and hospital length of stay for traumatic fracture patients requiring inpatient surgical care. Pre- and postoperative infection were both associated with similar increases in mortality risk.

Chronic Disease and Immunosuppression Increase the Risk for Nonvaccine Serotype Pneumococcal Disease: A Nationwide Population-based Study.

BACKGROUND: Demography is changing, with people living longer with comorbidities. In this nationwide population-based study, we investigated the serotype-specific invasive pneumococcal disease (IPD) risk in individuals with comorbidities, and effects of the pneumococcal conjugated vaccine (PCV) child immunization program. METHODS: Cases included 14 096 IPD episodes in Sweden during 2006-2015. Controls (n = 137 289), matched to cases by age, sex, region, and calendar time, were selected from the general population. Comorbidity data was obtained through health registers and grouped as immunocompromising (IC) or chronic medical conditions (CMC). RESULTS: The prevalence of CMC and IC among elderly cases was 33.9% and 39.4%. New risks identified for IPD were sarcoidosis, inflammatory polyarthropathies, systemic connective tissue, and neurological diseases. The odds ratio (OR) for IPD caused by non-PCV13 compared with PCV13 serotypes was higher in individuals with CMC/IC. Serotypes associated with the highest risk were 16F, 15C, 35F, 19F, and 23A (OR 3-5 for CMC, >10 for IC). Most comorbidities increased post-vaccination, and absolute increases of IPD caused by non-PCV13, PPV23-non-PCV13, and non-PCV13/non-PPV23 serotypes were higher in individuals with IC/CMC compared with healthy persons. Non-PCV13 serotypes 6C, 9N, 11A, 22F, 23A and 35F increased more in those with comorbidities. Mortality due to non-PCV13 serotypes increased in individuals with IC/CMC, while remaining stable in persons without comorbidities. CONCLUSIONS: The PCV child immunization program associates with an increased disease burden of non-vaccine serotypes in individuals with comorbidities. These data are important for vaccine design and optimization of current vaccination strategies.

Clinical phenotypes and outcomes of SARS-CoV-2, influenza, RSV and seven other respiratory viruses: a retrospective study using complete hospital data.

BACKGROUND: An understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare. Herein we sought to investigate such differences in patients positive for SARS-CoV-2 compared with influenza, respiratory syncytial virus (RSV) and other respiratory viruses. METHODS: We performed a retrospective cohort study of hospitalised adults and children (≤15 years) who tested positive for SARS-CoV-2, influenza virus A/B, RSV, rhinovirus, enterovirus, parainfluenza viruses, metapneumovirus, seasonal coronaviruses, adenovirus or bocavirus in a respiratory sample at admission between 2011 and 2020. RESULTS: A total of 6321 adult (1721 SARS-CoV-2) and 6379 paediatric (101 SARS-CoV-2) healthcare episodes were included in the study. In adults, SARS-CoV-2 positivity was independently associated with younger age, male sex, overweight/obesity, diabetes and hypertension, tachypnoea as well as better haemodynamic measurements, white cell count, platelet count and creatinine values. Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95% CI 3.51 to 5.59), RSV (aHR 3.81, 95% CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95% CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses. CONCLUSIONS: SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.

Bacterial meningitis: Aetiology, risk factors, disease trends and severe sequelae during 50 years in Sweden.

BACKGROUND: Bacterial meningitis (BM) is a rare but severe infection. Few population-based studies have characterised BM episodes and sequelae over long periods. METHODS: This was a population-based observational cohort study with national coverage, using data on aetiological pathogens, sex, premorbid conditions, steroid pretreatment, severe sequelae and birth, death and diagnosis dates collected from 10,339 patients with BM reported to the National Board of Health and Welfare in Sweden between 1964 and 2014. RESULTS: During the 50-year study period, the incidence of BM decreased in young children, but not in the elderly. The most common cause of BM was pneumococci (34%), followed by Haemophilus influenzae (26%), and meningococci (18%), mainly community acquired. Premorbid conditions were found in 20%. After the H. influenzae type b vaccine was introduced in 1993, the BM incidence decreased by 36%. Following pneumococcal conjugated vaccine introduction in 2009, the incidence and 30-day mortality from pneumococcal meningitis decreased by 64% and 100%, respectively, in previously healthy children, and the 30-day mortality decreased by 64% among comorbid adults. The BM incidence in immunosuppressed patients increased by 3% annually post vaccine introduction. The 30-day mortality was 3% in children and 14% in adults, and the rate of severe sequelae was 44%. On average, patients lost 11 years of healthy life due to BM. CONCLUSION: The introduction of conjugated vaccines into the childhood vaccination program has reduced the incidence of BM in young children, but not in adults. Post vaccine introduction, patients present with more premorbid conditions and other bacterial causes of BM, emphasising the need for a correct diagnosis when treating these infections.

Ventilator-Associated Lower Respiratory Tract Bacterial Infections in COVID-19 Compared With Non-COVID-19 Patients.

OBJECTIVES: Ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with prolonged length of stay and increased mortality. We aimed to investigate the occurrence of bacterial VA-LRTI among mechanically ventilated COVID-19 patients and compare these findings to non-COVID-19 cohorts throughout the first and second wave of the pandemic. DESIGN: Retrospective cohort study. SETTING: Karolinska University Hospital, Stockholm, Sweden. PATIENTS: All patients greater than or equal to 18 years treated with mechanical ventilation between January 1, 2011, and December 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort consisted of 20,223 ICU episodes (479 COVID-19), with a VA-LRTI incidence proportion of 30% (129/426) in COVID-19 and 18% (1,081/5,907) in non-COVID-19 among patients ventilated greater than or equal to 48 hours. The median length of ventilator treatment for COVID-19 patients was 10 days (interquartile range, 5-18 d), which was significantly longer than for all other investigated specific diagnoses. The VA-LRTI incidence rate per 1,000 ventilator days at risk was 31 (95% CI, 26-37) for COVID-19 and 34 (95% CI, 32-36) for non-COVID-19. With COVID-19 as reference, adjusted subdistribution hazard ratios for VA-LRTI was 0.29-0.50 (95% CI, < 1) for influenza, bacterial pneumonia, acute respiratory distress syndrome, and severe sepsis, but 1.38 (95% CI, 1.15-1.65) for specific noninfectious diagnoses. Compared with COVID-19 in the first wave of the pandemic, COVID-19 in the second wave had adjusted subdistribution hazard ratio of 1.85 (95% CI, 1.14-2.99). In early VA-LRTI Staphylococcus aureus was more common and Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli less common in COVID-19 patients, while Serratia species was more often identified in late VA-LRTI. CONCLUSIONS: COVID-19 is associated with exceptionally long durations of mechanical ventilation treatment and high VA-LRTI occurrence proportions. The incidence rate of VA-LRTI was compared with the pooled non-COVID-19 cohort, however, not increased in COVID-19. Significant differences in the incidence of VA-LRTI occurred between the first and second wave of the COVID-19 pandemic.

Peripheral Oxygen Saturation Facilitates Assessment of Respiratory Dysfunction in the Sequential Organ Failure Assessment Score With Implications for the Sepsis-3 Criteria.

OBJECTIVES: Sequential Organ Failure Assessment score is the basis of the Sepsis-3 criteria and requires arterial blood gas analysis to assess respiratory function. Peripheral oxygen saturation is a noninvasive alternative but is not included in neither Sequential Organ Failure Assessment score nor Sepsis-3. We aimed to assess the association between worst peripheral oxygen saturation during onset of suspected infection and mortality. DESIGN: Cohort study of hospital admissions from a main cohort and emergency department visits from four external validation cohorts between year 2011 and 2018. Data were collected from electronic health records and prospectively by study investigators. SETTING: Eight academic and community hospitals in Sweden and Canada. PATIENTS: Adult patients with suspected infection episodes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main cohort included 19,396 episodes (median age, 67.0 [53.0-77.0]; 9,007 [46.4%] women; 1,044 [5.4%] died). The validation cohorts included 10,586 episodes (range of median age, 61.0-76.0; women 42.1-50.2%; mortality 2.3-13.3%). Peripheral oxygen saturation levels 96-95% were not significantly associated with increased mortality in the main or pooled validation cohorts. At peripheral oxygen saturation 94%, the adjusted odds ratio of death was 1.56 (95% CI, 1.10-2.23) in the main cohort and 1.36 (95% CI, 1.00-1.85) in the pooled validation cohorts and increased gradually below this level. Respiratory assessment using peripheral oxygen saturation 94-91% and less than 91% to generate 1 and 2 Sequential Organ Failure Assessment points, respectively, improved the discrimination of the Sequential Organ Failure Assessment score from area under the receiver operating characteristics 0.75 (95% CI, 0.74-0.77) to 0.78 (95% CI, 0.77-0.80; p < 0.001). Peripheral oxygen saturation/Fio2 ratio had slightly better predictive performance compared with peripheral oxygen saturation alone, but the clinical impact was minor. CONCLUSIONS: These findings provide evidence for assessing respiratory function with peripheral oxygen saturation in the Sequential Organ Failure Assessment score and the Sepsis-3 criteria. Our data support using peripheral oxygen saturation thresholds 94% and 90% to get 1 and 2 Sequential Organ Failure Assessment respiratory points, respectively. This has important implications primarily for emergency practice, rapid response teams, surveillance, research, and resource-limited settings.

Bacterial co-infections in community-acquired pneumonia caused by SARS-CoV-2, influenza virus and respiratory syncytial virus.

BACKGROUND: A mismatch between a widespread use of broad-spectrum antibiotic agents and a low prevalence of reported bacterial co-infections in patients with SARS-CoV-2 infections has been observed. Herein, we sought to characterize and compare bacterial co-infections at admission in hospitalized patients with SARS-CoV-2, influenza or respiratory syncytial virus (RSV) positive community-acquired pneumonia (CAP). METHODS: A retrospective cohort study of bacterial co-infections at admission in SARS-CoV-2, influenza or RSV-positive adult patients with CAP admitted to Karolinska University Hospital in Stockholm, Sweden, from year 2011 to 2020. The prevalence of bacterial co-infections was investigated and compared between the three virus groups. In each virus group, length of stay, ICU-admission and 30-day mortality was compared in patients with and without bacterial co-infection, adjusting for age, sex and co-morbidities. In the SARS-CoV-2 group, risk factors for bacterial co-infection, were assessed using logistic regression models and creation of two scoring systems based on disease severity, age, co-morbidities and inflammatory markers with assessment of concordance statistics. RESULTS: Compared to influenza and RSV, the bacterial co-infection testing frequency in SARS-CoV-2 was lower for all included test modalities. Four percent [46/1243 (95% CI 3-5)] of all SARS-CoV-2 patients had a bacterial co-infection at admission, whereas the proportion was 27% [209/775 (95% CI 24-30)] and 29% [69/242 (95% CI 23-35)] in influenza and RSV, respectively. S. pneumoniae and S. aureus constituted the most common bacterial findings for all three virus groups. Comparing SARS-CoV-2 positive patients with and without bacterial co-infection at admission, a relevant association could not be demonstrated nor excluded with regards to risk of ICU-admission (aHR 1.53, 95% CI 0.87-2.69) or 30-day mortality (aHR 1.28, 95% CI 0.66-2.46) in adjusted analyses. Bacterial co-infection was associated with increased inflammatory markers, but the diagnostic accuracy was not substantially different in a scoring system based on disease severity, age, co-morbidities and inflammatory parameters [C statistic 0.66 (95% CI 0.59-0.74)], compared to using disease severity, age and co-morbidities only [C statistic 0.63 (95% CI 0.56-0.70)]. CONCLUSIONS: The prevalence of bacterial co-infections was significantly lower in patients with community-acquired SARS-CoV-2 positive pneumonia as compared to influenza and RSV positive pneumonia.

SARS-CoV-2 testing in patients with low COVID-19 suspicion at admission to a tertiary care hospital, Stockholm, Sweden, March to September 2020.

BackgroundUniversal SARS-CoV-2 testing at hospital admission has been proposed to prevent nosocomial transmission.AimTo investigate SARS-CoV-2 positivity in patients tested with low clinical COVID-19 suspicion at hospital admission.MethodsWe characterised a retrospective cohort of patients admitted to Karolinska University Hospital tested for SARS-CoV-2 by PCR from March to September 2020, supplemented with an in-depth chart review (16 March-12 April). We compared positivity rates in patients with and without clinical COVID-19 suspicion with Spearman's rank correlation coefficient. We used multivariable logistic regression to identify factors associated with test positivity.ResultsFrom March to September 2020, 66.9% (24,245/36,249) admitted patient episodes were tested; of those, 61.2% (14,830/24,245) showed no clinical COVID-19 suspicion, and the positivity rate was 3.2% (469/14,830). There was a strong correlation of SARS-CoV-2 positivity in patients with low vs high COVID-19 suspicion (rho = 0.92; p < 0.001).From 16 March to 12 April, the positivity rate was 3.9% (58/1,482) in individuals with low COVID-19 suspicion, and 3.1% (35/1,114) in asymptomatic patients. Rates were higher in women (5.0%; 45/893) vs men (2.0%; 12/589; p = 0.003), but not significantly different if pregnant women were excluded (3.7% (21/566) vs 2.2% (12/589); p = 0.09). Factors associated with SARS-CoV-2 positivity were testing of pregnant women before delivery (odds ratio (OR): 2.6; 95% confidence interval (CI): 1.3-5.4) and isolated symptoms in adults (OR: 3.3; 95% CI: 1.8-6.3).ConclusionsThis study shows a relatively high SARS-CoV-2 positivity rate in patients with low COVID-19 suspicion upon hospital admission. Universal SARS-CoV-2 testing of pregnant women before delivery should be considered.

Combination versus monotherapy as definitive treatment for Pseudomonas aeruginosa bacteraemia: a multicentre retrospective observational cohort study.

BACKGROUND: Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality. METHODS: This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009-15. We evaluated the association between ß-lactam plus aminoglycoside or quinolone combination therapy versus ß-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy. RESULTS: Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64-1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens. CONCLUSIONS: In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.

Treatment of community-acquired bacterial brain abscess: a survey among infectious diseases specialists in France, Sweden, Australia, and Denmark.

To examine antimicrobial management of brain abscess and prioritize future trials. Self-administered, Internet-based survey of practices for treatment of community-acquired bacterial brain abscess among infectious diseases (ID) specialists in France, Sweden, Australia, and Denmark during November 2019. Respondents were also asked to rank future randomized controlled trials (RCTs) from 1 (high priority) to 6 (low priority). 310 ID specialists (45% female) from France (35%), Sweden (29%), Australia (25%), and Denmark (11%) participated in the survey, primarily from university hospitals (69%) with an on-site neurosurgical department (61%). Preferred empiric intravenous (IV) antimicrobials were cefotaxime (154/273, 56%) or ceftriaxone (68/273, 25%) combined with metronidazole for a median of 4 weeks (IQR 4-6), 4 weeks (IQR 2-4), and 6 weeks (IQR 4-6) for aspirated, excised, and conservatively treated patients, respectively. Early transition to oral antimicrobials (i.e., < 4 weeks of IV antimicrobials) was used by 134/269 (50%), whereas consolidation therapy with oral antimicrobials after a standard IV regimen (i.e., 4-8 weeks) was used by 123/264 (47%). Median prioritization scores for future RCTs were as follows: 1 (IQR 1-2) for an early transition to oral antimicrobials and duration of therapy, 3 (IQR 2-4) for comparisons of antimicrobial regimens, use of adjunctive dexamethasone, and neurosurgical aspiration versus excision, and 4 (IQR 3-5) for intracavitary antimicrobial instillation and drainage, and for prophylactic anti-epileptic therapy. Willingness to include patients into RCTs reflected prioritization scores. Duration of intravenous antimicrobial treatment and use of oral antimicrobials varies substantially among ID specialists. RCTs are needed to define optimal treatment of brain abscess.

Characteristics and outcomes of patients with COVID-19 admitted to ICU in a tertiary hospital in Stockholm, Sweden.

BACKGROUND: Information on characteristics and outcomes of intensive care unit (ICU) patients with COVID-19 remains limited. We examined characteristics, clinical course and early outcomes of patients with COVID-19 admitted to ICU. METHODS: We included all 260 patients with COVID-19 admitted to nine ICUs at the Karolinska University Hospital (Stockholm, Sweden) between 9 March and 20 April 2020. Primary outcome was in-hospital mortality among patients with definite outcomes (discharged from ICU or death), as of 30 April 2020 (study end point). Secondary outcomes included ICU length of stay, the proportion of patients receiving mechanical ventilation and renal replacement therapy, and hospital discharge destination. RESULTS: Of 260 ICU patients with COVID-19, 208 (80.0%) were men, the median age was 59 (IQR 51-65) years, 154 (59.2%) had at least one comorbidity, and the median duration of symptoms preceding ICU admission was 11 (IQR 8-14) days. Sixty-two (23.8%) patients remained in ICU at study end point. Among the 198 patients with definite outcomes, ICU length of stay was 12 (IQR, 6-18) days, 163 (82.3%) received mechanical ventilation, 28 (14.1%) received renal replacement therapy, 60 (30.3%) died, 62 (31.3%) were discharged home, 47 (23.7%) were discharged to ward, and 29 (14.6%) were discharged to another health care facility. On multivariable logistic regression analysis, older age and admission from the emergency department was associated with higher mortality. CONCLUSION: This study presents detailed data on clinical characteristics and early outcomes of consecutive patients with COVID-19 admitted to ICU in a large tertiary hospital in Sweden.