Clinical presentation and outcomes of COVID-19 compared with other respiratory virus infections and hospital populations

As of September 2022, more than 600 million cases of coronavirus disease 2019 (COVID-19) and 6.5 million deaths have been officially reported to the World Health Organization (WHO). The unfolding pandemic has exerted enormous strains on healthcare systems worldwide yet to be fully understood. The overarching aim of this thesis was to characterize clinical presentation and outcomes in adult patients hospitalized with COVID-19 and compare these with patients hospitalized with other respiratory virus infections as well as other hospital populations. Six retrospective cohort studies were conducted, all set in Stockholm Region in Sweden. In study I, baseline characteristics, clinical presentation, and outcomes in patients hospitalized with COVID-19 were compared with patients hospitalized with influenza, respiratory syncytial virus (RSV) infection, and other respiratory virus infections. Despite being younger and having an overall better health status, adult patients hospitalized with COVID-19 had an increased risk of severe outcomes, in particular mortality, compared with the other infections. These risks were greater among the elderly and during the first months of the pandemic. In study II, the prevalence of bacterial co-infections in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive community-acquired pneumonia (CAP) upon hospital admission was compared with patients hospitalized with influenza virus positive CAP and RSV positive CAP. The occurrence of detected bacterial co-infection upon hospital admission was substantially lower in the SARS-CoV-2 cohort compared with both the influenza and the RSV cohort. In study III, we compared the occurrence of ventilator-associated lower respiratory tract infection (VA-LRTI) in patients mechanically ventilated with versus without COVID-19. The incidence rate was increased in the COVID-19 cohort when compared with influenza and other infectious diseases but decreased when compared with most of the non-infectious diseases. Further, the incidence rate was in the COVID-19 cohort increased during the second wave when compared with the first wave of the pandemic. In study IV, the incidence rate and 30-day mortality rate of hospital-onset bacteraemia (HOB) were compared among patients hospitalized with COVID-19 and patients hospitalized without COVID-19 both before and during the pandemic. The incidence as well as mortality of HOB was increased for both COVID-19 and non-COVID-19 patients during the pandemic when compared with patients hospitalized before the pandemic. In study V, we investigated one-year mortality among patients admitted to the intensive care unit (ICU) with versus without COVID-19. Furthermore, we compared the number of days alive and free from hospitalization during one year in those patients who were discharged alive from the ICU-associated hospitalization. An increased risk of acute mortality was observed in patients treated in the ICU with versus without COVID-19, primarily among the elderly. On the contrary, survivors of COVID-19 critical illness had compared with other critical illness survivors more days alive and free from further hospitalizations during the next year. In study VI, we investigated the occurrence and characteristics of post COVID-19 condition (PCC) diagnosis across different severities of the acute COVID-19 episode. The occurrence of PCC diagnosis was substantially higher in individuals hospitalized versus not hospitalized during the acute COVID-19 episode. Associations between health status factors and PCC diagnosis differed by severity of the acute COVID-19 episode, with more and stronger associations among those not hospitalized during the acute infection. Increases in outpatient healthcare utilization up to one year after the acute infection indicated an incomplete recovery in individuals diagnosed with PCC. Taken together, these studies contribute to our understanding of the clinical epidemiology of COVID-19, highlighting severe acute clinical outcomes in hospitalized patients as well as a different occurrence and trajectory of PCC across different severities of the acute infection. Given the life-saving rollout of COVID-19 vaccines and the evolving nature of the virus, the generalizability of these findings over time needs to be carefully considered. Further investigations of the acute and in particular long-term effects of COVID-19 are warranted. An improved understanding of how the pandemic has caused disruptions and backlogs in healthcare delivery is also necessary

Prophylactic anticoagulation with low molecular weight heparin in COVID-19: cohort studies in Denmark and Sweden

OBJECTIVES: To evaluate safety and effectiveness of prophylactic anticoagulation with low molecular weight heparin (LMWH) in individuals hospitalised for COVID-19. METHODS: Using healthcare records from the capital region of Denmark (March 2020-February 2021) and Karolinska University Hospital in Sweden (February 2020-September 2021), we conducted an observational cohort study comparing clinical outcomes 30 days after admission among individuals hospitalised for COVID-19 starting prophylactic LMWH during the first 48 hours of hospitalisation with outcomes among those not receiving prophylactic anticoagulation. We used inverse probability weighting to adjust for confounders and bias due to missing information. Risk ratios, risk differences and robust 95% confidence intervals (CI) were estimated using binomial regression. Country-specific risk ratios were pooled using random-effects meta-analysis. RESULTS: We included 1692 and 1868 individuals in the Danish and Swedish cohorts. Of these, 771 (46%) and 1167 (62%) received prophylactic LMWH up to 48 hours after admission. The combined mortality in Denmark and Sweden was 12% (N=432) and the pooled risk ratio was 0.89 (CI 0.61-1.29) comparing individuals who received LMWH to those who did not. The relative risk of ICU admission was 1.12 (CI 0.85-1.48), while we observed no increased risk of bleeding (RR 0.60, 0.14-2.59). The relative risk of venous thromboembolism was 0.68 (CI: 0.33-1.38) in Sweden. Less than 5 VTE events were observed among individuals receiving LMWH in Denmark, preventing a meaningful analysis. CONCLUSION: We found no benefit on mortality with prophylactic LMWH and no increased risk of bleeding among COVID-19 patients receiving prophylactic LMWH

Preparedness for chemical, radiologic and nuclear incidents among a sample of emergency physicians' and general practitioners' : a qualitative study

Purpose: This study describes preparedness of emergency physicians and general practitioners following chemical, radiological and nuclear incidents. Design/methodology/approach: Five emergency physicians and six general practitioners were interviewed individually, and data was analysed using qualitative content analysis. Findings: The study results showed that physicians' preparedness for chemical, radiological and nuclear incidents is linked to one main category: to be an expert and to seek expertise and two categories: preparations before receiving CRN patients, and physical examination and treatment of CRN patients with subcategories. Research limitations/implications: The results have implications for further research on the complexity of generalist vs specialist competence and knowledge when responding to chemical, radiological and nuclear incidents. Originality/value: This study provides insights regarding chemical, radiological and nuclear preparedness among physicians at emergency departments and primary healthcare centres

Clinical prediction models for mortality in patients with covid-19:external validation and individual participant data meta-analysis

OBJECTIVE: To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19. DESIGN: Two stage individual participant data meta-analysis. SETTING: Secondary and tertiary care. PARTICIPANTS: 46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021. DATA SOURCES: Multiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published in The BMJ, and through PROSPERO, reference checking, and expert knowledge. MODEL SELECTION AND ELIGIBILITY CRITERIA: Prognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor. METHODS: Eight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters. MAIN OUTCOME MEASURES: 30 day mortality or in-hospital mortality. RESULTS: Datasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al’s model (0.96, 0.59 to 1.55, 0.21 to 4.28). CONCLUSION: The prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care