A first-level customization study of SAPS II with Norwegian Intensive Care and Pandemic Registry (NIPaR) data.

BACKGROUND: Severity scores and mortality prediction models (MPMs) are important tools for benchmarking and stratification in the intensive care unit (ICU) and need to be regularly updated using data from a local and contextual cohort. Simplified acute physiology score II (SAPS II) is widely used in European ICUs. METHODS: A first-level customization was performed on the SAPS II model using data from the Norwegian Intensive Care and Pandemic Registry (NIPaR). Two previous SAPS II models (Model A: the original SAPS II model and Model B: a SAPS II model based on NIPaR data from 2008 to 2010) were compared to the new Model C. Model C was based on patients from 2018 to 2020 (corona virus disease 2019 patients omitted; n = 43,891), and its performances (calibration, discrimination, and uniformity of fit) compared to the previous models (Model A and Model B). RESULTS: Model C was better calibrated than Model A with a Brier score 0.132 (95% confidence interval 0.130-0.135) versus 0.143 (95% confidence interval 0.141-0.146). The Brier score for Model B was 0.133 (95% confidence interval 0.130-0.135). In the Cox's calibration regression α ≈ 0 and ß ≈ 1 for both Model C and Model B but not for Model A. Uniformity of fit was similar for Model B and for Model C, both better than for Model A, across age groups, sex, length of stay, type of admission, hospital category, and days on respirator. The area under the receiver operating characteristic curve was 0.79 (95% confidence interval 0.79-0.80), showing acceptable discrimination. CONCLUSIONS: The observed mortality and corresponding SAPS II scores have significantly changed during the last decades and an updated MPM is superior to the original SAPS II. However, proper external validation is required to confirm our findings. Prediction models need to be regularly customized using local datasets in order to optimize their performances.

Post-traumatic stress symptoms six months after ICU admission with COVID-19: Prospective observational study.

AIMS AND OBJECTIVES: The aim of this study was to investigate the prevalence of post-traumatic stress symptoms, and to identify possible predictive factors in Norwegian intensive care unit survivors, 6 months after admission to the intensive care unit with COVID-19. BACKGROUND: The SARS CoV-2 virus causing COVID-19 has spread worldwide since it was declared a pandemic in March 2020. The most severely ill patients have been treated in the intensive care due to acute respiratory failure and also acute respiratory distress syndrome. It is well documented that these severe conditions can lead to complex and long-lasting symptoms, such as psychological distress, and was, therefore, investigated for the specific COVID-19 population. DESIGN: Prospective observational study. METHODS: Clinical data and patient reported outcome measures were collected by the Norwegian Intensive Care and Pandemic Registry and by the study group 6 months after admission to an intensive care unit. RESULTS: Among 222 COVID-19 patients admitted to Norwegian intensive care units between 10 March and 6 July 2020, 175 survived. The study sample consisted of 131 patients who responded to at least one patient reported outcome measure at 6 months following admission. The primary outcome was self-reported post-traumatic stress symptoms, using the Impact of Event Scale-6 (n = 89). Of those, 22.5% reported post-traumatic stress symptoms 6 months after admission. Female gender, younger age and having a high respiratory rate at admission were statistically significant predictive factors for reporting post-traumatic stress symptoms. CONCLUSIONS: The result is in accordance with previously published research with comparable populations, suggesting that for many COVID-19 survivors psychological distress is a part of the post-acute sequelae. Results from the present study should be replicated in larger datasets. RELEVANCE TO CLINICAL PRACTICE: This project provides important insight to post-acute sequelae after COVID-19 that patients may experience after critical illness.

A multicenter international prospective study of the validity and reliability of a COVID-19-specific health-related quality of life questionnaire.

PURPOSE: To develop and validate a health-related quality of life (HRQoL) questionnaire for patients with current or previous coronavirus disease (COVID-19) in an international setting. METHODS: This multicenter international methodology study followed standardized guidelines for a four-phase questionnaire development. Here, we report on the pretesting and validation of our international questionnaire. Adults with current or previous COVID-19, in institutions or at home were eligible. In the pretesting, 54 participants completed the questionnaire followed by interviews to identify administration problems and evaluate content validity. Thereafter, 371 participants completed the revised questionnaire and a debriefing form to allow preliminary psychometric analysis. Validity and reliability were assessed (correlation-based methods, Cronbach's α, and intra-class correlation coefficient). RESULTS: Eleven countries within and outside Europe enrolled patients. From the pretesting, 71 of the 80 original items fulfilled the criteria for item-retention. Most participants (80%) completed the revised 71-item questionnaire within 15 min, on paper (n = 175) or digitally (n = 196). The final questionnaire included 61 items that fulfilled criteria for item retention or were important to subgroups. Item-scale correlations were > 0.7 for all but nine items. Internal consistency (range 0.68-0.92) and test-retest results (all but one scale > 0.7) were acceptable. The instrument consists of 15 multi-item scales and six single items. CONCLUSION: The Oslo COVID-19 QLQ-W61© is an international, stand-alone, multidimensional HRQoL questionnaire that can assess the symptoms, functioning, and overall quality of life in COVID-19 patients. It is available for use in research and clinical practice. Further psychometric validation in larger patient samples will be performed.

Age and product dependent vaccine effectiveness against SARS-CoV-2 infection and hospitalisation among adults in Norway: a national cohort study, July-November 2021.

BACKGROUND: COVID-19 vaccines have been crucial in the pandemic response and understanding changes in vaccines effectiveness is essential to guide vaccine policies. Although the Delta variant is no longer dominant, understanding vaccine effectiveness properties will provide essential knowledge to comprehend the development of the pandemic and estimate potential changes over time. METHODS: In this population-based cohort study, we estimated the vaccine effectiveness of Comirnaty (Pfizer/BioNTech; BNT162b2), Spikevax (Moderna; mRNA-1273), Vaxzevria (AstraZeneca; ChAdOx nCoV-19; AZD1222), or a combination against SARS-CoV-2 infections, hospitalisations, intensive care admissions, and death using Cox proportional hazard models, across different vaccine product regimens and age groups, between 15 July and 31 November 2021 (Delta variant period). Vaccine status is included as a time-varying covariate and all models were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data from the entire adult Norwegian population were collated from the National Preparedness Register for COVID-19 (Beredt C19). RESULTS: The overall adjusted vaccine effectiveness against infection decreased from 81.3% (confidence interval (CI): 80.7 to 81.9) in the first 2 to 9 weeks after receiving a second dose to 8.6% (CI: 4.0 to 13.1) after more than 33 weeks, compared to 98.6% (CI: 97.5 to 99.2) and 66.6% (CI: 57.9 to 73.6) against hospitalisation respectively. After the third dose (booster), the effectiveness was 75.9% (CI: 73.4 to 78.1) against infection and 95.0% (CI: 92.6 to 96.6) against hospitalisation. Spikevax or a combination of mRNA products provided the highest protection, but the vaccine effectiveness decreased with time since vaccination for all vaccine regimens. CONCLUSIONS: Even though the vaccine effectiveness against infection waned over time, all vaccine regimens remained effective against hospitalisation after the second vaccine dose. For all vaccine regimens, a booster facilitated recovery of effectiveness. The results from this support the use of heterologous schedules, increasing flexibility in vaccination policy.

COVID-19 Hospitalization Among Children <18 Years by Variant Wave in Norway.

OBJECTIVES: There is limited evidence on whether the relative severity of coronavirus disease 2019 (COVID-19) in children and adolescents differs for different severe acute respiratory syndrome coronavirus 2 variants. We compare the risk of hospitalization to acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C) among unvaccinated persons <18 years with COVID-19 (cases) between waves of the Alpha, Delta, and Omicron (sublineage BA.1) variants in Norway. METHODS: We used linked individual-level data from national registries to calculate adjusted risk ratios (aRR) with 95% confidence interval (CI) using multivariable log-binomial regression. We adjusted for variant wave, demographic characteristics, and underlying comorbidities. RESULTS: We included 10 538 Alpha (21 hospitalized with acute COVID-19, 7 MIS-C), 42 362 Delta (28 acute COVID-19, 14 MIS-C), and 82 907 Omicron wave cases (48 acute COVID-19, 7 MIS-C). The risk of hospitalization with acute COVID-19 was lower in the Delta (aRR: 0.53, 95% CI: 0.30-0.93) and Omicron wave (aRR: 0.40, 95% CI: 0.24-0.68), compared to the Alpha wave. We found no difference in this risk for Omicron compared to Delta. The risk of MIS-C was lower for Omicron, compared to Alpha (aRR: 0.09, 95% CI: 0.03-0.27) and Delta (aRR: 0.26, 95% CI: 0.10-0.63). CONCLUSIONS: We do not find clear evidence that different variants have influenced the risk of hospitalization with acute COVID-19 among unvaccinated children and adolescents in Norway. The lower risk of this outcome with Omicron and Delta may reflect changes in other factors over time, such as the testing strategy, maternal vaccination and/or hospitalization criteria. The emergence of Omicron has reduced the risk of MIS-C.

Milder disease trajectory among COVID-19 patients hospitalised with the SARS-CoV-2 Omicron variant compared with the Delta variant in Norway.

Using individual-level national registry data, we conducted a cohort study to estimate differences in the length of hospital stay, and risk of admission to an intensive care unit and in-hospital death among patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, compared with patients infected with Delta variant in Norway. We included 409 (38%) patients infected with Omicron and 666 (62%) infected with Delta who were hospitalised with coronavirus disease 2019 (COVID-19) as the main cause of hospitalisation between 6 December 2021 and 6 February 2022. Omicron patients had a 48% lower risk of intensive care admission (adjusted hazard ratios (aHR): 0.52, 95% confidence interval (CI): 0.34-0.80) and a 56% lower risk of in-hospital death (aHR: 0.44, 95%CI: 0.24-0.79) compared with Delta patients. Omicron patients had a shorter length of stay (with or without ICU stay) compared with Delta patients in the age groups from 18 to 79 years and those who had at least completed their primary vaccination. This supports growing evidence of reduced disease severity among hospitalised Omicron patients compared with Delta patients.

Acute kidney injury in patients with COVID-19 in the intensive care unit: evaluation of risk factors and mortality in a national cohort.

OBJECTIVES: Acute kidney injury (AKI) is a frequent complication among critical ill patients with COVID-19, but the actual incidence is unknown as AKI-incidence varies from 25% to 89% in intensive care unit (ICU) populations. We aimed to describe the prevalence and risk factors of AKI in patients with COVID-19 admitted to ICU in Norway. DESIGN: Nation-wide observational study with data sampled from the Norwegian Intensive Care and Pandemic Registry (NIPaR) for the period between 10 March until 31 December 2020. SETTING: ICU patients with COVID-19 in Norway. NIPaR collects data on intensive care stays covering more than 90% of Norwegian ICU and 98% of ICU stays. PARTICIPANTS: Adult patients with COVID-19 admitted to Norwegian ICU were included in the study. Patients with chronic kidney disease (CKD) were excluded in order to avoid bias from CKD on the incidence of AKI. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was AKI at ICU admission as defined by renal Simplified Acute Physiology Score in NIPaR. Secondary outcome measures included survival at 30 and 90 days after admission to hospital. RESULTS: A total number of 361 patients with COVID-19 were included in the analysis. AKI was present in 32.0% of the patients at ICU admission. The risk for AKI at ICU admission was related to acute circulatory failure at admission to hospital. Survival for the study population at 30 and 90 days was 82.5% and 77.6%, respectively. Cancer was a predictor of 30-day mortality. Age, acute circulatory failure at hospital admission and AKI at ICU admission were predictors of both 30-day and 90-day mortality. CONCLUSIONS: A high number of patients with COVID-19 had AKI at ICU admission. The study indicates that AKI at ICU admission was related to acute circulatory failure at hospital admission. Age, acute circulatory failure at hospital admission and AKI at ICU admission were associated with mortality.

Length of hospital stay and risk of intensive care admission and in-hospital death among COVID-19 patients in Norway: a register-based cohort study comparing patients fully vaccinated with an mRNA vaccine to unvaccinated patients.

OBJECTIVES: We estimated the length of stay (LoS) in hospital and the intensive care unit (ICU) and risk of admission to ICU and in-hospital death among COVID-19 patients ≥18 years in Norway who had been fully vaccinated with an mRNA vaccine (at least two doses or one dose and previous SARS-CoV-2 infection), compared to unvaccinated patients. METHODS: Using national registry data, we analyzed SARS-CoV-2-positive patients hospitalized in Norway between 1 February and 30 November 2021, with COVID-19 as the main cause of hospitalization. We ran Cox proportional hazards models adjusting for vaccination status, age, sex, county of residence, regional health authority, date of admission, country of birth, virus variant, and underlying risk factors. RESULTS: We included 716 fully vaccinated patients (crude overall median LoS: 5.2 days; admitted to ICU: 103 (14%); in-hospital death: 86 (13%)) and 2487 unvaccinated patients (crude overall median LoS: 5.0 days; admitted to ICU: 480 (19%); in-hospital death: 102 (4%)). In adjusted models, fully vaccinated patients had a shorter overall LoS in hospital (adjusted log hazard ratios (aHR) for discharge: 1.61, 95% CI: 1.24-2.08), shorter LoS without ICU (aHR: 1.27, 95% CI: 1.07-1.52), and lower risk of ICU admission (aHR: 0.50, 95% CI: 0.37-0.69) compared to unvaccinated patients. We observed no difference in the LoS in ICU or in risk of in-hospital death between fully vaccinated and unvaccinated patients. DISCUSSION: Fully vaccinated patients hospitalized with COVID-19 in Norway have a shorter LoS and lower risk of ICU admission than unvaccinated patients. These findings can support patient management and ongoing capacity planning in hospitals.

No difference in risk of hospitalization between reported cases of the SARS-CoV-2 Delta variant and Alpha variant in Norway.

OBJECTIVES: To estimate the risk of hospitalization among reported cases of the Delta variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared with the Alpha variant in Norway, and the risk of hospitalization by vaccination status. METHODS: A cohort study was conducted on laboratory-confirmed cases of SARS-CoV-2 in Norway, diagnosed between 3 May and 15 August 2021. Adjusted risk ratios (aRR) with 95% confidence intervals (CI) were calculated using multi-variable log-binomial regression, accounting for variant, vaccination status, demographic characteristics, week of sampling and underlying comorbidities. RESULTS: In total, 7977 cases of the Delta variant and 12,078 cases of the Alpha variant were included in this study. Overall, 347 (1.7%) cases were hospitalized. The aRR of hospitalization for the Delta variant compared with the Alpha variant was 0.97 (95% CI 0.76-1.23). Partially vaccinated cases had a 72% reduced risk of hospitalization (95% CI 59-82%), and fully vaccinated cases had a 76% reduced risk of hospitalization (95% CI 61-85%) compared with unvaccinated cases. CONCLUSIONS: No difference was found between the risk of hospitalization for Delta cases and Alpha cases in Norway. The results of this study support the notion that partially and fully vaccinated cases are highly protected against hospitalization with coronavirus disease 2019.

COVID-19 in patients with chronic inflammatory rheumatic joint disease. / Covid-19 hos pasienter med kronisk inflammatorisk leddsykdom.

BACKGROUND: Since patients with chronic inflammatory rheumatic joint diseases may be more prone to infections, we wished to investigate the incidence of COVID-19 in this group, and explore the possible significance of factors related to the rheumatic disease, the patient or the treatment. MATERIAL AND METHOD: Altogether 27 907 patients registered in the Norwegian Arthritis Registry (NorArthritis) were linked to the Norwegian Surveillance System for Communicable Diseases and the Norwegian Intensive Care and Pandemic Registry in order to find the incidence of COVID-19 in 2020, and the proportion of patients who were hospitalised. A standardised incidence ratio (SIR) was calculated by comparing with sex and age-specific incidence in the general population. Logistic regression analysis was used to investigate whether diagnosis, age, sex, disease activity, comorbidity or drug therapy had any bearing on the incidence. RESULTS: A total of 185 of the patients in NorArthritis tested positive for COVID-19, of whom 10 % were hospitalised. The incidence was lower than in the general population (SIR 0.84; 95 % confidence interval (CI): 0.72-0.97, P = 0.02). Young age and low disease activity were associated with higher incidence of infection. The other factors had no significant effect. INTERPRETATION: The fact that the incidence of COVID-19 was lower than in the general population, and that within the group it was lower in those with moderate/high disease activity and greater age, is most likely attributable to patients of advanced age with chronic active disease having protected themselves against infection to a greater degree.

COVID-19 in Cancer Patients, Risk Factors for Disease and Adverse Outcome, a Population-Based Study From Norway.

BACKGROUND: Cancer has been suggested as a risk factor for severe outcome of SARS-CoV-2 infection. In this population-based study we aimed to identify factors associated with higher risk of COVID-19 and adverse outcome. METHODS: Data on all confirmed SARS-CoV-2 positive patients in the period January 1 to May 31, 2020 were extracted from the Norwegian Surveillance System for Communicable Diseases. Data on cancer and treatment was available from the Cancer Registry of Norway, the Norwegian Patient Registry and the Norwegian Prescription Database. Deaths due to COVID-19 were extracted from the Cause of Death Registry. From the Norwegian Intensive Care and Pandemic Registry we retrieved data on admittance to hospital and intensive care. We determined rates of COVID-19 disease in cancer patients and the rest of the population. We also ran multivariate analyses adjusting for age and gender. RESULTS: A total of 8 410 patients were diagnosed with SARS-CoV-2 infection in Norway during the study period, of which 547 (6.5%) were cancer patients. Overall, we found similar age adjusted rates of COVID-19 in the population with cancer as in the population without cancer. Unadjusted analysis showed that patients having undergone major surgery within the past 3 months had an increased risk of COVID-19 while we did not find increased Odds Ratio (OR) related to other oncological treatment modalities. No patients treated with stem cell or bone marrow transplant were diagnosed with COVID-19. The fatality rate of COVID-19 among cancer patients was 0.10. This was similar to non-cancer patients, when adjusting for age and sex with OR (95% CI) for death= 0.99 (0.68-1.42). Patients with distant metastases had significantly increased OR of death due to COVID-19 disease of 9.31 (95% CI 2.60-33.34). For the combined outcome death and/or admittance to hospital due to COVID-19, we found significant two-fold increased risk estimates for patients diagnosed with cancer less than one 1 year ago (OR 2.08, 95% CI 1.14-3.80), for those treated with anti-cancer drugs during the past 3 months (OR 1.80, 95% CI 1.07-3.01) and for patients undergoing major surgery during the past 3 months (OR 2.19, 95% CI 1.40-3.44).

Hospitalisations for COVID-19 - a comparison of different data sources. / Sykehusinnleggelser med covid-19 ‒ en sammenligning av ulike datakilder.

BACKGROUND: Three different data sources exist for monitoring COVID-19-associated hospitalisations in Norway: The Directorate of Health, the Norwegian Intensive Care and Pandemic Registry (NIPaR), and the linking of the Norwegian Patient Registry (NPR) and the Norwegian Surveillance System for Communicable Diseases (MSIS). A comparison of results from different data sources is important to increase understanding of the data and to further optimise current and future surveillance. We compared results from the three data sources from March to June 2020. MATERIAL AND METHOD: We analysed the number of new admissions, as well as the total number of hospitalised patients and those on ventilatory support, reported per day and by regional health authority. The analysis was descriptive. RESULTS: The cumulative number of new admissions according to NPR-MSIS (n=1260) was higher than NIPaR (n=1153). The discrepancy was high early in the epidemic (93 as of 29 March). The trend in the number of hospitalised patients was similar for all three sources throughout the study period. NPR-MSIS overestimated the number of hospitalised patients on ventilatory support. INTERPRETATION: The discrepancy in new admissions between NIPaR and NPR-MSIS is primarily due to missing registrations for some patients admitted before NIPaR became operational. Basic information retrieved daily by the Directorate of Health give comparable results to more comprehensive daily information retrieval undertaken in NIPaR and NPR-MSIS, adjusted retrospectively. Further analysis is necessary regarding whether NIPaR and NPR-MSIS provide timely data and function as required in an emergency preparedness situation.