Development of a prognostic model of COVID-19 severity: a population-based cohort study in Iceland.

BACKGROUND: The severity of SARS-CoV-2 infection varies from asymptomatic state to severe respiratory failure and the clinical course is difficult to predict. The aim of the study was to develop a prognostic model to predict the severity of COVID-19 in unvaccinated adults at the time of diagnosis. METHODS: All SARS-CoV-2-positive adults in Iceland were prospectively enrolled into a telehealth service at diagnosis. A multivariable proportional-odds logistic regression model was derived from information obtained during the enrollment interview of those diagnosed between February 27 and December 31, 2020 who met the inclusion criteria. Outcomes were defined on an ordinal scale: (1) no need for escalation of care during follow-up; (2) need for urgent care visit; (3) hospitalization; and (4) admission to intensive care unit (ICU) or death. Missing data were multiply imputed using chained equations and the model was internally validated using bootstrapping techniques. Decision curve analysis was performed. RESULTS: The prognostic model was derived from 4756 SARS-CoV-2-positive persons. In total, 375 (7.9%) only required urgent care visits, 188 (4.0%) were hospitalized and 50 (1.1%) were either admitted to ICU or died due to complications of COVID-19. The model included age, sex, body mass index (BMI), current smoking, underlying conditions, and symptoms and clinical severity score at enrollment. On internal validation, the optimism-corrected Nagelkerke's R2 was 23.4% (95%CI, 22.7-24.2), the C-statistic was 0.793 (95%CI, 0.789-0.797) and the calibration slope was 0.97 (95%CI, 0.96-0.98). Outcome-specific indices were for urgent care visit or worse (calibration intercept -0.04 [95%CI, -0.06 to -0.02], Emax 0.014 [95%CI, 0.008-0.020]), hospitalization or worse (calibration intercept -0.06 [95%CI, -0.12 to -0.03], Emax 0.018 [95%CI, 0.010-0.027]), and ICU admission or death (calibration intercept -0.10 [95%CI, -0.15 to -0.04] and Emax 0.027 [95%CI, 0.013-0.041]). CONCLUSION: Our prognostic model can accurately predict the later need for urgent outpatient evaluation, hospitalization, and ICU admission and death among unvaccinated SARS-CoV-2-positive adults in the general population at the time of diagnosis, using information obtained by telephone interview.

[Effects of the COVID-19 pandemic and associated non-pharmaceutical interventions on diagnosis of myocardial infarction and selected infections in Iceland 2020].

INTRODUCTON: Nonpharmaceutical interventions to contain the spread of COVID-19 infections in Iceland in 2020 were successful, but the effects of these measures on incidence and diagnosis of other diseases is unknown. The aim of this study was to evaluate the impact of the COVID-19 pandemic on the diagnosis of myocardial infarction (MI) and selected infections with different transmission routes. MATERIALS AND METHODS: Health records of individuals 18 years or older who were admitted to Landspitali University Hospital (LUH) in 2016-2020 with pneumonia or MI were extracted from the hospital registry. We acquired data from the clinical laboratories regarding diagnostic testing for Chlamydia trachomatis, influenza, HIV and blood cultures positive for Enterobacterales species. Standardized incidence ratio (SIR) for 2020 was calculated with 95% confidence intervals (95%CI) and compared to 2016-2019. RESULTS: Discharge diagnoses due to pneumonia decreased by 31% in 2020, excluding COVID-19 pneumonia (SIR 0.69 (95%CI 0.64-0.75)). Discharge diagnoses of MI decreased by 18% (SIR 0.82 (95%CI 0.75-0.90)), and emergency cardiac catheterizations due to acute coronary syndrome by 23% (SIR 0.77 (95%CI 0.71-0.83)), while there was a 15% increase in blood stream infections for Enterobacterales species (SIR 1.15 (95%CI 1.04-1.28)). Testing for Chlamydia trachomatis decreased by 14.8% and positive tests decreased by 16.3%. Tests for HIV were reduced by 10.9%, while samples positive for influenza decreased by 23.6% despite doubling of tests being performed. CONCLUSION: The number of pneumonia cases of other causes than COVID-19 requiring admission dropped by a quarter in 2020. MI, chlamydia and influensa diagnoses decreased notably. These results likely reflect a true decrease, probably due to altered behaviour during the pandemic.

Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021.

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe.

Detailed Multiplex Analysis of SARS-CoV-2 Specific Antibodies in COVID-19 Disease.

A detailed understanding of the antibody response against SARS-CoV-2 is of high importance, especially with the emergence of novel vaccines. A multiplex-based assay, analyzing IgG, IgM, and IgA antibodies against the receptor binding domain (RBD), spike 1 (S1), and nucleocapsid proteins of the SARS-CoV-2 virus was set up. The multiplex-based analysis was calibrated against the Elecsys® Anti-SARS-CoV-2 assay on a Roche Cobas® instrument, using positive and negative samples. The calibration of the multiplex based assay yielded a sensitivity of 100% and a specificity of 97.7%. SARS-CoV-2 specific antibody levels were analyzed by multiplex in 251 samples from 221 patients. A significant increase in all antibody types (IgM, IgG, and IgA) against RBD was observed between the first and the third weeks of disease. Additionally, the S1 IgG antibody response increased significantly between weeks 1, 2, and 3 of disease. Class switching appeared to occur earlier for IgA than for IgG. Patients requiring hospital admission and intensive care had higher levels of SARS-CoV-2 specific IgA levels than outpatients. These findings describe the initial antibody response during the first weeks of disease and demonstrate the importance of analyzing different antibody isotypes against multiple antigens and include IgA when examining the immunological response to COVID-19.

Clinical spectrum of coronavirus disease 2019 in Iceland: population based cohort study.

OBJECTIVE: To characterise the symptoms of coronavirus disease 2019 (covid-19). DESIGN: Population based cohort study. SETTING: Iceland. PARTICIPANTS: All individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR) between 17 March and 30 April 2020. Cases were identified by three testing strategies: targeted testing guided by clinical suspicion, open invitation population screening based on self referral, and random population screening. All identified cases were enrolled in a telehealth monitoring service, and symptoms were systematically monitored from diagnosis to recovery. MAIN OUTCOME MEASURES: Occurrence of one or more of 19 predefined symptoms during follow-up. RESULTS: Among 1564 people positive for SARS-CoV-2, the most common presenting symptoms were myalgia (55%), headache (51%), and non-productive cough (49%). At the time of diagnosis, 83 (5.3%) individuals reported no symptoms, of whom 49 (59%) remained asymptomatic during follow-up. At diagnosis, 216 (14%) and 349 (22%) people did not meet the case definition of the Centers for Disease Control and Prevention and the World Health Organization, respectively. Most (67%) of the SARS-CoV-2-positive patients had mild symptoms throughout the course of their disease. CONCLUSION: In the setting of broad access to RT-PCR testing, most SARS-CoV-2-positive people were found to have mild symptoms. Fever and dyspnoea were less common than previously reported. A substantial proportion of SARS-CoV-2-positive people did not meet recommended case definitions at the time of diagnosis.

IFNL4 Genotypes Predict Clearance of RNA Viruses in Rwandan Children With Upper Respiratory Tract Infections.

Polymorphisms in the interferon lambda gene locus (IFNL) such as the IFNL4 genetic variants rs12979860 and rs368234815 are predictive of resolution of hepatitis C virus infection, but information about the impact of these variants in other infections is scarce. This study aimed at determining the potential impact of IFNL4 variation for the clearance of respiratory tract pathogens in Rwandan children (≤5 years old, n = 480) seeking medical care for acute respiratory infections. Nasopharyngeal swabs were retrieved from all children at the first hospital referral and from 161 children at follow-up visits 2 weeks later. The swabs were analyzed for pathogens by real-time PCR and for host cell IFNL4 genotype at rs12979860 and rs368234815. Approximately 1/3 of the children were homozygous for the rs12979860 T allele and the rs368234815 ΔG allele, which are overrepresented in subjects of African descent. These IFNL4 variants were significantly associated with reduced clearance of RNA viruses. Our results suggest that IFNL4 genotypes that are common among subjects of African descent may determine inefficacious clearance of RNA viruses from the respiratory tract.

Cumulative incidence of sickness absence and disease burden among the newly sick-listed, a cross-sectional population-based study.

BACKGROUND: Sickness absence is a public health problem with economic consequences for individuals and society. Although sickness absence and chronic diseases are correlated, few studies exist concerning the role of chronic disease in all-cause sickness absence. The aim was to assess the cumulative incidence of sickness absence and examine the accompanying burden of chronic diseases among the sick-listed. METHODS: A cross-sectional study was performed with data from 2008. Cumulative incidence of all-cause sickness absence (≥14 days) was calculated based on all newly sick-listed individuals (N = 12,543). The newly sick-listed sample and a randomized general population sample (n = 7,984) received a questionnaire (participation rates: 54% and 50%).To assess the burden of self-reported chronic diseases, standardized incidence ratios (SIR) were calculated. RESULTS: Estimated one-year cumulative incidence was 11.3% (95% CI: 11.2-11.3), 14.0% (13.9-14.1) for women and 8.6% (8.5-8.6) for men. Gender differences were consistent across all age groups, with highest cumulative incidence among women aged 51-64 years, 18.2% (18.0-18.5). For women, the burden of chronic disease was significantly higher for nine out of twelve disease groups, corresponding numbers for men were nine out of eleven disease groups (standardized for age and socio-economic status). Neoplastic diseases had the highest SIR with 4.3 (3.4-5.2) for women and 4.2 (2.8-5.6) for men. For psychiatric and rheumatic diseases the respective SIR's were 1.7 for women and 1.8 for men. The remaining disease groups had an elevated risk of 20-60% (SIR 1.2-1.6). The risk of reporting a co-morbidity was increased for women (SIR 1.4 (95% CI 1.4-1.5)) and men (SIR 1.5 (1.4-1.7)) among the sick-listed. CONCLUSIONS: Register data was used to estimate of the cumulative incidence of sickness absence in the general population. A higher burden of chronic disease among the newly sick-listed was found. Targeting long-term health problems may be an important public health strategy for reducing sickness absence.

[Use of hormone replacement therapy by Icelandic women in the years 1996-2001.].

INTRODUCTION: Since the late seventies the use of hormone replacement therapy by peri- and postmenopausal women has been steadily increasing. This was shown in a former study of hormonal use among Icelandic women who had responded to a questionnaire when attending cancer screening at the Cancer Detection Clinic (CDC) of the Icelandic Cancer Society in the years 1979-1996. This current study is an independent extension of the former study with the goal of investigating menopausal hormone use among Icelandic women during the period of 1996-2001 and comparing the results with the former study period of 1979-1995. MATERIAL AND METHODS: We used data from the CDC for the period of 1996-2001 and reviewed the responses from Icelandic women aged 40-69 years to questions regarding hormonal use. We investigated changes in the proportion of women using hormones, the proportion of women using combined hormone replacement therapy, the proportion using long-time hormone replacement therapy, and also the relationship between hormonal use and smoking. We also compared our results to the former study results. RESULTS: During the period 1996-2001, 16.649 women aged 40-69 years responded to the questionnaire on hormonal use. There was an increase in use during that period, and also an increase compared to the period 1979-1995. Women born 1941-1945 were more likely to have ever used hormones (68%) than women born 1931-35 (42%). Present use of hormones was most prevalent among 52-57 year old women (57%). The proportion of women aged 50-55 years reporting present use did not change over the period ( approximately 50%). Long term use increased steadily during the period. During 1996-98 the proportion of women who had used hormones for more than 5 years was 49%, compared to 67% of women 1999-2001. This is also a considerable increase compared to the former study period. In the years 1996-2001, 19% of the women reported hormone use for 14 years or more. Smoking was more common among ever users of hormone replacement therapy (63%) than among never users of hormone replacement therapy (53%). CONCLUSIONS: The proportion of women who had used hormones and the duration of hormone use increased steadily during the period of 1996-2001. There was also a considerable increase compared to the former study period.