key: cord-0755898-9p45kbs8
authors: Stridsman, Caroline; Vanfleteren, Lowie E.G.W.; Konradsen, Jon R.; Axelsson Fisk, Sten; Pedroletti, Christophe; Sjöö, Yvonne; Syk, Jörgen; Sterner, Therese; Lindberg, Anne; Tunsäter, Alf; Nyberg, Fredrik; Ekberg-Jansson, Ann; Karlsson Sundbaum, Johanna
title: Predictors of severe COVID-19 in a registry-based Swedish cohort of patients with COPD
date: 2021-11-11
journal: Eur Respir J
DOI: 10.1183/13993003.01920-2021
sha: d0a81396fbdcde8d28db159fee379d7e8f89209c
doc_id: 755898
cord_uid: 9p45kbs8

Older age, male sex, low educational level, symptom burden, degree of obstruction, underweight, obesity, comorbidity and prior COPD inpatient or secondary care predict severe COVID-19 in patients with COPD https://bit.ly/2VHZIEm

Odds ratios and 95% confidence intervals were generated using multivariable logistic models, with severe COVID-19 as a dependent variable. Clinical data from SNAR were included, and missing values were handled in two ways: missing as a separate category (models 1 and 4) and a complete case analysis (model 2) [7] . The impact of comorbidities was studied using complete register data (models 3 and 5). Models 1-3 had follow-up terminated on 9 December 2020, and models 4 and 5 on 11 September 2020.

Of the 68 902 COPD patients registered in SNAR on 9 December 2020, 991 (1.4%) met the definition of severe COVID-19 (98.3% U07.1). Of them, 683 (66%) were identified by inpatient care and 308 (34%) by death certificates, and up to 11 severe COVID-19 than without. Primary level of education was more common in severe COVID-19 (73.0% versus 70.6%; p=0.021), while current smoking was less common (23.0% versus 34.7%; p<0.001). Patients with severe COVID-19 had a higher mean CAT score than those without (14.6 versus 13.0; p<0.001), and a higher proportion had a CAT score ⩾18 (31.5% versus 22.2%; p<0.001), whereas those with CAT scores ⩾10 did not differ significantly. Medication-treated cardiovascular disease (80.6% versus 69.0%; p<0.001), diabetes (22.2% versus 16.2%; p<0.001), depression (35.4% versus 25.5%; p<0.001), and COPD treated in inpatient or secondary care in 2019 (25.3% versus 13.1%; p<0.001) were more common conditions among patients with severe COVID-19 than ones without.

Clinical data from SNAR showed that older age, male sex, primary education, secondary education, underweight, obesity, FEV 1 <50% pred, and a CAT score ⩾18 were all associated with severe COVID-19, while current smoking was inversely associated (model 1). The results were similar in the complete case analysis, except that level of education and BMI lost significance (model 2). Cardiovascular disease, diabetes and depression remained independent predictors of severe COVID-19 when adjusted for covariates (model 3). The pattern was similar when the follow-up was limited to 11 September (models 4 and 5) (table 1) .

To date, it is well-known that older age, male sex, obesity, cardiovascular disease, diabetes and low socioeconomic status are risk factors for severe COVID-19 in the general population [1, 8, 9] . To that list, decreased lung function, higher CAT score, underweight, depression and prior COPD treated in inpatient or secondary care can be added as factors predicting severe COVID-19 in patients with COPD. According to guidelines, these factors should be considered throughout the management of COPD [10] , and as highlighted in our result, also when identifying patients at risk for severe illness from COVID-19. When the risk of transmitting COVID-19 needs to be minimised, follow-up visits can be conducted by remote consultations (online, phone and/or video links). If airflow limitation requires confirmation during the consultation, personal portable spirometry can be used, supported by video conference technology [11] .

Surprisingly, current smoking was an inverse predictor in our study. However, it can be an age-related finding. The mean age in our cohort was above 70 years, and in another study, smokers more than 69 years old were not at any higher risk of COVID-19 than never-smokers, whereas the opposite was observed among younger individuals [12] . Even so, evidence strongly suggests the negative effects of smoking on COVID-19 at all ages [13, 14] , and the unexpected result requires further investigation.

A major strength of our study was the possibility to examine a large cohort of patients with COPD during a pandemic. Nonetheless, register studies have certain limitations, including the use of physician-diagnosed COPD for inclusion, the relatively crude definition of severe COVID-19, the lack of data regarding pharmacological COPD treatment and exacerbations and a variable amount of missing data. We handled missing data by using 1) missing as a separate category, to maintain statistical power; 2) a complete case analysis, which resulted in a loss of statistical power; and 3) a model including complete register data. When using missing as a separate category, the associations between severe COVID-19 and missing data on lung function and CAT indicate a selection bias. The delay in the delivery of data regarding death certificates from SCDR contributed to a different follow-up time for the combined outcome. Nevertheless, the Swedish COVID-19 strategy resulted in a rapid increase in cases and deaths during both endpoints [15] and our multivariable analyses were reassuringly similar when using 11 September as follow-up termination for both NPR and SCDR.

In conclusion, all clinical factors identified as predictors of severe COVID-19 in our study are important to monitor when managing patients with COPD. Beyond that, those patients need to be prioritised for vaccination.

Vanfleteren 2,3 , Jon R. Konradsen 4 , Sten Axelsson Fisk 5

4 Dept of Women's and Children's Health, Karolinska Institutet

Prevalence of comorbidities among individuals with COVID-19: a rapid review of current literature

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COPD and the risk of poor outcomes in COVID-19: a systematic review and meta-analysis

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Letter from Sweden

and personal fees from GSK, Novartis, Boehringer Ingelheim, Menarini, Resmed, Chiesi, AGA Linde, Zambon and Pulmonx. J. Syk reports consulting fees paid to their employer from Orion Pharma. T. Sterner has received personal fees from ALK Abello for lectures at sponsored meetings. A. Lindberg has received personal fees from AstraZeneca, Novartis, Boehringer Ingelheim and GlaxoSmithKline for advisory boards and/or lectures at sponsored meetings. A. Tunsäter has received personal fees from AstraZeneca, Novartis, Boehringer Ingelheim and GlaxoSmithKline for advisory boards and/or lectures at sponsored meetings. F. Nyberg was an employee of AstraZeneca until 2019, and holds some AstraZeneca shares. J.R. Konradsen, S. Axelsson Fisk, C. Pedroletti, Y. Sjöö, A. Ekberg-Jansson and J. Karlsson Sundbaum have no conflicts of interest. Support statement: This work was supported by the Swedish Heart-Lung Foundation under grant 20200308 and the Swedish Heart and Lung Association. Funding information for this article has been deposited with the Crossref Funder Registry.