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      Multi-organ assessment in mainly non-hospitalized individuals after SARS-CoV-2 infection: The Hamburg City Health Study COVID programme

      research-article
      1 , 2 , 1 , 2 , 3 , 4 , 1 , 2 , 1 , 2 , 5 , 6 , 4 , 7 , 7 , 6 , 8 , 8 , 3 , 9 , 10 , 11 , 4 , 12 , 10 , 4 , 1 , 2 , 5 , 6 , 1 , 2 , 5 , 1 , 2 , 6 , 6 , 12 , 13 , 14 , 1 , 2 , 6 , 1 , 2 , 8 , 3 , 1 , 5 , 15 , 16 , 1 , 2 , 5 , 17 , 1 , 18 , 19 , 6 , 1 , 2 , 5 , 17 , 1 , 2 , 5
      European Heart Journal
      Oxford University Press
      COVID-19, Sequelae, Matched controls, Multi-organ assessment

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          Abstract

          Aims

          Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population.

          Methods and results

          Four hundred and forty-three mainly non-hospitalized individuals were examined in median 9.6 months after the first positive SARS-CoV-2 test and matched for age, sex, and education with 1328 controls from a population-based German cohort. We assessed pulmonary, cardiac, vascular, renal, and neurological status, as well as patient-related outcomes. Bodyplethysmography documented mildly lower total lung volume (regression coefficient −3.24, adjusted P = 0.014) and higher specific airway resistance (regression coefficient 8.11, adjusted P = 0.001) after SARS-CoV-2 infection. Cardiac assessment revealed slightly lower measures of left (regression coefficient for left ventricular ejection fraction on transthoracic echocardiography −0.93, adjusted P = 0.015) and right ventricular function and higher concentrations of cardiac biomarkers (factor 1.14 for high-sensitivity troponin, 1.41 for N-terminal pro-B-type natriuretic peptide, adjusted P ≤ 0.01) in post-SARS-CoV-2 patients compared with matched controls, but no significant differences in cardiac magnetic resonance imaging findings. Sonographically non-compressible femoral veins, suggesting deep vein thrombosis, were substantially more frequent after SARS-CoV-2 infection (odds ratio 2.68, adjusted P < 0.001). Glomerular filtration rate (regression coefficient −2.35, adjusted P = 0.019) was lower in post-SARS-CoV-2 cases. Relative brain volume, prevalence of cerebral microbleeds, and infarct residuals were similar, while the mean cortical thickness was higher in post-SARS-CoV-2 cases. Cognitive function was not impaired. Similarly, patient-related outcomes did not differ.

          Conclusion

          Subjects who apparently recovered from mild to moderate SARS-CoV-2 infection show signs of subclinical multi-organ affection related to pulmonary, cardiac, thrombotic, and renal function without signs of structural brain damage, neurocognitive, or quality-of-life impairment. Respective screening may guide further patient management.

          Graphical Abstract

          Graphical Abstract

          The key question is: How does a mild to moderate course of SARS-CoV-2 infection in mainly non-hospitalized individuals impact intermediate-term organ-specific functions in comparison to the general population? The key findings are (i) a mild to moderate course of SARS-CoV-2 infection is associated with subsequent signs of subclinical multi-organ affection; (ii) associations mainly affect the pulmonary, cardiac, coagulation, and renal system; and (iii) no systematic associations with structural brain damage, neurocognition, or quality of life were observed. The take-home message is systematic screening of multi-organ function even after mild to moderate SARS-CoV-2 infection is recommended to identify individuals at risk and initiate appropriate preventive therapies.

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          Most cited references38

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          A new equation to estimate glomerular filtration rate.

          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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            mice: Multivariate Imputation by Chained Equations inR

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              6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

              Background The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. Methods We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5–6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. Findings In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0–65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5–6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5–6, and median CT scores were 3·0 (IQR 2·0–5·0) for severity scale 3, 4·0 (3·0–5·0) for scale 4, and 5·0 (4·0–6·0) for scale 5–6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80–3·25) for scale 4 versus scale 3 and 4·60 (1·85–11·48) for scale 5–6 versus scale 3 for diffusion impairment; OR 0·88 (0·66–1·17) for scale 4 versus scale 3 and OR 1·77 (1·05–2·97) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58–0·96) for scale 4 versus scale 3 and 2·69 (1·46–4·96) for scale 5–6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. Interpretation At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. Funding National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.
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                Author and article information

                Journal
                Eur Heart J
                Eur Heart J
                eurheartj
                European Heart Journal
                Oxford University Press
                0195-668X
                1522-9645
                06 January 2022
                06 January 2022
                : ehab914
                Affiliations
                [1 ] Department of Cardiology, University Heart and Vascular Center , Hamburg, Germany
                [2 ] Population Health Research Department, University Heart and Vascular Center , Hamburg, Germany
                [3 ] Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf , Hamburg, Germany
                [4 ] Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf , Hamburg, Germany
                [5 ] German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Luebeck , Hamburg, Germany
                [6 ] Department of Neurology, University Medical Center Hamburg-Eppendorf , Hamburg, Germany
                [7 ] Clinic and Policlinic for Psychiatry and Psychotherapy, University Clinic Hamburg-Eppendorf , Hamburg, Germany
                [8 ] Department of Medical Psychology, University Medical Center Hamburg-Eppendorf (UKE) , Hamburg, Germany
                [9 ] Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg , Germany
                [10 ] III. Department of Medicine, University Medical Center Hamburg-Eppendorf , Hamburg, Germany
                [11 ] Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf , Hamburg, Germany
                [12 ] Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg- Eppendorf , Hamburg, Germany
                [13 ] Center for Thrombosis and Hemostasis (CTH), Johannes Gutenberg University Medical Center , Mainz, Germany
                [14 ] Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland , Dublin, Ireland
                [15 ] Hospital Itzehoe, Pneumology , Itzehoe, Germany
                [16 ] Airway Research Center North (ARCN), German Center for Lung Research (DZL), LungenClinic Grosshansdorf , Grosshansdorf, Germany
                [17 ] University Center of Cardiovascular Science, University Heart and Vascular Center , Hamburg, Germany
                [18 ] Cardio-CARE, Medizincampus Davos , Davos, Switzerland
                [19 ] School of Mathematics, Statistics and Computer Science, University of KwaZulu-Natal , Pietermaritzburg, South Africa
                Author notes
                Corresponding author. Tel: +49 40 7410 53972/56800, Fax: +49 40 7410 53622, Email: s.blankenberg@ 123456uke.de
                [†]

                These authors contributed equally.

                Author information
                https://orcid.org/0000-0002-1235-5066
                https://orcid.org/0000-0002-5211-5593
                https://orcid.org/0000-0003-0406-3319
                https://orcid.org/0000-0003-2434-1822
                https://orcid.org/0000-0002-5092-8179
                https://orcid.org/0000-0001-7175-5062
                https://orcid.org/0000-0001-8391-3988
                https://orcid.org/0000-0002-2591-6387
                https://orcid.org/0000-0002-9468-7944
                https://orcid.org/0000-0002-5102-0955
                https://orcid.org/0000-0002-8065-8683
                https://orcid.org/0000-0001-6288-7389
                https://orcid.org/0000-0003-3774-6765
                https://orcid.org/0000-0001-6426-7167
                https://orcid.org/0000-0003-4594-5975
                https://orcid.org/0000-0001-5956-0051
                https://orcid.org/0000-0003-1625-5721
                https://orcid.org/0000-0001-5375-0030
                https://orcid.org/0000-0002-6999-2787
                https://orcid.org/0000-0002-6302-8671
                https://orcid.org/0000-0002-8386-5397
                https://orcid.org/0000-0002-4785-1449
                https://orcid.org/0000-0003-3814-6542
                Article
                ehab914
                10.1093/eurheartj/ehab914
                8755397
                34999762
                83cc9beb-f08c-4b4d-b56a-c7ee51df350b
                © The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 06 October 2021
                : 24 December 2021
                : 25 December 2021
                Page count
                Pages: 14
                Funding
                Funded by: Senat und Behörde für Wissenschaft;
                Award ID: E43026-03.HCHS
                Funded by: Deutsche Forschungsgemeinschaft, doi 10.13039/501100001659;
                Award ID: TH1106/5-1
                Award ID: AA93/2-1
                Funded by: euCanSHare;
                Award ID: 825903-euCanSHare H2020
                Funded by: Foundation Leducq;
                Award ID: 16 CVD 03
                Funded by: Innovative medicine initiative;
                Award ID: 116074
                Funded by: Deutsche Gesetzliche Unfallversicherung, doi 10.13039/501100003417;
                Categories
                Fast Track Clinical Research
                AcademicSubjects/MED00200
                Custom metadata
                PAP

                Cardiovascular Medicine
                covid-19,sequelae,matched controls,multi-organ assessment
                Cardiovascular Medicine
                covid-19, sequelae, matched controls, multi-organ assessment

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