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      Post-acute sequelae of COVID-19 among hospitalized patients in Estonia: Nationwide matched cohort study

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          Abstract

          Background

          Post-acute COVID-19 sequelae refers to a variety of health complications involving different organ systems that have been described among individuals after acute phase of illness. Data from unselected population groups with long-time follow up is needed to comprehensively describe the full spectrum of post-acute COVID-19 complications.

          Methods

          In this retrospective nationwide cohort study, we used data obtained from electronic health record database. Our primary cohort were adults hospitalized with confirmed COVID-19 and matched (age, sex, Charlson Comorbidity Index) unaffected controls from general population. Individuals included from February 2020 until March 2021 were followed up for 12 months. We estimated risks of all-cause mortality, readmission and incidence of 16 clinical sequelae after acute COVID-19 phase. Using a frailty Cox model, we compared incidences of outcomes in two cohorts.

          Results

          The cohort comprised 3949 patients older than 18 years who were alive 30 days after COVID-19 hospital admission and 15511 controls. Among cases 40.3% developed at least one incident clinical sequelae after the acute phase of SARS-CoV-2 infection, which was two times higher than in general population group. We report substantially higher risk of all-cause mortality (adjusted hazard ratio (aHR) = 2.57 (95%CI 2.23–2.96) and hospital readmission aHR = 1.73 (95%CI 1.58–1.90) among hospitalized COVID-19 patients. We found that the risks for new clinical sequalae were significantly higher in COVID-19 patients than their controls, especially for dementia aHR = 4.50 (95% CI 2.35–8.64), chronic lower respiratory disease aHR = 4.39 (95% CI 3.09–6.22), liver disease aHR 4.20 (95% CI 2.01–8.77) and other (than ischemic) forms of heart diseases aHR = 3.39 (95%CI 2.58–4.44).

          Conclusion

          Our results provide evidence that the post-acute COVID-19 morbidity within the first year after COVID-19 hospitalization is substantial. Risks of all-cause mortality, hospitalisation and majority of clinical sequelae were significantly higher in hospitalized COVID-19 patients than in general population controls and warrant targeted prevention efforts.

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          A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation

          Mary Charlson, Peter Pompei, Kathy Ales … (1987)
          The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
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            6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

            Chaolin Huang, Lixue Huang, Yeming Wang … (2021)
            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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              Characteristics of SARS-CoV-2 and COVID-19

              Ben Hu, Hua Guo, Peng Zhou … (2020)
              Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19), which threatens human health and public safety. In this Review, we describe the basic virology of SARS-CoV-2, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses. We summarize current knowledge of clinical, epidemiological and pathological features of COVID-19, as well as recent progress in animal models and antiviral treatment approaches for SARS-CoV-2 infection. We also discuss the potential wildlife hosts and zoonotic origin of this emerging virus in detail.
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                Author and article information

                Contributors
                Anna Tisler:
                ORCID: https://orcid.org/0000-0002-2055-9421
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Oliver Stirrup: Role: ConceptualizationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Heti Pisarev: Role: ConceptualizationRole: Data curationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – review & editing
                Ruth Kalda: Role: Data curationRole: Funding acquisitionRole: Project administrationRole: Writing – review & editing
                Tatjana Meister: Role: Funding acquisitionRole: ResourcesRole: ValidationRole: Writing – review & editing
                Kadri Suija: Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: ValidationRole: Writing – review & editing
                Raivo Kolde: Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: ValidationRole: Writing – review & editing
                Marko Piirsoo: Role: Data curationRole: Funding acquisitionRole: ResourcesRole: ValidationRole: Writing – review & editing
                Anneli Uusküla: Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Aqeel M. Alenazi: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS One
                Journal ID (publisher-id): plos
                Title: PLOS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 23 November 2022
                Publication date Collection: 2022
                Publication date PMC-release: 23 November 2022
                Volume: 17
                Issue: 11
                Electronic Location Identifier: e0278057
                Affiliations
                [1 ] Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia
                [2 ] Institute for Global Health, University College London, London, United Kingdom
                [3 ] Institute of Computer Science, University of Tartu, Tartu, Estonia
                [4 ] Institute of Technology, University of Tartu, Tartu, Estonia
                Prince Sattam bin Abdulaziz University, SAUDI ARABIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-2055-9421
                Article
                Publisher ID: PONE-D-22-19899
                DOI: 10.1371/journal.pone.0278057
                PMC ID: 9683565
                PubMed ID: 36417409
                SO-VID: 328dac7a-78bb-4432-aef4-43010875d09a
                Copyright © © 2022 Tisler et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 14 July 2022
                Date accepted : 9 November 2022
                Page count
                Figures: 2, Tables: 2, Pages: 14
                Funding
                Funded by: Estonian Research Council
                Award ID: PRG1197, PRG198
                Award Recipient :
                Research was carried out with the support of Estonian Research Council. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Grants: PRG1197, PRG198.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Medical Conditions
                Subject: Infectious Diseases
                Subject: Viral Diseases
                Subject: Covid 19
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: RNA viruses
                Subject: Coronaviruses
                Subject: SARS coronavirus
                Subject: SARS CoV 2
                Subject: Biology and life sciences
                Subject: Microbiology
                Subject: Medical microbiology
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Coronaviruses
                Subject: SARS coronavirus
                Subject: SARS CoV 2
                Subject: Medicine and health sciences
                Subject: Pathology and laboratory medicine
                Subject: Pathogens
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Coronaviruses
                Subject: SARS coronavirus
                Subject: SARS CoV 2
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral pathogens
                Subject: Coronaviruses
                Subject: SARS coronavirus
                Subject: SARS CoV 2
                Subject: Medicine and Health Sciences
                Subject: Endocrinology
                Subject: Endocrine Disorders
                Subject: Diabetes Mellitus
                Subject: Type 2 Diabetes
                Subject: Type 2 Diabetes Risk
                Subject: Medicine and Health Sciences
                Subject: Medical Conditions
                Subject: Metabolic Disorders
                Subject: Diabetes Mellitus
                Subject: Type 2 Diabetes
                Subject: Type 2 Diabetes Risk
                Subject: Medicine and Health Sciences
                Subject: Epidemiology
                Subject: Medical Risk Factors
                Subject: Medicine and Health Sciences
                Subject: Medical Conditions
                Subject: Cardiovascular Diseases
                Subject: Cardiovascular Disease Risk
                Subject: Medicine and Health Sciences
                Subject: Cardiology
                Subject: Cardiovascular Medicine
                Subject: Cardiovascular Diseases
                Subject: Cardiovascular Disease Risk
                Subject: Medicine and Health Sciences
                Subject: Medical Conditions
                Subject: Infectious Diseases
                Subject: Respiratory Infections
                Subject: Medicine and Health Sciences
                Subject: Medical Conditions
                Subject: Respiratory Disorders
                Subject: Respiratory Infections
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Respiratory Disorders
                Subject: Respiratory Infections
                Subject: Medicine and Health Sciences
                Subject: Health Care
                Subject: Health Care Facilities
                Subject: Hospitals
                Subject: Biology and Life Sciences
                Subject: Population Biology
                Subject: Population Metrics
                Subject: Death Rates
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.
                Outbreaks COVID-19

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