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      Two-Year Health Outcomes in Hospitalized COVID-19 Survivors in China

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          Key Points

          Question

          What are the 2-year health outcomes among patients hospitalized for COVID-19 in China?

          Findings

          In this longitudinal cohort study that included 1864 patients, the most common symptoms at 2 years after SARS-CoV-2 infection were fatigue, chest tightness, anxiety, dyspnea, and myalgia, and most symptoms resolved from 1-year to 2-year follow-up, although the incidence of dyspnea showed no significant change. Patients with severe disease during hospitalization, especially those who required intensive care unit admission, had higher risks of persistent symptoms and higher chronic obstructive pulmonary disease assessment test scores.

          Meaning

          These findings suggest that prolonged symptoms may persist in a proportion of COVID-19 survivors for 2 years after SARS-CoV-2 infection.

          Abstract

          This cohort study assesses the health outcomes among hospitalized COVID-19 survivors over 2 years to identify factors associated with increased risk of persistent symptoms.

          Abstract

          Importance

          Relatively little is known about the persistence of symptoms in patients with COVID-19 for more than 1 year after their acute illness.

          Objective

          To assess the health outcomes among hospitalized COVID-19 survivors over 2 years and to identify factors associated with increased risk of persistent symptoms.

          Design, Setting, and Participants

          This was a longitudinal cohort study of patients who survived COVID-19 at 2 COVID-19–designated hospitals in Wuhan, China, from February 12 to April 10, 2020. All patients were interviewed via telephone at 1 year and 2 years after discharge. The 2-year follow-up study was conducted from March 1 to April 6, 2022. Statistical analysis was conducted from April 20 to May 5, 2022. The severity of disease was defined by World Health Organization guideline for COVID-19.

          Exposures

          COVID-19.

          Main Outcomes and Measures

          The main outcome was symptom changes over 2 years after hospital discharge. All patients completed a symptom questionnaire for evaluation of symptoms, along with a chronic obstructive pulmonary disease assessment test (CAT) at 1-year and 2-year follow-up visits.

          Results

          Of 3988 COVID-19 survivors, a total of 1864 patients (median [IQR] age, 58.5 [49.0-68.0] years; 926 male patients [49.7%]) were available for both 1-year and 2-year follow-up visits. The median (IQR) time from discharge to follow-up at 2 years was 730 (719-743) days. At 2 years after hospital discharge, 370 patients (19.8%) still had symptoms, including 224 (12.0%) with persisting symptoms and 146 (7.8%) with new-onset or worsening of symptoms. The most common symptoms were fatigue, chest tightness, anxiety, dyspnea, and myalgia. Most symptoms resolved over time, but the incidence of dyspnea showed no significant change (1-year vs 2-year, 2.6% [49 patients] vs 2.0% [37 patients]). A total of 116 patients (6.2%) had CAT total scores of at least 10 at 2 years after discharge. Patients who had been admitted to the intensive care unit had higher risks of persistent symptoms (odds ratio, 2.69; 95% CI, 1.02-7.06; P = .04) and CAT scores of 10 or higher (odds ratio, 2.83; 95% CI, 1.21-6.66; P = .02).

          Conclusions and Relevance

          In this cohort study, 2 years after hospital discharge, COVID-19 survivors had a progressive decrease in their symptom burden, but those with severe disease during hospitalization, especially those who required intensive care unit admission, had higher risks of persistent symptoms. These results are related to the original strain of the virus, and their relevance to infections with the Omicron variant is not known.

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          Most cited references34

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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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            Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies

            The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening 1,2 to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A–F)—a grouping that is highly concordant with knowledge-based structural classifications 3–5 . Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A–D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309) 6 and group F (for example, CR3022) 7 , which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants.
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              A clinical case definition of post-COVID-19 condition by a Delphi consensus

              People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                15 September 2022
                September 2022
                15 September 2022
                : 5
                : 9
                : e2231790
                Affiliations
                [1 ]Department of Respiratory Medicine, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China
                [2 ]Department of Rehabilitation, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
                [3 ]Department of Outpatient, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China
                [4 ]Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China
                [5 ]Wuhan Huoshenshan Hospital, Wuhan, China
                [6 ]Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China
                [7 ]Department of Medical and Research Management, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China
                [8 ]Wuhan Taikang Tongji Hospital, Wuhan, China
                [9 ]Department of Trauma Medical Center, Daping Hospital, State Key laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, China
                [10 ]Institute of Infection and Immunology, University of London, London, United Kingdom
                [11 ]GlaxoSmithKline, Brentford, United Kingdom
                [12 ]Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China
                Author notes
                Article Information
                Accepted for Publication: July 27, 2022.
                Published: September 15, 2022. doi:10.1001/jamanetworkopen.2022.31790
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Yang X et al. JAMA Network Open.
                Corresponding Authors: Li Li, MD, Department of Respiratory Medicine, Daping Hospital, Third Military Medical University Army Medical University, Chongqing 400042, China ( dpyyhxlili@ 123456tmmu.edu.cn ); Bin Cao, MD, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, China ( caobin_ben@ 123456163.com ).
                Author Contributions: Dr Li had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Ms Yang, Mr Hou, Ms Shen, Mr M. Zhang, Ms K. Zhang, and Ms F. Wang contributed equally to this work.
                Concept and design: Ma, He, G. Cao, Jiang, B. Cao, Li.
                Acquisition, analysis, or interpretation of data: Yang, Hou, Shen, M. Zhang, K. Zhang, F. Wang, Liu, Ma, Cheng, Kang, Hu, M. Wang, Zeng, Y. Wang, Jones, Li.
                Drafting of the manuscript: Yang, Hou, Shen, M. Zhang, G. Cao, Jiang, Li.
                Critical revision of the manuscript for important intellectual content: Yang, K. Zhang, F. Wang, Liu, Ma, Cheng, Kang, Hu, M. Wang, Zeng, Y. Wang, He, G. Cao, Jiang, Jones, B. Cao, Li.
                Statistical analysis: Shen, Ma, Zeng.
                Obtained funding: Ma, Cheng, Li.
                Administrative, technical, or material support: Liu, Y. Wang, He, B. Cao.
                Supervision: G. Cao, Li.
                Conflict of Interest Disclosures: None reported.
                Funding/Support: This work was supported by the National Natural Science Foundation of China (81672287), the Joint Scientific Research Project of the Chongqing Health Commission and the Science and Technology Commission (2020FYYX213), the Outstanding Youth Science Fund of Chongqing (cstc2020jcyjjqX0014), Chongqing Talent Fund (CQYC202005003), Chongqing Special Project for Academicians (cstc2020yszx-jcyjX0004), and the Science Foundation for Outstanding Young People of the Army Medical University.
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Article
                zoi220899
                10.1001/jamanetworkopen.2022.31790
                9478774
                36107425
                09d0dc51-a6ba-48d1-89d7-5686d3618139
                Copyright 2022 Yang X et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 8 June 2022
                : 27 July 2022
                Categories
                Research
                Original Investigation
                Online Only
                Global Health

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