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      Post-COVID syndrome. A case series and comprehensive review

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      Author(s): a , b , * , a , b , a , b , a , a , a , b , a , Post-COVID study group c , a , a , a
      Publication date (Electronic):
      Journal: Autoimmunity Reviews
      Publisher: Elsevier B.V.
      Keywords: Post-COVID syndrome, Post-COVID, Long COVID, Prolonged COVID, Post-acute COVID-19, COVID-19, CI, Confidence interval, COMPASS 31, Composite autonomic symptom score 31, COVID-19, Coronavirus disease 2019, DLCO, Diffusing capacity for carbon monoxide, ECLIA, Electrochemiluminescence immunoassay, ELISA, Enzyme-linked immunosorbent assay, ICU, Intensive care unit, IQR, Interquartile range, NA, Not applicable/available, PCS, Post-COVID syndrome, POTS, Postural orthostatic tachycardia syndrome, PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses, RBD, Receptor binding domain, S/Co, Signal-to-cut-off, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, TNF, Tumor necrosis factor

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          Abstract

          The existence of a variety of symptoms with a duration beyond the acute phase of COVID-19, is referred to as post-COVID syndrome (PCS). We aimed to report a series of patients with PCS attending a Post-COVID Unit and offer a comprehensive review on the topic. Adult patients with previously confirmed SARS-CoV-2 infection were systematically assessed through a semi-structured and validated survey. Total IgG, IgA and IgM serum antibodies to SARS-CoV-2 were evaluated by an electrochemiluminescence immunoassay. A systematic review of the literature and meta-analysis were conducted, following PRISMA guidelines. Univariate and multivariate methods were used to analyze data. Out of a total of 100 consecutive patients, 53 were women, the median of age was 49 years (IQR: 37.8–55.3), the median of post-COVID time after the first symptoms was 219 days (IQR: 143–258), and 65 patients were hospitalized during acute COVID-19. Musculoskeletal, digestive (i.e., diarrhea) and neurological symptoms including depression (by Zung scale) were the most frequent observed in PCS patients. A previous hospitalization was not associated with PCS manifestation. Arthralgia and diarrhea persisted in more than 40% of PCS patients. The median of anti-SARS-CoV-2 antibodies was 866.2 U/mL (IQR: 238.2–1681). Despite this variability, 98 patients were seropositive. Based on autonomic symptoms (by COMPASS 31) two clusters were obtained with different clinical characteristics. Levels of anti-SARS-CoV-2 antibodies were not different between clusters. A total of 40 articles (11,196 patients) were included in the meta-analysis. Fatigue/muscle weakness, dyspnea, pain and discomfort, anxiety/depression and impaired concentration were presented in more than 20% of patients reported. In conclusion, PCS is mainly characterized by musculoskeletal, pulmonary, digestive and neurological involvement including depression. PCS is independent of severity of acute illness and humoral response. Long-term antibody responses to SARS-CoV-2 infection and a high inter-individual variability were confirmed. Future studies should evaluate the mechanisms by which SARS-CoV-2 may cause PCS and the best therapeutic options.

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)
          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            Incidence of thrombotic complications in critically ill ICU patients with COVID-19

            F.A. Klok, M.J.H.A. Kruip, N.J.M. van der Meer … (2020)
            Introduction COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available. Methods We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital. Results We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications. Conclusion The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.
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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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                Author and article information

                Journal
                Journal ID (nlm-ta): Autoimmun Rev
                Journal ID (iso-abbrev): Autoimmun Rev
                Title: Autoimmunity Reviews
                Publisher: Elsevier B.V.
                ISSN (Print): 1568-9972
                ISSN (Electronic): 1873-0183
                Publication date PMC-release: 10 September 2021
                Publication date (Electronic): 10 September 2021
                Electronic Location Identifier: 102947
                Affiliations
                [a ]Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
                [b ]Clínica del Occidente, Bogotá, Colombia
                [c ]School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
                Author notes
                [* ]Corresponding author at: Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad Del Rosario, Carrera 24 # 63c 69, 110010 Bogotá, Colombia.
                Article
                Publisher Item ID: S1568-9972(21)00222-6 Publisher ID: 102947
                DOI: 10.1016/j.autrev.2021.102947
                PMC ID: 8428988
                PubMed ID: 34509649
                SO-VID: 72ba614e-9600-40f7-bd97-d4190312c735
                Copyright © © 2021 Elsevier B.V. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 17 June 2021
                Date accepted : 26 June 2021
                Categories
                Subject: Review

                ScienceOpen disciplines: Immunology
                Keywords: post-covid syndrome,post-covid,long covid,prolonged covid,post-acute covid-19,covid-19,ci, confidence interval,compass 31, composite autonomic symptom score 31,covid-19, coronavirus disease 2019,dlco, diffusing capacity for carbon monoxide,eclia, electrochemiluminescence immunoassay,elisa, enzyme-linked immunosorbent assay,icu, intensive care unit,iqr, interquartile range,na, not applicable/available,pcs, post-covid syndrome,pots, postural orthostatic tachycardia syndrome,prisma, preferred reporting items for systematic reviews and meta-analyses,rbd, receptor binding domain,s/co, signal-to-cut-off,sars-cov-2, severe acute respiratory syndrome coronavirus 2,tnf, tumor necrosis factor
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: post-covid syndrome, post-covid, long covid, prolonged covid, post-acute covid-19, covid-19, ci, confidence interval, compass 31, composite autonomic symptom score 31, covid-19, coronavirus disease 2019, dlco, diffusing capacity for carbon monoxide, eclia, electrochemiluminescence immunoassay, elisa, enzyme-linked immunosorbent assay, icu, intensive care unit, iqr, interquartile range, na, not applicable/available, pcs, post-covid syndrome, pots, postural orthostatic tachycardia syndrome, prisma, preferred reporting items for systematic reviews and meta-analyses, rbd, receptor binding domain, s/co, signal-to-cut-off, sars-cov-2, severe acute respiratory syndrome coronavirus 2, tnf, tumor necrosis factor

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