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      Síndrome post-COVID: Un documento de reflexión y opinion Translated title: Post-COVID syndrome: A reflection and opinion paper

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      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18
      Revista Española de Quimioterapia
      Sociedad Española de Quimioterapia
      COVID, síndrome post-COVID, COVID prolongado, neurología, cardiología, psiquiatría, pediatría, reumatología, síndrome post UCI, COVID, post-COVID syndrome, prolonged COVID, long-term-COVID, neurology, cardiology, psychiatry, pediatrics, rheumatology, Post ICU syndrome (PICUS)

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          RESUMEN

          Un elevado porcentaje de las personas que han padecido COVID refieren, tras la recuperación de la fase aguda de la enfermedad, una serie de manifestaciones clínicas tanto subjetivas como objetivas que se prolongan más allá de 3 semanas e incluso de 3 meses del cuadro clínico original. No existe todavía una nomenclatura consensuada para referirse a este cuadro, pero quizá la más usada es la de síndrome post-COVID. El Comité Científico sobre COVID del Colegio de Médicos de Madrid ha discutido este problema con una aproximación multidisciplinar en la que han participado, internistas, infectólogos, psiquiatras, neumólogos, cirujanos, geriatras, pediatras, microbiólogos, médicos de familia y otros especialistas, tratando de acopiar la información existente y discutiéndola en el grupo.

          Las manifestaciones clínicas son muy variables y oscilan entre cuadros de simple cansancio y persistencia de lesiones pulmonares fibrosantes con alteraciones objetivas de la función pulmonar. El síndrome post-COVID parece particularmente frecuente y grave en aquellos adultos que han precisado ingreso en Unidades de Cuidados Intensivos y tiene un comportamiento peculiar en un grupo muy reducido de niños.

          El síndrome post-COVID, de existencia indudable, no es, a primera vista, claramente diferenciable del que se produce tras otras enfermedades víricas agudas y tras estancias prolongadas en UCI por enfermedades de otra naturaleza. Por tanto, ofrece oportunidades excelentes de investigación para clarificar su patogenia y posiblemente la de otras entidades afines.

          Es posible que progresivamente se produzca una demanda asistencial incrementada entre los millones de personas que han sufrido y superado el COVID agudo para la cuál las autoridades sanitarias debieran diseñar mecanismos de gestión ágil de una asistencia que posiblemente requerirá de grupos multidisciplinares bien coordinados.

          Este documento, estructurado en preguntas sobre distintos aspectos del síndrome post-COVID, intenta poner en escena el estado actual de este problema.

          ABSTRACT

          A high proportion of people who have suffered from COVID-19 report, after recovery from the acute phase of the disease, clinical manifestations, both subjective and objective, that continue beyond 3 weeks or even 3 months after the original clinical disease. There is still no agreed nomenclature to refer to this condition, but perhaps the most commonly used is post-COVID syndrome. The Scientific Committee on COVID of the Madrid College of Physicians (ICOMEM) has discussed this problem with a multidisciplinary approach in which internists, infectious disease specialists, psychiatrists, pneumologists, surgeons, geriatricians, pediatricians, microbiologists, family physicians and other specialists have participated, trying to gather the existing information and discussing it in the group.

          The clinical manifestations are very variable and range from simple fatigue to persistent fibrosing lung lesions with objective alterations of pulmonary function. Post-COVID syndrome seems to be particularly frequent and severe in adults who have required admission to Intensive Care Units and has a peculiar behavior in a very small group of children.

          The post-COVID syndrome, which undoubtedly exists, is at first sight not clearly distinguishable from clinical manifestations that which occur after other acute viral diseases and after prolonged stays in ICUs due to other diseases. Therefore, it offers excellent research opportunities to clarify its pathogenesis and possibly that of other related entities.

          It is possible that progressively there will be an increased demand for care among the millions of people who have suffered and overcome acute COVID for which the health authorities should design mechanisms for the agile management of care that will possibly require well-coordinated multidiscipli-nary groups.

          This paper, structured in questions on different aspects of the post-COVID syndrome, attempts to stage the current state of this problem.

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          Most cited references92

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          COVID-19: consider cytokine storm syndromes and immunosuppression

          As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%, 1 compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. 2 Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections 3 and occurs in 3·7–4·3% of sepsis cases. 4 Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients. 5 A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α. 6 Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin (mean 1297·6 ng/ml in non-survivors vs 614·0 ng/ml in survivors; p 39·4°C 49 Organomegaly None 0 Hepatomegaly or splenomegaly 23 Hepatomegaly and splenomegaly 38 Number of cytopenias * One lineage 0 Two lineages 24 Three lineages 34 Triglycerides (mmol/L) 4·0 mmol/L 64 Fibrinogen (g/L) >2·5 g/L 0 ≤2·5 g/L 30 Ferritin ng/ml 6000 ng/ml 50 Serum aspartate aminotransferase <30 IU/L 0 ≥30 IU/L 19 Haemophagocytosis on bone marrow aspirate No 0 Yes 35 Known immunosuppression † No 0 Yes 18 The Hscore 11 generates a probability for the presence of secondary HLH. HScores greater than 169 are 93% sensitive and 86% specific for HLH. Note that bone marrow haemophagocytosis is not mandatory for a diagnosis of HLH. HScores can be calculated using an online HScore calculator. 11 HLH=haemophagocytic lymphohistiocytosis. * Defined as either haemoglobin concentration of 9·2 g/dL or less (≤5·71 mmol/L), a white blood cell count of 5000 white blood cells per mm3 or less, or platelet count of 110 000 platelets per mm3 or less, or all of these criteria combined. † HIV positive or receiving longterm immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine).
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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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              Persistent Symptoms in Patients After Acute COVID-19

              This case series describes COVID-19 symptoms persisting a mean of 60 days after onset among Italian patients previously discharged from COVID-19 hospitalization.
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                Author and article information

                Journal
                Rev Esp Quimioter
                Rev Esp Quimioter
                Sociedad Española de Quimioterapia
                Revista Española de Quimioterapia
                Sociedad Española de Quimioterapia
                0214-3429
                1988-9518
                20 April 2021
                2021
                : 34
                : 4
                : 269-279
                Affiliations
                [1 ]Emérito asistencial, Comunidad de Madrid. Servicio de Microbiología Clínica y E. Infecciosas del Hospital General Universitario Gregorio Marañón, Universidad Complutense. CIBERES. Ciber de Enfermedades Respiratorias. Madrid
                [2 ]Servicio de Microbiología. Hospital Ramón y Cajal e Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Red Española de Investigación en Patología Infecciosa (REIPI). Madrid.
                [3 ]Emérita. Servicio de Neumología. Hospital General Universitario Gregorio Marañón, Universidad Complutense. Madrid
                [4 ]Servicio de Cirugía General. Hospital Clínico Universitario de San Carlos. Universidad Complutense. Madrid.
                [5 ]Servicio de Cardiología. Hospital Príncipe de Asturias. Universidad de Alcalá de Henares. Madrid.
                [6 ]Servicio de Geriatría. Hospital Central de la Cruz-Roja. Universidad Alfonso X el Sabio. Madrid.
                [7 ]Servicio de Urgencias. Hospital Clínico Universitario de San Carlos. Universidad Complutense. Madrid.
                [8 ]Servicio de Pediatría y ACES. Hospital General Universitario Gregorio Marañón, Universidad Complutense. Madrid
                [9 ]Servicio de Medicina Intensiva. Hospital Universitario de Torrejón. Universidad Francisco de Vitoria. Madrid.
                [10 ]Servicio de Geriatría. Hospital Clínico Universitario de San Carlos. Universidad Complutense. Madrid.
                [11 ]Servicio de Cardiología. Hospital General Universitario Gregorio Marañón, Universidad Europea. Madrid
                [12 ]Medicina de Familia. Enfermedades Infecciosas. Madrid.
                [13 ]Servicio de E. Infecciosas. Hospital Ramón y Cajal. Universidad de Alcalá de Henares. Madrid.
                [14 ]Departamento de Salud Pública. Universidad Autónoma. Madrid.
                [15 ]Servicio de Medicina Interna. Hospital Ruber Internacional. Madrid
                [16 ]Psiquiatra. Unidad Post-Covid 19. H Central de la Cruz Roja. Madrid
                [17 ]Servicio de neurología. Hospital Clínico de San Carlos. Madrid.
                [18 ]Sección de E. Infecciosas Pediátricas. Servicio de Pediatría y ACES. Hospital General Universitario Gregorio Marañón.
                Author notes
                Correspondencia: Emilio Bouza Servicio de Microbiología Clínica y Enfermedades Infecciosas del Hospital General Universitario Gregorio Marañón, Universidad Complutense. CIBERES. Ciber de Enfermedades Respiratorias. Madrid E-mail: emilio.bouza@ 123456gmail.com
                [*]

                Comité Científico sobre COVID-19 del Ilustre Colegio Oficial de Médicos de Madrid (ICOMEM)

                [**]

                Colaboradores puntuales en el presente documento

                Article
                revespquimioter-34-269
                10.37201/req/023.2021
                8329562
                33878844
                517a6e43-2819-4730-bb2b-9f661b6e9450
                © The Author 2021

                Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)( https://creativecommons.org/licenses/by-nc/4.0/).

                History
                : 01 March 2021
                : 18 March 2021
                Categories
                Revisión

                covid,síndrome post-covid,covid prolongado,neurología,cardiología,psiquiatría,pediatría,reumatología,síndrome post uci,post-covid syndrome,prolonged covid,long-term-covid,neurology,cardiology,psychiatry,pediatrics,rheumatology,post icu syndrome (picus)

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