Long-term consequences of SARS-COV2 infection: Long-Covid patterns and possible public health implications

Ausín-García, Cristina; Cervilla-Muñoz, Eva; Millán-Nuñez-Cortés, Jesús

doi:10.1016/j.medcli.2021.02.022

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Large number of people have been discharged from hospital in need of a close follow-up due to the post-acute and long-term consequences.<a class="elsevierStyleCrossRef" href="#bib0030">1</a> The long term clinical sequelae of SARS-COV2 outbreak are starting to be described. Some of them had been previously reported in the survivors of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).<a class="elsevierStyleCrossRef" href="#bib0035">2</a> In a recent meta-analysis from these previous outbreaks, lung function abnormalities, psychological impairment and reduced exercise capacity were common and could persist beyond 6 months after the infection.<a class="elsevierStyleCrossRef" href="#bib0035">2</a>We aimed to develop a follow-up unit to assess and respond to the needs of those with ongoing symptoms from a whole patient perspective. The term “Long Covid” has emerged to refer to those people who remain unwell four weeks beyond the initial onset of the acute infection.<a class="elsevierStyleCrossRef" href="#bib0040">3</a>During the medium and long-term follow up we have identified three main “Long Covid” patterns. We have evaluated a check list of symptoms including dyspnea, exercise capacity, fatigue, cough, fever, chest pain, increased heart rate with exertion, smell and taste persistent disorders, headache, arthralgia and myalgia as well as psychological and neurocognitive impairment. At the same time, laboratory analysis, radiological studies and lung function tests have been performed.From the patterns we have observed, lung abnormalities in both radiological studies and pulmonary function tests seem to be more frequent in those who had experienced a severe clinical course during the acute phase of the infection, including acute respiratory distress syndrome (ARDS), need for UCI admission, non-invasive or invasive mechanical ventilation, treatment with corticosteroids or immunomodulatory drugs among others. Pulmonary function tests impairments include low-grade restriction in the spirometry test and mild decrease of diffusing capacity of the lungs for carbon monoxide (DLCO). At the same time these patients usually have either pulmonary fibrosis changes or ground glass opacities and areas of organizing pneumonia (OP). If there is evidence of OP clinical improvement could be possible after prolonged treatment with corticosteroids.The two other patterns identified might occur independently from the severity of the acute infection being present even in those who had an outpatient management with mild symptoms.There is a group of patients who remains with a significant dyspnea and heart rate increase on exertion. Sometimes they also complain about oppressive and intermittent chest pain, not associated with elevation in biochemical markers of myocardial damage. The pulmonary function tests and radiological studies do not show abnormalities. This is the subgroup of people who seems to benefit the most from prompt intensive respiratory rehabilitation programs and progressive aerobic physical activity.<a class="elsevierStyleCrossRef" href="#bib0045">4</a> Concomitant comorbidities such as obesity and active smoking need to be approached in order to favor a better and faster clinical improvement.Finally, a wide variety of symptoms might be present alone or together with the previous respiratory patterns. Predominant ongoing symptoms are severe fatigue, low-grade fever, headache, dizziness, arthralgia and myalgia, memory loss and cognitive blunting (“brain fog”). These symptoms persist even in young people with no previous associated underlying comorbidities. It is of notice that nutritional, hormonal, inflammatory and autoimmunity parameters are usually within normal ranges in these cases.As we have observed, “Long-Covid” seems to be a multisystemic syndrome with yet unknown physiopathological mechanisms. It has been suggested a possible miscommunication in the inflammatory response pathways and other immune disorders,<a class="elsevierStyleCrossRef" href="#bib0045">4</a> persistent viremia or viral particles in different tissues due to a poor antibody response, reinfection or relapse.<a class="elsevierStyleCrossRef" href="#bib0040">3</a> At the same time physical deconditioning and mental factors in the setting of posttraumatic stress, pandemic situations and familiar losses may also play a significant role that interferes with the recovery. Post-infectious fatigue has also been described in previous epidemics and in the setting of viral and bacterial infections and in some cases, it might persist many years after the infection onset.<a class="elsevierStyleCrossRef" href="#bib0045">4</a>Given the wide variety of medium and long-term manifestations observed in evolution, periodic assessment and monitoring of multi-organ function is necessary to understand the consequences and mechanisms of this syndrome. It would be also interesting to identify clinical, laboratory parameters, immunological and genetic factors that could be predictors of Long-Covid development.<a class="elsevierStyleCrossRefs" href="#bib0045">4,5</a>Long-Covid might have several implications not only for the affected population itself but also for public health systems. From our point of view, it is important to accomplish a comprehensive approach of these patients avoiding multiple consultations to different departments and aiming to create specific Post-Covid follow-up units." "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "‘Long-COVID’: a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Mandal" 1 => "J. Barnett" 2 => "S.E. Brill" 3 => "J.S. Brown" 4 => "E.K. Denneny" 5 => "S.S. 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Salawu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2340/16501977-2694" "Revista" => array:4 [ "tituloSerie" => "J Rehabil Med" "fecha" => "2020" "paginaInicial" => "52" "itemHostRev" => array:3 [ "pii" => "S2253654X20300251" "estado" => "S300" "issn" => "2253654X" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of post-acute covid-19 in primary care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "T. Greenhalgh" 1 => "M. Knight" 2 => "C. A’Court" 3 => "M. Buxton" 4 => "L. Husain" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmj.m3026" "Revista" => array:4 [ "tituloSerie" => "Br Med J" "fecha" => "2020" "volumen" => "370" "paginaInicial" => "m3026" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Post-viral fatigue and COVID-19: lessons from past epidemics" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.F. Islam" 1 => "J. Cotler" 2 => "L.A. Jason" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/21641846.2020.1778227" "Revista" => array:5 [ "tituloSerie" => "Fatigue" "fecha" => "2020" "volumen" => "8" "paginaInicial" => "61" "paginaFinal" => "69" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, et al. Attributes and predictors of Long-COVID: analysis of COVID cases and their symptoms collected by the Covid Symptoms Study App. [e-Pub Ahead of Print]. <a target="_blank" href="doi:10.1101/2020.10.19.20214494">http://dx.doi.org/10.1101/2020.10.19.20214494</a>." ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00257753/0000015700000007/v1_202109300523/S002577532100213X/v1_202109300523/en/main.assets" "Apartado" => array:4 [ "identificador" => "66430" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas al Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/00257753/0000015700000007/v1_202109300523/S002577532100213X/v1_202109300523/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002577532100213X?idApp=UINPBA00004N"]

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