key: cord-0697399-h4ary01j authors: d'Ettorre, Gabriele; Gentilini Cacciola, Elio; Santinelli, Letizia; De Girolamo, Gabriella; Spagnolello, Ornella; Russo, Alessandro; Tarsitani, Lorenzo; Ciccozzi, Massimo; Mastroianni, Claudio M.; d'Ettorre, Gabriella; Ceccarelli, Giancarlo title: Covid‐19 sequelae in working age patients: A systematic review date: 2021-10-22 journal: J Med Virol DOI: 10.1002/jmv.27399 sha: d938620dbf5b08a6421664432b288ec61dcd6b4c doc_id: 697399 cord_uid: h4ary01j Despite the SARS‐CoV‐2 pandemic not yet being under control, post‐Covid‐19 syndrome is already a challenging topic: long‐term multiorgan sequelae, although increasingly described, have not yet been systematized. As post‐Covid‐19 syndrome can significantly impact both the working capacity and the relationship life of surviving patients, we performed a systematic review of the evidence published over the last year and currently available in medical literature search databases (MEDLINE/Pubmed) and searching clinical trial registries, to evaluate the available evidence among workers. From 31 publications that initially matched inclusion criteria, 13 studies have been considered suitable for relevance and age of subjects. A wide range of patients (16%–87%) have post‐Covid syndrome; pneumological and neuropsychological symptoms were the most common disorders reported. The most frequent organic sequel found in post‐Covid patients was pulmonary fibrosis. The number of symptoms during acute SARS‐CoV‐2 infection, severity of the disease, and high serum levels of d‐dimer were related to high risk of post‐Covid syndrome. In conclusion, post‐Covid‐19 syndrome can significantly impact the health conditions of surviving patients. Rehabilitation and follow‐up in multidisciplinary rehabilitation programs should be considered for working‐age patients. highlights that many people with post-Covid syndrome can also experience generalized pain, fatigue, persisting high temperature, and psychiatric problems. In addition to the aforementioned post-Covid syndrome, evidence is growing on the sequelae of Covid extending beyond 3 weeks from the onset of first symptoms, which are defined as post-acute Covid. 5 Given that the post-Covid syndrome and postacute Covid include persistent symptoms that could be related to residual inflammation (convalescent phase), organ damage, nonspecific effects from the hospitalization or prolonged ventilation (postintensive care syndrome), social isolation, or impact on preexisting health conditions, to date, we can not accurately predict who will become a long hauler patient. 6, 7 As a recent article in Science notes, people only mildly affected by Covid still can have lingering symptoms, and people who were severely ill can be back to normal two months later. 8 [10] [11] [12] These patients presented multiple neurological complications such as neuropathy, myopathy, and generalized deconditioning, often associated with prolonged intensive care hospitalization; psychological and mood-related effects following severe illness are also reported. 13, 14 Given the current concern with the Covid pandemic, a summary of the evidence is required to allow policymakers to enact guidance for preventing and managing sequelae of the infection. In urgent circumstances such as the ongoing pandemic, rapid reviews are recommended by the WHO. 15 We conducted a review of the literature on post-Covid syndrome and postacute Covid in patients aged 15-67 years and, therefore, considered in working age. The aim of the present systematic review was to assess both occurrence and risk factors for sequelae of Covid in patients who have returned to microbiological normalization after the infection by SARS-CoV-2. We conducted a systematic review of literature from February 2020 to January 31, 2021, regarding post-Covid symptoms and/ or signs in working-age patients (aged 15-67 years) who recovered from the infection. The methods and selection criteria adopted were based on consultation of different sources. Initially, MEDLINE/Pubmed databases were used; afterward, the reference sections of the selected publications were scanned for additional relevant studies satisfying the adopted criteria. The keywords used to identify articles for this review were: "post-Covid-19 syndrome," "postacute Covid-19," "long hauler Covid-19," "Covid-19," "SarsCoV-2," "occurrence," and "prevalence." The keywords were systematically combined to review the literature search. For example, "post-Covid-19 syndrome" and "occurrence" and "long hauler Covid-19" were one of the adopted combinations. We aimed to identify original articles (i.e., nonreviews) using the abovementioned keywords with the following exclusion criteria: 1 not written in English; 2 studies focused on postinfection diseases not related to the COVID-19 pandemic; and 3 qualitative studies. The screening of articles was carried out in two phases. In the first phase, articles were screened based on title and abstract. The abstracts of all the selected titles were sorted for more detailed information. Two independent reviewers (G. d'E. and P. V.) read the abstracts and categorized them as relevant, not relevant, or possibly relevant. In the second phase, the full-text articles were assessed for eligibility. Two reviewers (G. d'E. and P. V.) independently applied inclusion and exclusion criteria to potentially eligible papers, and both reviewers then independently extracted data from the original articles. Any disagreements were independently checked by a third reviewer (G. C.), and a consensus was reached. Every full-text article that met the inclusion criteria was reviewed and categorized based on its subject matter; this systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Our research of the two literature databases resulted in a total of 31 publications that matched our inclusion criteria. Eighteen of these were removed because they were deemed irrelevant (i.e., not concerning working-age patients). Therefore, 13 papers remained in the study ( Figure 1 ). Post-Covid symptoms and/or signs were reported by a wide range of patients (between 16.36% and 87%); the most fre- Thus, for patients who have marked raised D-dimer, pulmonary rehabilitation is needed subsequently even in the absence of severe respiratory symptoms. The main common nonspecific neurological symptoms include headaches (up to 38%), muscle weakness, dizziness, and cognitive blunting ("brain fog"), which frequently co-occur with fatigue and breathlessness, particularly in hospitalized patients. Interestingly, the study by Huang et al. 16 This review of the literature has some methodological limitations that should be highlighted, in particular: (1) currently systematic studies on the topic are still lacking and this can limit the quality of the observations, (2) psychiatric studies have been carried out in specific geographic areas and need to be confirmed by parallel studies obtained in other countries, in fact, the extensibility of the results obtained to other cultural contexts may not be directly accepted and may be influenced by peculiar social and cultural aspects of the area where the study was carried out. Despite these limitations, the findings of our review highlight a significant risk for sequelae of Covid in the working-age population. In particular, respiratory and neurological signs and/or symptoms were the most frequent concerns persisting after recovery from SARS-Cov-2 infection, also in mild versions of the disease. Healthcare organizations and policy makers should focus attention on rehabilitation programs targeted at the improvement of health status of discharged patients through a structured multidisciplinary Planning for the post-COVID syndrome: how payers can mitigate long-term complications of the pandemic COVID-19 "Long-Hauler As their numbers grow, COVID-19 "long haulers" stump experts SIGN and RCGP set out further details about the UK guideline on management of the long-term effects of COVID-19 Management of postacute covid-19 in primary care Post-acute COVID-19 Syndrome. Incidence and risk factors: a Mediterranean cohort study The "post-COVID" syndrome: How deep is the damage The long haul Gemelli Against COVID-19 Post-Acute Care Study Group. 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