[en] The long-term consequences of the coronavirus disease 19 (COVID-19) are likely to be frequent but results hitherto are inconclusive. Therefore, we aimed to define the incidence of long-term COVID signs and symptoms as defined by the World Health Organization, using a systematic review and meta-analysis of observational studies. A systematic search in several databases was carried out up to 12 January 2022 for observational studies reporting the cumulative incidence of long COVID signs and symptoms divided according to body systems affected. Data are reported as incidence and 95% confidence intervals (CIs). Several sensitivity and meta-regression analyses were performed. Among 11,162 papers initially screened, 196 were included, consisting of 120,970 participants (mean age: 52.3 years; 48.8% females) who were followed-up for a median of six months. The incidence of any long COVID symptomatology was 56.9% (95% CI 52.2-61.6). General long COVID signs and symptoms were the most frequent (incidence of 31%) and digestive issues the least frequent (7.7%). The presence of any neurological, general and cardiovascular long COVID symptomatology was most frequent in females. Higher mean age was associated with higher incidence of psychiatric, respiratory, general, digestive and skin conditions. The incidence of long COVID symptomatology was different according to continent and follow-up length. Long COVID is a common condition in patients who have been infected with SARS-CoV-2, regardless of the severity of the acute illness, indicating the need for more cohort studies on this topic.
Disciplines :
Public health, health care sciences & services
Author, co-author :
Di Gennaro, Francesco; Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari, Aldo Moro, Bari, Italy
Belati, Alessandra; Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari, Aldo Moro, Bari, Italy
Tulone, Ottavia; Department of Internal Medicine and Geriatrics, University of Palermo Geriatric Unit, Via del Vespro 141, 90127, Palermo, Italy
Diella, Lucia; Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari, Aldo Moro, Bari, Italy
Fiore Bavaro, Davide; Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari, Aldo Moro, Bari, Italy
Bonica, Roberta; Department of Internal Medicine and Geriatrics, University of Palermo Geriatric Unit, Via del Vespro 141, 90127, Palermo, Italy
Genna, Vincenzo; Department of Internal Medicine and Geriatrics, University of Palermo Geriatric Unit, Via del Vespro 141, 90127, Palermo, Italy
Smith, Lee; Centre for Health, Wellbeing, and Performance, Anglia Ruskin University, Cambridge, UK
Trott, Mike; Centre for Public Health, Queen's University Belfast, Belfast, UK
Bruyère, Olivier ; Université de Liège - ULiège > Unité de recherche Santé publique, épidémiologie et économie de la santé (URSAPES)
Mirarchi, Luigi; Department of Internal Medicine and Geriatrics, University of Palermo Geriatric Unit, Via del Vespro 141, 90127, Palermo, Italy
Cusumano, Claudia; Department of Internal Medicine and Geriatrics, University of Palermo Geriatric Unit, Via del Vespro 141, 90127, Palermo, Italy
Dominguez, Ligia Juliana; Department of Internal Medicine and Geriatrics, University of Palermo Geriatric Unit, Via del Vespro 141, 90127, Palermo, Italy ; Faculty of Medicine and Surgery, University Kore of Enna, Enna, Italy
Saracino, Annalisa; Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari, Aldo Moro, Bari, Italy
Veronese, Nicola; Department of Internal Medicine and Geriatrics, University of Palermo Geriatric Unit, Via del Vespro 141, 90127, Palermo, Italy. nicola.veronese@unipa.it
Barbagallo, Mario; Department of Internal Medicine and Geriatrics, University of Palermo Geriatric Unit, Via del Vespro 141, 90127, Palermo, Italy
World Health Organization (2022) Weekly operational update on COVID-19; Issue No. 97. https://www.who.int/publications/m/item/weekly-operational-update-on-covid-19---30-march-2022#.YkwrvaHCh8g.link. Accessed 03/30/2022
Sanchez-Ramirez DC, Normand K, Zhaoyun Y, Torres-Castro R (2021) Long-term impact of COVID-19: a systematic review of the literature and meta-analysis. Biomedicines 9:900 DOI: 10.3390/biomedicines9080900
Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, Villapol S (2021) More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Sci Rep 11:1–12 DOI: 10.1038/s41598-021-95565-8
Baig AM (2020) Chronic COVID syndrome: need for an appropriate medical terminology for long-COVID and COVID long-haulers. J Med Virol. 10.1002/jmv.26624 DOI: 10.1002/jmv.26624
World Health Organization (2021) A clinical case definition of post COVID-19 condition by a Delphi consensus, 6 October 2021. World Health Organization
Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B (2022) Global prevalence of post COVID-19 condition or long COVID: a meta-analysis and systematic review. J Infect Dis. 10.1093/infdis/jiac136 DOI: 10.1093/infdis/jiac136
Stavem K, Ghanima W, Olsen MK, Gilboe HM, Einvik G (2021) Prevalence and determinants of fatigue after COVID-19 in non-hospitalized subjects: a population-based study. Int J Environ Res Public Health 18:2030 DOI: 10.3390/ijerph18042030
Natarajan A, Shetty A, Delanerolle G, Zeng Y, Zhang Y, Raymont V, Rathod S, Halabi S, Elliot K, Phiri P (2022) A systematic review and meta-analysis of long COVID symptoms. medRxiv. 10.1101/2022.03.08.22272091 DOI: 10.1101/2022.03.08.22272091
Han Q, Zheng B, Daines L, Sheikh A (2022) Long-term sequelae of COVID-19: a systematic review and meta-analysis of one-year follow-up studies on post-COVID symptoms. Pathogens 11:269 DOI: 10.3390/pathogens11020269
Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (2019) Cochrane handbook for systematic reviews of interventions. John Wiley & Sons DOI: 10.1002/9781119536604
Sarkis-Onofre R, Catalá-López F, Aromataris E, Lockwood C (2021) How to properly use the PRISMA statement. Syst Rev 10:1–3 DOI: 10.1186/s13643-021-01671-z
Luchini C, Stubbs B, Solmi M, Veronese N (2017) Assessing the quality of studies in meta-analyses: advantages and limitations of the Newcastle Ottawa scale. World J Meta-Anal 5:80–84 DOI: 10.13105/wjma.v5.i4.80
Luchini C, Veronese N, Nottegar A, Shin JI, Gentile G, Granziol U, Soysal P, Alexinschi O, Smith L (2021) Assessing the quality of studies in meta-research: review/guidelines on the most important quality assessment tools. Pharm Stat 20:185–195 DOI: 10.1002/pst.2068
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188 DOI: 10.1016/0197-2456(86)90046-2
Dyussenbayev A (2017) Age periods of human life. Adv Soc Sci Res J. 10.14738/assrj.46.2924 DOI: 10.14738/assrj.46.2924
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558 DOI: 10.1002/sim.1186
Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634 DOI: 10.1136/bmj.315.7109.629
Michelen M, Manoharan L, Elkheir N, Cheng V, Dagens A, Hastie C, O’Hara M, Suett J, Dahmash D, Bugaeva P (2021) Characterising long COVID: a living systematic review. BMJ Glob Health 6:e005427 DOI: 10.1136/bmjgh-2021-005427
Groff D, Sun A, Ssentongo AE, Ba DM, Parsons N, Poudel GR, Lekoubou A, Oh JS, Ericson JE, Ssentongo P (2021) Short-term and long-term rates of postacute sequelae of SARS-CoV-2 infection: a systematic review. JAMA Netw Open 4:e2128568–e2128568 DOI: 10.1001/jamanetworkopen.2021.28568
Veronese N, Bonica R, Cotugno S, Tulone O, Camporeale M, Smith L, Trott M, Bruyere O, Mirarchi L, Rizzo G (2022) Interventions for improving long COVID-19 symptomatology: a systematic review. Viruses 14:1863 DOI: 10.3390/v14091863
Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S (2003) One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 348:683–693 DOI: 10.1056/NEJMoa022450
Ahmed H, Patel K, Greenwood DC, Halpin S, Lewthwaite P, Salawu A, Eyre L, Breen A, O’Connor R, Jones A (2020) Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: a systematic review and meta-analysis. J Rehabil Med. 10.2340/16501977-2694 DOI: 10.2340/16501977-2694
Ngai JC, Ko FW, Ng SS, To KW, Tong M, Hui DS (2010) The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status. Respirology 15:543–550 DOI: 10.1111/j.1440-1843.2010.01720.x
Moldofsky H, Patcai J (2011) Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol 11:1–7 DOI: 10.1186/1471-2377-11-37
Stewart S, Newson L, Briggs TA, Grammatopoulos D, Young L, Gill P (2021) Long COVID risk-a signal to address sex hormones and women’s health. Lancet Regional Health-Eur 11:100242 DOI: 10.1016/j.lanepe.2021.100242
Sudre C, Murray B, Varsavsky T, Graham M, Penfold R, Bowyer R, Pujol JC, Klaser K, Antonelli M, Canas L (2020) Attributes and predictors of long-COVID: analysis of COVID cases and their symptoms collected by the COVID symptoms study app. Nat Med 27(4):626–631 DOI: 10.1038/s41591-021-01292-y
Jovanoski N, Chen X, Becker U, Zalocusky K, Chawla D, Tsai L, Borm M, Neighbors M, Yau V (2021) Severity of COVID-19 and adverse long-term outcomes: a retrospective cohort study based on a US electronic health record database. BMJ Open 11:e056284 DOI: 10.1136/bmjopen-2021-056284
Fernández-Lázaro D, González-Bernal JJ, Sánchez-Serrano N, Navascués LJ, Ascaso-del-Río A, Mielgo-Ayuso J (2020) Physical exercise as a multimodal tool for COVID-19: could it be used as a preventive strategy? Int J Environ Res Public Health 17:8496 DOI: 10.3390/ijerph17228496
Gilbody SM, Song F, Eastwood AJ, Sutton A (2000) The causes, consequences and detection of publication bias in psychiatry. Acta Psychiatr Scand 102:241–249 DOI: 10.1034/j.1600-0447.2000.102004241.x
