More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis

Sandra Lopez-Leon, Talia Wegman-Ostrosky, Carol Perelman, Rosalinda Sepulveda, Paulina A Rebolledo, Angelica Cuapio, Sonia Villapol, Sandra Lopez-Leon, Talia Wegman-Ostrosky, Carol Perelman, Rosalinda Sepulveda, Paulina A Rebolledo, Angelica Cuapio, Sonia Villapol

Abstract

COVID-19, caused by SARS-CoV-2, can involve sequelae and other medical complications that last weeks to months after initial recovery, which has come to be called Long-COVID or COVID long-haulers. This systematic review and meta-analysis aims to identify studies assessing long-term effects of COVID-19 and estimates the prevalence of each symptom, sign, or laboratory parameter of patients at a post-COVID-19 stage. LitCOVID (PubMed and Medline) and Embase were searched by two independent researchers. All articles with original data for detecting long-term COVID-19 published before 1st of January 2021 and with a minimum of 100 patients were included. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. Heterogeneity was assessed using I2 statistics. The Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) reporting guideline was followed. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included. The follow-up time ranged from 15 to 110 days post-viral infection. The age of the study participants ranged between 17 and 87 years. It was estimated that 80% (95% CI 65-92) of the patients that were infected with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). All meta-analyses showed medium (n=2) to high heterogeneity (n=13). In order to have a better understanding, future studies need to stratify by sex, age, previous comorbidities, severity of COVID-19 (ranging from asymptomatic to severe), and duration of each symptom. From the clinical perspective, multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.

Conflict of interest statement

Conflict of interest statement

SLL is an employee of Novartis Pharmaceutical Company; the statements presented in the paper do not necessarily represent the position of the company. The remaining authors have no competing interests to declare.

Figures

Figure 1.. Study selection.
Figure 1.. Study selection.
Preferred items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Out of 15,917 identified studies and after application of the inclusion and exclusion criteria, 15 studies were included in the quantitative synthesis.
Figure 2.. Long-term effects of coronavirus disease…
Figure 2.. Long-term effects of coronavirus disease 2019 (COVID-19).
The meta-analysis of the studies included an estimate for one symptom or more reported that 80% of the patients with COVID-19 have long-term symptoms. Abbreviations: C-reactive protein (CRP), computed tomography (CT), Interleukin-6 (IL-6), N-terminal (NT)-pro hormone BNP (NT-proBNP), Obsessive Compulsive Disorder (OCD), Post-traumatic stress disorder (PTSD).

References

    1. Hannah Ritchie EO-O, Diana Beltekian, Edouard Mathieu, Joe Hasell, Bobbie Macdonald, Charlie Giattino, and Max Roser. Coronavirus Pandemic (COVID-19). 2021.
    1. Tenforde MW, Kim SS, Lindsell CJ, et al. Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network - United States, March-June 2020. MMWR Morb Mortal Wkly Rep 2020; 69(30): 993–8.
    1. Townsend L, Dowds J, O’Brien K, et al. Persistent Poor Health Post-COVID-19 Is Not Associated with Respiratory Complications or Initial Disease Severity. Ann Am Thorac Soc 2021.
    1. Gemelli Against C-P-ACSG. Post-COVID-19 global health strategies: the need for an interdisciplinary approach. Aging Clin Exp Res 2020; 32(8): 1613–20.
    1. Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ 2020; 370: m3026.
    1. Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Res 2021; 49(D1): D1534–D40.
    1. Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015; 350: g7647.
    1. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4: 1.
    1. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T. Meta-analysis of prevalence. J Epidemiol Community Health 2013; 67(11): 974–8.
    1. Xiong Q, Xu M, Li J, et al. Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study. Clin Microbiol Infect 2021; 27(1): 89–95.
    1. Goertz YMJ, Van Herck M, Delbressine JM, et al. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? ERJ Open Res 2020; 6(4).
    1. Carfi A, Bernabei R, Landi F, Gemelli Against C-P-ACSG. Persistent Symptoms in Patients After Acute COVID-19. JAMA 2020; 324(6): 603–5.
    1. Alwan NA. Track COVID-19 sickness, not just positive tests and deaths. Nature 2020; 584(7820): 170.
    1. Townsend L, Dyer AH, Jones K, et al. Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLoS One 2020; 15(11): e0240784.
    1. Neufeld KJ, Leoutsakos JS, Yan H, et al. Fatigue Symptoms During the First Year Following ARDS. Chest 2020; 158(3): 999–1007.
    1. Wostyn P. COVID-19 and chronic fatigue syndrome: Is the worst yet to come? Med Hypotheses 2021; 146: 110469.
    1. Vink M, Vink-Niese A. Could Cognitive Behavioural Therapy Be an Effective Treatment for Long COVID and Post COVID-19 Fatigue Syndrome? Lessons from the Qure Study for Q-Fever Fatigue Syndrome. Healthcare (Basel) 2020; 8(4).
    1. Lamprecht B. [Is there a post-COVID syndrome?]. Pneumologe (Berl) 2020: 1–4.
    1. Pallanti S, Grassi E, Makris N, Gasic GP, Hollander E. Neurocovid-19: A clinical neuroscience-based approach to reduce SARS-CoV-2 related mental health sequelae. J Psychiatr Res 2020; 130: 215–7.
    1. Nath A. Long-Haul COVID. Neurology 2020; 95(13): 559–60.
    1. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Mil Med 2015; 180(7): 721–3.
    1. Proal A, Marshall T. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity. Front Pediatr 2018; 6: 373.
    1. Kingstone T, Taylor AK, O’Donnell CA, Atherton H, Blane DN, Chew-Graham CA. Finding the ‘right’ GP: a qualitative study of the experiences of people with long-COVID. BJGP Open 2020; 4(5).
    1. Maury A, Lyoubi A, Peiffer-Smadja N, de Broucker T, Meppiel E. Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: A narrative review for clinicians. Rev Neurol (Paris) 2020.
    1. Baldini T, Asioli GM, Romoli M, et al. Cerebral venous thrombosis and SARS-CoV-2 infection: a systematic review and meta-analysis. Eur J Neurol 2021.
    1. Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry 2020; 7(7): 611–27.
    1. Bacaro V, Chiabudini M, Buonanno C, et al. Insomnia in the Italian Population During Covid-19 Outbreak: A Snapshot on One Major Risk Factor for Depression and Anxiety. Front Psychiatry 2020; 11: 579107.
    1. Mieczkowska K, Deutsch A, Borok J, et al. Telogen effluvium: a sequela of COVID-19. Int J Dermatol 2021; 60(1): 122–4.
    1. Zhao YM, Shang YM, Song WB, et al. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine 2020; 25: 100463.
    1. Ng CK, Chan JW, Kwan TL, et al. Six month radiological and physiological outcomes in severe acute respiratory syndrome (SARS) survivors. Thorax 2004; 59(10): 889–91.
    1. Wang Q, Zhang Z, Shi Y, Jiang Y. Emerging H7N9 influenza A (novel reassortant avian-origin) pneumonia: radiologic findings. Radiology 2013; 268(3): 882–9.
    1. Huang Y, Tan C, Wu J, et al. Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase. Respir Res 2020; 21(1): 163.
    1. Hui DS, Joynt GM, Wong KT, et al. Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors. Thorax 2005; 60(5): 401–9.
    1. Rouse BT, Sehrawat S. Immunity and immunopathology to viruses: what decides the outcome? Nat Rev Immunol 2010; 10(7): 514–26.
    1. Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020; 368(6490): 473–4.
    1. Ngai JC, Ko FW, Ng SS, To KW, Tong M, Hui DS. The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status. Respirology 2010; 15(3): 543–50.
    1. Suliman YA, Dobrota R, Huscher D, et al. Brief Report: Pulmonary Function Tests: High Rate of False-Negative Results in the Early Detection and Screening of Scleroderma-Related Interstitial Lung Disease. Arthritis Rheumatol 2015; 67(12): 3256–61.
    1. Jason L, Benton M, Torres-Harding S, Muldowney K. The impact of energy modulation on physical functioning and fatigue severity among patients with ME/CFS. Patient Educ Couns 2009; 77(2): 237–41.
    1. White PD, Goldsmith KA, Johnson AL, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377(9768): 823–36.
    1. Andrews PJ, Pendolino AL, Ottaviano G, et al. Olfactory and taste dysfunction among mild-to-moderate symptomatic COVID-19 positive health care workers: An international survey. Laryngoscope Investig Otolaryngol 2020; 5(6): 1019–28.
    1. Carvalho-Schneider C, Laurent E, Lemaignen A, et al. Follow-up of adults with noncritical COVID-19 two months after symptom onset. Clin Microbiol Infect 2020.
    1. Chopra V, Flanders SA, O’Malley M, Malani AN, Prescott HC. Sixty-Day Outcomes Among Patients Hospitalized With COVID-19. Ann Intern Med 2020.
    1. Galvan-Tejada CE, Herrera-Garcia CF, Godina-Gonzalez S, et al. Persistence of COVID-19 Symptoms after Recovery in Mexican Population. Int J Environ Res Public Health 2020; 17(24).
    1. Garrigues E, Janvier P, Kherabi Y, et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect 2020; 81(6): e4–e6.
    1. Horvath L, Lim JWJ, Taylor JW, et al. Smell and taste loss in COVID-19 patients: assessment outcomes in a Victorian population. Acta Otolaryngol 2020: 1–5.
    1. Kamal M, Abo Omirah M, Hussein A, Saeed H. Assessment and characterisation of post-COVID-19 manifestations. Int J Clin Pract 2020: e13746.
    1. Mandal S, Barnett J, Brill SE, et al. ‘Long-COVID’: a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19. Thorax 2020.
    1. Munro KJ, Uus K, Almufarrij I, Chaudhuri N, Yioe V. Persistent self-reported changes in hearing and tinnitus in post-hospitalisation COVID-19 cases. Int J Audiol 2020; 59(12): 889–90.
    1. Sonnweber T, Boehm A, Sahanic S, et al. Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients’ performance: a prospective observational cohort study. Respir Res 2020; 21(1): 276.
    1. Taquet M, Luciano S, Geddes JR, Harrison PJ. Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. Lancet Psychiatry 2020.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren