World Health Organization. Post COVID-19 condition (Long COVID). https://www.who.int/europe/news-room/fact-sheets/item/post-covid-19-condition (2022).
Greenhalgh, T., Sivan, M., Perlowski, A. & Nikolich, J. Z. Long COVID: a clinical update. Lancet 404, 707–724 (2024).
Fang, Z., Ahrnsbrak, R. & Rekito, A. Evidence mounts that about 7% of US adults have had long COVID. JAMA 332, 5–6 (2024).
Xie, Y., Choi, T. & Al-Aly, Z. Postacute sequelae of SARS-CoV-2 infection in the pre-Delta, Delta, and Omicron eras. N. Engl. J. Med. 391, 515–525 (2024).
Davis, H. E., McCorkell, L., Vogel, J. M. & Topol, E. J. Author Correction: Long COVID: major findings, mechanisms and recommendations. Nat. Rev. Microbiol. 21, 408 (2023).
Bowe, B., Xie, Y. & Al-Aly, Z. Postacute sequelae of COVID-19 at 2 years. Nat. Med. 29, 2347–2357 (2023).
National Academy of Sciences. A long COVID definition. https://nap.nationalacademies.org/catalog/27768/a-long-covid-definition-a-chronic-systemic-disease-state-with (2024).
National Institute of Health and Care Excellence (NICE). COVID-19 rapid guideline: managing the long-term effects of COVID-19. https://www.nice.org.uk/guidance/ng188 (2024).
Sanchez-Ramirez, D. C., Normand, K., Zhaoyun, Y. & Torres-Castro, R. Long-term impact of COVID-19: a systematic review of the literature and meta-analysis. Biomedicines 9, 900 (2021).
Di Fusco, M. et al. Impact of COVID-19 and effects of booster vaccination with BNT162b2 on six-month long COVID symptoms, quality of life, work productivity and activity impairment during Omicron. J. Patient Rep. Outcomes 7, 77 (2023).
Lambert, N. et al. The other COVID-19 survivors: timing, duration, and health impact of post-acute sequelae of SARS-CoV-2 infection. J. Clin. Nurs. 33, 76–88 (2022).
Wolff Sagy, Y., Feldhamer, I., Brammli-Greenberg, S. & Lavie, G. Estimating the economic burden of long-Covid: the additive cost of healthcare utilisation among COVID-19 recoverees in Israel. BMJ Glob. Health 8, e012588 (2023).
Al-Aly, Z. et al. Long COVID science, research and policy. Nat. Med. 30, 2148–2164 (2024).
Byambasuren, O., Stehlik, P., Clark, J., Alcorn, K. & Glasziou, P. Effect of covid-19 vaccination on long covid: systematic review. BMJ Med. 2, e000385 (2023).
Català, M. et al. The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia. Lancet Respir. Med 12, 225–236 (2024).
Malden, D. E. et al. Post-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection. Nat. Commun. 15, 4101 (2024).
De Domenico, M. Prevalence of long COVID decreases for increasing COVID-19 vaccine uptake. PLOS Glob. Public Health 3, e0001917 (2023).
Brannock, M. D. et al. Long COVID risk and pre-COVID vaccination in an EHR-based cohort study from the RECOVER program. Nat. Commun. 14, 2914 (2023).
Ceban, F. et al. COVID-19 vaccination for the prevention and treatment of long COVID: a systematic review and meta-analysis. Brain Behav. Immun. 111, 211–229 (2023).
Gao, P., Liu, J. & Liu, M. Effect of COVID-19 vaccines on reducing the risk of long COVID in the real world: a systematic review and meta-analysis. Int J. Environ. Res. Public Health 19, 12422 (2022).
Trinh, N. T. et al. Effectiveness of COVID-19 vaccines to prevent long COVID: data from Norway. Lancet Respir. Med. 12, e33–e34 (2024).
Lundberg-Morris, L. et al. Covid-19 vaccine effectiveness against post-covid-19 condition among 589722 individuals in Sweden: population based cohort study. BMJ 383, e076990 (2023).
Marra, A. R. et al. The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research. Antimicrob. Steward Health Epidemiol. 3, e168 (2023).
World Health Organization. Classification of Omicron (B.1.1.529): SARS-CoV-2 variant of concern. https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern (2021).
Hattab, D., Amer, M. F. A., Al-Alami, Z. M. & Bakhtiar, A. SARS-CoV-2 journey: from alpha variant to Omicron and its sub-variants. Infection 52, 767–786 (2024).
World Health Organization. COVID-19 epidemiological update—13 August 2024. (2024). https://www.who.int/publications/m/item/covid-19-epidemiological-update-edition-170.
Watanabe, A., Iwagami, M., Yasuhara, J., Takagi, H. & Kuno, T. Protective effect of COVID-19 vaccination against long COVID syndrome: a systematic review and meta-analysis. Vaccine 41, 1783–1790 (2023).
Gutfreund, M. C. et al. The effectiveness of the COVID-19 vaccines in the prevention of post-COVID conditions in children and adolescents: a systematic literature review and meta-analysis. Antimicrobial Steward Health Epidemiol. 4, e54 (2024).
Domenech-Montoliu, S. et al. Long COVID prevalence and the impact of the third SARS-CoV-2 vaccine dose: a cross-sectional analysis from the third follow-ip of the Borriana cohort, Valencia, Spain (2020-2022). Vaccines 11, 1590 (2023).
Mazzitelli, M. et al. Risk of hospitalization and sequelae in patients with COVID-19 treated with 3-day early remdesivir vs. controls in the vaccine and Omicron era: a real-life cohort study. J. Med. Virol. 95, e28660 (2023).
Razzaghi, H. et al. Vaccine effectiveness against long COVID in children. Pediatrics 153, e2023064446 (2024).
Hammel, I. S., Tosi, D. M., Tang, F., Pott, H. & Ruiz, J. G. Frailty as a risk factor for post-acute sequelae of COVID-19 among US veterans during the Delta and Omicron waves. J. Am. Geriatr. Soc. 71, 3826–3835 (2023).
Congdon, S. et al. Nirmatrelvir/ritonavir and risk of long COVID symptoms: a retrospective cohort study. Sci. Rep. 13, 19688 (2023).
Hedberg, P. & Naucler, P. Post-COVID-19 condition after SARS-CoV-2 infections during the Omicron surge vs the delta, alpha, and wild type periods in Stockholm, Sweden. J. Infect. Dis. 229, 133–136 (2024).
Wander, P. L. et al. Rates of ICD-10 Code U09.9 documentation and clinical characteristics of VA patients with post-COVID-19 condition. JAMA Netw. Open 6, e2346783 (2023).
Wu, Q. et al. Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescents. EClinicalMedicine 79, 102962 (2024).
Cortellini, A. et al. SARS-CoV-2 Omicron (B.1.1.529)-related COVID-19 sequelae in vaccinated and unvaccinated patients with cancer: results from the OnCovid registry. Lancet Oncol. 24, 335–346 (2023).
Sun, X. et al. Postacute sequelae SARS-CoV-2 infection by vaccination status: a six-month latent class analysis. medRxiv. (2023).
Ballouz, T. et al. Post COVID-19 condition after Wildtype, Delta, and Omicron SARS-CoV-2 infection and prior vaccination: pooled analysis of two population-based cohorts. PLoS One 18, e0281429 (2023).
Gallant, M., Mercier, K., Rioux-Perreault, C., Lemaire-Paquette, S. & Piché, A. Prevalence of persistent symptoms at least 1 month after SARS-CoV-2 Omicron infection in adults. J. Assoc. Med. Microbiol. Infect. Dis. Can. 8, 57–63 (2023).
Herting, A. et al. Clinical outcomes of SARS-CoV-2 breakthrough infections in liver transplant recipients during the Omicron wave. Viruses 15, 297 (2023).
Kahlert, C. R. et al. Post-acute sequelae after severe acute respiratory syndrome coronavirus 2 infection by viral variant and vaccination status: a multicenter cross-sectional study. Clin. Infect. Dis. 77, 194–202 (2023).
Reme, B. A., Gjesvik, J. & Magnusson, K. Predictors of the post-COVID condition following mild SARS-CoV-2 infection. Nat. Commun. 14, 5839 (2023).
Spiliopoulos, L. et al. Post-acute symptoms 4 months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study. Am. J. Epidemiol. 193, 1106–1114 (2023).
Woldegiorgis, M., Cadby, G., Ngeh, S. & Korda, R. Long COVID in a highly vaccinated population infected during a SARS-CoV-2 Omicron wave—Australia, 2022. medRxiv. (2023).
Diexer, S. et al. Association between virus variants, vaccination, previous infections, and post-COVID-19 risk. Int. J. Infect. Dis. 136, 14–21 (2023).
de Bruijn, S. et al. Lower prevalence of post-Covid-19 condition following Omicron SARS-CoV-2 infection. Heliyon 10, e28941 (2024).
Thaweethai, T. et al. Development of a definition of postacute sequelae of SARS-CoV-2 infection. JAMA 329, 1934–1946 (2023).
Nehme, M. et al. Prevalence of post-coronavirus disease condition 12 weeks after Omicron infection compared with negative controls and association with vaccination status. Clin. Infect. Dis. 76, 1567–1575 (2023).
Brown, M. et al. Ongoing symptoms and functional impairment 12 weeks after testing positive for SARS-CoV-2 or influenza in Australia: an observational cohort study. BMJ Public Health 1, e000060 (2023).
Richard, S. A. et al. Decreased self-reported physical fitness following SARS-CoV-2 infection and the impact of vaccine boosters in a cohort study. Open Forum Infect. Dis. 10, ofad579 (2023).
Antonelli, M. et al. SARS-CoV-2 infection following booster vaccination: illness and symptom profile in a prospective, observational community-based case-control study. J. Infect. 87, 506–515 (2023).
Di Fusco, M. et al. Effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine against long COVID symptoms: a US nationwide study. Vaccines 12, 183 (2024).
Li, J., Nadua, K., Chong, C. Y. & Yung, C. F. Long COVID prevalence, risk factors and impact of vaccination in the paediatric population: a survey study in Singapore. Ann. Acad. Med Singap. 52, 522–532 (2023).
AlBahrani, S. et al. Self-reported long COVID-19 symptoms are rare among vaccinated healthcare workers. J. Infect. Public Health 16, 1276–1280 (2023).
Mikolajczyk, R. et al. Risk of post-COVID condition under hybrid immunity—results from the German National Cohort (NAKO). SSRN 89, 106206 (2023).
Huh, K. et al. Vaccination and the risk of post-acute sequelae after COVID-19 in the Omicron-predominant period. Clin. Microbiol Infect. 30, 666–673 (2024).
Higgins J. P. T., T. J., Chandler J, Li T, Page MJ, Welch V, eds. Cochrane Handbook for Systematic Reviews of Interventions [Internet]. Version 6.4 Cochrane, updated August 2023. [cited 2024 May 28]. Available from: https://training.cochrane.org/handbook/current.
Marra, A. R. et al. The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post-COVID-19 conditions: a systematic literature review and meta-analysis. Antimicrob. Steward Health Epidemiol. 2, e192 (2022).
Man, M. A. et al. Impact of pre-infection COVID-19 vaccination on the incidence and severity of post-COVID syndrome: a systematic review and meta-analysis. Vaccines 12, 189 (2024).
Rudolph, A. E. et al. Factors affecting the impact of COVID-19 vaccination on post COVID-19 conditions among adults: a systematic literature review. medRxiv. 2024.2010.2002.24314603 (2024).
Al-Aly, Z., Bowe, B. & Xie, Y. Long COVID after breakthrough SARS-CoV-2 infection. Nat. Med 28, 1461–1467 (2022).
Tsampasian, V. et al. Risk factors associated with post-COVID-19 condition: a systematic review and meta-analysis. JAMA Intern. Med. 183, 566–580 (2023).
Mikolajczyk, R. et al. Likelihood of post-COVID condition in people with hybrid immunity; data from the German National Cohort (NAKO). J. Infect. 89, 106206 (2024).
Bowe, B., Xie, Y. & Al-Aly, Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nat. Med. 28, 2398–2405 (2022).
Barboza, A. Long COVID in a multicentric Brazilian cohort: acute phase symptom burden and second booster dose vaccination effects. (SSRN, 2023).
Proal, A. D. et al. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nat. Immunol. 24, 1616–1627 (2023).
Altmann, D. M., Whettlock, E. M., Liu, S., Arachchillage, D. J. & Boyton, R. J. The immunology of long COVID. Nat. Rev. Immunol. 23, 618–634 (2023).
Peluso, M. J. & Deeks, S. G. Mechanisms of long COVID and the path toward therapeutics. Cell 187, 5500–5529 (2024).
Chen, H. Transfer of IgG from long COVID patients induces symptomology in mice. bioRxiv. (2024).
Wong, C. What causes long COVID? Case builds for rogue antibodies. Nature 630, 798–799 (2024).
Eberhardt, N. et al. SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels. Nat. Cardiovasc. Res. 2, 899–916 (2023).
Grady, C. B. et al. Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with long COVID. medRxiv. (2024).
Herbert, C. et al. Relationship between acute SARS-CoV-2 viral clearance with long COVID symptoms: a cohort study. medRxiv. (2024).
Antar, A. A. R. et al. Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection. Front. Immunol. 14, 1147549 (2023).
Ozonoff, A. et al. Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study. Nat. Commun. 15, 216 (2024).
Lu, S. et al. Early biological markers of post-acute sequelae of SARS-CoV-2 infection. Nat. Commun. 15, 7466 (2024).
von Hippel, P. T. The heterogeneity statistic I(2) can be biased in small meta-analyses. BMC Med. Res. Methodol. 15, 35 (2015).
Mohammed, I. et al. The efficacy and effectiveness of the COVID-19 vaccines in reducing infection, severity, hospitalization, and mortality: a systematic review. Hum. Vaccin Immunother. 18, 2027160 (2022).
Rijnhart, J. J. M., Rabbers, A. & Rizzuto, S. Also long overdue: consideration of collider bias in guidelines and tools for systematic reviews and meta-analyses of observational studies. Int. J. Epidemiol. 53, dyae147 (2024).
Griffith, G. J. et al. Collider bias undermines our understanding of COVID-19 disease risk and severity. Nat. Commun. 11, 5749 (2020).
Di Fusco, M. et al. Impact of COVID-19 and effects of BNT162b2 on patient-reported outcomes: quality of life, symptoms, and work productivity among US adult outpatients. J. Patient Rep. Outcomes 6, 123 (2022).
Chaichana, U. et al. Definition of post-COVID-19 condition among published research studies. JAMA Netw. Open 6, e235856 (2023).
Woodrow, M. et al. Systematic review of the prevalence of long COVID. Open Forum Infect. Dis. 10, ofad233 (2023).
Wisnivesky, J. P. et al. Long-term persistence of neutralizing antibodies to SARS-CoV-2 following infection. J. Gen. Intern Med 36, 3289–3291 (2021).
UK Health Security Agency. A guide to the COVID-19 autumn vaccination. https://www.gov.uk/government/publications/covid-19-vaccination-autumn-booster-resources/a-guide-to-the-covid-19-autumn-vaccination#:~:text=The%20Coronavirus%20(COVID%2D19),protect%20them%20ahead%20of%20winter. (2024).
Dashtban, A. et al. Vaccinations, cardiovascular drugs, hospitalization, and mortality in COVID-19 and long COVID. Int. J. Infect. Dis. 146, 107155 (2024).
Walter, N. et al. A comprehensive report of German nationwide inpatient data on the post-COVID-19 syndrome including annual direct healthcare costs. Viruses 14, 2600 (2022).
Pike, J., Kompaniyets, L., Lindley, M. C., Saydah, S. & Miller, G. Direct medical costs associated with post-COVID-19 conditions among privately insured children and adults. Prev. Chronic Dis. 20, E06 (2023).
Gandjour, A. Long COVID: costs for the German economy and health care and pension system. BMC Health Serv. Res. 23, 641 (2023).
Page, M. J. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J. Surg. 88, 105906 (2021).
Centers for Disease Control and Prevention. Post-COVID conditions: information for healthcare providers. https://archive.cdc.gov/#/details?q=long%20covid&start=0&rows=10&url=https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-conditions.html (2022).
Wells G. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (2013).
JBI. Critical appraisal tools. https://jbi.global/critical-appraisal-tools (2024).
Guyatt, G. H., Oxman, A. D., Schünemann, H. J., Tugwell, P. & Knottnerus, A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J. Clin. Epidemiol. 64, 380–382 (2011).
Hightower, A. W., Orenstein, W. A. & Martin, S. M. Recommendations for the use of Taylor series confidence intervals for estimates of vaccine efficacy. Bull. World Health Organ. 66, 99–105 (1988).
DerSimonian, R. & Laird, N. Meta-analysis in clinical trials. Control Clin. Trials 7, 177–188 (1986).
Egger, M., Davey Smith, G., Schneider, M. & Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ 315, 629–634 (1997).
