The most effective way to prevent long COVID is to reduce the risk and severity of acute coronavirus disease 2019 (COVID-19) infection through vaccination and infection prevention strategies, including mask wearing, social distancing, and hand hygiene.[4]Centers for Disease Control and Prevention. COVID-19: clinical overview of long COVID. Feb 2025 [internet publication].
https://www.cdc.gov/covid/hcp/clinical-overview
[39]Català M, Mercadé-Besora N, Kolde R, 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. 2024 Jan 11:S2213-2600(23)00414-9.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00414-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/38219763?tool=bestpractice.com
[40]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. 2022 Sep 29;19(19):12422.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9566528
http://www.ncbi.nlm.nih.gov/pubmed/36231717?tool=bestpractice.com
[90]Hedberg P, Granath F, Bruchfeld J, et al. Post COVID-19 condition diagnosis: a population-based cohort study of occurrence, associated factors, and healthcare use by severity of acute infection. J Intern Med. 2023 Feb;293(2):246-58.
https://www.doi.org/10.1111/joim.13584
http://www.ncbi.nlm.nih.gov/pubmed/36478477?tool=bestpractice.com
[92]Al-Aly Z. Prevention of long COVID: progress and challenges. Lancet Infect Dis. 2023 Jul;23(7):776-7.
https://www.doi.org/10.1016/S1473-3099(23)00287-6
http://www.ncbi.nlm.nih.gov/pubmed/37156258?tool=bestpractice.com
See Coronavirus disease 2019 (COVID-19).
Vaccination leads to more infections being asymptomatic, as well as patients having fewer common and persistent symptoms beyond 28 days post-COVID-19 compared with those who were unvaccinated; this is supported by data from several studies.[39]Català M, Mercadé-Besora N, Kolde R, 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. 2024 Jan 11:S2213-2600(23)00414-9.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00414-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/38219763?tool=bestpractice.com
[42]Richard SA, Pollett SD, Fries AC, et al. Persistent COVID-19 symptoms at 6 months after onset and the role of vaccination before or after SARS-CoV-2 infection. JAMA Netw Open. 2023 Jan 3;6(1):e2251360.
https://www.doi.org/10.1001/jamanetworkopen.2022.51360
http://www.ncbi.nlm.nih.gov/pubmed/36652247?tool=bestpractice.com
[49]Antonelli M, Penfold RS, Merino J, et al. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Lancet Infect Dis. 2022 Jan;22(1):43-55.
https://www.doi.org/10.1016/S1473-3099(21)00460-6
http://www.ncbi.nlm.nih.gov/pubmed/34480857?tool=bestpractice.com
[54]Azzolini E, Levi R, Sarti R, et al. Association between BNT162b2 vaccination and long COVID after infections not requiring hospitalization in health care workers. JAMA. 2022 Aug 16;328(7):676-8.
https://www.doi.org/10.1001/jama.2022.11691
http://www.ncbi.nlm.nih.gov/pubmed/35796131?tool=bestpractice.com
[93]Ayoubkhani D, Bermingham C, Pouwels KB, et al. Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study. BMJ. 2022 May 18;377:e069676.
https://www.doi.org/10.1136/bmj-2021-069676
http://www.ncbi.nlm.nih.gov/pubmed/35584816?tool=bestpractice.com
[94]Arnold DT, Milne A, Samms E, et al. Symptoms after COVID-19 vaccination in patients with persistent symptoms after acute infection: a case series. Ann Intern Med. 2021 Sep;174(9):1334-6.
https://www.doi.org/10.7326/M21-1976
http://www.ncbi.nlm.nih.gov/pubmed/34029484?tool=bestpractice.com
[95]Whittaker HR, Gulea C, Koteci A, et al. GP consultation rates for sequelae after acute covid-19 in patients managed in the community or hospital in the UK: population based study. BMJ. 2021 Dec 29;375:e065834.
https://www.doi.org/10.1136/bmj-2021-065834
http://www.ncbi.nlm.nih.gov/pubmed/34965929?tool=bestpractice.com
[96]Wisnivesky JP, Govindarajulu U, Bagiella E, et al. Association of vaccination with the persistence of post-COVID symptoms. J Gen Intern Med. 2022 May;37(7):1748-53.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906626
http://www.ncbi.nlm.nih.gov/pubmed/35266128?tool=bestpractice.com
The decrease in prevalence of long COVID appears to be dose dependent in vaccinated individuals: in an observational cohort study in healthcare workers in Italy, 42% of unvaccinated patients, 30% of patients with one vaccine dose, and 17% of patients with two vaccine doses experienced symptoms of long COVID (odds ratio [OR] 0.25, 95% CI 0.07 to 0.87). Ultimately, of those who had three doses of vaccine, only 16% experienced long COVID (OR 0.16, 95% CI 0.03 to 0.84).[54]Azzolini E, Levi R, Sarti R, et al. Association between BNT162b2 vaccination and long COVID after infections not requiring hospitalization in health care workers. JAMA. 2022 Aug 16;328(7):676-8.
https://www.doi.org/10.1001/jama.2022.11691
http://www.ncbi.nlm.nih.gov/pubmed/35796131?tool=bestpractice.com
Primary prevention includes not only preventing the symptoms of acute COVID-19, but managing the severity of acute COVID-19 in an effort to prevent long COVID. Evidence suggests that antiviral drugs (e.g., nirmatrelvir/ritonavir, molnupiravir) may reduce the risk of long COVID. Studies have found that nirmatrelvir/ritonavir and molnupiravir reduce the risk by 26% and 14%, respectively.[97]Xie Y, Choi T, Al-Aly Z. Association of treatment with nirmatrelvir and the risk of post-COVID-19 condition. JAMA Intern Med. 2023 Jun 1;183(6):554-64.
https://www.doi.org/10.1001/jamainternmed.2023.0743
http://www.ncbi.nlm.nih.gov/pubmed/36951829?tool=bestpractice.com
[98]Xie Y, Choi T, Al-Aly Z. Molnupiravir and risk of post-acute sequelae of covid-19: cohort study. BMJ. 2023 Apr 25;381:e074572.
https://www.doi.org/10.1136/bmj-2022-074572
http://www.ncbi.nlm.nih.gov/pubmed/37161995?tool=bestpractice.com
[99]Suran M. VA finds Nirmatrelvir associated with lower risk of long COVID. JAMA. 2022 Dec 27;328(24):2386.
https://www.doi.org/10.1001/jama.2022.20051
http://www.ncbi.nlm.nih.gov/pubmed/36573990?tool=bestpractice.com
Remdesivir was shown to reduce the risk of long COVID by 35.9% in one observational study of hospitalized individuals.[100]Boglione L, Meli G, Poletti F, et al. Risk factors and incidence of long-COVID syndrome in hospitalized patients: does remdesivir have a protective effect? QJM. 2022 Jan 9;114(12):865-71.
https://www.doi.org/10.1093/qjmed/hcab297
http://www.ncbi.nlm.nih.gov/pubmed/34850210?tool=bestpractice.com
However, a randomized controlled trial comparing treatment with remdesivir to standard care in 208 patients found no long-term benefit for remdesivir in patients hospitalized due to COVID-19.[101]Nevalainen OPO, Horstia S, Laakkonen S, et al. Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial. Nat Commun. 2022 Oct 18;13(1):6152.
https://www.doi.org/10.1038/s41467-022-33825-5
http://www.ncbi.nlm.nih.gov/pubmed/36257950?tool=bestpractice.com
Another observational study found no benefit of nirmatrelvir/ritonavir for the prevention of long COVID.[102]Durstenfeld MS, Peluso MJ, Lin F, et al. Association of nirmatrelvir for acute SARS-CoV-2 infection with subsequent Long COVID symptoms in an observational cohort study. J Med Virol. 2024 Jan;96(1):e29333.
https://onlinelibrary.wiley.com/doi/10.1002/jmv.29333
http://www.ncbi.nlm.nih.gov/pubmed/38175151?tool=bestpractice.com