Submitted:
03 June 2025
Posted:
04 June 2025
You are already at the latest version
Abstract
Keywords:
1. Introduction
2. Materials and Methods
2.1. Protocol and Registration
2.2. Eligibility Criteria
2.3. Information Sources
2.4. Search
2.5. Selection of Sources of Evidence
2.6. Data Charting Process
2.7. Data Items
2.8. Critical Appraisal of Individual Sources of Evidence
2.9. Synthesis of Results
3. Results
3.1. Selection of Evidence Sources
3.2. Characteristics and Results of the Sources of Evidence
3.3 Population study
3.4. Definitions of Long COVID
- SARS-CoV-2 infection: All eight articles, as a requirement, include a history of acute COVID-19 infection; 37.5% (3) of the studies describe the need for a positive laboratory test for SARS-CoV-2, and 12.5% (1) include suspicion and confirmation of acute infection.
- Symptoms: The persistence of symptoms from the acute stage was considered by 100% (8) of the studies; remitting and recurrent symptoms and symptom progression were not included in any definition. 62.5% (5) described developing new symptoms after the acute stage of infection.
- Time of presentation: 100% (8) of the studies describe a specific time of permanence of symptomatology following acute infection. 50% (4) consider 12 weeks or more, 12.5% (1) describe 8 weeks or more, and 37.5% (3) use 4 weeks or more as a defining criterion.
3.5. Vaccination Status
3.6. Reducing the Incidence of Long COVID
3.7. The severity of Symptoms Related to Long COVID
3.8. Duration of Long COVID Symptoms
4. Discussion
4.1. What is Already Known About This Topic
4.2. Main Findings
4.3. Implications for Public Health in the Americas. A call to action
4.4. Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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| Author, year | Country | Design | Number of participants | |
|---|---|---|---|---|
| Sex n, (%) | Age, years | |||
| Angarita-Fonseca, 20236 | Latin-America | Cross-sectional study | Men: 840 (34.1); Women:1,626 (65.9) |
Mean (SD): 39.5 (53.3) |
| Berry, 202323 | Bonaire | Retrospective cohort study | Men: 10 (21.2); Women:37 (78.8) |
Median (range): 47 (14 - 89) |
| Marra, 202321 | Brazil | Case-control study | Men: 1,950 (27.6); Women: 5,101 (72.4) |
Mean (SD): General: 37.5 (NR) Cases: 38.1 (8.7); Controls: 37.2 (9.0) |
| Neves, 202322 | Brazil | Prospective cohort study | Men: 338 (56.1); Women: 264 (43.9) |
Mean (SD): 51 (12) |
| Nuñez, 20237 | Mexico | Prospective cohort study | Men: 126 (65.6); Women: 66 (34.4) |
Median (range): 53 (45 - 64) |
| Batista, 202425 | Brazil | Cross-sectional study | Men: 59 (11.9); Women: 437 (88.1) |
NR |
| Del Carpio-Orantes, 202424 | Mexico | Cross-sectional study | Men: 65 (32,0); Women: 138 (68,0%) |
Mean (SD): 41.8 (11.3) |
| Fuller, 202426 | Brazil | Prospective cohort study | Men: 88 (31.8); Women: 188 (68.2) |
Median (range): 45 (18 - 88) |
| Author, year | “Fully vaccinated” status | Vaccine type | Long-COVID definition | Efficacy measures | Conclusions | Limitations |
|---|---|---|---|---|---|---|
| Angarita-Fonseca, 20236 | Two doses | NR | Individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. | Outcome: Risk of development of LCC. Multivariable logistic regression.
|
Fully vaccinated patients were less likely to have LCC compared with unvaccinated or partially vaccinated subjects. | The design of the study allows the occurrence of the different bias. Data collection (electronic survey) and the non-probabilistic sampling, decrease the methodological quality of the study, the effect size, and the potential generalization of results. |
| Berry, 202323 | At least one dose of the Pfizer vaccine at least 8 weeks after SARS-CoV-2 infection | mRNA: 36, Unvaccinated: 11 |
Individuals with a laboratory-confirmed SARS-CoV-2 positive test result, for whom at least one symptom self-attributed to the experienced SARS-CoV-2 infection lasted longer than four weeks. | Outcome: Self-reported change in symptom severity. Multiple covariate adjusted linear regression model. Regression coefficients and 95% CI:
|
Vaccination wassignificantly associated with reduced severity of heart palpitations. | Small sample size; residual confounding may exist due to unmeasured confounding variables; the collection of data outcome data at one point in time, at different intervals since infection (and vaccination, for those applicable limited the comparison of severity scores of Long-COVID symptoms at multiple moments after initial infection at an individual level; Authors reported a linear regression using cathegorical variables to report the effect measures. |
| Marra, 202321 | Analysis were performed whether 1,2,3, or 4 doses were administered. | Inactivated virus= 3,259; Viral vector= 3,255; mRNA=148 |
Signs and symptoms that developed during or following a SARS-CoV-2 RT-PCR confirmed infection, continued for >4 weeks, and could not explained by an alternative diagnosis. | Outcome: Risk of development of long COVID. Logistic Regression multivariable analysis.
|
Four doses of COVID-19 vaccines is associated with a lower probability of develop Long-COVID. | As the study was performed only in Healthcare personnel with positive COVID-19 laboratory results, some infected individuals with no laboratory confirmed results may be lost. Also, information bias could be present. |
| Neves, 202322 | Two doses | Homologous inactivated whole-virion vaccine: 189 (36%); Homologous mRNA vaccine: 24 (5%); Homologous viral-vector vaccine:96 (19%); Heterologous inactivated + mRNA: 86 (17%); Heterologous inactivated + viral vector: 44 (9%); Heterologous mRNA + viral vector: 68 (13%); Other heterologous regimens: 5 (1%) |
Physical complaints newly developed during or after the acute phase, persisting for >12 weeks, and not explained by an alternative diagnosis. | Complete vaccination schedule and the risk of Long COVID. HR: 0.89; 95% CI: 0.57–1.41 |
Complete vaccination schedule was not statistically significant with the risk of develop Long-COVID | A relatively modest participation rate, Also, notable qualitative disparities emerged between survey responders and nonresponders, especially regarding the vaccination rates and the acute-phase symptoms |
| Nuñez, 20237 | At least one dose of any SARS-CoV-2 vaccine at least 14 days before the date on which symptoms of acute infection began | NR | Patients experiencing any symptoms not present before acute COVID-19 onset, and that persisted for longer than 90 days after acute COVID-19 onset. | Outcome: probability to experience a shorter time to PCC resolution. HR: 3.16; 95%CI 1.21-8.26 |
Prior SARS-CoV-2 vaccination and acute COVID-19 symptom were associated with a shorter time to Long-COVID resolution. | Study power/sample size calculations were not performed given the explorative nature of this study and the lack of reliable data on PCC prevalence when it was designed. |
| Batista, 202425 | NR | NR | Symptoms that remain or appear for the first time within three months of SARS-CoV-2 infection. | NR± | The occurrence of prolonged COVID was higher among those who were unvaccinated compared with those who received COVID-19 vaccine. | The sampling method used. The survey was published on social networks, which may have limited its representation of the Brazilian population. Self-selection bias. |
| Del Carpio-Orantes, 202424 | One dose or more | NR | Persistence of COVID-19 symptoms four weeks after the acute episode. |
|
In the present analysis, no risk association was found with the history of vaccination. | The design of the study does not permit to establish proper associations, and the low number of participants. |
| Fuller, 202426 | Two or more doses | NR | Symptoms that began within three months of the positive SARS-CoV-2 test. | Outcome: Persistence of Long COVID in not fully vaccinated people. HR: 1·96, 95 % CI: 1·03–3·7 |
There was a significant association between the persistence of Long-COVID over time with not being fully vaccinated. | The fact that was a single center study with a small sample size. The frequency of comorbidities was high among participants, which may restrict the generalizability of our findings to healthier populations. Furthermore, since the analysis was conducted during the Omicron period, there were no participants who remained uninfected with COVID-19. |
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