Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis

Watanabe, Atsuyuki; Iwagami, Masao; Yasuhara, Jun; Takagi, Hisato; Kuno, Toshiki

doi:10.1016/j.vaccine.2023.02.008

Cited by 139 publications

(111 citation statements)

References 42 publications

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“…Our findings are consistent with descriptive data from self-selecting respondents collected by Long Covid patient support groups, which suggest that the majority of respondents who have Long Covid developed it after their first infection [3]. However, most participants were unvaccinated when they were first infected, and being vaccinated is associated with a reduced risk of developing Long Covid following SARS-CoV-2 infection [14][15][16]. In addition, reinfections became more common following the emergence of the Omicron variant [2], and the risk of Long Covid has previously been shown to be lower for infections compatible with the Omicron variants compared with the Delta variant [17,18].…”

Section: Comparison With Other Studiessupporting

confidence: 85%

Risk of new-onset Long Covid following reinfection with SARS-CoV-2: community-based cohort study

Bosworth

Shenhuy

Walker

et al. 2023

Preprint

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Background: Little is known about the risk of Long Covid following reinfection with SARS-CoV-2. We estimated the likelihood of new-onset, self-reported Long Covid after a second SARS-CoV-2 infection, and compared to a first infection. Methods: We included UK COVID-19 Infection Survey participants who tested positive for SARS-CoV-2 between 1 November 2021 and 8 October 2022. The primary outcome was self-reported Long Covid 12 to 20 weeks after each infection. Separate analyses were performed for those <16 years and ≥16 years. We estimated adjusted odds ratios (aORs) for new-onset Long Covid using logistic regression, comparing second to first infections, controlling for socio-demographic characteristics and calendar date of infection, plus vaccination status in those ≥16 years. Results: Overall, Long Covid was reported by those ≥16 years after 4.0% and 2.4% of first and second infections, respectively; the corresponding estimates among those <16 years were 1.0% and 0.6%. The aOR for Long Covid after second compared to first infections was 0.72 (95% confidence interval: 0.63-0.81) for those ≥16 years and 0.93 (0.57-1.53) for those <16 years. Conclusions: The risk of new-onset Long Covid after a second SARS-CoV-2 infection is lower than that after a first infection for those ≥16 years, though there is no evidence of a difference in risk for those <16 years. However, there remains some risk of new-onset Long Covid after a second infection, with around 1 in 40 of those ≥16 years and 1 in 165 of those <16 years reporting Long Covid after a second infection.

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Section: Comparison With Other Studiessupporting

confidence: 85%

Risk of new-onset Long Covid following reinfection with SARS-CoV-2: community-based cohort study

Bosworth

Shenhuy

Walker

et al. 2023

Preprint

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“…Time zero (T0) for this study was the time of positive COVID-19 laboratory test plus 28 days. This 28 day period was implemented as Long COVID is only diagnosable 28 days after COVID-19 infection [7][8][9][10]. If we did not implement this 28 day wait, then we would be artificially and uniformly increasing the time to event.…”

Section: Populationmentioning

confidence: 99%

“…In practice, however, Long COVID is defined in many ways and not necessarily in a consistent manner [6]. One common difference in studies of Long COVID is that some studies analyze time from infection until the abatement of COVID-19 symptoms while others focus on the time to development of new Long COVID symptoms following a COVID-19 infection [7][8][9]. Another common variation among studies of Long COVID is a difference in observation window, which varies between 4 weeks to 1 year following COVID-19 infection, with further variation on whether the study period includes or starts after the recommended 28 days post-COVID-19 infection wait period before identifying a patient as having Long COVID [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, studies and subsequent meta-analyses of the effect of vaccination after COVID-19 on risk of Long COVID are fewer in number. Additionally, there is great heterogeneity in results, with the effect of vaccination after COVID-19 on risk of Long COVID having been show to either decrease, increase, or have no effect on the incidence or likelihood of Long COVID [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Effect of vaccination on time till Long COVID, a comparison of two ways to model effect of vaccination and two outcome definitions

Smits

Rodriguez

Gratzl

et al. 2023

Preprint

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Long COVID, or post-COVID syndrome, is a constellation of symptoms observed in patients at least four weeks after COVID-19 infection. We analyzed the effect of COVID-19 vaccination status on risk of either developing Long COVID symptoms or being diagnosed with Long COVID. In separate analyses we compared the effect of vaccination status at time of COVID-19 infection and the effect of vaccination status as a time-dependent covariate where vaccination could occur at any point with respect to COVID-19 infection. To address this question, we identified a subset of adult patients from Truveta Data who experienced a COVID-19 infection as indicated by a positive laboratory test between 2021-10-01 and 2022-11-31. We considered two distinct ways of modeling the effect of vaccination status (time-independent and time-dependent) and two distinct outcomes of interest (Long COVID symptoms or diagnosis with Long COVID), representing four distinct analyses. The presence of Long COVID symptoms was defined as the presence of one or more new symptoms consistent with COVID-19/Long COVID at least four weeks post COVID-19 infection. Diagnosis of Long COVID was determined by the presence of one or more ICD-10-CM or SNOMED-CT codes explicitly identifying a patient as having been diagnosed with Long COVID. Our analysis focusing on the effect of COVID-19 vaccination status at time of COVID-19 infection found that patients who had completed a primary COVID-19 vaccination sequence or had completed a primary vaccination sequence and received a booster dose at time of COVID-19 infection were on average at lower risk of either developing Long COVID symptoms or being diagnosed with Long COVID than unvaccinated patients (vaccinated versus unvaccinated HR of symptoms 0.9 [0.87-0.94], HR of diagnosis 0.86 [0.74-0.99]; vaccinated and boosted versus unvaccinated HR of symptoms 0.87 [0.83-0.91], HR of diagnosis 0.81 [0.69-0.95]). We do not find evidence that having received a booster dose in addition to having completed a primary vaccination sequence offers additional protection over having completed the primary sequence alone (vaccinated and boosted versus vaccinated HR of symptoms 0.96 [0.91-1.01], HR of diagnosis 0.94-1.13) . Our analysis of COVID-19 vaccination status modeled as a time-dependent covariate yielded similar results for patients who had completed a primary COVID-19 vaccination sequence or had completed a primary vaccination sequence and a booster dose. Both groups were on average at lower risk of developing Long COVID symptoms or being diagnosed with Long COVID than patients who where never vaccinated (vaccinated versus unvaccinated HR of symptoms 0.91 [0.88-0.95], HR of diagnosis 0.86 [0.75-0.99]; vaccinated and boosted versus unvaccinated HR of symptoms 0.88 [0.85-0.91], HR of diagnosis 0.77 [0.67-0.9]). As with the time-independent analysis, we also find that having completed a booster dose in addition to a primary COVID-19 vaccination sequence does not provide additional protection from developing Long COVID symptoms or being diagnosed with Long COVID over having completed the primary sequence alone (vaccinated and boosted versus vaccinated HR of symptoms 0.96 [0.92-1.01], HR of diagnosis 0.89 [0.76-1.06]) . We find that completing a primary vaccination sequence is associated with a decreased risk of developing Long COVID symptoms or being diagnosed with Long COVID compared with no vaccination regardless of whether vaccination status is modeled as a time-independent or time-dependent covariate. We find a similar protective effect in patients who have completed a primary vaccination sequence and a booster dose when compared to the those who are unvaccinated. However, we do not find evidence for a difference in protective effect between patients who have completed a primary vaccination sequence and a booster dose and those patients who have only completed a primary vaccination sequence. Our results support the growing evidence that having complete a primary vaccination sequence is protective against the development of Long COVID symptoms or the diagnosis of Long COVID.

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“…There are no treatments yet identified to reduce the risk of developing Long COVID. Vaccination reduces but does not eliminate the risk of Long COVID [2]. Higher acute viral load or prolonged viral shedding may be associated with increased risk of Long COVID [3, 4].…”

Section: Introductionmentioning

confidence: 99%

Association of Nirmatrelvir/Ritonavir Treatment with Long COVID Symptoms in an Online Cohort of Non-Hospitalized Individuals Experiencing Breakthrough SARS-CoV-2 Infection in the Omicron Era

Durstenfeld

Peluso²,

Lin³

et al. 2023

Preprint

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BackgroundOral nirmatrelvir/ritonavir is a treatment for COVID-19, but whether treatment during the acute phase reduces the risk of developing Long COVID is unknown.MethodsUsing the Covid Citizen Science (CCS) online cohort, we surveyed individuals who reported their first SARS-CoV-2 positive test between March and August 2022 regarding Long COVID symptoms. We excluded those who were pregnant, unvaccinated, hospitalized for COVID-19, or received other antiviral therapy. The primary exposure was oral nirmatrelvir/ritonavir. The primary outcome was the presence of any Long COVID symptoms reported on cross-sectional surveys in November and December 2022. We used propensity-score models and inverse probability of treatment weighting to adjust for differences in treatment propensity. Our secondary question was whether symptom or test positivity rebound were associated with Long COVID.Results4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the survey. Median age was 55 years and 66% were female. We did not identify an association between nirmatrelvir/ritonavir treatment and Long COVID symptoms (OR 1.15; 95%CI 0.80-1.64). Among n=666 treated with nirmatrelvir/ritonavir who responded who responded to questions about rebound, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR 1.34; 95%CI 0.74-2.41; p=0.33).ConclusionsWithin this cohort, treatment with nirmatrelvir/ritonavir among vaccinated, non-hospitalized individuals was not associated with lower prevalence of Long COVID symptoms or severity of Long COVID. Experiencing rebound symptoms or test positivity is not strongly associated with developing Long COVID.

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Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis

Cited by 139 publications

References 42 publications

Risk of new-onset Long Covid following reinfection with SARS-CoV-2: community-based cohort study

Risk of new-onset Long Covid following reinfection with SARS-CoV-2: community-based cohort study

Effect of vaccination on time till Long COVID, a comparison of two ways to model effect of vaccination and two outcome definitions

Association of Nirmatrelvir/Ritonavir Treatment with Long COVID Symptoms in an Online Cohort of Non-Hospitalized Individuals Experiencing Breakthrough SARS-CoV-2 Infection in the Omicron Era

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