Table 2.
Summary of findings table for the main outcomes of PCC development or remission. Separated by odds ratios/hazard ratios, number of vaccine doses, and type of vaccine
| Population: general population who had COVID-19 Setting: any Exposure: COVID-19 vaccination by dose 1, 2, 3, or more, specified in the question. Comparison: no COVID-19 vaccination or vaccinated with different dose/timing specified in the question | ||||||
|---|---|---|---|---|---|---|
| Illustrative comparative in cases of PCC per 100 COVID-19 cases | ||||||
| Exposure | Baseline without vaccine | Corresponding risk with vaccine | Relative effect (95%CI) (OR/HR/IRR) | Number of participants (studies) | Certainty of the evidence (GRADE) | Comments |
| Question 1: the risk of developing PCC or PCC symptoms in those vaccinated before (n=12) COVID-19 | ||||||
| PCC – 1 dose | 25 | 16 (7.8–32.8) | pOR 0.64 (0.31–1.31) | 340,315 [4] | * Very low |
One dose of COVID-19 vaccine prior to COVID-19 may have little to no effect on the risk of developing PCC, but the evidence is very uncertain. High heterogeneity (I2 99.2) across studies and 95% prediction interval (0.02–20.9). Studies were from early 2021 at the beginning of COVID-19 vaccine rollout [23, 33, 34, 37] |
| 25 |
24.0 (22.3–25.8) |
HR 0.96 (0.89–1.03) | 18,958 [1] | * Very low |
One dose of COVID-19 vaccine may have little to no effect on the risk of developing PCC within six months of having COVID-19, but the evidence is very uncertain [38] | |
| PCC – 2 doses | 25 |
16.8 (15.0–18.5) | pOR 0.67 (0.60–0.74) | 324,055 [5] | *** Moderate |
Two doses of COVID-19 vaccine prior to COVID-19 likely reduces the risk of developing PCC. Moderate heterogeneity (I2 59.9%) across studies and 95% prediction interval (0.49–0.91) suggests the results are precise [29, 31, 32, 34, 36] |
| 25 |
20.3 (16.8–24.5) |
pHR 0.81 (0.67–0.98) | 417,322 [4] | * Very low |
Two doses of COVID-19 vaccine prior to COVID-19 may have little to no effect on the average hazard of developing PCC, but the evidence is uncertain. High heterogeneity (I2 = 96.6%) and the 95% prediction interval (0.40–1.66) suggest the results are imprecise [28, 31, 35, 38] | |
| PCC – 1 or 2 doses | 25 |
12.3 (7.8–19.8) | OR 0.49 (0.31–0.79) | 1350 [1] | * Very low |
The association of one or two doses of COVID-19 vaccine prior to COVID-19 on the odds of developing PCC in one study was consistent with the two-dose meta-analysis; however, a single study is considered uncertain evidence [30] |
| PCC – 3 doses | 25 |
11.3 (2.5–49.8) |
OR 0.45 (0.10–1.99) | 1350 [1] | * Very low |
The evidence is very uncertain about the effect of three doses of COVID-19 vaccine prior to COVID-19 on the odds of developing PCC in one study [30]. The study was under powered and reported results for the Delta wave and Omicron wave (I2 = 30.9%), the latter showed an association |
| PCC – mRNA vs adenovirus vaccines | 25 |
15.5 (12.8–18.8) vs. 12.5 (9.3–17.3) | adenovirus OR 0.62 (0.51–0.75) vs. mRNA OR 0.50 (0.37–0.69) | 6180 [1] | * Very low |
Receiving either an mRNA vaccine (BNT162b2/mRNA-1273) or an adenovirus vaccine (ChAdOx1-S) prior to COVID-19 showed an equivalent reduction in the odds of developing PCC, but the evidence is uncertain [29] |
| 25 |
22.3 (20.3–24.3) |
HR 0.89 (0.81–0.97) | 147,414 [1] | * Very low |
Receiving an mRNA vaccine (BNT162b2/mRNA-1273) compared to adenovirus vaccine (Ad26.COV2.S) prior to COVID-19 may further reduce the hazard of developing PCC. Overall vaccination was associated with an aHR 0.85 (0.82–0.89) in vaccinated compared to unvaccinated individuals [28], but the evidence is uncertain | |
| Question 2: the risk of developing PCC or PCC symptoms in those vaccinated with one dose after COVID-19 based on time from infection to vaccination (1 study) | ||||||
| PCC- 1 dose | 25 | vaccinated post COVID-19 0–4 wks: 9.5 (8.8–10.3) 4–8 wks: 13.5 (12.8–14.3) 8-12 wks: 18.8 (17.8–19.5) | aOR for those vaccinated post COVID-19 0-4 wks: 0.38 (0.35–0.41) 4-8 wks: 0.54 (0.51–0.57) 8-12 wks: 0.75 (0.71–0.78) |
240,648 [1] | * Very low |
One dose of COVID-19 vaccination after COVID-19 may result in a reduction in the odds of developing PCC and the effect may be stronger if the vaccine is received within 4 weeks of COVID-19 compared to later time points up to 12 weeks; however, the evidence is very uncertain [37] |
| Question 2: the risk of developing PCC or PCC symptoms in those vaccinated before COVID-19 vs. after COVID-19 (1 study) | ||||||
| PCC- 2 doses | 25 | 22.8 (18.8–27.5) | aIRR 0.91 (0.75–1.10) |
2535 [1] | * Very low |
There was no association with the timing of vaccination, two doses before or after COVID-19; however, the evidence is very uncertain [35] |
| Question 3: the resolution of PCC after COVID-19 vaccination among those with PCC (4 studies, cannot be combined) | ||||||
| PCC – 1 and 2 doses | 25 | Change in level After 1 dose 21.8 (20.3–23.3) After two doses 19.8 (18.7–21.1) |
aOR Change in level 1 dose: 0.87 (0.81–0.93) 2 doses: 0.91 (0.86–0.97) Change in trajectory per week after 1 dose: 1.01 (1.00–1.02) 2 doses: 0.99 (0.98–1.00) |
13,356 [1] | * Very low |
The odds of PCC persisting after vaccination may decrease after each dose of vaccine; however, between the first and second doses the trajectory may increase slightly but was shown to be flat and decreasing slightly after the second dose; the evidence is very uncertain [42] |
| PCC- 1 and 2 doses | 25 | 1 dose 20.5 (15.3–27) 2 doses 15 (10.8–20.8) |
aOR 1 dose 0.82 (0.61–1.08) 2 doses 0.60 (0.43–0.83) |
1596 [1] | * Very low |
Vaccination may be associated with a reduced odds of persistent PCC symptoms after two doses of COVID-19 vaccine; however, the evidence is very uncertain [49] |
| PCC- 1 dose | 25 | 15.9 (4.3–54.3) | aOR 1.57 (0.46–5.84) |
72 [1] | * Very low |
The odds of recovery from PCC after the first COVID-19 vaccination was the same as the unvaccinated; however, the evidence is very uncertain [46] |
| PCC- 1 dose | 25 | 12.7 | Remission in vaccinated 16.6% and in unvaccinated 7.5%. aHR remission 1.93 (1.18–3.14) |
910 [1] | * Very low |
The rate of remission of PCC 3 months after baseline in the vaccinated group (1 dose) may be almost double that of the unvaccinated group; however, the evidence is very uncertain [45] |
Note: The illustrative example is based on a PCC prevalence of 25% in the unvaccinated population. For explanations see the GRADE data in Supplementary Table S2.
Abbreviations: aHR, adjusted HR; aIRR, adjusted incidence rate ratio; aOR, adjusted OR; CI, confidence interval; GRADE, grade of evidence; HR, hazard ratio; OR: odds ratio; pHR: pooled HR; pOR: pooled odds ratio.
*The basis for the assumed risk was a base rate of 25.0% (95%CI 21.5–28.8) reported by unvaccinated Canadians and 13.2% (11.3–15.3%) for those with two doses of COVID-19 vaccine up to 31 August 2022 in the Canadian COVID-19 Antibody and Health Survey [39]. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the intervention group and the relative effect of the intervention (and its 95% CI). GRADE, grade of evidence based on a four-star scale of **** high confidence to * very low confidence in the evidence.