Table 2.
Studies investigating SARS-CoV-2 vaccination for the treatment of long COVID (n = 9).
| Study | Country | Study Design | Sample Source | Total Sample | Vaccination Status | Long COVID Definition/Persistent COVID-19 Symptoms | Summary of Findings |
|---|---|---|---|---|---|---|---|
| Arnold et al., 2021 | England | Case Series (with prospective enrolment) | North Bristol NHS Trust |
n = 36 Age range: ≥18 Median (IQR) age: 64 (53–73) Sex (%F/%M): 42/58 |
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Among the 159 long COVID symptoms reported prior to vaccination, 37/159 (23.2%) had improved, 9/159 (5.6%) had worsened, and 113/159 (71.1%) were unchanged at a median of 30 days (IQR 26–36) post vaccination. There was no significant worsening in quality-of-life metrics before vs. after vaccination (t test p > 0.1 for all SF-36 comparisons). Mental well-being (ascertained via the WEMWBS) was stable in vaccinated participants before and after vaccination (median, 49 [IQR 42–54] vs. 50 [IQR 40–59], respectively). There was no difference in outcome measure between the Pfizer-BioNTech vs. Oxford-AstraZeneca vaccines (t test p > 0.1). |
| Ayoubkhani et al., 2021* | United Kingdom | Prospective Cohort (uncontrolled) | Office for National Statistics (ONS) COVID-19 Infection Survey (CIS) |
n = 28 356 Age range: 18–69 Mean (SD) age*: 46 (14) Sex (%F/%M)*: 55.6/44.4 88.7% white* *at the last study visit |
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First SARS-CoV-2 vaccination was associated with an initial 12.8% decrease (95% CI −18.6% to −6.6%) in the odds of Long COVID but increasing by 0.3% (95% CI −0.6% to + 1.2%) per week after the date of first vaccination. Second SARS-CoV-2 vaccination was associated with an 8.8% decrease (95% CI −14.1% to −3.1%) in the odds of Long COVID, with the odds subsequently decreasing by 0.8% (-1.2% to −0.4%) per week after the date of second vaccination. First vaccination was associated with an initial 12.3% decrease (95% CI −19.5% to −4.5%) in the odds of activity-limiting Long COVID, followed by an increase of 0.9% (-0.2% to + 1.9%) per week until receiving the second dose. Second vaccination was associated with an initial 9.1% decrease (-15.6% to −2.1%) in the odds, followed by a decrease of 0.5% (-1.0% to + 0.05%) per week. The odds of experiencing most symptoms, as well as more than 3 or 5 symptoms together, initially numerically decreased after each vaccination. After first vaccination, the largest numerical decreases were observed for loss of smell (-12.5%, 95% CI −21.5% to −2.5%), loss of taste (-9.2%, 95% CI −19.8% to + 2.7%), and trouble sleeping (-8.8%, 95% CI −19.4% to + 3.3%). After second vaccination, the largest numerical decreases were observed for fatigue (-9.7%, 95% CI −16.5% to −2.4%), headache (-9.0%, 85% CI −18.1% to + 1.0%), and trouble sleeping (-9.0%, 95% CI −18.2% to + 1.2%). Trends were generally upwards between the first and second vaccinations, with most returning to a declining or flat trend after the second dose. There were no statistical differences in post-vaccination Long COVID trajectories between participants that received a first dose of the adenoviral vector vs. mRNA COVID-19 vaccines (initial 14.9% decrease [95% CI −21.8% to −7.5%] for adenoviral vector vs. initial 8.9% decrease [95% CI −18.2% to + 1.4%] for mRNA). Similarly, the decreases in the long COVID odds following second dose were numerically similar between vaccine types, at 8.7% decrease (-15.4% to −1.4%) for adenoviral vector and 8.9% decrease (-17.6% to + 0.7%) for mRNA SARS-CoV-2 vaccines. |
| Gaber et al., 2021 | England | Cross-sectional | Wrightington, Wigan, and Leigh NHS Trust Hospitals |
n = 67 Age range: 18–65 Mean age: N/A Sex (%F/%M)*: 91/9 Healthcare workers *includes individuals who refused the vaccine (n = 10) |
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(45/67) 67% of respondents did not report any changes in long COVID symptoms several weeks following SARS-CoV-2 vaccination, (14/67) 21% reported improvement of symptoms and, (8/67) 12% reported worsening of symptoms. The symptom which was most frequently reported to have worsened following SARS-CoV-2 vaccination was fatigue (reported by 3/67). |
| Scherlinger et al., 2021 | France | Cross-sectional | French social media platforms and patient associations |
n = 567 Age range: ≥18 Median (IQR) age: 44 (25–75) Sex (%F/%M): 83.4/16.6 |
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201/380 (52.8%) PASC patients reported an impact on symptoms following SARS-CoV-2 vaccination. A global worsening of symptom severity was reported by 117/380 (31%) of PASC patients, mostly represented by worsening of fever/chills (74%), gastro-intestinal symptoms (70%), paresthesia (64%) and arthralgia (63%). Conversely, a global improvement was reported by 83/380 (21.8%) PASC patients and was mainly driven by the improvement of anosmia (62%) and brain fog (51%). The SARS-CoV-2 vaccine impact on PASC symptoms lasted more than 2 weeks in 72.6% of patients reporting improvement and 63.7% of patients reporting worsening. The impact of SARS-CoV-2 vaccination on PASC was not different depending on the vaccine administered (p = 0.60). Amongst unvaccinated participants with pre-existing PASC (170/567 [30%]), the most cited reasons for postponing the COVID-19 vaccine were fear of worsening PASC symptoms (55.9%) and the belief that vaccination was contraindicated because of PASC (15.6%). |
| Schultheiß et al., 2021 | Germany | Cross-sectional | DigiHero cohort (recruited via direct mailing to citizens of Halle, Germany) |
n = 294 Age range: >14 Median (IQR) age*: 51.2 (15–83) Median (IQR) age**: 50 (17–81) Sex (%F/%M)*: 62.4/37.6 Sex (%F/%M)**:61.1/38.9 *n = 258 (87.8%) participants with confirmed prior COVID-19 **n = 36 (12.2%) without prior COVID-19 |
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Post-infection vaccination was not associated with resolution of PASC. 80 (40.8%) vaccinated individuals reported ongoing symptoms, whereas 24 (38.7%) unvaccinated individuals reported ongoing symptoms. Furthermore, the percentage of post-infection vaccinations was identical in patients with PASC that experienced resolution of their symptoms and in those that reported ongoing PASC. From the 175 individuals with reported PASC, 104 individuals still had ongoing symptoms at the time of analysis, while 71 had resolved PASC. Out of the 104 individuals with ongoing symptoms, 80 (76.9%) were vaccinated post-infection, whereas out of the 71 individuals with resolved PASC, 54 (76.1%) were vaccinated post-infection. |
| Simon et al., 2021** | United States | Retrospective Cohort | Arcadia Data Research |
n = 240 648 Age range: N/A Mean (SD) age: N/A Sex (%F/%M): 59.9/40.1 |
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Individuals whose first SARS-CoV-2 vaccination occurred within 12 weeks following COVID-19 diagnosis were significantly less likely to report long COVID symptoms than if they had remained unvaccinated, with earlier vaccine administration post-diagnosis associated with a greater likelihood of not reporting long COVID. Parenthetically, those who received their first within four weeks of infection were 4–6 times less likely to report multiple long COVID symptoms, and those who received their first dose 4–8 weeks after diagnosis were 3 times less likely to report multiple long COVID symptoms compared to those who remained unvaccinated. |
| Strain et al., 2022* | United Kingdom, Israel, Russia,India, South Africa | Cross-sectional | Social media and/or direct mailing to long COVID support groups |
n = 812 Age range: N/A Mean (SD) age: N/A Sex (%F/%M): 80.3/19.7 90.8% white |
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470/812 (57.9%) of participants reported improvements in long COVID symptoms at least one week following first SARS-CoV-2 vaccination, 145/812 (17.9%) reported deterioration, and 197/812 (24.3%) reported no change. 24/812 (3%) reported that all of their long COVID symptoms deteriorated, compared to 221/812 (27.2%) that all their symptoms improved. 424/812 (52.3%) reported that the improvement of symptoms had abated by the time they completed the survey, with the median duration of improvement between 14 and 21 days. For those who experienced worsening, 406/412 (50%) had recovered by the time of the survey, with the median time to improvement being 3–7 days, suggesting the deterioration was a vaccination reaction rather than true exacerbation of long COVID. Larger improvements in symptom severity scores were seen in those receiving mRNA vaccines compared to adenoviral vector vaccines (58% improvement vs. 19% deterioration for AstraZeneca, 56% improvement vs. 18% deterioration for Pfizer, and 66% improvement vs. 12% deterioration for Moderna vaccine, with the rest reporting no difference). The average improvement across all symptoms was 22.6% of the baseline symptom score after the AstraZeneca/Oxford vaccine, 24.4% after the Pfizer/BioNTech vaccine, and 31.0% in recipients of the Moderna (p = 0.003 compared to the AZ/Oxford vaccine and p = 0.01 compared to Pfizer/BioNTech). The second SARS-CoV-2 vaccine dose was associated with a modest further improvement in symptoms or maintenance of benefit, but results were not statistically significant. |
| Tran et al., 2021 | France | ProspectiveCohort (target trial emulation) | ComPaRe long COVID cohort |
n = 910 Age range: ≥ 18 Median (IQR) age: 47 (40–54) Sex (%F/%M)*: 80.5/19.5 Hospitalized/non-hospitalized: 8.9/91.1 |
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At the 120 day follow-up, long COVID symptoms were less severe in the vaccinated group (mean [SD] ST score in the vaccination group 13.0 [9.4] vs. 14.8 [9.8] in the control group; mean difference: −1.8, 95% CI −2.5 to −1.0), and had double the rate of patients in complete remission (remission rate 16.6% vaccinated vs. 7.5% unvaccinated, HR: 1.97, 95% CI 1.23–3.15). Furthermore, the impact of long COVID on patients’ lives was significantly lower in the vaccination group than in the control group. The mean (SD) long COVID IT score was 24.3 (16.7) in the vaccinated group and 27.6 (16.7) in the unvaccinated group (mean difference: −3.3, 95% CI −6.2 to −0.5). |
| Wanga et al., 2021 | United States | Cross-sectional | Non-probability based internet panel survey conducted by Porter Novelli Public Services and ENGINE Insights |
n = 3126 Age range: ≥ 18 Mean (SD) age: N/A Sex (%F/%M)*: 48.5/51.5 Sex (%F/%M)**: 51.5/48.5 *positive COVID-19 test result **negative COVID-19 test result |
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Among those who reported any long-term symptom(s), more respondents who received a positive test result than those who received a negative test result reported that having long-term symptoms motivated them to receive or consider receiving a COVID-19 vaccine (11.0% vs. 7.0%), and believed that receiving the vaccine made their long-term symptoms better (28.7% vs. 15.7%; p = 0.023), or that their symptoms were gone before receiving the vaccine (28.4% versus 13.1%). A similar percentage of respondents who received a positive test result (16.1%) and those who received a negative test result (11.2%) reported that receiving the vaccine made their long-term symptoms worse (p = 0.271), whereas 26.4% of respondents who received a positive test result and 59.2% of those who received a negative test result believed that receiving a vaccine did not affect their symptoms (p < 0.001). |
**Simon et al. reported on both vaccination prior to development of long COVID, and vaccination post factum.
Acronyms: N/A: Not Available, PASC: Post-Acute Sequelae of COVID-19.