Post-COVID-19 Vaccination and Long COVID: Insights from Patient-Reported Data
Abstract
:1. Introduction
2. Materials and Methods
2.1. Inclusion and Exclusion Criteria
2.2. Statistical Analyses
2.3. Ethics Approval
3. Results
3.1. Stanford PASC Clinic Cohort
3.2. Multinational Survey Cohort
4. Discussion
Strengths and Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Antonelli, M.; Penfold, R.S.; Merino, J.; Sudre, C.H.; Molteni, E.; Berry, S.; Canas, L.S.; Graham, M.S.; Klaser, K.; Modat, M.; 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, 22, 43–55. [Google Scholar] [CrossRef] [PubMed]
- Moghadas, S.M.; Vilches, T.N.; Zhang, K.; Wells, C.R.; Shoukat, A.; Singer, B.H.; Meyers, L.A.; Neuzil, K.M.; Langley, J.M.; Fitzpatrick, M.C.; et al. The Impact of Vaccination on Coronavirus Disease 2019 (COVID-19) Outbreaks in the United States. Clin. Infect. Dis. 2021, 73, 2257–2264. [Google Scholar] [CrossRef] [PubMed]
- Watson, O.J.; Barnsley, G.; Toor, J.; Hogan, A.B.; Winskill, P.; Ghani, A.C. Global impact of the first year of COVID-19 vaccination: A mathematical modelling study. Lancet Infect. Dis. 2022, 22, 1293–1302. [Google Scholar] [CrossRef] [PubMed]
- Iacobucci, G. COVID-19: Vaccines have saved at least 1.4 million lives in Europe, WHO reports. BMJ 2024, 384, q125. [Google Scholar] [CrossRef]
- Centers for Disease Control and Prevention. Clinical Guidance for COVID-19 Vaccination. CDC. Published 25 May 2022. Available online: https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html (accessed on 21 November 2024).
- Mumtaz, A.; Sheikh, A.A.E.; Khan, A.M.; Khalid, S.N.; Khan, J.; Nasrullah, A.; Sagheer, S.; Sheikh, A.B. COVID-19 Vaccine and Long COVID: A Scoping Review. Life 2022, 12, 1066. [Google Scholar] [CrossRef]
- Notarte, K.I.; Catahay, J.A.; Velasco, J.V.; Pastrana, A.; Ver, A.T.; Pangilinan, F.C.; Peligro, P.J.; Casimiro, M.; Guerrero, J.J.; Gellaco, M.M.L.; et al. Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: A systematic review. eClinicalMedicine 2022, 53, 101624. [Google Scholar] [CrossRef]
- Yoo, S.M.; Liu, T.C.; Motwani, Y.; Sim, M.S.; Viswanathan, N.; Samras, N.; Hsu, F.; Wenger, N.S. Factors Associated with Post-Acute Sequelae of SARS-CoV-2 (PASC) After Diagnosis of Symptomatic COVID-19 in the Inpatient and Outpatient Setting in a Diverse Cohort. J. Gen. Intern. Med. 2022, 37, 1988–1995. [Google Scholar] [CrossRef]
- CDC. Nearly One in Five American Adults Who Have Had COVID-19 Still Have “Long COVID”. 22 June 2022. Available online: https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/20220622.htm (accessed on 11 September 2024).
- Davis, H.E.; McCorkell, L.; Vogel, J.M.; Topol, E.J. Long COVID: Major findings, mechanisms and recommendations. Nat. Rev. Microbiol. 2023, 21, 133–146. [Google Scholar] [CrossRef]
- Mahony, L.O.; Buwalda, T.; Blair, M.; Forde, B.; Lunjani, N.; Ambikan, A.; Neogi, U.; Barrett, P.; Geary, E.; O’Connor, N.; et al. Impact of Long COVID on health and quality of life. HRB Open Res. 2022, 5, 31. [Google Scholar] [CrossRef]
- Byambasuren, O.; Stehlik, P.; Clark, J.; Alcorn, K.; Glasziou, P. Effect of COVID-19 vaccination on long covid: Systematic review. BMJ Med. 2023, 2, e000385. [Google Scholar] [CrossRef]
- Wisnivesky, J.P.; Govindarajulu, U.; Bagiella, E.; Goswami, R.; Kale, M.; Campbell, K.N.; Meliambro, K.; Chen, Z.; Aberg, J.A.; Lin, J.J. Association of Vaccination with the Persistence of Post-COVID Symptoms. J. Gen. Intern. Med. 2022, 37, 1748–1753. [Google Scholar] [CrossRef] [PubMed]
- Semmler, A.; Mundorf, A.K.; Kuechler, A.S.; Schulze-Bosse, K.; Heidecke, H.; Schulze-Forster, K.; Schott, M.; Uhrberg, M.; Weinhold, S.; Lackner, K.J.; et al. Chronic Fatigue and Dysautonomia Following COVID-19 Vaccination Is Distinguished from Normal Vaccination Response by Altered Blood Markers. Vaccines 2023, 11, 1642. [Google Scholar] [CrossRef] [PubMed]
- Krumholz, H.M.; Wu, Y.; Sawano, M.; Shah, R.; Zhou, T.; Arun, A.S.; Khosla, P.; Kaleem, S.; Vashist, A.; Bhattacharjee, B.; et al. Post-Vaccination Syndrome: A Descriptive Analysis of Reported Symptoms and Patient Experiences after COVID-19 Immunization. MedRxiv 2023. [Google Scholar] [CrossRef]
- Larsen, N.W.; Stiles, L.E.; Shaik, R.; Schneider, L.; Muppidi, S.; Tsui, C.T.; Geng, L.N.; Bonilla, H.; Miglis, M.G. Characterization of autonomic symptom burden in long COVID: A global survey of 2314 adults. Front. Neurol. 2022, 13, 1012668. [Google Scholar] [CrossRef]
- Bonilla, H.; Quach, T.C.; Tiwari, A.; Bonilla, A.E.; Miglis, M.; Yang, P.C.; Eggert, L.E.; Sharifi, H.; Horomanski, A.; Subramanian, A.; et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic. Front. Neurol. 2023, 14, 1090747. [Google Scholar] [CrossRef]
- Eastin, E.; Machnik, J.; Larsen, N.; Seliger, J.; Geng, L.N.; Bonilla, H.; Yang, P.; Stiles, L.; Miglis, M.G. Evaluating Long-Term Autonomic Dysfunction and Functional Impacts of Long COVID: A Follow-up Study. medRxiv 2024. [Google Scholar] [CrossRef]
- Mehta, C.R.; Patel, N.R. A network algorithm for performing Fisher’s exact test in r × c contingency tables. J. Am. Stat. Assoc. 1983, 78, 427–434. [Google Scholar] [CrossRef]
- Wynberg, E.; Han, A.X.; Boyd, A.; van Willigen, H.D.; Verveen, A.; Lebbink, R.; van der Straten, K.; Kootstra, N.; van Gils, M.J.; Russell, C.; et al. The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): A prospective cohort study. Vaccine 2022, 40, 4424–4431. [Google Scholar] [CrossRef]
- Li, H.; Li, Y.; Liu, J.; Liu, J.; Han, J.; Yang, L. Vaccination reduces viral load and accelerates viral clearance in SARS-CoV-2 Delta variant-infected patients. Ann. Med. 2023, 55, 419–427. [Google Scholar] [CrossRef]
- Proal, A.D.; VanElzakker, M.B.; Aleman, S.; Bach, K.; Boribong, B.P.; Buggert, M.; Cherry, S.; Chertow, D.S.; Davies, H.E.; Dupont, C.L.; et al. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nat. Immunol. 2023, 24, 1616–1627. [Google Scholar] [CrossRef]
- Fischer, C.; Willscher, E.; Paschold, L.; Gottschick, C.; Klee, B.; Diexer, S.; Bosurgi, L.; Dutzmann, J.; Sedding, D.; Frese, T.; et al. SARS-CoV-2 vaccination may mitigate dysregulation of IL-1/IL-18 and gastrointestinal symptoms of the post-COVID-19 condition. npj Vaccines 2024, 9, 23. [Google Scholar] [CrossRef] [PubMed]
- Guo, M.; Liu, X.; Chen, X.; Li, Q. Insights into new-onset autoimmune diseases after COVID-19 vaccination. Autoimmun. Rev. 2023, 22, 103340. [Google Scholar] [CrossRef] [PubMed]
- Gazitt, T.; Eviatar, T.; Shear, J.; Meidan, R.; Furer, V.; Feld, J.; Haddad, A.; Elias, M.; Hijazi, N.; Stein, N.; et al. Development of Autoantibodies Following BNT162b2 mRNA COVID-19 Vaccination and Their Association with Disease Flares in Adult Patients with Autoimmune Inflammatory Rheumatic Diseases (AIIRD) and the General Population: Results of 1-Year Prospective Follow-Up Study. Vaccines 2023, 11, 476. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.; Xu, Z.; Wang, P.; Li, X.M.; Shuai, Z.W.; Ye, D.Q.; Pan, H.F. New-onset autoimmune phenomena post-COVID-19 vaccination. Immunology 2022, 165, 386–401. [Google Scholar] [CrossRef]
- Yeh, L.Y.; Chang, C.Y.; Chang, R.; Wei, J.C.C. COVID-19 vaccine triggers autoimmune disease? Possible mechanism and current evidence. Int. J. Rheum. Dis. 2024, 27, e14963. [Google Scholar] [CrossRef]
- Jara, L.J.; Vera-Lastra, O.; Mahroum, N.; Pineda, C.; Shoenfeld, Y. Autoimmune post-COVID vaccine syndromes: Does the spectrum of autoimmune/inflammatory syndrome expand? Clin. Rheumatol. 2022, 41, 1603–1609. [Google Scholar] [CrossRef]
- Mundorf, A.K.; Semmler, A.; Heidecke, H.; Schott, M.; Steffen, F.; Bittner, S.; Lackner, K.J.; Schulze-Bosse, K.; Pawlitzki, M.; Meuth, S.G.; et al. Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS). Vaccines 2024, 12, 790. [Google Scholar] [CrossRef]
- Scholkmann, F.; May, C.A. COVID-19, post-acute COVID-19 syndrome (PACS, “long COVID”) and post-COVID-19 vaccination syndrome (PCVS, “post-COVIDvac-syndrome”): Similarities and differences. Pathol. Res. Pract. 2023, 246, 154497. [Google Scholar] [CrossRef]
- Li, Y.; Li, J.; Dang, Y.; Chen, Y.; Tao, C. COVID-19 Vaccine Adverse Events in the United States: A Temporal and Spatial Analysis (Preprint). JMIR Public Health Surveill. 2024, 10, e51007. [Google Scholar] [CrossRef]
- Raethke, M.; van Hunsel, F.; Luxi, N.; Lieber, T.; Bellitto, C.; Mulder, E.; Ciccimarra, F.; Riefolo, F.; Thurin, N.H.; Roy, D.; et al. Frequency and timing of adverse reactions to COVID-19 vaccines; A multi-country cohort event monitoring study. Vaccine 2024, 42, 2357–2369. [Google Scholar] [CrossRef]
- Schäfer, I.; Oltrogge, J.H.; Nestoriuc, Y.; Warren, C.V.; Brassen, S.; Blattner, M.; Lühmann, D.; Tinnermann, A.; Scherer, M.; Büchel, C. Expectations and Prior Experiences Associated With Adverse Effects of COVID-19 Vaccination. JAMA Netw. Open 2023, 6, e234732. [Google Scholar] [CrossRef] [PubMed]
- Hoffman, Y.S.G.; Levin, Y.; Palgi, Y.; Goodwin, R.; Ben-Ezra, M.; Greenblatt-Kimron, L. Vaccine hesitancy prospectively predicts nocebo side-effects following COVID-19 vaccination. Sci. Rep. 2022, 12, 20018. [Google Scholar] [CrossRef] [PubMed]
- Haas, J.W.; Bender, F.L.; Ballou, S.; Kelley, J.M.; Wilhelm, M.; Miller, F.G.; Rief, W.; Kaptchuk, T.J. Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials: A Systematic Review and Meta-analysis. JAMA Netw. Open 2022, 5, e2143955. [Google Scholar] [CrossRef] [PubMed]
- Mori, M.; Yokoyama, A.; Shichida, A.; Sasuga, K.; Maekawa, T.; Moriyama, T. Impact of Sex and Age on mRNA COVID-19 Vaccine-Related Side Effects in Japan. Microbiol. Spectr. 2022, 10, e01309-22. [Google Scholar] [CrossRef]
- ElSawi, H.A.; Elborollosy, A. Immune-mediated adverse events post-COVID vaccination and types of vaccines: A systematic review and meta-analysis. Egypt. J. Intern. Med. 2022, 34, 44. [Google Scholar] [CrossRef]
- Abdullah, M.; Chai, P.S.; Chong, M.Y.; Tohit, E.R.M.; Ramasamy, R.; Pei, C.P.; Vidyadaran, S. Gender effect on in vitro lymphocyte subset levels of healthy individuals. Cell. Immunol. 2012, 272, 214–219. [Google Scholar] [CrossRef]
- Pauklin, S.; Sernández, I.V.; Bachmann, G.; Ramiro, A.R.; Petersen-Mahrt, S.K. Estrogen directly activates AID transcription and function. J. Exp. Med. 2009, 206, 99–111. [Google Scholar] [CrossRef]
- Furman, D.; Hejblum, B.P.; Simon, N.; Jojic, V.; Dekker, C.L.; Thiébaut, R.; Tibshirani, R.J.; Davis, M.M. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc. Natl. Acad. Sci. USA 2014, 111, 869–874. [Google Scholar] [CrossRef]
- Dou, D.R.; Zhao, Y.; Belk, J.A.; Zhao, Y.; Casey, K.M.; Chen, D.C.; Li, R.; Yu, B.; Srinivasan, S.; Abe, B.T.; et al. Xist ribonucleoproteins promote female sex-biased autoimmunity. Cell 2024, 187, 733–749.e16. [Google Scholar] [CrossRef]
- Sylvester, S.V.; Rusu, R.; Chan, B.; Bellows, M.; O’Keefe, C.; Nicholson, S. Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: A review. Curr. Med. Res. Opin. 2022, 38, 1391–1399. [Google Scholar] [CrossRef]
- Ballouz, T.; Menges, D.; Anagnostopoulos, A.; Domenghino, A.; Aschmann, H.E.; Frei, A.; Fehr, J.S.; Puhan, M.A. Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: Population based, longitudinal cohort study. BMJ 2023, 381, e074425. [Google Scholar] [CrossRef]
- Pelà, G.; Goldoni, M.; Solinas, E.; Cavalli, C.; Tagliaferri, S.; Ranzieri, S.; Frizzelli, A.; Marchi, L.; Mori, P.A.; Majori, M.; et al. Sex-Related Differences in Long-COVID-19 Syndrome. J. Women’s Health 2002, 31, 620–630. [Google Scholar] [CrossRef]
Worse (n = 29) | Same (n = 77) | Improved (n = 22) | p-Value * | |
---|---|---|---|---|
Proportion of Patients | 22.7% | 60.2% | 17.2% | |
Age Median (Quartiles) | 46 (32, 56) | 48 (35, 59) | 49 (43.3, 56.3) | 0.940 |
Sex | 0.218 | |||
M (n = 53) | 8 (27.6%) | 36 (46.8%) | 9 (40.9%) | |
F (n = 75) | 21 (72.4%) | 41 (53.2%) | 13 (59.1%) | |
Race | 0.557 | |||
White (n = 64) | 16 (55.2%) |
36 (46.8%) |
12 (54.5%) | |
Asian (n = 22) | 5 (17.2%) |
11 (14.3%) |
6 (27.3%) | |
Hispanic (n = 18) | 2 (6.9%) |
14 (18.2%) |
2 (9.1%) | |
Black (n = 8) | 2 (6.9%) |
6 (7.8%) |
0 (0.0%) | |
More than one race (n = 1) | 1 (3.4%) |
0 (0.0%) |
0 (0.0%) | |
Unknown (n = 15) | 3 (10.3%) |
10 (13.0%) | 2 (9.1%) | |
BMI Median (Quartiles) | 23.4 (21.5, 30.9) |
28.3 (22.9, 33.0) |
32.7 (27.4, 36.1) | 0.026 |
Comorbidities | ||||
HIV | 0 (0%) | 0 (0%) | 0 (0%) | |
CLD | 3 (10.3%) | 13 (16.9%) | 2 (9.1%) | 0.629 |
HTN | 5 (17.2%) | 19 (24.7%) | 4 (18.2%) | 0.757 |
DM | 2 (6.9%) | 5 (6.5%) | 1 (4.5%) | 1.000 |
CVD | 2 (6.9%) | 2 (2.6%) | 0 (0%) | 0.349 |
Cirrhosis | 1 (3.4%) | 0 (0%) | 0 (0%) | 0.398 |
Median COVID date | 7 December 2020 | 20 December 2020 | 21 December 2020 | 0.823 |
Days between COVID and 1st vaccine Median (Quartiles) | 115 (92, 168) |
122 (80, 192) |
120 (92, 192) | 0.738 |
Number of vaccinations | 0.188 | |||
1 (n = 14) | 7 (24.1%) |
6 (7.8%) |
1 (4.5%) | |
2 (n = 80) | 17 (58.6%) |
48 (62.3%) |
15 (68.2%) | |
3 (n = 32) | 5 (17.2%) |
22 (28.6%) |
5 (22.7%) | |
4 (n = 2) | 0 (0.0%) |
1 (1.3%) |
1 (4.5%) |
Worse (n = 98) | Same (n = 293) | Improved (n = 93) | p-Value * | |
---|---|---|---|---|
Proportion of Patients | 20.2% | 60.5% | 19.2% | |
Age Median (Quartiles) | 48.5 (41.3, 57.0) | 50.0 (41.3, 56.0)] | 48.0 (2.0, 55.0) | 0.823 |
Sex | 0.095 | |||
Male (n = 56) | 10 (10.2%) | 29 (9.9%) | 17 (18.3%) | |
Female (n = 428) | 88 (89.8%) | 264 (90.1%) | 76 (81.7%) | |
Race | 0.493 | |||
White (n = 430) | 86 (87.8%) | 264 (90.1%) | 80 (86.0%) | |
Other (n = 54) | 12 (12.2%) | 29 (9.9%) | 13 (14.0%) | |
Country | 0.308 | |||
USA (n = 380) | 72 (73.5%) | 236 (80.5%) | 72 (77.4%) | |
Other (n = 104) | 26 (26.5%) | 57 (19.5%) | 21 (22.6%) | |
BMI Median (Quartiles) | 25.2 (22.0, 29.7) | 25.7 (23.2, 30.5) | 26.6 (23.2, 30.5) | 0.435 |
Median COVID date | 11 July 2020 | 17 July 2020 | 29 May 2020 | 0.754 |
Vaccine type | 0.121 | |||
Pfizer (n = 268) | 52 (53.1%) | 159 (54.3%) | 57 (61.2%) | |
Moderna (n = 162) | 32 (32.7%) | 98 (33.4%) | 32 (34.4%) | |
J&J (n = 27) | 8 (8.2%) | 19 (6.5%) | 0 (0.0%) | |
AstraZeneca (n = 24) | 6 (6.1%) | 15 (5.1%) | 3 (3.2%) | |
Other (n = 3) | 0 (0.0%) | 2 (0.7%) | 1 (1.1%) | |
Days between COVID and last vaccine Median (Quartiles) | 412.5 (207, 621.8) | 682 (423, 858.8) | 687.5 (527.5, 919.3) | 0.183 |
Boosters | <0.001 | |||
No | 30 (30.6%) | 25 (8.5%) | 5 (5.4%) | |
Single monovalent booster | 41 (41.8%) | 107 (36.5%) | 22 (23.7%) | |
Both monovalent and bivalent booster | 27 (27.6%) | 161 (54.9%) | 66 (71.0%) |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Quach, T.C.; Miglis, M.G.; Tian, L.; Bonilla, H.; Yang, P.C.; Grossman, L.; Paleru, A.; Xin, V.; Tiwari, A.; Shafer, R.W.; et al. Post-COVID-19 Vaccination and Long COVID: Insights from Patient-Reported Data. Vaccines 2024, 12, 1427. https://doi.org/10.3390/vaccines12121427
Quach TC, Miglis MG, Tian L, Bonilla H, Yang PC, Grossman L, Paleru A, Xin V, Tiwari A, Shafer RW, et al. Post-COVID-19 Vaccination and Long COVID: Insights from Patient-Reported Data. Vaccines. 2024; 12(12):1427. https://doi.org/10.3390/vaccines12121427
Chicago/Turabian StyleQuach, Tom C., Mitchell G. Miglis, Lu Tian, Hector Bonilla, Phillip C. Yang, Lauren Grossman, Amogha Paleru, Vincent Xin, Anushri Tiwari, Robert W. Shafer, and et al. 2024. "Post-COVID-19 Vaccination and Long COVID: Insights from Patient-Reported Data" Vaccines 12, no. 12: 1427. https://doi.org/10.3390/vaccines12121427
APA StyleQuach, T. C., Miglis, M. G., Tian, L., Bonilla, H., Yang, P. C., Grossman, L., Paleru, A., Xin, V., Tiwari, A., Shafer, R. W., & Geng, L. N. (2024). Post-COVID-19 Vaccination and Long COVID: Insights from Patient-Reported Data. Vaccines, 12(12), 1427. https://doi.org/10.3390/vaccines12121427