(2022) 19:100
Yamamoto ﻿Virology Journal
https://doi.org/10.1186/s12985-022-01831-0

Open Access

COMMENT

Adverse effects of COVID‑19 vaccinesand measures to prevent them
Kenji Yamamoto*

Abstract
Recently, The Lancet published a study on the effectiveness of COVID-19 vaccines and the waning of immunity withtime. The study showed that immune function among vaccinated individuals 8 months after the administration of
two doses of COVID-19 vaccine was lower than that among the unvaccinated individuals. According to European
Medicines Agency recommendations, frequent COVID-19 booster shots could adversely affect the immune response
and may not be feasible. The decrease in immunity can be caused by several factors such as N1-methylpseudouridine, the spike protein, lipid nanoparticles, antibody-dependent enhancement, and the original antigenic stimulus.
These clinical alterations may explain the association reported between COVID-19 vaccination and shingles. As asafety measure, further booster vaccinations should be discontinued. In addition, the date of vaccination should berecorded in the medical record of patients. Several practical measures to prevent a decrease in immunity have beenreported. These include limiting the use of non-steroidal anti-inflammatory drugs, including acetaminophen to maintain deep body temperature, appropriate use of antibiotics, smoking cessation, stress control, and limiting the useof lipid emulsions, including propofol, which may cause perioperative immunosuppression. In conclusion, COVID-19
vaccination is a major risk factor for infections in critically ill patients.
Keywords: COVID-19, Risk factor, Critically ill patients, Vaccination, Vaccine-acquired immunodeficiency syndrome
Dear Editor,
The coronavirus disease (COVID-19) pandemic has
led to the widespread use of genetic vaccines, including
mRNA and viral vector vaccines. In addition, booster
vaccines have been used, but their effectiveness against
the highly mutated spike protein of Omicron strains islimited. Recently, The Lancet published a study on theeffectiveness of COVID-19 vaccines and the waning of
immunity with time [1]. The study showed that immune
function among vaccinated individuals 8 months after
the administration of two doses of COVID-19 vaccine
was lower than that among unvaccinated individuals.
These findings were more pronounced in older adults*Correspondence: yamamoto@okamura.or.jp
Department of Cardiovascular Surgery, Center of Varicose Veins, Okamura
Memorial Hospital, 293‑1 Kakita Shimizu‑cho, Sunto‑gun, Shizuoka 411‑0904,
Japan

and individuals with pre-existing conditions. According
to the European Medicines Agency’s recommendations,frequent COVID-19 booster shots could adversely affectthe immune response and may not be feasible [2]. Several
countries, including Israel, Chile, and Sweden, are offering the fourth dose to only older adults and other groups
rather than to all individuals [3].
The decrease in immunity is caused by several factors. First, N1-methylpseudouridine is used as a substitute for uracil in the genetic code. The modified protein
may induce the activation of regulatory T cells, resulting in decreased cellular immunity [4]. Thereby, thespike proteins do not immediately decay following theadministration of mRNA vaccines. The spike proteinspresent on exosomes circulate throughout the bodyfor more than 4 months [5]. In addition, in vivo studies
have shown that lipid nanoparticles (LNPs) accumulate
in the liver, spleen, adrenal glands, and ovaries [6], and© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to theoriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of thislicence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Yamamoto ﻿Virology Journal(2022) 19:100

that LNP-encapsulated mRNA is highly inflammatory[7]. Newly generated antibodies of the spike protein damage the cells and tissues that are primed to produce spike
proteins [8], and vascular endothelial cells are damagedby spike proteins in the bloodstream [9]; this may damage the immune system organs such as the adrenal gland.
Additionally, antibody-dependent enhancement may
occur, wherein infection-enhancing antibodies attenuate the effect of neutralizing antibodies in preventing
infection [10]. The original antigenic sin [11], that is, theresidual immune memory of the Wuhan-type vaccine
may prevent the vaccine from being sufficiently effective
against variant strains. These mechanisms may also be
involved in the exacerbation of COVID-19.
Some studies suggest a link between COVID-19 vaccines and reactivation of the virus that causes shingles[12, 13]. This condition is sometimes referred to as vaccine-acquired immunodeficiency syndrome [14]. Since
December 2021, besides COVID-19, Department of Cardiovascular Surgery, Okamura Memorial Hospital, Shizuoka, Japan (hereinafter referred to as “the institute”)
has encountered cases of infections that are difficult tocontrol. For example, there were several cases of suspected infections due to inflammation after open-heart
surgery, which could not be controlled even after several
weeks of use of multiple antibiotics. The patients showedsigns of being immunocompromised, and there were afew deaths. The risk of infection may increase. Various
medical algorithms for evaluating postoperative prognosis may have to be revised in the future. The media haveso far concealed the adverse events of vaccine administration, such as vaccine-induced immune thrombotic
thrombocytopenia (VITT), owing to biased propaganda.
The institute encounters many cases in which this cause
is recognized. These situations have occurred in waves;however, they are yet to be resolved despite the measures implemented to routinely screen patients admitted
for surgery for heparin-induced thrombocytopenia (HIT)
antibodies. Four HIT antibody-positive cases have been
confirmed at the institute since the start of vaccination;
this frequency of HIT antibody-positive cases has rarely
been observed before. Fatal cases due to VITT following
the administration of COVID-19 vaccines have also beenreported [15].
As a safety measure, further booster vaccinations
should be discontinued. In addition, the date of vaccination and the time since the last vaccination should berecorded in the medical record of patients. Owing to
the lack of awareness of this disease group among physicians and general public in Japan, a history of COVID19 vaccination is often not documented, as it is in thecase of influenza vaccination. The time elapsed since

Page 2 of 3

the last COVID-19 vaccination may need to be considered when invasive procedures are required. Several
practical measures that can be implemented to preventa decrease in immunity have been reported [16]. These
include limiting the use of non-steroidal anti-inflammatory drugs, including acetaminophen, to maintaindeep body temperature, appropriate use of antibiotics,
smoking cessation, stress control, and limiting the useof lipid emulsions, including propofol, which may cause
perioperative immunosuppression [17].
To date, when comparing the advantages and disadvantages of mRNA vaccines, vaccination has beencommonly recommended. As the COVID-19 pandemic
becomes better controlled, vaccine sequelae are likely
to become more apparent. It has been hypothesizedthat there will be an increase in cardiovascular diseases, especially acute coronary syndromes, caused by
the spike proteins in genetic vaccines [18, 19]. Besides
the risk of infections owing to lowered immune functions, there is a possible risk of unknown organ damage
caused by the vaccine that has remained hidden without apparent clinical presentations, mainly in the circulatory system. Therefore, careful risk assessments prior
to surgery and invasive medical procedures are essential. Randomized controlled trials are further needed toconfirm these clinical observations.
In conclusion, COVID-19 vaccination is a major risk
factor for infections in critically ill patients.
Abbreviations
COVID-19: Coronavirus disease 2019; HIT: Heparin-induced thrombocytopenia; LPN: Lipid nanoparticle; VITT: Vaccine-induced immune thrombotic
thrombocytopenia.
Acknowledgements
The author would like to thank Editage (www.​edita​ge.​com) for English
language editing.
Author contributions
KY wrote the entire manuscript text and reviewed it. The author read andapproved the finalmanuscript.
Funding
None.
Availability of data and materials
Not applicable.

Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The author declares that he has no competing interests.

Yamamoto ﻿Virology Journal(2022) 19:100

Page 3 of 3

Received: 20 March 2022 Accepted: 1 June 2022

18. Gundry SR. Observational findings of PULS cardiac test findings for
inflammatory markers in patients receiving mRNA vaccines. Circulation.
2021;144(suppl_1):A10712–A10712. https://​doi.​org/​10.​1161/​circ.​144.​
suppl_1.​10712.
19. Lai FTT, Li X, Peng K, Huang L, Ip P, Tong X, et al. Carditis After COVID-19
vaccination with a messenger RNA vaccine and an inactivated virus vaccine: a case-control study. Ann Intern Med. 2022;175:362–70. https://​doi.​
org/​10.​7326/​M21-​3700.

References
1. Nordström P, Ballin M, Nordström A. Risk of infection, hospitalisation, anddeath up to 9 months after a second dose of COVID-19 vaccine: a retrospective, total population cohort study in Sweden. Lancet. 2022;399:814–
23. https://​doi.​org/​10.​1016/​S0140-​6736(22)​00089-7.
2. European Centre for Disease Prevention and Control. Interim publichealth considerations for the provision of additional COVID-19 vaccine
doses. https://​www.​ecdc.​europa.​eu/​en/​publi​catio​ns-​data/​covid-​19-​public-​health-​consi​derat​ions-​addit​ional-​vacci​ne-​doses. Accessed 4 May 2022.
3. Mallapaty S. Fourth dose of COVID vaccine offers only slight boost
against Omicron infection. Nature. 2022. https://​doi.​org/​10.​1038/​
D41586-​022-​00486-9.
4. Krienke C, Kolb L, Diken E, Streuber M, Kirchhoff S, Bukur T, et al. A noninflammatory mRNA vaccine for treatment of experimental autoimmune
encephalomyelitis. Science. 2021;371:145–53. https://​doi.​org/​10.​1126/​
scien​ce.​aay36​38.
5. Bansal S, Perincheri S, Fleming T, Poulson C, Tiffany B, Bremner RM,
et al. Cutting edge: circulating exosomes with COVID spike protein are
induced by BNT162b2 (Pfizer–BioNTech) vaccination prior to development of antibodies: a novel mechanism for immune activation by mRNA
vaccines. J Immunol. 2021;207:2405–10. https://​doi.​org/​10.​4049/​jimmu​
nol.​21006​37.
6. BNT162b2 Module 2.4. Nonclinical Overview. FDACBER-2021-4379-0000681 JW-v-HHS-prod-3-02418.pdf (judicialwatch.
org) Access 6 May 2022.
7. Ndeupen S, Qin Z, Jacobsen S, Bouteau A, Estanbouli H, Igyártó BZ. The
mRNA-LNP platform’s lipid nanoparticle component used in preclinicalvaccine studies is highly inflammatory. Science. 2021;24:103479. https://​doi.​org/​10.​1016/j.​isci.​2021.​103479.
8. Yamamoto K. Risk of heparinoid use in cosmetics and moisturizers inindividuals vaccinated against severe acute respiratory syndrome coronavirus. Thromb J. 2021. https://​doi.​org/​10.​1186/​s12959-​021-​00320-8.
9. Lei Y, Zhang J, Schiavon CR, He M, Chen L, Shen H, et al. SARS-CoV-2 spike
protein impairs endothelial function via downregulation of ACE 2. Circ
Res. 2021;128:1323–6. https://​doi.​org/​10.​1161/​CIRCR​ESAHA.​121.​318902.
10. Liu Y, Soh WT, Kishikawa JI, Hirose M, Nakayama EE, Li S, et al. An
infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by
antibodies. Cell. 2021;184:3452-66.e18. https://​doi.​org/​10.​1016/j.​cell.​2021.​
05.​032.
11. Cho A, Muecksch F, Schaefer-Babajew D, Wang Z, Finkin S, Gaebler C,
et al. Anti-SARS-CoV-2 receptor-binding domain antibody evolution aftermRNA vaccination. Nature. 2021;600:517–22. https://​doi.​org/​10.​1038/​
s41586-​021-​04060-7.
12. Desai HD, Sharma K, Shah A, Patoliya J, Patil A, Hooshanginezhad Z, et al.
Can SARS-CoV-2 vaccine increase the risk of reactivation of Varicellazoster. Systematic review. J Cosmet Dermatol. 2021;20:3350–61. https://​doi.​org/​10.​1111/​jocd.​14521.
13. Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, et al.
Safety of the BNT162b2 mRNA Covid-19 v in a nationwide setting. N Engl
J Med. 2021;385:1078–90. https://​doi.​org/​10.​1056/​NEJMO​A2110​475/​
SUPPL_​FILE/​NEJMO​A2110​475_​DISCL​OSURES.​PDF.
14. Seneff S, Nigh G, Kyriakopoulos AM, McCullough PA. Innate immune suppression by SARS-CoV-2 mRNA vaccinations: the role of G-quadruplexes,
exosomes, and MicroRNAs. Food Chem Toxicol. 2022;164:113008. https://​doi.​org/​10.​1016/J.​FCT.​2022.​113008.
15. Lee EJ, Cines DB, Gernsheimer T, Kessler C, Michel M, Tarantino MD, et al.
Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination. Am J Hematol. 2021;96:534–7. https://​doi.​org/​10.​1002/​AJH.​26132.
16. Yamamoto K. Five important preventive measures against the exacerbation of coronavirus disease. Anaesthesiol Intensive Ther. 2021;53:358–9.
https://​doi.​org/​10.​5114/​ait.​2021.​108581.
17. Yamamoto K. Risk of propofol use for sedation in COVID-19 patient.
Anaesthesiol Intensive Ther. 2020;52:354–5. https://​doi.​org/​10.​5114/​ait.​
2020.​100477.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Ready to submit your research ? Choose BMC and benefit from:• fast, convenient online submission• thorough peer review by experienced researchers in your field• rapid publication on acceptance• support for research data, including large and complex data types• gold Open Access which fosters wider collaboration and increased citations• maximum visibility for your research: over 100M website views per year
At BMC, research is always in progress.
Learn more biomedcentral.com/submissions