International Reviews of Immunology

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Adverse rare events to vaccines for COVID-19:

From hypersensitivity reactions to thrombosis and
thrombocytopenia

Natalija Novak, Leticia Tordesillas & Beatriz Cabanillas

To cite this article: Natalija Novak, Leticia Tordesillas & Beatriz Cabanillas (2021): Adverse
rare events to vaccines for COVID-19: From hypersensitivity reactions to thrombosis and
thrombocytopenia, International Reviews of Immunology, DOI: 10.1080/08830185.2021.1939696

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International Reviews of Immunology
https://doi.org/10.1080/08830185.2021.1939696

Review

Adverse rare events to vaccines for COVID-19: From hypersensitivity

reactions to thrombosis and thrombocytopenia
Natalija Novak a, Leticia Tordesillasb and Beatriz Cabanillasc
a
Department of Dermatology and Allergy, University Hospital, Bonn, Germany; bDepartment of Tumor Biology, H. Lee Moffitt Cancer
Center and Research Institute, Tampa, FL, USA; cDepartment of Allergy, Research Institute Hospital 12 de Octubre, Madrid, Spain

ABSTRACT ARTICLE HISTORY

Vaccines for the prevention of coronavirus disease 2019 (COVID-19) started to be developed Received 26 April 2021
since the initiation of the COVID-19 pandemic. Up to now, four vaccines have been authorized Accepted 29 May 2021
by international agencies such as European Medicines Agency (EMA). Two are DNA vaccines KEYWORDS
(ChAdOx1 nCov-19 and Ad26.COV2.S) and two mRNA vaccines (BNT162b2 and mRNA-1273). Allergy; COVID-19;
The administration of the vaccines has been associated with a strong decrease in the hypersensitivity; thrombosis;
infections by SARS-CoV-2 and deaths associated with it. However, in parallel to these results, vaccines
some rare adverse events have also been described. In that sense, events of thrombosis,
thrombocytopenia, and hemorrhage have been described in close temporal proximity to
the administration of the DNA vaccines ChAdOx1 nCov-19 and Ad26.COV2.S, but also mRNA
vaccines. Recent scientific reports have been released with updated information on the
possible association of thrombotic thrombocytopenia and COVID-19 vaccines. On the other
hand, since the initiation of the vaccination campaigns, adverse hypersensitivity reactions
have been described after mRNA and DNA vaccines administration for COVID-19. Although
globally these adverse events are rare, a high proportion of the world population will be
exposed to these vaccines. For that reason, their safety and tolerance should be carefully
considered. In this review, we provide an updated review of the last scientific findings that
can explain the rare side effects that the vaccines for COVID-19 can produce.

1. Vaccines for COVID-19: DNA and mRNA that is based on the chemical association of polyeth-
vaccines ylene glycol (PEG) to the LNP surface. On the other
hand, the DNA vaccines ChAdOx1 nCov-19 and
Four vaccines for the prevention of coronavirus dis- Ad26.COV2.S are based on adenovirus vectors (Figure
ease 2019 (COVID-19) produced by severe acute 2). Ad26.COV2.S vaccine contains a replicant deficient
respiratory syndrome coronavirus 2 (SARS-CoV-2) human adenovirus type 26 vector and the ChAdOx1
have been authorized by European Medicines Agency nCov-19 vaccine (also named AZD1222, commercial
(EMA) so far. Two are mRNA vaccines: BNT162b2 name: Vaxzevria) is based on the replication-deficient
developed by Pfizer-BioNTech and mRNA-1273 devel- chimpanzee adenovirus vector ChAdOx1 containing
oped by Moderna Therapeutics. The other two are the gene that encodes the glycoprotein spike (S) anti-
DNA vaccines: ChAdOx1 nCov-19 produced by gen of SARS-CoV-2.
AstraZeneca and Ad26.COV2.S produced by The administration of the vaccines for COVID-19
Janssen-Johnson&Johnson. The approvals were based to the general population has been associated with
on randomized, blinded, controlled clinical trials [1–3, an important drop in new infections with SARS-CoV-2
52]. Both mRNA vaccines BNT162b2 and mRNA-1273 and a decrease in deaths due to COVID-19 [4,5].
are based on a mRNA molecule that encodes the viral However, since the initiation of the administration of
spike (S) glycoprotein of SARS-CoV-2. The mRNA the vaccines for COVID-19 in December 2020, adverse
molecule on these vaccines is surrounded by a lipid events have also been described. The mRNA vaccines
nanoparticle (LNP) that provides stability (Figure 1). were the first to be administrated and for those vac-
In order to increase the vaccine efficiency and deliv- cines, some cases of adverse hypersensitivity reactions
ery, the LNP was subjected to a process of PEGylation, were reported [6]. The DNA vaccine ChAdOx1

CONTACT Beatriz Cabanillas [email protected] Department of Allergy, Research Institute Hospital 12 de Octubre de Madrid, Avenida
de Córdoba s/n, 28041 Madrid, Spain.
© 2021 Taylor & Francis Group, LLC
2 N. NOVAK ET AL.

Figure 1. Graphic representation of the active component of the mRNA vaccines for COVID-19. BNT162b2 and mRNA-1273
(PEGylated LNP surrounding the mRNA molecule encoding the viral spike (S) glycoprotein of SARS-CoV-2). The list of ingredients
of each vaccine is depicted and the components with allergic potential are highlighted in red color and represented in the
center of the figure. Biorender software was used to create this figure under an academic license.

nCov-19 was also involved in hypersensitivity reac- and a reevaluation of the vaccine safety by EMA [7].
tions, and it has been recently linked, together to the EMA concluded that although the causal link of very
other DNA vaccine Ad26.COV2.S, to rare thrombotic rare events of thrombosis and ChAdOx1 nCov-19
events. Cases of thrombotic events have also been vaccine has not been proven, the connection cannot
described in close temporal proximity with the admin- be excluded. Consequently, the safety information of
istration of mRNA vaccines. In this review, we sum- the vaccine was updated including the warning on
marize the current knowledge regarding the safety of the rare events of thrombotic thrombocytopenia as a
the currently available vaccines for COVID-19 with potential rare side effect. EMA highlighted that the
special attention to the last scientific advancements benefits of the ChAdOx1 nCov-19 vaccine continue
made on the adverse events that these vaccines to outweigh the risks. However, the agency advised
might induce. that the scientific bases of the potential side effects
require investigation [8]. Cases of thrombosis in close
temporary proximity to the administration of the vac-
2. Thrombotic thrombocytopenia after
cine Ad26.COV2.S have also been recently reported
administration of vaccines for COVID-19
in the USA [9–11], which prompted FDA to halt the
Recent adverse events involving thrombocytopenia, administration of the vaccine and to stop its distri-
thrombosis, and hemorrhage, that include a few cases bution in Europe in order to perform a reevaluation
of deaths, in temporal proximity to the administration of the possible side effects linked with the cases of
of ChAdOx1 nCov-19 vaccine, promoted the tempo- thrombosis. Recent scientific reports have deepened
rary suspension of the administration of the vaccine onto the possible link of the adverse events of
by different European countries on March 15, 2021,
 International Reviews of Immunology 3

Figure 2. Graphic representation of the active component of the DNA vaccines for COVID-19. ChAdOx1 nCov-19 and Ad26.
COV2.S (replicant deficient adenovirus vector containing the DNA molecule encoding the viral spike (S) glycoprotein of SARS-CoV-2).
The list of ingredients of each vaccine is depicted and the component with allergic potential is highlighted in red color and
represented in the center of the figure. Biorender software was used to create this figure under an academic license.

thrombotic thrombocytopenia and COVID-19 vaccines of IgG antibodies against the complex formed by plate-
[10,12,13]. let factor 4 (PF4) and the heparin analogue poly(vinyl
sulfonate) [13]. The second case series involved 11
patients in Germany and Austria (age: 22 to 49.
2.1. Vaccine-induced immune thrombotic Female: male 9:2) that developed thrombocytopenia
thrombocytopenia: a rare new syndrome and thrombosis after 5 to 16 days of receiving ChAdOx1
Initial studies described a syndrome potentially induced nCov-19 vaccine. The patients presented one or more
by the ChAdOx1 nCov-19 vaccine, or at least in close thrombotic events and one patient experienced intra-
temporary proximity to the administration of the vac- cranial hemorrhage. The most common type of throm-
cine, that consisted of severe thrombocytopenia and bosis among the patients was cerebral venous
thrombosis. The studies were based on three case thrombosis. Six of the patients had a fatal outcome.
series of 39 patients in total recently published in the All patients in which antibodies against PF4-heparin
New England Journal of Medicine [12–14]. The first were tested (9 out of 11) had positive results that went
one described 5 health workers in Norway, (age: 32 along with positive platelet-activation assay [12]. The
to 54. Female: male 4:1) that experienced venous third study included 23 patients (age: 21 to 77. Female:
thromboembolism and concomitant severe thrombo- male 14:9) in the United Kingdom that experienced
cytopenia after 7 to 10 days of receiving the first dose thrombosis and thrombocytopenia 6 to 24 days after
of ChAdOx1 nCov-19 vaccine. Four of these patients receiving ChAdOx1 nCov-19 vaccine. The thrombotic
had thrombosis in cerebral veins experiencing intra- events were mainly cerebral venous thrombosis.
cranial hemorrhage which was fatal for three of them. Antibodies against PF4 were positive in 22 patients
Immunoassays detected in all the patients high levels and 7 out of 23 patients had a fatal outcome [14].
4 N. NOVAK ET AL.

Figure 3. Immune mechanism involved in heparin-induced thrombocytopenia (HIT). In the presence of heparin, complexes
between PF4 (which is released from platelets) and heparin or polyanions can be formed. HIT is characterized by the presence
of IgG antibodies against the complexes formed by PF4-heparin or PF4-polyanions. These antibodies can bind to the FcγRIIa
receptor of platelets promoting their activation, aggregation, and release of procoagulant platelets microparticles with the
potential to induce thrombosis. Biorender software was used to create this figure under an academic license.

The presence of such antibodies against PF4-heparin well-defined prothrombotic disorder triggered by the
and the clinical associated picture in close temporal administration of heparin in different forms (unfrac-
connection with the vaccine administration prompted tionated heparin or low-molecular-weight heparin),
the authors of the studies to define the adverse events and it is caused by IgG antibodies against complexes
as a new syndrome named vaccine-induced immune of heparin bound to PF4. Such antibodies can activate
thrombotic thrombocytopenia (VITT), which seems and aggregate platelets by binding to the FcγRIIa
to be a variant of heparin-induced thrombocytopenia receptor, which can induce a decreasing number of
(HIT) (Figure 3). None of the 39 cases in the three platelets, by platelet consumption, and elicit the
studies were administrated with heparin before the release of procoagulant platelets microparticles that
initiation of the symptoms [12–14]. HIT is a can lead to thrombosis (Figure 3). HIT antibodies
 International Reviews of Immunology 5

can also bind to the FcγRI receptor in monocytes general population. An excess of 11 events per
which seems to be associated with thrombin gener- 100,000 individuals was found in the vaccinated
ation. When the thrombocytopenia leads to throm- cohort compared with the expected events in the
bosis the syndrome is called heparin-induced general population in relation to venous thrombo-
thrombotic thrombocytopenia (HITT) which can be embolism, which included cerebral venous thrombo-
life-threatening [15,16]. Antibodies against sis. The authors argued that although such events
PF4-heparin are not uncommon in patients that indeed exceed those of the general population, the
receive heparin, but HITT is only developed in rare absolute risk remained relatively low if the benefits
cases. Other triggers different from heparin can also of the vaccines for COVID-19 are considered [24].
induce similar prothrombotic syndromes that clini-
cally and serologically resembles HIT. That is the
case of specific polyanionic drugs or infections pro- 2.1.1. mRNA vaccines and thrombotic events
duced by bacteria or viruses. mRNA vaccines for COVID-19 have also been liked
Since the publication of the studies described with some cases of thrombosis. In that respect, a case
above, several individual cases of cerebral venous of distal deep vein thrombosis (with the implication
thrombosis or ischemic stroke in close temporal prox- of peroneal vein) in a 66-year-old woman or acute
imity with the administration of the vaccine ChAdOx1 coronary tree thrombosis in an 86-year-old man after
nCov-19 have been published. Most of the cases were administration of BNT162b2 have been reported
accompanied with thrombocytopenia and were [53,54]. Cases of thrombocytopenia within 2 weeks
described in patients under 60 years of age [17–23]. from the administration of BNT162b2 and mRNA-1273
For the vaccine Ad26.COV2.S, a case series of cere- have also been reported [55]. In this context, a
bral venous sinus thrombosis after receiving the vac- descriptive analysis of the thrombotic events in close
cine between March 2 to April 21, 2021 and extracted temporal proximity with the administration of the
from the US database VAERS (Vaccine Adverse Event vaccines BNT162b2, mRNA-1273, and ChAdOx1
Reporting System), has been reported. The clinical nCov-19 reported to the World Health Organization
information of the cases was reviewed by physician Global Database for Individual Case Safety Reports
investigators following standard methods. The case (VigiBase) from December 13, 2020, to March 16,
series included 12 patients (age: 18 to 59. Female: 2021, found a rate of 0.21 cases of thrombotic events
male 12:0) that had cerebral venous sinus thrombosis including cerebral venous thrombosis, per 1 million
and thrombocytopenia beginning 6 to 15 days after individuals vaccinated-days. The events were described
receiving Ad26.COV2.S vaccine. Seven patients out of in association with both mRNA vaccines (BNT162b2
12 also experienced intracerebral hemorrhage. Three and mRNA-1273) and the DNA vaccine analyzed
patients had a fatal outcome. Similar to the cases (ChAdOx1 nCov-19) [25]. However, there is still a
described for ChAdOx1 nCov-19 vaccine, most of the lack of studies analyzing if a causation can be estab-
patients (n = 11) with reactions after Ad26.COV2.S lished. Initial data on the association of thrombocy-
vaccination, had antibodies against PF4 [9,11]. topenia and mRNA vaccines seem to indicate a lack
Additionally, individual cases have also been reported, of association (Lee et al. 2021), while the rate of
in that sense, one recent article has reported a case thrombotic events in individuals administrated with
of extensive thrombosis and severe thrombocytopenia DNA vaccines for COVID-19, although low, seems to
in a 48-year-old woman that received the vaccine be higher than the rate that is expected in the general
14 days before the onset of the symptoms. The patient population [24]. Further studies will be necessary to
presented antibodies against PF4-polyanion. Similar deep on this important aspect.
to the adverse events produced by ChAdOx1 nCov-19,
the symptoms potentially induced by the Ad26.
2.2. Potential triggers
COV2.S resembles HIT [10].
Facing the question of whether there is a possible In the adverse events potentially produced by DNA
association between the thrombotic events and the vaccines for COVID-19, authors speculated that the
administration of the DNA vaccines for COVID-19, antibodies against PF4-heparin found in the patients,
studies have started to evaluate if causation between could correspond to autoantibodies induced by the
both facts can be established. In that respect, a study inflammation produced by the vaccination or could
performed in Denmark and Norway compared the correspond to antibodies triggered by the vaccine itself
rates of thromboembolic events after vaccination with having those antibodies cross-reactivity properties
ChAdOx1 nCov-19 and with those produced in the with PF4 and platelets [12]. From the list of vaccine
6 N. NOVAK ET AL.

components of ChAdOx1 nCov-19 and Ad26.COV2.S, could give a hint of potential VITT [12]. The Society
it has been proposed that the active component itself of Thrombosis and Haemostasis Research (GTH) has
(ChAdOx1 adenovirus vector or adenovirus type 26 recently issued a guide for the recognition, diagnosis,
vector containing the DNA of spike) and/or the mech- and treatment of COVID-19 vaccine-related throm-
anism that derives from it could have a role in the bosis [29].
aforementioned adverse reactions in certain individ-
uals. In that sense, it is known that certain
replication-deficient adenovirus vectors derived from 3. Hypersensitivity reactions to the COVID-19
human adenovirus are linked with thrombocytopenia vaccines
through binding and activation of platelets that are 3.1. Immediate type reactions: anaphylaxis
lately removed by tissue macrophages [26]. However,
the role of the specific adenovirus vector of the vac- The vaccines for COVID-19 have also been associated
cine ChAdOx1 nCov-19 or Ad26.COV2.S in the with adverse immediate hypersensitivity reactions. The
thrombotic events should be further analyzed and Center for Disease Control and Prevention (CDC) and
elucidated. Greinacher et al., proposed that the DNA Food and Drug Administration (FDA) through the
component in the vaccine in a free form could also Vaccine Adverse Event Reporting System (VAERS) have
have a role in the reactions since they have previously analyzed the suspected anaphylactic cases to the mRNA
shown that DNA and RNA can form different com- vaccines BNT162b2 and mRNA-1273 in the USA during
plexes with PF4 that can bind and induce antibodies different periods in December 2020 and January 2021
to PF4-heparin in mice [27]. The potential trigger [30,31]. The reports found a prevalence of 11.1 cases
that could be implicated in the thrombotic events in of anaphylactic reactions per million of administrated
relation to the mRNA vaccines should be also BNT162b2 vaccines and 2.5 cases per million of admin-
elucidated. istrated mRNA-1273 vaccines. In contrast to the poten-
tial side effect of thrombotic events, for the anaphylactic
reactions to mRNA vaccines for COVID-19 no deaths
2.3. Clinical implications were reported. The anaphylactic reactions to these vac-
The Pharmacovigilance Risk Assessment Committee cines usually occurred within 45 minutes of the vaccine
(PRAC) from EMA, which is the committee respon- administration and most of the patients required emer-
sible for assessing and monitoring the safety of human gency room care. Most of the patients that experienced
medicines, stated on 29th March 2021, that ChAdOx1 anaphylaxis due to the COVID-19 vaccine administra-
nCov-19 vaccine could be associated with thrombotic tion had a history of allergic reactions to medicaments,
events and thrombocytopenia. Although the causal routine vaccines, contrast media, insect stings, etc.
link was not proven at that time the agency men- Interestingly, most of the adverse allergic reactions were
tioned that the link cannot be excluded. The infor- described in women (100% in the case of the
mation on the potential side effects of the vaccine mRNA-1273 vaccine and 90% in the case of the
was updated including the warning on the rare events BNT162b2 vaccine), a fact that can be partially explained
of thrombotic thrombocytopenia. In relation to this, by the circumstance that the proportion of women vac-
EMA advised that in the case of presentation of symp- cinated at the time of the reports was higher [30,31].
toms such as severe or persistent headache, blurred Reports from CDC on the anaphylactic reactions after
vision, persistent bleeding, leg swelling, shortness of the administration of the DNA vaccines ChAdOx1
breath, chest or persistent abdominal pain, and skin nCov-19 or Ad26.COV2.S have not been released so
bruising or round, pinpoint spots beyond the site of far, however, cases of allergy-like reactions have been
vaccination after vaccination with ChAdOx1 nCov-19, described [32] and advisory statements in the product
medical attention should be sought [8]. Similar rec- information of all the COVID-19 vaccines regarding
ommendations were issued for the vaccine Ad26. severe allergic reactions have been included.
COV2.S [28]. Greinacher et al. advised that clinicians
should be aware of these rare thrombotic events that
3.2. Delayed type reactions
can be clinically apparent after 5 to 20 days of vacci-
nation with ChAdOx1 nCov-19 vaccine. They propose Delayed hypersensitivity reactions after the adminis-
that ELISAs for the detection of antibodies against tration of vaccines for COVID-19 have also been
PF4-heparin, which are widely available, could be used described and those reactions seem to occur more
to investigate potential VITT. A positive result in such frequently than anaphylactic reactions. In that sense,
a test in patients without recent exposure to heparin an international registry study analyzed 414 cutaneous
 International Reviews of Immunology 7

reactions after the administration of the mRNA vac- she was unaware of her PEG allergy, possibly due to
cines BNT162b2 and mRNA-1273 from 24th December a misdiagnosis of the specific excipient to which she
2020 to 14th February 2021. The study found a wide was allergic to. The diagnosis of PEG allergy is usually
variety of reactions, being the most frequent delayed difficult to establish due to the widespread use of
large local reactions mainly after the administration PEG and its presence in multiple drugs and cosmetic
of mRNA-1273 vaccine. Other frequent reactions con- products [37]. Despite this fact, a current revision of
sisted of local reactions at the site of injection, urti- FDA data has found an average of four anaphylactic
caria, and morbilliform eruptions. Other less usual reactions to PEG per year in individuals exposed to
cutaneous manifestations were also described in this PEG-containing drugs for colonoscopy or laxatives
study [33]. Some of these manifestations mimicked [38]. Sensitization to PEG seems to depend on the
previously described cutaneous manifestations that the molecular weight (MW) of PEG and an individual
virus SARS-CoV-2 itself can induce [51]. In the inter- threshold seems to exist [39]. PEG molecule contained
national registry, more than 50% of the patients that in the mRNA vaccines for COVID-19 has a MW of
had a delayed hypersensitivity reaction did not expe- 2000 g/mol and for that reason is denominated
rience a reaction to the second dose [33]. Further PEG-2000 (Figure 1). Another excipient contained in
reports have described similar manifestations in indi- the mRNA vaccine mRNA-1273 denominated tro-
vidual cases, such as a case of a morbilliform rash methamine (also named trometamol) (Figure 1) has
after the administration of both the first and second been previously linked to allergic reactions. In that
doses of the BNT162b2 vaccine [50] or a case series sense, adverse allergic reactions to
from Italy including 11 patients with transient cuta- tromethamine-containing iodinated contrast medium
neous manifestations after the administration of (IOM) or gadolinium-based contrast agents (GBCA)
BNT162b2 vaccine [34]. In another case, the same have been described [40]. In its CDC report, 20% of
vaccine in its first dose induced a persistent maculo- the patients with anaphylactic reactions to mRNA-1273
papular exanthema involving 30% of the body. The vaccine had a history of anaphylactic reactions to
patient also presented with liver damage, although its gadolinium, iodine, or intravenous contrast media [31].
connection with the BNT162b2 vaccine was not An excipient contained in the DNA vaccines
explored and will need a deeper study. The patient ChAdOx1 nCov-19 and Ad26.COV2.S denominated
was not administrated with the second vaccine dose polysorbate 80, which is an emulsifier and stabilizer
due to the persistency of the reaction induced by the analogue of PEG, has been pointed out as a possible
first dose [35]. Delayed inflammatory skin reactions culprit of hypersensitivity reactions on the DNA vac-
after the administration of the DNA vaccine ChAdOx1 cines for COVID-19 (Figure 2). In the scientific lit-
nCov-19 has also been described [36]. erature, allergic reactions to polysorbates, although
rare, have been described in association with medi-
cines and vaccines containing this compound
3.3. Potential triggers
[38,41–43].
Some components of the vaccines for COVID-19 have
been pointed out as the possible responsible(s) of the
3.4. Clinical implications
hypersensitivity reactions, due to scientific data on
their potential as allergenic compounds. In that sense, Safety statements on the potential side effect of hyper-
some of the excipients contained in the mRNA and sensitivity due to the administration of mRNA and
DNA vaccines have been previously involved in hyper- DNA vaccines for COVID-19 have been updated in
sensitivity allergic reactions and some studies are the product information by international regulatory
beginning to analyze their possible role in the reac- agencies. Furthermore, the European Academy of
tions to the COVID-19 vaccines ([37,49]. Excipients Allergy and Clinical Immunology (EAACI) has issued
such as PEG contained in the mRNA vaccines a guideline on the diagnosis and management of
BNT162b2 and mRNA-1273 as part of the PEGylated potential allergic reactions after the administration of
LNP has been previously described as a compound COVID-19 vaccines [44]. In that sense, only previous
with the potential to induce severe allergic reactions. history of allergic reactions to any component con-
A recent study found that PEG was the culprit of the tained in the vaccines for COVID-19 is a contrain-
anaphylactic reaction that a 52-year-old woman expe- dication for the administration of the vaccines.
rienced after receiving the BNT162b2 vaccine. However, a history of allergic reactions to aeroaller-
Interestingly, the patient had a history of drug allergy gens, foods, or insect venoms is not described as a
and she was previously sensitized to PEG, although contraindication. In the cases of patients with allergy
8 N. NOVAK ET AL.

to medicaments of routine vaccines, a careful assess- Declaration of interest

ment of the exact compound to which the patient is
The authors declare no conflicts of interest.
allergic should be performed.

Funding
4. Other vaccines for COVID-19
This study was supported by a grant from the research
Other vaccines for COVID-19 are under rolling review program Talento Investigador of the Community of Madrid
by EMA, that is the case of CVnCoV (developed by (Regional Ministry of Science, Universities, and Innovation,
CureVac AG), NVX-CoV2373 (developed by Novavax Madrid, Spain), and a grant from Strategic Health Action
(AES 2020), Carlos III Health Institute, Spanish Ministry
CZ AS), and Sputnik V (Gam-COVID-Vac, developed of Science and Innovation (to B.C.) (co-funded by European
by Russia’s Gamaleya National Center of Epidemiology Regional Development Fund) (grant number: PI20/00351).
and Microbiology). CVnCoV is a mRNA vaccine, B.C. is senior researcher in the research program Talento
NVX-CoV2373 is a protein-based vaccine, and Sputnik Investigador of the Community of Madrid (number:
V is a DNA vaccine [45–47]. These vaccines contain 2019-T1/BIO-12690).
among their ingredients excipients that have been
pointed out as possible triggers of adverse events in ORCID
the mRNA and DNA vaccines described in this review.
In that respect, CVnCoV vaccine contains a PEG-ylated Beatriz Cabanillas http://orcid.org/0000-0002-5351-8140
lipid, Sputnik V is based on adenovirus vectors and
NVX-CoV2373 contains polysorbate 80. Some of these References
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