\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[T2A]{fontenc}
\usepackage[ngerman,greek,polish,english]{babel}



\usepackage{float}








\begin{document}

\title{Rare adverse events following Covid-19 vaccination: A review}



\author[1]{Mohammad Barary}%
\author[2]{Zeinab Mohseni Afshar}%
\author[3]{Jackson J. Liang}%
\author[4]{Akanksha Sharma}%
\author[5]{Marzieh Pirzadeh}%
\author[5]{Arefeh Babazadeh}%
\author[5]{Erfan Hashemi}%
\author[1]{Niloofar Deravi}%
\author[5]{Sadaf Abdi}%
\author[1]{Amirreza Allahgholipour}%
\author[5]{Rezvan Hosseinzadeh}%
\author[5]{Zahra Vaziri}%
\author[4]{Terence T. Sio}%
\author[6]{Mark J. M. Sullman}%
\author[5]{Soheil Ebrahimpour}%
\affil[1]{Shahid Beheshti University of Medical Sciences}%
\affil[2]{Kermanshah University of Medical Sciences}%
\affil[3]{University of Michigan}%
\affil[4]{Mayo Clinic Scottsdale}%
\affil[5]{Babol University of Medical Science}%
\affil[6]{University of Nicosia}%


\vspace{-1em}



  
  \date{May 26, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection has caused many complications, the invention of coronavirus
disease 2019 (Covid-19) vaccines has also brought about several adverse
events, from common side effects to unexpected and rare ones. Common
vaccine-related adverse reactions manifest locally or systematically
following any vaccine, including Covid-19 vaccines. Certain side
effects, known as adverse events of special interest (AESI), are unusual
and need more evaluation. Here, we discuss some of the most important
rare adverse events of Covid-19 vaccines.%
\end{abstract}%



\sloppy


\textbf{Rare adverse events following Covid-19 vaccination: A review}

\textbf{Running title:} Rare adverse events of Covid-19 vaccines

Zeinab Mohseni Afshar\textsuperscript{1}, Jackson J.
Liang\textsuperscript{2}, Akanksha Sharma\textsuperscript{3}, Marzieh
Pirzadeh\textsuperscript{4}, Arefeh Babazadeh\textsuperscript{5}, Erfan
Hashemi\textsuperscript{4}, Niloofar Deravi\textsuperscript{6}, Sadaf
Abdi\textsuperscript{4}, Amirreza Allahgholipour\textsuperscript{7},
Rezvan Hosseinzadeh\textsuperscript{4}, Zahra Vaziri\textsuperscript{4},
Terence T. Sio\textsuperscript{8}, Mark J. M. Sullman\textsuperscript{9,
10}, Mohammad Barary\textsuperscript{11, 12, *}, Soheil
Ebrahimpour\textsuperscript{5, *}

1- Clinical Research Development Center, Imam Reza Hospital, Kermanshah
University of Medical Sciences, Kermanshah, Iran

2- Division of Cardiovascular Medicine, Cardiac Arrhythmia Service,
University of Michigan, Ann Arbor, Michigan, USA

3- Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USA

4- Student Research Committee, Babol University of Medical Sciences,
Babol, Iran

5- Infectious Diseases and Tropical Medicine Research Center, Health
Research Institute, Babol University of Medical Sciences, Babol, Iran

6- Student Research Committee, School of Medicine, Shahid Beheshti
University of Medical Sciences, Tehran, Iran

7- Student Research Committee, School of Nursing and Midwifery, Shahid
Beheshti University of Medical Sciences, Tehran, Iran

8- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona, USA

9- Department of Social Sciences, University of Nicosia, Nicosia, Cyprus

10- Department of Life and Health Sciences, University of Nicosia,
Nicosia, Cyprus

11- Student Research Committee, Virtual School of Medical Education and
Management, Shahid Beheshti University of Medical Sciences, Tehran, Iran

12- Students' Scientific Research Center (SSRC), Tehran University of
Medical Sciences, Tehran, Iran

\textbf{Correspondence:}

Mohammad Barary, Student Research Committee, Babol University of Medical
Sciences, Babol, Iran. Tel: +989112101377, Fax: +98-1132207918, Email:
m.barary@mubabol.ac.ir, m-barary@student.tums.ac.ir

Soheil Ebrahimpour, Infectious Diseases and Tropical Medicine Research
Center, Health Research Institute, Babol University of Medical Sciences,
Babol, Iran. Tel: +989111149309, Fax: +98-1132207918, Email:
drsoheil1503@yahoo.com

\textbf{Abstract}

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection has caused many complications, the invention of coronavirus
disease 2019 (Covid-19) vaccines has also brought about several adverse
events, from common side effects to unexpected and rare ones. Common
vaccine-related adverse reactions manifest locally or systematically
following any vaccine, including Covid-19 vaccines. Certain side
effects, known as adverse events of special interest (AESI), are unusual
and need more evaluation. Here, we discuss some of the most important
rare adverse events of Covid-19 vaccines.

\textbf{Keywords:} Covid-19; SARS-CoV-2; Drug-Related Side Effects
and~Adverse~Reactions

\textbf{Abbreviations}

SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Covid-19,
coronavirus disease 2019; AESI, adverse events of special interest; AHA,
acquired hemophilia A; FVIII, factor VIII; aPTT, activated partial
thromboplastin time; rFVIIa, recombinant activated factor VII; aPCC,
activated prothrombin complex concentrate; ITP, Immune-mediated
thrombocytopenia; ICH, intracranial hemorrhage; AEFI, adverse events
following immunization; CARPA, complement activation pseudo-allergy;
PEG, polyethylene glycol; CLS, Capillary leak syndrome; PCLS, pulmonary
CLS; SCLS, systemic CLS; RRT, renal replacement therapy; TSH,
thyroid-stimulating hormone; T3, triiodothyronine; T4, thyroxine; HA,
Hyaluronic acid; PCT, proximal convoluted tubules; ACE2,
angiotensin-converting enzyme 2; CT, computed tomography; EM, Erythema
multiforme; VAERS, vaccine Adverse Event Reporting System; DIC,
Disseminated intravascular coagulation; POBA, plain old balloon
angioplasty; DVT, Deep venous thrombosis; PTE, pulmonary
thromboembolism; VTE, venous thromboembolic disease; CTPA, computed
pulmonary tomography angiography; VITT, vaccine-induced immune
thrombotic thrombocytopenia; CVST, cerebral venous sinus thrombosis;
PF4, platelet factor 4; SAH, Subarachnoid hemorrhage; ICH, intracerebral
hemorrhage; SVT, Splanchnic vein thrombosis; BCG, Bacillus
Calmette-Guerin; HPV, human papillomavirus; KD, Kikuchi's disease; SLE,
systemic lupus erythematosus; AAION, Arteritic anterior ischemic optic
neuropathy; AZOOR, acute zonal occult outer retinopathy; OCT, optic
coherence tomography; FA, Fluorescein angiography; ERG,
electroretinography; FAF, fundus autofluorescence; AMNR, Acute macular
neuro-retinopathy; PAMM, Paracentral acute middle maculopathy; CSR,
Central serous retinopathy; RPE, retinal pigment epithelium; RRD,
rhegmatogenous retinal detachment; POCUS, point-of-care ultrasound; VKH,
Vogt-Koyanagi-Harada; AMPPE, acute posterior multifocal placoid pigment
epitheliopathy; RF, Rheumatoid factor; EBV, Epstein-Barr virus; MI,
Myocardial infarction; PCI, Percutaneous coronary intervention; MIS-C,
multisystem inflammatory syndrome in children; TTE, Trans-thoracic
echocardiography; RT-PCR, reverse transcriptase-polymerase chain
reaction; GBS, Guillain-Barr\selectlanguage{ngerman}é syndrome; EMG/NCV, Electromyography and
nerve conduction velocity; DOACs, direct oral anticoagulants; CD,
Cluster of differentiation; TM, Transverse myelitis; NMO, neuromyelitis
optica; CSF, cerebrospinal fluid.

\textbf{Introduction}

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection has caused many complications, the invention of coronavirus
disease 2019 (Covid-19) vaccines has also brought about several adverse
events, from common side effects to unexpected and rare
ones.\textsuperscript{1} Common vaccine-related side adverse reactions
are those manifested locally or systematically following any vaccine,
including Covid-19 vaccines. Local reactions include erythema,
tenderness, induration, and, rarely, abscess formation at the injection
site. In contrast, systemic side effects include fever, chills,
headache, cough, coryza, and rarely anaphylactic
reactions.\textsuperscript{2} However, certain side effects, known as
adverse events of special interest (AESI), could manifest as autoimmune
diseases or involve various organs, such as renal, dermatologic,
hematologic, lymphatics, ocular, gastrointestinal, cardiovascular, and
neurologic systems, are unusual and need more evaluation.
\textsuperscript{1} Some adverse events have never happened with other
previously administered vaccines (Figure 1). Examples are those related
to the hyperthrombotic condition induced by the Covid-19 vaccines that
have been discussed in several articles. \textsuperscript{3} Among the
reported side effects of Covid-19 vaccines, some rare adverse events
have been discussed here. First, their proposed pathophysiology is
described, and the possible diagnostic approaches along with recommended
treatment options are demonstrated.

\textbf{Autoimmune complications}

\textbf{Acquired hemophilia A}

Acquired hemophilia A (AHA) is a very rare autoimmune-hematologic
disorder within the immune system that is aroused by a trigger to
produce auto-antibodies against clotting factor VIII (FVIII
inhibitor)\textsuperscript{4}. It is suggested to be associated with
predisposing factors, such as autoimmune diseases, drugs, pregnancy,
infections, and malignancy. AHA major presentations include bruise or
ecchymosis in the skin, mostly in the extremities, but it may progress
to muscles and mucosal layers. However, joint involvement is not
included despite the hereditary type \textsuperscript{5}. Recently, few
case reports have introduced SARS-CoV-2 mRNA vaccines as a possible
trigger for AHA without other predicting conditions
\textsuperscript{6-8}. There are also several reports on exhibiting AHA
following SARS-CoV-2 infection\textsuperscript{5}. Presumed
pathophysiology can be the antigenic mimicry of SARS-CoV-2 and FVIII,
leading to uncontrollable degradation of FVIII. Autoimmune response may
be conducted by various underlying causes such as certain genetic
polymorphism and activation of previously existing autoimmune B/T cells
\textsuperscript{9}. Laboratory confirming evidence include prolonged
activated partial thromboplastin time (aPTT), decreased level of FVIII,
and elevated FVIII inhibitor\textsuperscript{4}. Mentioned cases
diagnosed with vaccination caused AHA within days to weeks following
receiving first/second doses of Moderna (mRNA1273) or Pfizer-BioNTech
(BNT162b2) vaccines\textsuperscript{5,6,8,9}. Cases were mostly
discharged after a few days of treatment. AHA treatment methods consist
of two major issues: 1) homeostasis normalization. First, it is
important to complete the coagulation cascade with recombinant activated
factor VII (rFVIIa) and activated prothrombin complex concentrate
(aPCC); and 2) immune suppressive therapy should be conducted by
corticosteroids (high dose prednisone mostly), cyclophosphamide, and
rituximab (in refractory cases) \textsuperscript{4}.

\textbf{Immune-mediated thrombocytopenia}

Immune-mediated thrombocytopenia (ITP) is an autoimmune disorder in
which platelets destroy by autoantibodies. Etiology mostly includes
autoimmunity, but it can also occur secondary to viral infections and
even vaccination. In the past years, after the beginning of the Covid-19
vaccination, several ITP cases have been reported, mainly following mRNA
vaccines \textsuperscript{10}. In terms of de novo ITP, which happens
within days, hypothesized pathophysiology encompasses molecular mimicry
and cross-reaction of antibodies against vaccine components and
platelets antigens. \textsuperscript{9} Albeit, in case of a flare-up of
pre-existing ITP occurring in hours, the underlying mechanism amplifies
prior immune response \textsuperscript{9}. It is worth noting that the
measured incidence of secondary ITP after vaccination has been lower
than expected ITP in the general population so far.
\textsuperscript{11}However, since the exact differentiation of
coincidental ITP and ITP related to vaccination is not possible right
now, immediate treatment should be performed to prevent severe outcomes
\textsuperscript{11}. Patients present with mild to severe symptoms due
to platelets count. In moderate thrombocytopenia, symptoms generally
include petechiae, purpura, bruising, and mucosal bleeding.
\textsuperscript{12} Platelet count under 5,000/\selectlanguage{greek}µ\selectlanguage{english}L is life-threatening
with a high risk of intracranial hemorrhage (ICH). \textsuperscript{12}
Treatment typically consists of IV fluids, corticosteroids, IVIG,
platelet transfusion, rituximab, and thrombopoietic agents (e.g.,
romiplostim, eltrombopag).\textsuperscript{12} A better approach has
been suggested to start the initial treatment with corticosteroids
(e.g., dexamethasone, methylprednisone) and IVIG. \textsuperscript{12}
Further, if the platelets count did not rise, other agents could be
added. Since rituximab response in about 8 weeks and alter the body's
reaction to the vaccine, it should be excluded from initial
treatment\textsuperscript{12}.

\textbf{Anaphylaxis}

There are two types of adverse events following immunization (AEFI)
after receiving vaccines; non-allergic reactions are normal expected
immune responses to including pain in the injection site, nausea, fever,
chill, and fatigue, while allergic reactions are caused by body
hypersensitivity to vaccines' adjuvant (not an active ingredient) such
as excipients. Allergic reactions may involve any body part and can
exhibit mild-severe symptoms in different patients, including flush,
pruritus, facial edema, tachycardia, laryngeal edema, and
diarrhea\textsuperscript{13}. Anaphylaxis is perceived as an allergic
AEFI with a very low incidence among vaccine receivers (1 in a million
doses) and a higher rate in women, which is increasingly garnering
attraction these days \textsuperscript{14}. Underlying pathophysiology
has been proposed to be IgE-mediated type one hypersensitivity
\textsuperscript{15}. However, there are a few other explanations as
well. For example, complement activation pseudo-allergy (CARPA) is
mostly instigated through C3a and C4a components without the involvement
of IgE. Direct interaction of double-stranded RNA applied in vaccines
and mast cells is also possible, but it is reported to be unlikely due
to a lack of evidence in previous in vitro studies \textsuperscript{16}.
For an IgE-mediated allergy, there should be prior contact with the
allergen. To further decipher, polyethylene glycol (PEG) or Macrogol and
polysorbate 80 have been reported as the most suspected component for
vaccine-related anaphylaxis. PEG2000 has been utilized in SARS-CoV-2
mRNA vaccines as an excipient to facilitate mRNA delivery into cells.
Note that it has a widespread application in medications and foods.
Moreover, polysorbate 80 is a PEG-derived molecule with a lower weight
recruited in many vaccines and medications \textsuperscript{13}. Their
similar structures lead to a cross-reactivity. It is worth noting that
most of the reported cases had a prior allergy to foods, drugs, or
vaccines \textsuperscript{17}.

Anaphylaxis mainly occurs in the first 15 minutes after vaccination.
Symptoms mainly encompass sensation of throat closure, upper airway
swelling, nausea-vomiting, tachycardia, difficulty breathing without
wheeze or stridor, angioedema, hypotension, and dry
cough\textsuperscript{17}. Diagnosis is primarily clinical and needs
immediate actions because it can be potentially fatal despite its very
low incidence. Treatment includes urgent intra-muscular injection of
epinephrine (0.01 mg/kg) and assessing airway, breathing, circulation,
and mental status at the same time. \textsuperscript{13} Epinephrine
injection repeats every 5-15 minutes if the symptoms stay resilient up
to the maximum allowed dose of 0.5 mg in adults (0.3 mg in prepubertal
children). \textsuperscript{13} Antihistamine and glucocorticoids are
second-line drugs mainly for skin and mucosal reactions. Note that PEG
or polysorbate have been added to some of this medication which should
not use as a treatment in patients with suspected allergy to these
components \textsuperscript{13}.

\textbf{Capillary leak syndrome}

Capillary leak syndrome (CLS) is the leakage of fluids in the vessels
into the extravascular space. There are two types of classification for
this disease; 1) idiopathic with unknown cause and secondary to
underlying causes, 2) pulmonary CLS (PCLS), which mainly involves the
lung and pleura, and systemic CLS (SCLS), which rarely consists of lungs
edema \textsuperscript{18,19}. Predisposing factors for secondary CLS
include hematologic malignancies, medical treatment, and viral
infections \textsuperscript{20}. In the last year, several case reports
of developing pulmonary or systemic CLS following SARS-CoV-2 infection
and vaccination \textsuperscript{18,21}. Precise pathophysiology has yet
needed to be elucidated. However, the assumed mechanism is dysregulation
in inflammatory response leading to cytokine storm (i.e., viral
sepsis).\textsuperscript{19} High levels of pro-inflammatory agents in
addition to a hypoxic condition, pathogens' invasion, and immune cells'
activity injure the epithelial-endothelial integrity causing
permeability in the vascular wall and extravasation of exudative
fluids.\textsuperscript{19} It has been demonstrated that
hypoalbuminemia is a frequent finding in Covid-19 cases, representing
the severity of injury to the epithelial-endothelial barrier
\textsuperscript{19}. Both PCLS and SCLS have been reported after
SARS-CoV-2 infection so far\textsuperscript{18}. However, CLS cases
following Covid-19 vaccination had a previously diagnosed SCLS or
suspicious history of SCLS symptoms\textsuperscript{21,22}. SCLS
generally leads to anasarca, hypotensive shock, hemoconcentration,
hypoalbuminemia, monoclonal gammopathy, compartment syndrome, and
multiple organ failure in more severe cases\textsuperscript{21}. It is
worth noting that the diagnosis of SCLS is a diagnosis of exclusion
(other causes of shock) \textsuperscript{20}. Lab data predominantly
encompass hypoalbuminemia and increased level of creatinine, lactate
dehydrogenase, creatine kinase, aspartate aminotransferase.
\textsuperscript{18} The interval between vaccine administration and
appearance of symptoms was about 1-2 days.\textsuperscript{18} For
treatment, it has been suggested that the underlying conditions and
ongoing damages should be managed. For example, albumin administration
may even exacerbate the edema because vascular permeability is present
continuously. \textsuperscript{18}Therefore, agents preserving
epithelial-endothelial integrity can be beneficial, including solnatide,
FX06, and B\selectlanguage{greek}β\selectlanguage{english}15-42. Vasopressors (e.g., norepinephrine, vasopressin, and
epinephrine), antibiotics, volume replacement, high dose of
corticosteroid, IVIG (1 g/kg) are also pivotal. In the case of
compartment syndrome, fasciotomy, and in the case of acute renal injury,
renal replacement therapy (RRT) may be needed. \textsuperscript{18}
Moreover, prophylaxis with IVIG has been proposed as prevention in
patients with prior SCLS who undergo vaccination. \textsuperscript{18}

\textbf{IgA vasculitis and leukocytoclastic vasculitis (hypersensitivity
vasculitis)}

Another worrisome issue following Covid-19 vaccination is the
probability of new-onset emergence or exacerbation of pre-existing
autoimmune diseases \textsuperscript{23}. There have been rare reports
of IgA vasculitis reactivation, previously known as Henoch-Sch\selectlanguage{ngerman}önlein
Purpura, following the Covid-19 vaccination \textsuperscript{24-26}. IgA
vasculitis causes skin, joints, intestines, and kidneys' small blood
vessels to inflate and bleed. The pathogenesis underlying IgA vasculitis
is yet to be known completely. However, the role of genetic,
environmental factors, vaccines, malignancies, and infections have been
reported \textsuperscript{27}. The most common feature of the disease is
the presence of purplish, especially on the buttocks and lower legs.
Elevated CRP, ESR, Urea, Creatinine, serum amyloid A levels, IgM, IgA,
and anti-spike IgG could suggest IgA vasculitis associated with Covid-19
vaccination. Methylprednisolone, Deflazacort, and Paracetamol were
prescribed in the mentioned cases\textsuperscript{27,28}. Similarly,
cases of leukocytoclastic vasculitis were reported following Covid-19
mRNA-based vaccines. Histopathological evaluations and direct
immunofluorescence analysis helped make the diagnosis of
leukocytoclastic vasculitis. Prednisolone taper was prescribed for the
mentioned cases \textsuperscript{29-31}.

\textbf{Urticarial vasculitis}

Urticarial vasculitis following Covid-19 vaccination has been reported.
Urticarial vasculitis is an inflammatory skin disorder manifested by the
presence of urticarial rashes lasting more than a day and healing with
hyperpigmentation. Covid-19 vaccine-induced urticarial vasculitis is
characterized by elevated red rashes on the skin, which are itchy.
Elevated CRP and histopathological evaluations also help the diagnosis
of the disease. In this case, oral indomethacin, levocetirizine tablet,
and topical calamine lotion could be prescribed \textsuperscript{32}.

\textbf{Cutaneous vasculitis}

Cutaneous vasculitis is an inflammatory disease that affects dermal
blood vessel walls. The skin is normally involved. Cutaneous vasculitis
can reflect a cutaneous component of systemic vasculitis, a
skin-dominant or skin-limited expression or variant of systemic
vasculitis, or be a single-organ vasculitis per se. The diagnosis is
often based on physical examination and skin biopsy\textsuperscript{33}.
The occurrence of a peculiar post-Covid-19 vaccination maculopapular
rash characterized by lymphocytic vasculitis as the main histological
finding was recently reported. The rash responded to systemic
antihistamine and local steroid therapy\textsuperscript{34}.

\textbf{Rheumatoid arthritis and reactive arthritis}

There have been reports of a rheumatoid arthritis flare-up following the
Covid-19 vaccination. Moreover, rheumatoid arthritis exacerbation has
also been reported after the Covid-19 vaccination\textsuperscript{35},
which had been previously observed following tetanus, rubella, hepatitis
B, and influenza vaccines\textsuperscript{36}. The mechanism underlying
this flare-up could be possibly attributed to the molecular mimicry or
non-specific adjuvant effect. Elevated ESR and CRP levels with abnormal
ultrasound evaluation of the swollen limb and arthrocentesis were
suggestive for the flare-up of rheumatoid arthritis in these cases.
Intra-articular steroids could be prescribed in these
cases\textsuperscript{37}. Besides, a case of reactive arthritis has
been reported following the SARS-CoV-2 vaccine in a 23-year-old woman
treated with intra-articular betamethasone\textsuperscript{35,38}.

\textbf{IgA nephropathy}

IgA nephropathy has been similarly reported following Covid-19 mRNA
vaccines \textsuperscript{39}. IgA nephropathy is a complex immune
disorder with IgA deposition in the mesangial layer. In these cases, the
development of IgA nephropathy could be speculated due to an elevated
response of immune cells in the germinal center, leading to massive
antibody production and increased production of pathogenic IgA similar
to immunization with influenza vaccine. The cases had gross hematuria.
Urine analysis, Kidney ultrasound, evaluation of immunoglobulin A
levels, and kidney biopsy were suggestive for IgA nephropathy in the
mentioned cases. Losartan and methylprednisolone were prescribed in
these cases. \textsuperscript{40-42} showed proteinuria.

\textbf{Thyroiditis}

Subacute thyroiditis, also known as De Quervain's thyroiditis, has been
another rare adverse event with an immunological source following the
Covid-19 vaccination \textsuperscript{43-47}. It is a self-limited
thyroid inflammation for weeks to months which commonly happens
following a viral upper respiratory tract
infection\textsuperscript{48,49}. This post-vaccine effect has been
presented with new-onset thyroid dysfunction in recently vaccinated
individuals and appears to be of female predominance. The relationship
between subacute thyroiditis and the type of Covid-19 vaccine is unclear
as it has occurred following various vaccine platforms, including
Sinovac, AstraZeneca, Bharat, Moderna, Pfizer. This phenomenon was
previously reported following H1N1, seasonal influenza, and hepatitis B
vaccines\textsuperscript{50-53}. Vaccines' adjuvants are supposed to be
responsible for these reactions by stimulating immunogenic
cross-reactivity, causing autoimmune/inflammatory syndrome induced by
adjuvants (ASIA syndrome) \textsuperscript{47,54}. After vaccination,
subacute thyroiditis can develop due to ASIA syndrome, including
Covid-19 vaccines \textsuperscript{54}. The development of ASIA syndrome
could be attributed to the molecular mimicry, polyclonal activation of B
cells, and immunological imbalance of the host \textsuperscript{47}. In
addition to ASIA syndrome, the interaction between SARS-CoV-2 spike
protein with angiotensin-converting enzyme 2 (ACE2) receptor, which is
wildly expressed on thyroid cells, is another mechanism associated with
thyroiditis induction in vector-based vaccines such as
AstraZeneca\textsuperscript{44}. Clinical manifestations associated with
thyroiditis include pharyngitis, moderate fever, diffuse myalgia, and
cervical pain that radiates to the jaw and ears. Subacute thyroiditis is
often associated with negative anti-thyroglobulin and anti-thyroid
peroxidase antibodies \textsuperscript{49}.

In the mentioned cases, suppressed thyroid-stimulating hormone (TSH)
levels accompanied by elevated triiodothyronine (T3) and thyroxine (T4),
increased levels of inflammatory markers (ESR, CRP), ultrasound
findings, negative thyroid antibodies helped in diagnosing subacute
thyroiditis. Methylprednisolone, propranolol, and ibuprofen were
prescribed in these cases\textsuperscript{47,49,55}. In this relation,
cases of Grave's disease have also been reported following receiving the
SARS-CoV-2 vaccine with elevated anti-thyroid
antibodies\textsuperscript{56}.

\textbf{Dermal filler reaction}

Hyaluronic acid (HA) is a natural polysaccharide that has been widely
utilized in cosmetics \textsuperscript{57}. Reaction to HA fillers is
rare and typically self-limited. So far, triggers such as infections
(e.g., flu-like illnesses) and vaccination (e.g., influenza vaccine)
have been reported to exhibit filler reactions. Furthermore, several
cases have been identified following anti-SARS-CoV-2 mRNA vaccines
recently. Two cases with dermal fillers had developed swelling in lips
and face in the third phase of the Moderna vaccine
trial.\textsuperscript{58} There are two possible explanations for its
pathophysiology. The first assumption is that the action of nonactive
components in vaccines cross-reacting with filler's molecules and
provokes an immune response. \textsuperscript{59} The second hypothesis
supports the alleviation of ACE2 conversion by mRNA vaccines, leading to
pro-inflammatory ACE2 in the skin and inflammation. Reactions are type
four hypersensitivity or delayed immune reactions mediated by T
lymphocytes. \textsuperscript{59} Patients generally present with
flu-like symptoms and swelling of filler region days after vaccination.
Tenderness, swelling, erythema, and nodules can be seen in the
examination. \textsuperscript{59} Since most of the lesions have been
resolved spontaneously, observation and follow-up is the first approach.
However, in case of not improving nodules with pain, tenderness, or
erythema, intervention is necessary. \textsuperscript{59} Antibiotics
including tetracycline and macrolides should be administered for 3-5
days. If the nodule is non-inflammatory, hyaluronidase with or without
intralesional steroids can be utilized to resolve
it.\textsuperscript{59} Moreover, drainage of the nodule should be
considered if the mass fluctuates. Interestingly, in some trials, low
doses of ACE inhibitors have been used for 3-5 days which showed a
significant effect in resolving the reactions. \textsuperscript{59}

\textbf{Renal complications}

Kidneys can be widely affected by SARS-CoV-2 due to the high expression
of ACE2, which is expressed more in proximal convoluted tubules (PCT).
Therefore, the most common type of injury following Covid-19 infection
is tubular injury. Other reported clinical pictures include nephrotic
syndrome and glomerular injury (e.g., minimal change
disease)\textsuperscript{60,61}. Several case reports of acute kidney
injuries in patients with or without prior renal pathology following
vaccination\textsuperscript{62-64}. The pathophysiology of SARS-CoV-2
related renal injury is presumed to be multifactorial through direct
(i.e., virus or vaccine components) or indirect (i.e., immune-mediated
like cytokine storm or hyperactivity of T cells) effects
\textsuperscript{65}. After vaccination conducted by clinical symptoms,
suspension to kidney injury encompass oliguria or anuria, edema or
anasarca, hypertension, and dyspnea due to pleural effusion
\textsuperscript{60}. Laboratory data confirming the diagnosis include a
variety of renal-associated factors' impairment due to underlying
pathology. For instance, minimal change disease exhibits proteinuria,
normal to increased creatinine, and podocyte injury in lite microscopy
assay \textsuperscript{63}. Acute tubular necrosis can be presented with
increased creatinine and urea nitrogen, proteinuria, hypoalbuminemia,
biopsy findings of diffuse PCT injury, lymphocyte infiltration, and cell
necrosis\textsuperscript{60,61}.

Furthermore, hypodensity of renal parenchyma may have been seen in
computed tomography (CT) \textsuperscript{65}. Treatment consists of two
important approaches; firstly, kidney protection from further injury by
adjusting input and output fluids, excluding nephrotoxic drugs, and
monitoring creatinine level. Secondly, early immunosuppressive therapy
(non-selective or selective) or RRT due to patient
condition\textsuperscript{65,66}.

\textbf{Dermatologic complications}

\textbf{Erythema multiforme}

Erythema multiforme (EM), an inflammatory dermatologic disorder, is
mostly linked to infections (most commonly: herpes simplex
and\emph{Mycoplasma pneumoniae} ), although various triggers, such as
many other infectious agents, immunizations, medications, and even
various diseases, have also been identified. Acral, targetoid papules,
consisting of three distinct concentric zones, are the hallmark lesions
of this disease. It is necessary to emphasize that vaccine-induced EM
has been known for a long time, with 984 cases reported to the Vaccine
Adverse Event Reporting System (VAERS) \textsuperscript{67}.
Furthermore, EM-like reactions both as typical acral lesions in younger
individuals and more widespread, atypical lesions in adults have already
been linked to SARS-CoV-2 infection. \textsuperscript{68}. The structure
codified in mRNA Covid-19 vaccines, SARS-CoV-2 spike protein, was shown
immunohistochemically in eccrine ducts epithelium and endothelial cells
in those individuals. EM is a rare adverse effect of many other
vaccines, and recent studies link this reaction to mRNA
vaccines\textsuperscript{69}. It has been suggested that a T-cell
trigger by viral antigen-positive cells containing the HSV-DNA
polymerase gene plays an important role in EM pathogenesis, and it
causes viral gene expression in the recruitment and skin
\textsuperscript{70}. EM's clinical manifestations are diverse, and they
can also manifest as atypical palpable lesions with erythematous dusky
bodies surrounded by a paler halo. To rule out inflammatory, autoimmune,
or malignant disorders, swabs are performed for HSV-PCR, Tzanck smear,
or other serological tests. Direct and indirect immunofluorescence may
be useful in differentiating EM and distinguishing it from other lesions
of bullous vesicles. EM is managed with symptomatic treatments. The
lesions may heal in 3 to 6 weeks, but patients with severe EM may need
to be hospitalized for antiviral therapy, hydration, analgesics, and
systemic steroids \textsuperscript{67,70}.

\textbf{Chilblains}

Repeated exposure to cold air may cause inflammation in small blood
vessels, called chilblains, causing swelling, blistering, itching, and
red patches on hands and feet \textsuperscript{71}. The exact
pathophysiology remains unclear since the chilblain-like lesions due to
Covid-19 are common features with idiopathic and autoimmune-related
chilblains. Covid-19 has various clinical manifestations, including
pernio/chilblains-like lesions, a condition termed ''Covid-19 toes.''
However, after receiving the vaccines, this condition is associated with
Covid-19 \textsuperscript{72}. These lesions have been reported
post-Pfizer and CoronaVac (inactivated vaccine)
vaccinations\textsuperscript{73,74}. These lesions could be extremely
painful and last for up to 150 days after vaccination
\textsuperscript{75,76}. An anticoagulant therapy (apixaban) and
low-dose aspirin were prescribed for the patient until circulating
immune complexes were obtained after 14 days \textsuperscript{75}.

\textbf{Hematologic complications}

\textbf{Disseminated intravascular coagulation}

Disseminated intravascular coagulation) DIC) leads to extensive fibrin
deposition with the formation of extensive microvascular
thrombosis\textsuperscript{77}. During coagulation, coagulation factors
decrease, and platelets accumulate, thereby reducing clotting
protein\textsuperscript{77}. Infection by the SARS-CoV-2 increases the
risk for systematic multi-organ complications and venous, arterial
thromboembolism \textsuperscript{77}. CT scan demonstrated multiple
subacute intra-axial hemorrhages in atypical locations, such as the
right frontal and the temporal lobes. A successive CT angiography of the
chest added the findings of multiple contrast-filling defects with
multi-vessel involvement: at the level of the left interlobar artery, of
the right middle lobe segmental branches of the left upper lobe
segmental branches, and the right interlobar artery\textsuperscript{77}.
A plain old balloon angioplasty (POBA) of the right coronary artery was
conducted, with the restoration of distal flow but with the persistence
of extensive thrombosis of the vessel\textsuperscript{77}. An abdomen CT
angiography demonstrated filling defects at the right supra-hepatic vein
level and the left portal branch level. Bilaterally, it was adrenal
hemorrhage and blood in the pelvis\textsuperscript{77}. An MRI on the
same day demonstrated the presence of an acute basilar thrombosis
associated with the superior sagittal sinus thrombosis. Alternative
HIT-compatible anticoagulants prescribe in case of acute
thrombocytopenia/thrombosis \textsuperscript{77}.

\textbf{Deep vein thrombosis and pulmonary thromboembolism}

Deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) exist
on the spectrum of venous thromboembolic disease
(VTE)\textsuperscript{78}. DVT is known as the formation of blood clots
(thrombi) in the deep veins. It normally affects the deep leg veins
(e.g., the calf veins, popliteal vein, or femoral vein) or the deep
veins of the pelvis. DVT is a potentially dangerous condition, leading
to preventable morbidity and mortality \textsuperscript{79}. PE occurs
when a thrombus migrates from the venous circulation to the pulmonary
vasculature lodging in the pulmonary arterial system. The clinical
manifestation of acute PE ranges from incidentally discovered and
asymptomatic to massive PE, leading to death \textsuperscript{78}.
Post-vaccination DVT and PTE have been reported in a few cases
worldwide. Duplex ultrasonography of the lower limbs demonstrated acute
DVT involving the superficial femoral, common femoral, popliteal,
anterior tibial, posterior tibial, and deep calf
veins\textsuperscript{80}. The patient underwent computed pulmonary
tomography angiography (CTPA) due to tachycardia, which demonstrated
saddle thrombus in the bifurcation of the pulmonary trunk and 40
extensive bilateral main pulmonary arteries emboli extending to both
lobar segmental and subsegmental branches \textsuperscript{80}.

Sporadic cases report viral vector vaccines injection, vaccine-induced
immune thrombotic thrombocytopenia (VITT), and cerebral venous sinus
thrombosis (CVST). Generally, CVST occurs in young adults, particularly
young women. In most cases, a risk factor is identified in
patients\textsuperscript{81-84}. With disease progression, focal
neurological deficits may develop due to seizure and venous infarction,
more commonly observed in patients with CVST than the other stroke
subtypes. Full recovery is achievable with timely disease diagnosis and
treatment\textsuperscript{85}. The SARS-CoV-2 infection has also been
proved to lead to CVST development in several studies
\textsuperscript{85,86}. SARS-CoV-2 VITT is a novel phenomenon occurring
in post-viral vector Covid-19 vaccines.

Contrary to the previous reports of post-vaccination thrombotic
thrombocytopenia, CVST is reported in these patients after the Covid-19
vaccination. Clinically, VITT mimics spontaneous autoimmune
heparin-induced thrombocytopenia (HIT). HIT occurs due to the complexion
of heparin with platelet factor 4 (PF4) platelet-activating IgG
antibodies. Next, the mentioned complex binds to the FcR\selectlanguage{greek}γ\selectlanguage{english}IIA receptors
in platelets, activates platelets, and forms platelet
microparticles\textsuperscript{87}. After that, microparticles start to
form blood clots inducing the prothrombotic cascade, leading to platelet
depletion and thrombocytopenia. Also, the reticuloendothelial system,
especially the spleen, aggregates thrombocytopenia through
antibody-coated platelets removal \textsuperscript{87-90}. Vaccine
interaction with PF4 is considered a potential role in VITT
pathogenesis.

This phenomenon may be attributed to the possible binding of
vaccine-free DNA to PF4, which may trigger the PF4-reactive
autoantibodies in the setting of VITT \textsuperscript{91}. 1) Moderate
to severe thrombocytopenia. Note that mild thrombocytopenia may be
observed in some cases, especially in the initial stages of VITT, 3)
Thrombosis often occurs in the CVST forms (patients may have a headache)
or splanchnic veins thrombosis (patients may have back or abdominal pain
(or both), in addition to nausea and vomiting). Less commonly, arterial
thrombosis may occur, and 4) ELISA confirm positive PF4 ``HIT''
(heparin-induced thrombocytopenia) \textsuperscript{92}. Temporary
headaches are among the common side effect of vaccination, though
persistent headache, petechiae, blurred vision, easy bruising, or
bleeding suggests considering CVST after VITT \textsuperscript{92}.
Subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH) were
observed in nearly half of the patients. Patients' platelet count ranged
between 5,000-127,000/\selectlanguage{greek}µ\selectlanguage{english}L, and D-dimer and PF4 IgG Assay were positive in
most cases. Of 49 CVST patients, a minimum of 19 patients died (39\%)
due to CVST and VITT complications \textsuperscript{93}. Heparin should
not be administered in suspected cases until ruled out
VITT\textsuperscript{92}. Close teamwork among hematologists, vascular
neurologists, and other relevant consultants is the cornerstone of CVST
and VITT-associated systemic thrombosis management \textsuperscript{85}.
Despite the limited data regarding treatment strategies, daily IVIG
administration (1 g/kg body weight) for two days is recommended
following sending PF4 antibodies \textsuperscript{85}. IVIG hinders
antibody-mediated platelet clearance; also, it may block FcR\selectlanguage{greek}γ\selectlanguage{english}IIa
receptors of platelets and thus lead to downregulation of platelet
activation \textsuperscript{88}.

Moreover, some experts have suggested administering high-dose
glucocorticoids, which enhance the platelet count within
days\textsuperscript{88}. On the other hand, plasmapheresis may be
considered a potential therapeutic approach since it may temporarily
remove pathologic antibodies and correct the
coagulopathy\textsuperscript{94}. Platelet transfusion is
contraindicated since it may lead to additional antibody-mediated
platelet activation and coagulopathy \textsuperscript{94}. Non-heparin
anticoagulants, such as direct thrombin inhibitors (bivalirudin,
argatroban), indirect (antithrombin-dependent) factor Xa inhibitors
(fondaparinux, danaparoid), and direct oral factor Xa inhibitors
(rivaroxaban, apixaban), at their therapeutic anticoagulant dosage may
be considered\textsuperscript{91}. In patients with severe
thrombocytopenia (i.e., \textless{} 20,000/\selectlanguage{greek}µ\selectlanguage{english}L) or patients with reduced
fibrinogen levels, alteration of dosing strategy is mandatory
\textsuperscript{85}. Parenteral drugs with a short half-life are
preferred in critically ill patients \textsuperscript{85,91}. In
patients with secondary ICH, anticoagulation is obligatory in CVST for
progressive thrombosis prevention \textsuperscript{85}. In patients with
full platelet count recovery, with no other contraindications, it is
recommended to use vitamin K antagonists or direct oral anticoagulants
for chronic/subacute management \textsuperscript{85}.

\textbf{Splanchnic vein thrombosis}

Splanchnic vein thrombosis (SVT), including mesenteric, portal, splenic
vein thrombosis, and the Budd-Chiari syndrome, manifests venous
thromboembolism in an unusual site. Portal vein thrombosis and
Budd-Chiari syndrome are the most and the least common presentations of
SVT, respectively. In February 2021, a considerable number of VTE in
unusual sites (CVST and SVT) in combination with thrombocytopenia were
observed in individuals receiving the Covid-19 vaccine; which on March
15, 2021, in several countries, including Austria, Germany, the United
Kingdom, France, and Norway, prompted the temporary suspension of the
administration of such vaccination by the EMA \textsuperscript{95,96}.
Other cases of SVT have also been reported after the Covid-19
vaccination \textsuperscript{91}. All patients manifested concomitant
thrombocytopenia (median nadir of a platelet count of 20,000/\selectlanguage{greek}µ\selectlanguage{english}L; range
between 9,000-\textsuperscript{10}7,000/\selectlanguage{greek}µ\selectlanguage{english}L), and none of the patients
had previously received any form of heparin earlier than the onset of
symptoms. Diagnostic evaluation is usually affected by the lack of
specificity of clinical manifestations: the presence of one or more risk
factors in a patient with a high clinical suspicion could indicate---the
execution of diagnostic tests. Doppler ultrasonography is the first-line
diagnostic tool since its accurate and has wide availability.

Further assessments, such as magnetic resonance angiography and computed
tomography, should be executed in cases with suspected SVT-related
complications, suspected thrombosis of the mesenteric veins, or complete
information after Doppler ultrasonography \textsuperscript{97}. Symptom
onset started between 4--16 days post-vaccine administration. The same
treatment as VITT (mentioned earlier) was also suggested for
SVT\textsuperscript{91}.

\textbf{Lymphadenitis}

Besides the abundant reports of prominent lymphadenopathy, there have
been several cases of silent lymphadenopathy following Covid-19
vaccination in women undergoing imaging for breast cancer
screening\textsuperscript{98-102}. Lymph node enlargement has not
conclusively been the result of the Covid-19 vaccines. This phenomenon
has previously been reported following Bacillus Calmette-Guerin (BCG),
smallpox, human papillomavirus (HPV), H1N1 influenza A virus, and
anthrax vaccines\textsuperscript{103-109}. However, none of these
vaccines have been administered massively as SARS-CoV-2 vaccines, and
clinical experience suggests a notably higher incidence of
lymphadenopathy following Covid-19 vaccines than other vaccines.
Lymphadenitis and lymphadenopathy associated with Covid-19 vaccination
usually occur within 4 weeks of administration and have been reported in
almost all body parts, including axillary, pectoral, supraclavicular,
cervical, inguinal, and even intraparotid regions
\textsuperscript{102,110-112}. The axillary region seems to be the most
common location for vaccine-associated lymph node enlargement. However,
the increasing rate of supraclavicular lymphadenopathy following
vaccination indicates that vaccines are injected at a higher location
than recommended \textsuperscript{113}. This complication has been
detected through ultrasound, PET/CT imaging, or MRI in post-Covid-19
vaccinated individuals \textsuperscript{98}.

Nonetheless, we should not underestimate the significance of evaluation
for malignant causes of lymphadenopathy in vaccinated individuals since
vaccination is a well-known but uncommon cause of lymphadenopathy. Fine
needle aspiration is the best method for excluding cancer and
metastasis\textsuperscript{114}. Nevertheless, unnecessary biopsies of
benign reactive lymph nodes should be avoided \textsuperscript{115}.
Therefore, there should be a protocol for evaluation. Some authorities
believe that if lymphadenopathy appears within 6 weeks of vaccination in
a patient with no history of malignancy, the problem is ipsilateral to
the vaccine injection site. It is supposed to be vaccine-related;
otherwise, assessment for other causes, particularly neoplasms, should
be done\textsuperscript{116,117}. In individuals with pre-existing
unilateral cancer, vaccination should be given contralaterally if
possible to avoid misinterpretation \textsuperscript{118}.

Another interesting phenomenon following the Covid-19 vaccination has
been Kikuchi's disease (KD), histiocytic necrotizing lymphadenitis,
presents with cervical lymphadenopathy or fever of unknown
origin\textsuperscript{119}. The etiology of this disease is not yet
determined; however, pathogens such as Epstein-Barr virus,
cytomegalovirus, varicella-zoster virus, human immunodeficiency
virus,\emph{Yersinia enterocolitica} , and \emph{Toxoplasma gondii} ,
and autoimmune disorders such as systemic lupus erythematosus (SLE),
antiphospholipid antibody syndrome, and scleroderma have been attributed
to this condition \textsuperscript{120}. There have been rare reports of
KD following human papillomavirus and influenza
vaccines\textsuperscript{121,122}. The diagnosis of this condition is
confirmed and differentiated from malignancies by histopathology and the
presence of necrosis without granulocytic cells.

\textbf{Ocular complications}

\textbf{AAION and AZOOR}

Various studies reported vaccine-induced ophthalmic events previously.
Arteritic anterior ischemic optic neuropathy (AAION) and bilateral acute
zonal occult outer retinopathy (AZOOR) are described as an abrupt
presentation of photopsia and scotomas due to the damage of external
retinal zones has been reported as an adverse event. The pathophysiology
for developing AZOOR and AAION could be ascribed to the cross-reaction
of neutralizing antibodies against SARS-CoV-2 spike protein or activated
helper T cells after vaccination that react with proteins and antigens
in large arteries, outer retinal layers, and retinal pigment epithelial
cells. Presentation of these ocular manifestations after the second dose
of a vaccine shot accompanied by high levels of ESR and CRP in both
cases strongly supports immune system overactivity patronaging this
assertion. Diagnosis of AAION was performed based on temporal artery
biopsy, macular optic coherence tomography (OCT), Fluorescein
angiography (FA), indocyanine green angiography (ICG), fixed and
multi-luminance electroretinography (ERG), multifocal ERG as well as
images of ganglion cell complex and retinal nerve fiber layer.

Similarly, OCT, fixed and ERG, multifocal ERG, FA, ICG, and fundus
autofluorescence (FAF) were applied to diagnose AZOOR. Corticosteroid
pulse, oral prednisolone followed by Tocilizumab was administrated in
the case of AAION. AZOOR was also treated with an intravitreal implant
of dexamethasone \textsuperscript{123}.

\textbf{Acute macular neuro-retinopathy}

Acute macular neuro-retinopathy (AMNR) is a rare condition with the
sudden presentation of one or more paracentral scotomas causing either
temporary or permanent visual impairment. The pathophysiology underlying
AMNR development has not been identified yet \textsuperscript{124};
however, a few cases of AMNR have been reported following the first shot
of the Covid-19 vaccination. Diagnostic evaluations including
ophthalmoscopy, OCT, swept-source optical OCT, and microperimetry were
all suggestive for AMNR in these patients. The use of oral
contraceptives is associated with AMNR development which further
supports Covid-19 vaccine-induced AMNR as one of the cases was consuming
OCP \textsuperscript{125,126}.

\textbf{Paracentral acute middle maculopathy}

Paracentral acute middle maculopathy (PAMM) is described as the presence
of a hyper-reflective band at the level of the inner nuclear layer
visualized in OCT, which indicates infarction of the inner nuclear
layer. Impaired perfusion of the retinal capillary system can be
associated with several causes, including occlusion of the central
retinal vein, retinal artery occlusion, and the non-proliferative
diabetic form of diabetic retinopathy causing inner nuclear layer
infarction\textsuperscript{127}. PAMN has been reported, followed by the
Sinopharm vaccine. The mentioned case developed uncontrollable
hypertension 20 minutes after the vaccine shot, accompanied by the
simultaneous development of left eye inferior scotoma and headache.
Visual acuity was decreased on admission. OCT angiography and fundus
examination were all indicative of PAMM\textsuperscript{128}.

\textbf{Central serous retinopathy/chorioretinopathy}

Central serous retinopathy (CSR), a common ocular disease, is described
as retinal pigment epithelium (RPE) decompensation, leading to the
detachment of either neurosensory retina or serous pigment epithelium.
Symptoms of CSR include blurred vision, metamorphopsia, micropsia,
dyschromatopsia, or even asymptomatic. Although CRS's pathophysiology
has not been completely understood, increased permeability and thickness
of choroid due to ischemia, inflammation, or hydrostatic forces have
been proposed as the possible mechanism \textsuperscript{129}. mRNA
vaccines induced CSR have been postulated to develop due to the presence
of polyethylene glycol used in vaccine formulation, causing anaphylaxis,
choroid vessel thickening, and neovascularization. Possible release of
endogenous cortisol triggered by mRNA vaccines is also hypothesized to
be associated with CSR development after vaccination as high cortisol
levels in serum are associated with CSR. Another probable mechanism for
post-vaccination CSR is extracellular RNA presence which induces
increased endothelial cell permeability and thrombus formation, which is
also compatible with lobular ischemia seen in CSR. CSR has been
previously reported, followed by smallpox, yellow fever, influenza, and
anthrax vaccine. CSR development followed by Pfizer vaccine was reported
69 hours after the injection. OCT, OCT angiography, and FA were all
suggestive for CSR. Spironolactone 50 mg daily was prescribed, and the
patient became asymptomatic with normal visual tests after three
months\textsuperscript{130}.

\textbf{Bilateral Retinal Detachment}

Retinal detachment is an emergency medical condition that requires
prompt treatment, leading to permanent blindness. There are three types
of retinal detachments, including tractional and exudative, which are
non-rhegmatogenous, and rhegmatogenous retinal detachment (RRD), which
is the most common point-of-care ultrasound (POCUS) of the eye was
suggestive for non-posterior vitreous detachment that is a form of RRD
which round holes that are associated with local thinning or atrophy of
retina including lattice degeneration. The patient then undergoes
bilateral vitrectomies \textsuperscript{131}.

\textbf{Uveitis}

Uveitis is a threatening, inflammatory eye disorder considered an
ophthalmic emergency. Uveitis develops mostly due to autoimmune
reactions, ocular trauma, infection, or it may be
isolated\textsuperscript{132}. Uveitis development following vaccination
can present with a wide range of ocular manifestations such as redness
of the eye, blurred vision, floaters, and sensitivity to the light.
Conjunctival hyperemia and eye pain can also be the clinical
manifestations associated with vaccine-associated
uveitis\textsuperscript{132}. Vaccine-associated uveitis has been
previously reported following almost all the vaccines currently
employed, such as hepatitis B vaccine, the commonest vaccine-related
uveitis, human papillomavirus, and influenza
vaccine\textsuperscript{133}. The pathophysiology underlying the
development of vaccine-associated uveitis could be attributed to
autoimmune mechanisms caused by the vaccine. The possible mechanisms
involved in this autoimmunity includes molecular mimicry due to the
resemblance of uveal self-peptides and vaccine peptides, cytokine
production, new antigen induction, surface antigen modification, B cell
polyclonal activation, and adjuvants induced inflammatory
destruction\textsuperscript{134}.

Most cases of vaccine-associated uveitis are anterior, transient, not
severe, and respond to topical steroids promptly; However, there have
been reports of posterior uveitis and pan-uveitis, including
Vogt-Koyanagi-Harada (VKH) and acute posterior multifocal placoid
pigment epitheliopathy (AMPPE) in severe cases following vaccination.
Previous studies showed conjunctival hyperemia, photophobia, decreased
visual acuity, and eye pain. Laboratory data, including WBC count, CRP,
and ESR levels, were normal with negative ANA and rheumatoid factor
(RF). Slit-lamp examination and OCT results were suggestive for uveitis.
Dexamethasone eye drops six times a day and atropine 1\% (cycloplegic
agent) twice daily was prescribed for patient 143. Several diffuse
scleral hyperemia lesions were observed on slit photos. Scleritis
resolved one week after prescribing topical steroids for the
patient\textsuperscript{128}. Pan uveitis-associated Covid-19 vaccine
has also been reported with substantial vision loss, ocular pain, and
light sensitivity. Fluorescein angiography, OCT imaging, and B-scan were
used to diagnose OCT and B-scan showing choroidal thickening. Oral
prednisolone (50 mg/kg) and Difluprednate eye drop were prescribed for
patient \textsuperscript{133}.

Vogt-Koyanagi-Harada syndrome is a rare granulomatous inflammatory
disorder that targets pigmented structures, including the inner ear,
eye, meninges, hair, and skin. The disease causes non-necrotizing
panuveitis and exudative retinal detachment. The pathophysiology
underlying VKH has been mediated by Th1 lymphocytes against melanocyte
antigenic components. A case of VHK has been reported 4 days, followed
by the Covid-19 vaccine with bilateral acute vision loss. Slit photo,
OCT, and Fundus examination helped diagnose VKH. Oral systemic
prednisolone (1.5 mg/kg) was prescribed for the patient
daily\textsuperscript{135}.

\textbf{Gastrointestinal complications}

\textbf{Autoimmune hepatitis}

Autoimmune hepatitis is characterized by inflammatory liver disease,
which can be triggered by various factors such as viruses, bacteria,
drugs, and some substances in genetically predisposed patients. Acute
autoimmune hepatitis has been reported to develop, followed by
hepatotropic viruses, such as hepatitis A, B, and C viruses, and
non-hepatotropic viruses, including Epstein-Barr virus
(EBV)\textsuperscript{136}. Recently infection with SARS-CoV-2 has been
associated with autoimmune hepatitis development. Furthermore,
autoimmune hepatitis happened following Covid-19 mRNA
vaccines\textsuperscript{137,138}. As autoimmune conditions leading to
tissue destruction following severe SARS-CoV-2 infection have been
reported, it could be similarly stated that molecular mimicry is
responsible for the development of autoimmune hepatitis in these
cases\textsuperscript{137}. The cases were negative for viral hepatitis
(hepatitis A, B, C, and E, cytomegalovirus, EBV, herpes simplex virus,
and HIV). Laboratory data showed elevated bilirubin, albumin, and liver
enzymes, suggestive of hepatocellular injury. Double-stranded DNA
antibodies (dsDNA) and antinuclear antibodies (ANA) were positive in
these cases with elevated IgG levels. There was no evidence of biliary
lithiasis or dilation. Histopathological evaluations were also
compatible with autoimmune hepatitis, showing portal inflammation,
interface hepatitis, rosette formation, and eosinophils, which increase
the possibility for drug-induced autoimmune hepatitis in mentioned
cases. Budesonide or prednisolone 20 mg daily can be administrated to
treat Covid-19 vaccine induced autoimmune hepatitis.

\textbf{Cardiovascular complications}

\textbf{Myocardial infarction}

Myocardial infarction (MI) is a term used for an event of a heart attack
due to the formation of plaques in the arteries' interior walls,
resulting in reduced blood flow to the heart and injuring heart muscles
because of lack of oxygen supply \textsuperscript{139}. MI is a rare
complication of the post-Covid-19 vaccine, but it is a major problem,
and it can be a life-threatening adverse event. There are some potential
explanations of myocardial infarction after the Covid-19 vaccine. First,
prothrombotic immune thrombocytopenia induced by the vaccine has
similarities to heparin-induced thrombocytopenia leading to thrombotic
manifestation. Second, Covid-19 vaccines increase demand of the heart as
a contributing factor, then causes a demand-supply mismatch. Third, this
can result from Kounis syndrome, defined as an acute coronary syndrome
caused by an allergic reaction or a strong immune reaction to various
substances, including excipients, drugs, or other substances. MI
clinical manifestations include chest pain which travels from left arm
to neck, shortness of breath, sweating, nausea, vomiting, abnormal heart
beating, anxiety, fatigue, weakness, stress,
depression\textsuperscript{140,141}. Paraclinic findings would be
Non-ST-elevation and ST-elevation with or without T segment inversion
and even reciprocal changes in ECG, abnormal motion of the wall in
echocardiography, high-level biomarkers such as Creatine-Kinase-MB
isoform and Cardiac Troponin (the biomarker of choice), cardiac troponin
I is the gold standard of MI diagnosis, and angiography to localized
blot clots formation in coronary vessels\textsuperscript{142}. The aim
of myocardial infarction management is thrombolysis and reperfusion of
the myocardium, although a variety of drugs such as anti-platelets
(aspirin), heparin, anti-anginal (\selectlanguage{greek}β-\selectlanguage{english}blockers, and nitrates) might also
be considered. Percutaneous coronary intervention (PCI) is for
reperfusion of the myocardium. If there is no emergency percutaneous
coronary intervention facility, thrombolytic therapy with 1.5 million
IU/h intravenous streptokinases can be
administered\textsuperscript{140}.

\textbf{Myocarditis and pericarditis}

Pericarditis is~inflammation of the pericardium, a two-thin-layer
sac-like structure that surrounds the heart, and also myocarditis is
inflammation of the myocardium (heart muscle). This inflammation can
result from an immune response to an infection or other
substances\textsuperscript{143}. Viral infections, such as adenovirus,
coxsackievirus, herpes virus, influenza, and even SARS-CoV-2, are the
most common cause of myocarditis and pericarditis\textsuperscript{144}.
Previously, myocarditis and pericarditis have been reported after
smallpox vaccination and less after Other live viral vaccines (including
measles-mumps-rubella, varicella, oral polio, or yellow fever vaccine).
Recently myocarditis and pericarditis have been reported due to Covid-19
vaccination, especially mRNA vaccines\textsuperscript{145}.

For this reason, FDA attached a caution about the risk of
myopericarditis to the information sheet of mRNA anti-SARS-CoV-2
vaccines\textsuperscript{146}. Immunopathological mechanisms of Covid-19
vaccination can be theoretical risks of myocarditis and pericarditis of
post-Covid-19 vaccination\textsuperscript{147}. Potential hypothesized
mechanisms include 1) very high antibody generation response, similar to
the multisystem inflammatory syndrome in children (MIS-C) associated
with SARS-CoV-2 infection, 2) anti-idiotype cross-reactive
antibody-mediated cytokine expression induction in the myocardium, 3)
non-specific innate inflammatory response or a molecular mimicry
mechanism between the viral spike protein and an unknown cardiac
protein, and 4) immunogen potential of RNA itself in vaccine and
adjuvant effect production by cytokine activation of pre-existing
autoreactive immune cells \textsuperscript{146}.

Although it was difficult to separate myocarditis from pericarditis from
the published cases, the most common signs and symptoms are not
effort-related chest pain but positional and worsened by deep breathing,
which may be followed by fever, and less common are dyspnea, cough, and
headache. Furthermore, symptoms onset occurred between 1-7 days after
vaccination\textsuperscript{146,147}. Diagnosis is based on medical
history and physical examination, echocardiography, ECG findings, blood
test. Cardiac MRI and biopsy are confirmation diagnostic evaluations,
but these are not available in most centers. Therefore, abnormal Lab
findings, including troponin, brain natriuretic peptide, erythrocyte
sedimentation rate, C-reactive protein, and cardiac antibodies when
coupled with a concerning clinical presentation and ECG, can be used to
make a presumptive diagnosis\textsuperscript{148}. The most common
changes in a post-Covid-19 vaccination patient's ECG are diffuse ST
elevation and ST depression without reciprocal changes,
T-inversion,~sinus tachycardia associated~with non-specific ST/T-wave
changes. Trans-thoracic echocardiography (TTE) and CMR are used to
diagnose effusion and pericardial thickening\textsuperscript{143,148}.
Due to inflammation and high troponin, CRP may become high because of
muscle damage resulting from myocarditis\textsuperscript{146}.

First step evaluation should be ECG and laboratory tests such as CBC,
electrolytes, renal and liver function test, CRP and troponin level, and
SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR)
test. Notice that normal ECG presentation and Normal troponin level do
not rule out isolated pericarditis. Cardiac MRI should be performed if
the clinical findings are highly probable and the cardiac troponin level
is elevated \textsuperscript{145}. There is not enough evidence to
support anti-inflammatory drug prescription for all patients post
Covid-19 vaccination myocarditis or pericarditis. Generally, based on
the evidence we have, pain management and NSAIDs with or without
colchicine can be used for mild or moderate. Also, in severe cases, IVIG
and corticosteroids might be considered. In unstable hemodynamic
patients, inotrope drug and cardiogenic shock management might be
required \textsuperscript{145,146,148}

\textbf{Neurologic complications}

\selectlanguage{ngerman}\textbf{Guillain-Barré syndrome}

Guillain-Barré syndrome (GBS) is a rare acute severe acquired
immune-mediated inflammatory polyradiculoneuropathy that affects
peripheral nerves\textsuperscript{149}. The exact pathophysiology is not
fully understood, but it often occurs after a recent
infection\textsuperscript{150}. \emph{Campylobacter jejuni} , CMV, HEV,
Epstein--Barr virus, influenza, mycoplasma pneumoniae, and Zika virus
are the most common infection associated with GBS \textsuperscript{151}.
also, recently, GBS after the Covid-19 infection has been reported, but
on the other hand, we have some cases of GBS-related post-Covid-19
vaccination.\textsuperscript{151,152} Since the Covid-19 vaccines cause
immunization against SARS-CoV-2 infection spike proteins, which bind to
gangliosides and glycoproteins on cell surfaces, the causal connection
could be the cross-reaction between antibodies is produced by Covid-19
vaccines and GBS\textsuperscript{153}. Progressive, ascending,
symmetrical flaccid paralysis of the limbs, simultaneously with hypo or
areflexia, is the typical clinical pattern of the
GBS\textsuperscript{154} and even may include cranial nerve and
respiratory muscle involvement. However, based on some reports about
GBS-related post-Covid-19 vaccination, we have, it seems bifacial
weakness may be the characteristic clinical manifestation of GBS-related
post-Covid-19 vaccination\textsuperscript{155}. The diagnosis as GBS
diagnostic criteria is mainly based on history and physical
examination\textbf{,} ~Electromyography and nerve conduction velocity
(EMG/NCV) studies, and cerebrospinal fluid analysis as a confirmation
diagnostic test.\textbf{~} GBS treatment would be intravenous
immunoglobulin~IVIg (0.4 g/kg/day for 5 days) and plasma
exchange\textsuperscript{150,151,154}.

\textbf{Stroke}

An ischemic stroke could happen because of coagulopathy, blood clot
formation, and thrombosis in the vasculature that carries blood to the
brain\textsuperscript{156}. However, stroke and cerebral accidents are
coagulopathy- and thrombosis-related complications of the Covid-19. Some
evidence of coagulopathy and cerebral vascular accident after the
Covid-19 vaccination has recently been reported\textsuperscript{157}.
The definite underlying mechanism is unknown. It may mimic
heparin-induced thrombocytopenia with existing anti-PF4 but in the
absence of heparin, also known as VITT \textsuperscript{89}. Clinical
manifestation based on which vessel is affected would vary, but sudden
unilateral weakness or numbness in the face or arm and legs, speech
difficulty, hearing or sight loss in one or both eyes, dizziness, and
confusion are the most common signs and symptoms. Platelet
count~\emph{\textless{}~} 100,000/\selectlanguage{greek}µ\selectlanguage{english}L~with a high D-dimer level and an
inappropriately low fibrinogen level would be typical laboratory
findings \textsuperscript{89}.

Therefore, this is a rare but life-threatening adverse event that needs
critical and rapid management. This phenomenon should be considered in
patients with focal neurological deficits or other serious neurological
disorders, with platelet counts under 100,000/\selectlanguage{greek}µ\selectlanguage{english}L up to one month after
the Covid-19 vaccination. First step evaluation includes brain CT scan
with additional venography and lab test like CBC, Retic counts,
peripheral blood smear, PT, aPTT, fibrinogen, D-dimer test,
antiphospholipid LDH level, paroxysmal nocturnal screening, and
ADAMTS-13 should be done for suspected cases. Also, serum samples for
anti-PF4 antibodies should be sent immediately\textsuperscript{89}.
Since diagnosis and management of these critical and challenging
situations will need close collaboration, hematologist and neurologist
consultation is another main part of the better management and should be
prepared. It should be noticed that for VITT management, heparin drugs
in all forms (unfractionated heparin, or low-molecular-weight heparin,
e.g., enoxaparin) and platelets transfusion because of exacerbation are
all avoided\textsuperscript{89}. Nevertheless, you can use non-heparin
agents like direct oral anticoagulants (DOACs, fondaparinux, danaparoid,
or argatroban) depending on the clinical picture for anticoagulation.
Also, IVIG administration is recommended (1 g/kg, which can be given in
divided doses over two days)\textsuperscript{89,158}.

\textbf{Bell's palsy}

Acute onset peripheral mononeuropathy can cause paresis or paralysis of
the facial nerve (seventh cranial nerve, IV) and is also known as Bell's
palsy. Bell's palsy is the most common sudden onset mononeuropathy and
has a very potent predilection for women\textsuperscript{159}. Diabetes,
obesity, hypertension, pregnancy and upper respiratory tract infection
could be risk factors of the condition\textsuperscript{160}. Although
the exact pathophysiology is unknown, this phenomenon could result from
cranial nerve VII inflammation and edema caused by viral
infections\textsuperscript{160}. The relationship between the intranasal
influenza vaccine and Bell's palsy was shown in
2004\textsuperscript{160}. However, we had reports about bell's
palsy-related SARS-CoV-2 infection\textsuperscript{161}, but even some
reports about bell's palsy occurring after the Covid-19 vaccination have
been addressed recently\textsuperscript{162}. The mechanism of bell's
palsy-related Covid-19 -the vaccine is under investigation, but there is
some potential explanation hypothesis. First, the mRNA vaccines are
associated with interferon type 1 and can cause transient lymphopenia
about 1-3 days after administration, on the other hand, Cluster of
differentiation (CD) 3 and 4 are down in the acute phase of bell's
palsy. Second, Alpha interferon which is a type of interferon 1 can
cause tolerance disruption of myelin sheath
antigen\textsuperscript{163}. Therefore SARS-CoV-2 vaccination should be
considered as an additional reason for Bell's palsy besides other causes
like idiopathic and viruses\textsuperscript{163}. The diagnosis is based
on clinical presentation and no additional test. Although Bell's palsy
will be cured spontaneously in many cases, a high-dose
corticosteroid\textbf{~} as a routine dosage based on guidelines would
be helpful, and in severe cases, antiviral agents such as valacyclovir
or acyclovir might be effective to enhance outcome\textsuperscript{159}.

\textbf{Transverse myelitis}

Transverse myelitis (TM) is a rare, acquired focal neurological disorder
resulting from an inflammatory condition that affects the spinal cord
without any compression. Demyelinating disorders such as multiple
sclerosis, neuromyelitis optica (NMO), infections, and vaccines are the
most common causes\textsuperscript{164}. Although post-vaccination
transverse myelitis is uncommon, some studies TM-related vaccines after
diphtheria, Tetanus, pertussis, measles, mumps, rubella, HBV, seasonal
influenza, oral polio vaccine administration have been reported.
Recently, transverse myelitis following Covid-19 vaccination has been
reported \textsuperscript{165}. The definitive mechanism of this
condition is not obvious. Some supposals can justify this phenomenon,
but molecular mimicry is the most common mechanism because of the
similarity between microbial pathogen antigens and
self-antigens\textsuperscript{166}. Clinical manifestations vary based
on the place of involvement, but transverse myelitis is described by the
sudden onset of acute or sub-acute bilateral sensory-motor and autonomic
dysfunction with a clearly defined sensory level\textsuperscript{166}.
Most patients present with legs and arms weakness, pain, tingling,
burning sensation, sensory alteration, bladder dysfunction, urinary
retention, defecation disturbance, paraplegia, hyperactive
reflexes\textsuperscript{164,166}. In general, the first step in
transverse myelitis diagnosis is history and physical examination. The
next step would be ruling out the compressive etiologies by
gadolinium-enhanced MRI and after structural abnormality investigation,
cerebrospinal fluid (CSF) analysis for inflammation and define
demyelinating extension.

Further workup may be performed to investigate other possible causes
like infections or vitamin B12 deficiency\textsuperscript{167}.
Currently, we do not have specified guidelines for the treatment of TM
following Covid-19 vaccination\textsuperscript{164}, but treatment would
be the administration of steroids (1 g intravenous methylprednisolone
daily for 3-5 days). Plasmapheresis therapy can be used if the patient's
symptoms do not improve\textsuperscript{165,168,169}.

\textbf{Conclusion}

There have been abundant reports of adverse events following Covid-19
vaccines, though many of which are self-limited and non-serious.
Nevertheless, some of the rare adverse events are reported to be
life-threatening (Table 1). Therefore, it is vital to monitor at-risk
vaccinated people for such adverse events, and if necessary, appropriate
diagnostic modalities and therapeutic options should be utilized to
minimize such catastrophic events. Also, as the incidence of such rare
adverse events is significantly lower after administering Covid-19
vaccines than the disease itself, the benefits of vaccination outweigh
its risks for all genders and age groups. Hence, all stakeholders,
medical professionals, and governments should encourage people to
receive the Covid-19 vaccine.

\textbf{Acknowledgments}

The authors would like to thank the clinical research development center
of Imam Reza Hospital, Kermanshah University of Medical Sciences, for
their kind support\textbf{.} Figure 1 is created with BioRender.com

\textbf{Data Availability Statement}

The data that support the findings of this study are available from the
corresponding author upon reasonable request.

\textbf{Conflict of interest disclosure}

TTS reports that he provides strategic and scientific recommendations as
a member of the Advisory Board and speaker for Novocure, Inc. and also
as a member of the Advisory Board to Galera Therapeutics, which are not
in any way associated with the content or disease site as presented in
this manuscript.~All other authors have no relevant financial interests
to be declared.

\textbf{Author Contributions}

\begin{itemize}
\tightlist
\item
  \textbf{ZMA:} Data collection and writing the manuscript.
\item
  \textbf{JJL:} Helped with manuscript writing and contributed
  substantial revisions to the manuscript's content.
\item
  \textbf{AS:} Helped with manuscript writing and contributed
  substantial revisions to the manuscript's content.
\item
  \textbf{MP:} Data collection and helped with manuscript writing.
\item
  \textbf{AB:} Data collection and helped with manuscript writing.
\item
  \textbf{EH:} Data collection and helped with manuscript writing.
\item
  \textbf{ND:} Data collection and helped with manuscript writing.
\item
  \textbf{SA:} Data collection and helped with manuscript writing.
\item
  \textbf{AA:} Helped with manuscript writing and contributed
  substantial revisions to the manuscript's content.
\item
  \textbf{RH:} Visualization, software, and helped with manuscript
  writing.
\item
  \textbf{ZV:} Helped with manuscript writing and contributed
  substantial revisions to the manuscript's content.
\item
  \textbf{TTS:} Helped with manuscript writing and contributed
  substantial revisions to the manuscript's content.
\item
  \textbf{MJMS:} Helped with manuscript writing and contributed
  substantial revisions to the manuscript's content.
\item
  \textbf{MB:} Data collection, helped with manuscript writing, and
  contributed substantial revisions to the manuscript's content.
\item
  \textbf{SE:} Design of the research study, supervision
\end{itemize}

\textbf{References}

1. Li X, Ostropolets A, Makadia R, et al. Characterising the background
incidence rates of adverse events of special interest for covid-19
vaccines in eight countries: multinational network cohort
study.\emph{BMJ} . 2021;373:n1435. doi:10.1136/bmj.n1435

2. COVID C, Team R. Allergic reactions including anaphylaxis after
receipt of the first dose of Moderna COVID-19 Vaccine---United States,
December 21, 2020--January 10, 2021. \emph{Morbidity and Mortality
Weekly Report} . 2021;70(4):125.

3. Mohseni Afshar Z, Babazadeh A, Janbakhsh A, et al. Vaccine-induced
immune thrombotic thrombocytopenia after vaccination against Covid-19: A
clinical dilemma for clinicians and patients. \emph{Rev Med Virol} . Jul
1 2021:e2273. doi:10.1002/rmv.2273

4. Ichikawa S, Kohata K, Okitsu Y, et al. Acquired hemophilia A with
sigmoid colon cancer: successful treatment with rituximab followed by
sigmoidectomy. \emph{Int J Hematol} . Jul 2009;90(1):33-36.
doi:10.1007/s12185-009-0347-9

5. Hafzah H, McGuire C, Hamad A. A Case of Acquired Hemophilia A
Following SARS-CoV-2 Infection. \emph{Cureus} . Jul 2021;13(7):e16579.
doi:10.7759/cureus.16579

6. Radwi M, Farsi S. A case report of acquired hemophilia following
COVID-19 vaccine. \emph{J Thromb Haemost} . Jun 2021;19(6):1515-1518.
doi:10.1111/jth.15291

7. Farley S, Ousley R, Van Wagoner N, Bril F. Autoimmunity after
Coronavirus Disease 2019 (COVID-19) Vaccine: A Case of Acquired
Hemophilia A. \emph{Thromb Haemost} . Aug 5 2021;doi:10.1055/a-1579-5396

8. Cittone MG, Battegay R, Condoluci A, et al. The statistical risk of
diagnosing coincidental acquired hemophilia A following anti-SARS-CoV-2
vaccination. \emph{J Thromb Haemost} . Sep 2021;19(9):2360-2362.
doi:10.1111/jth.15421

9. Portuguese AJ, Sunga C, Kruse-Jarres R, Gernsheimer T, Abkowitz J.
Autoimmune- and complement-mediated hematologic condition recrudescence
following SARS-CoV-2 vaccination. \emph{Blood Adv} . Jul 13
2021;5(13):2794-2798. doi:10.1182/bloodadvances.2021004957

10. Fueyo-Rodriguez O, Valente-Acosta B, Jimenez-Soto R, et al.
Secondary immune thrombocytopenia supposedly attributable to COVID-19
vaccination. \emph{BMJ Case Rep} . May 31
2021;14(5)doi:10.1136/bcr-2021-242220

11. Welsh KJ, Baumblatt J, Chege W, Goud R, Nair N. Thrombocytopenia
including immune thrombocytopenia after receipt of mRNA COVID-19
vaccines reported to the Vaccine Adverse Event Reporting System
(VAERS).\emph{Vaccine} . Jun 8 2021;39(25):3329-3332.
doi:10.1016/j.vaccine.2021.04.054

12. Lee EJ, Cines DB, Gernsheimer T, et al. Thrombocytopenia following
Pfizer and Moderna SARS-CoV-2 vaccination. \emph{Am J Hematol} . May 1
2021;96(5):534-537. doi:10.1002/ajh.26132

13. Kim MA, Lee YW, Kim SR, et al. COVID-19 Vaccine-associated
Anaphylaxis and Allergic Reactions: Consensus Statements of the KAAACI
Urticaria/Angioedema/Anaphylaxis Working Group. \emph{Allergy Asthma
Immunol Res} . Jul 2021;13(4):526-544. doi:10.4168/aair.2021.13.4.526

14. Tanno LK, Castells M, Caminati M, Senna G, Demoly P. Anaphylaxis and
Coronavirus Disease 2019 vaccine: a danger relationship? \emph{Curr Opin
Allergy Clin Immunol} . Oct 1 2021;21(5):411-417.
doi:10.1097/ACI.0000000000000778

15. Abi Zeid Daou C, Natout MA, El Hadi N. Biphasic anaphylaxis after
exposure to the first dose of Pfizer-BioNTech COVID-19 mRNA
vaccine.\emph{J Med Virol} . Oct 2021;93(10):6027-6029.
doi:10.1002/jmv.27109

16. Cabanillas B, Akdis CA, Novak N. COVID-19 vaccine anaphylaxis: IgE,
complement or what else? A reply to: ''COVID-19 vaccine anaphylaxis: PEG
or not?''. \emph{Allergy} . Jun 2021;76(6):1938-1940.
doi:10.1111/all.14725

17. Lee E, Lee YK, Kim TE, et al. Reports of anaphylaxis after
coronavirus disease 2019 vaccination, South Korea, 26 February to 30
April 2021. \emph{Euro Surveill} . Aug
2021;26(33)doi:10.2807/1560-7917.ES.2021.26.33.2100694

18. Bahloul M, Ketata W, Lahyeni D, et al. Pulmonary capillary leak
syndrome following COVID-19 virus infection. \emph{J Med Virol} . Jan
2021;93(1):94-96. doi:10.1002/jmv.26152

19. Wu MA, Fossali T, Pandolfi L, et al. Hypoalbuminemia in COVID-19:
assessing the hypothesis for underlying pulmonary capillary
leakage.\emph{J Intern Med} . Jun 2021;289(6):861-872.
doi:10.1111/joim.13208

20. Case R, Ramaniuk A, Martin P, Simpson PJ, Harden C, Ataya A.
Systemic Capillary Leak Syndrome Secondary to Coronavirus Disease
2019.\emph{Chest} . Dec 2020;158(6):e267-e268.
doi:10.1016/j.chest.2020.06.049

21. Matheny M, Maleque N, Channell N, et al. Severe Exacerbations of
Systemic Capillary Leak Syndrome After COVID-19 Vaccination: A Case
Series. \emph{Ann Intern Med} . Jun 15 2021;doi:10.7326/L21-0250

22. Choi GJ, Baek SH, Kim J, et al. Fatal Systemic Capillary Leak
Syndrome after SARS-COV-2Vaccination in Patient with Multiple
Myeloma.\emph{Emerg Infect Dis} . Aug 30
2021;27(11)doi:10.3201/eid2711.211723

23. Silva TF, Tomiotto-Pellissier F, Sanfelice RA, et al. A 21st Century
Evil: Immunopathology and New Therapies of COVID-19. \emph{Front
Immunol} . 2020;11:562264. doi:10.3389/fimmu.2020.562264

24. Obeid M, Fenwick C, Pantaleo G. Reactivation of IgA vasculitis after
COVID-19 vaccination. \emph{Lancet Rheumatol} . Sep 2021;3(9):e617.
doi:10.1016/S2665-9913(21)00211-3

25. Negrea L, Rovin BH. Gross hematuria following vaccination for severe
acute respiratory syndrome coronavirus 2 in 2 patients with IgA
nephropathy. \emph{Kidney Int} . Jun 2021;99(6):1487.
doi:10.1016/j.kint.2021.03.002

26. Rahim SEG, Lin JT, Wang JC. A case of gross hematuria and IgA
nephropathy flare-up following SARS-CoV-2 vaccination. \emph{Kidney Int}
. Jul 2021;100(1):238. doi:10.1016/j.kint.2021.04.024

27. Sirufo MM, Raggiunti M, Magnanimi LM, Ginaldi L, De Martinis M.
Henoch-Sch\selectlanguage{ngerman}önlein Purpura Following the First Dose of COVID-19 Viral
Vector Vaccine: A Case Report. \emph{Vaccines} . 2021;9(10):1078.

28. Obeid M, Fenwick C, Pantaleo G. Reactivation of IgA vasculitis after
COVID-19 vaccination. \emph{The Lancet Rheumatology} . 2021;3(9):e617.

29. Cohen SR, Prussick L, Kahn JS, Gao DX, Radfar A, Rosmarin D.
Leukocytoclastic vasculitis flare following the COVID-19
vaccine.\emph{Int J Dermatol} . Aug 2021;60(8):1032-1033.
doi:10.1111/ijd.15623

30. Bostan E, Gulseren D, Gokoz O. New-onset leukocytoclastic vasculitis
after COVID-19 vaccine. \emph{Int J Dermatol} . Oct
2021;60(10):1305-1306. doi:10.1111/ijd.15777

31. singh Arora K, Ariff M, Malik R, Kasar A, Patel C. COVID-19 Pfizer
Vaccine associated case of Leukocytoclastic vasculitis. \emph{Cureus
Journal of Medical Science} . 2021;

32. Dash S, Behera B, Sethy M, Mishra J, Garg S. COVID-19
vaccine-induced urticarial vasculitis. \emph{Dermatol Ther} . Aug 8
2021:e15093. doi:10.1111/dth.15093

33. Frumholtz L, Laurent-Roussel S, Lipsker D, Terrier B. Cutaneous
Vasculitis: Review on Diagnosis and Clinicopathologic
Correlations.\emph{Clin Rev Allergy Immunol} . Oct 2021;61(2):181-193.
doi:10.1007/s12016-020-08788-4

34. Vassallo C, Boveri E, Brazzelli V, et al. Cutaneous lymphocytic
vasculitis after administration of COVID-19 mRNA vaccine. \emph{Dermatol
Ther} . Jul 30 2021:e15076. doi:10.1111/dth.15076

35. Terracina KA, Tan FK. Flare of rheumatoid arthritis after COVID-19
vaccination. \emph{The Lancet Rheumatology} . 2021;

36. Ray P, Black S, Shinefield H, et al. Risk of rheumatoid arthritis
following vaccination with tetanus, influenza and hepatitis B vaccines
among persons 15--59 years of age. \emph{Vaccine} .
2011;29(38):6592-6597.

37. Bixio R, Bertelle D, Masia M, Pistillo F, Carletto A, Rossini M.
Incidence of Disease Flare After BNT162b2 Coronavirus Disease 2019
Vaccination in Patients With Rheumatoid Arthritis in Remission.\emph{ACR
Open Rheumatol} . Sep 2 2021;doi:10.1002/acr2.11336

38. An QJ, Qin DA, Pei JX. Reactive arthritis after COVID-19
vaccination. \emph{Hum Vaccin Immunother} . Sep 2 2021;17(9):2954-2956.
doi:10.1080/21645515.2021.1920274

39. Horino T. IgA nephropathy flare-up following SARS-CoV-2
vaccination.\emph{QJM} . Aug 20 2021;doi:10.1093/qjmed/hcab223

40. Hanna C, Hernandez LPH, Bu L, et al. IgA nephropathy presenting as
macroscopic hematuria in 2 pediatric patients after receiving the Pfizer
COVID-19 vaccine. \emph{Kidney international} . 2021;100(3):705-706.

41. Abramson M, Mon-Wei Yu S, Campbell KN, Chung M, Salem F. IgA
Nephropathy After SARS-CoV-2 Vaccination. \emph{Kidney Med} . Sep-Oct
2021;3(5):860-863. doi:10.1016/j.xkme.2021.05.002

42. Plasse R, Nee R, Gao S, Olson S. Acute kidney injury with gross
hematuria and IgA nephropathy after COVID-19 vaccination. \emph{Kidney
Int} . Oct 2021;100(4):944-945. doi:10.1016/j.kint.2021.07.020

43. Oyibo SO. Subacute Thyroiditis After Receiving the
Adenovirus-Vectored Vaccine for Coronavirus Disease
(COVID-19).\emph{Cureus} . Jun 2021;13(6):e16045.
doi:10.7759/cureus.16045

44. Ratnayake GM, Dworakowska D, Grossman AB. Can COVID\selectlanguage{english}-19 immunisation
cause subacute thyroiditis? \emph{Clinical Endocrinology} . 2021;

45. Franquemont S, Galvez J. Subacute Thyroiditis After mRNA Vaccine for
Covid-19. \emph{Journal of the Endocrine Society} . 2021;5(Suppl
1):A956.

46. Norouzi G. Subacute Thyroiditis Following COVID-19
Vaccination.\emph{Authorea Preprints} . 2021;

47. \selectlanguage{polish}İ\selectlanguage{english}remli BG, \selectlanguage{polish}Ş\selectlanguage{english}endur SN, \selectlanguage{ngerman}Ünlütürk U. Three Cases of Subacute
Thyroiditis Following SARS-CoV-2 Vaccine: Post-vaccination ASIA
Syndrome. \emph{The Journal of Clinical Endocrinology \& Metabolism} .
2021;

48. Stasiak M, Lewinski A. New aspects in the pathogenesis and
management of subacute thyroiditis. \emph{Rev Endocr Metab Disord} . May
5 2021:1-13. doi:10.1007/s11154-021-09648-y

49. Sahin Tekin M, Saylisoy S, Yorulmaz G. Subacute thyroiditis
following COVID-19 vaccination in a 67-year-old male patient: a case
report. \emph{Hum Vaccin Immunother} . Jul 1 2021:1-3.
doi:10.1080/21645515.2021.1947102

50. Girgis CM, Russo RR, Benson K. Subacute thyroiditis following the
H1N1 vaccine. \emph{J Endocrinol Invest} . Jul-Aug 2010;33(7):506.
doi:10.1007/BF03346633

51. Altay FA, Guz G, Altay M. Subacute thyroiditis following seasonal
influenza vaccination. \emph{Hum Vaccin Immunother} . Apr 2
2016;12(4):1033-4. doi:10.1080/21645515.2015.1117716

52. Toft J, Larsen S, Toft H. Subacute thyroiditis after hepatitis B
vaccination. \emph{Endocr J} . Feb 1998;45(1):135.

53. Hsiao JY, Hsin SC, Hsieh MC, Hsia PJ, Shin SJ. Subacute thyroiditis
following influenza vaccine (Vaxigrip®) in a young female. \emph{The
Kaohsiung journal of medical sciences} . 2006;22(6):297-300.

54. Bragazzi NL, Hejly A, Watad A, Adawi M, Amital H, Shoenfeld Y. ASIA
syndrome and endocrine autoimmune disorders. \emph{Best Pract Res Clin
Endocrinol Metab} . Jan 2020;34(1):101412.
doi:10.1016/j.beem.2020.101412

55. Bornemann C, Woyk K, Bouter C. Case Report: Two Cases of Subacute
Thyroiditis Following SARS-CoV-2 Vaccination. \emph{Front Med
(Lausanne)} . 2021;8:737142. doi:10.3389/fmed.2021.737142

56. Vera-Lastra O, Ordinola Navarro A, Cruz Domiguez MP, Medina G,
Sanchez Valadez TI, Jara LJ. Two Cases of Graves' Disease Following
SARS-CoV-2 Vaccination: An Autoimmune/Inflammatory Syndrome Induced by
Adjuvants. \emph{Thyroid} . Sep 2021;31(9):1436-1439.
doi:10.1089/thy.2021.0142

57. Goa KL, Benfield P. Hyaluronic acid. A review of its pharmacology
and use as a surgical aid in ophthalmology, and its therapeutic
potential in joint disease and wound healing. \emph{Drugs} . Mar
1994;47(3):536-66. doi:10.2165/00003495-199447030-00009

58. Ghasemi S, Dashti M. Fight against COVID-19 with mRNA vaccines and
interaction with Dermal fillers. \emph{Clin Exp Vaccine Res} . May
2021;10(2):151-153. doi:10.7774/cevr.2021.10.2.151

59. Michon A. Hyaluronic acid soft tissue filler delayed inflammatory
reaction following COVID-19 vaccination - A case report. \emph{J Cosmet
Dermatol} . Sep 2021;20(9):2684-2690. doi:10.1111/jocd.14312

60. Nlandu YM, Makulo JR, Pakasa NM, et al. First Case of
COVID-19-Associated Collapsing Glomerulopathy in Sub-Saharan
Africa.\emph{Case Rep Nephrol} . 2020;2020:8820713.
doi:10.1155/2020/8820713

61. Raza A, Estepa A, Chan V, Jafar MS. Acute Renal Failure in
Critically Ill COVID-19 Patients With a Focus on the Role of Renal
Replacement Therapy: A Review of What We Know So Far. \emph{Cureus} .
Jun 3 2020;12(6):e8429. doi:10.7759/cureus.8429

62. Lebedev L, Sapojnikov M, Wechsler A, et al. Minimal Change Disease
Following the Pfizer-BioNTech COVID-19 Vaccine. \emph{Am J Kidney Dis} .
Jul 2021;78(1):142-145. doi:10.1053/j.ajkd.2021.03.010

63. Lim JH, Han MH, Kim YJ, et al. New-onset Nephrotic Syndrome after
Janssen COVID-19 Vaccination: a Case Report and Literature
Review.\emph{J Korean Med Sci} . Aug 2 2021;36(30):e218.
doi:10.3346/jkms.2021.36.e218

64. Leclerc S, Royal V, Lamarche C, Laurin LP. Minimal Change Disease
With Severe Acute Kidney Injury Following the Oxford-AstraZeneca
COVID-19 Vaccine: A Case Report. \emph{Am J Kidney Dis} . Oct
2021;78(4):607-610. doi:10.1053/j.ajkd.2021.06.008

65. Sanchez Tinajero A, Gonzalez Cueto E, Martinez Orozco JA, Becerril
Vargas E, Ruiz Santillan DP, Resendiz Escobar H. A 65-Year-Old Woman
with a History of Type 2 Diabetes Mellitus and Hypertension and a 15-Day
History of Dry Cough and Fever Who Presented with Acute Renal Failure
Due to Infection with SARS-Cov-2. \emph{Am J Case Rep} . Jul 25
2020;21:e926737. doi:10.12659/AJCR.926737

66. Eder M, Strassl R, Klager J, Aigner C, Thalhammer F, Kikic Z.
COVID-19: IgG seroconversion under intensive glucocorticoid treatment in
a high-risk patient with minimal change disease. \emph{Wien Klin
Wochenschr} . Apr 2021;133(7-8):412-413. doi:10.1007/s00508-020-01776-w

67. Su JR, Haber P, Ng CS, et al. Erythema multiforme, Stevens Johnson
syndrome, and toxic epidermal necrolysis reported after vaccination,
1999-2017. \emph{Vaccine} . Feb 11 2020;38(7):1746-1752.
doi:10.1016/j.vaccine.2019.12.028

68. Rongioletti F, Ferreli C, Sena P, Caputo V, Atzori L.
Clinicopathologic correlations of COVID-19-related cutaneous
manifestations with special emphasis on histopathologic
patterns.\emph{Clin Dermatol} . Jan-Feb 2021;39(1):149-162.
doi:10.1016/j.clindermatol.2020.12.004

69. Bonino CB, Arias NM, Rico ML-P, et al. Atypical erythema multiforme
related to BNT162b2 (Pfizer-BioNTech) COVID-19
vaccine.\emph{International journal of dermatology} .
2021;doi:https://doi.org/10.1111/ijd.15894

70. Samim F, Auluck A, Zed C, Williams PM. Erythema multiforme: a review
of epidemiology, pathogenesis, clinical features, and
treatment.\emph{Dent Clin North Am} . Oct 2013;57(4):583-96.
doi:10.1016/j.cden.2013.07.001

71. Clinic M. Chilblains. Mayo Clinic.

72. Ayatollahi A, Hosseini H, Firooz R, Firooz A. COVID-19 vaccines:
What dermatologists should know? \emph{Dermatol Ther} . Jul 7
2021;n/a(n/a):e15056. doi:10.1111/dth.15056

73. Pileri A, Guglielmo A, Raone B, Patrizi A. Chilblain lesions after
COVID-19 mRNA vaccine. \emph{Br J Dermatol} . Jul 2021;185(1):e3.
doi:10.1111/bjd.20060

74. Temiz SA, Abdelmaksoud A, Dursun R, Vestita M. Acral chilblain-like
lesions following inactivated SARS-CoV-2 vaccination. \emph{Int J
Dermatol} . Sep 2021;60(9):1152-1153. doi:10.1111/ijd.15619

75. Davido B, Mascitti H, Fortier-Beaulieu M, Jaffal K, de Truchis P.
`Blue toes' following vaccination with the BNT162b2 mRNA COVID-19
vaccine. \emph{Journal of Travel Medicine} . 2021;28(4):taab024.

76. Piccolo V, Bassi A, Argenziano G, et al. BNT162b2 mRNA COVID\selectlanguage{english}-19
vaccine\selectlanguage{english}-induced chilblain\selectlanguage{english}-like lesions reinforces the hypothesis of
their relationship with SARS\selectlanguage{english}-CoV\selectlanguage{english}-2. \emph{Journal of the European
Academy of Dermatology and Venereology} . 2021;

77. D'Agostino V, Caranci F, Negro A, et al. A Rare Case of Cerebral
Venous Thrombosis and Disseminated Intravascular Coagulation Temporally
Associated to the COVID-19 Vaccine Administration. \emph{J Pers Med} .
Apr 8 2021;11(4)doi:10.3390/jpm11040285

78. Turetz M, Sideris AT, Friedman OA, Triphathi N, Horowitz JM.
Epidemiology, Pathophysiology, and Natural History of Pulmonary
Embolism. \emph{Semin Intervent Radiol} . Jun 2018;35(2):92-98.
doi:10.1055/s-0038-1642036

79. Kesieme E, Kesieme C, Jebbin N, Irekpita E, Dongo A. Deep vein
thrombosis: a clinical review. \emph{J Blood Med} . 2011;2:59-69.
doi:10.2147/JBM.S19009

80. Greinacher A, Langer F, Makris M, et al. Vaccine-induced immune
thrombotic thrombocytopenia (VITT): Update on diagnosis and management
considering different resources. \emph{J Thromb Haemost} . Jan
2022;20(1):149-156. doi:10.1111/jth.15572

81. Shakibajahromi B, Borhani-Haghighi A, Haseli S, Mowla A. Cerebral
venous sinus thrombosis might be under-diagnosed in the COVID-19
era.\emph{Eneurologicalsci} . 2020;20

82. Shakibajahromi B, Borhani-Haghighi A, Ghaedian M, et al. Early,
delayed, and expanded intracranial hemorrhage in cerebral venous
thrombosis. \emph{Acta Neurol Scand} . Dec 2019;140(6):435-442.
doi:10.1111/ane.13164

83. Shakibajahromi B, Haghighi AB, Salehi A, et al. Clinical and
radiological characteristics and predictors of outcome of cerebral
venous sinus thrombosis, a hospital-based study. \emph{Acta Neurol Belg}
. Aug 2020;120(4):845-852. doi:10.1007/s13760-018-1009-6

84. Mowla A, Shakibajahromi B, Shahjouei S, et al. Cerebral venous sinus
thrombosis associated with SARS-CoV-2; a multinational case
series.\emph{J Neurol Sci} . Dec 15 2020;419:117183.
doi:10.1016/j.jns.2020.117183

85. Furie KL, Cushman M, Elkind MSV, Lyden PD, Saposnik G, American
Heart Association/American Stroke Association Stroke Council L.
Diagnosis and Management of Cerebral Venous Sinus Thrombosis With
Vaccine-Induced Immune Thrombotic Thrombocytopenia. \emph{Stroke} . Jul
2021;52(7):2478-2482. doi:10.1161/STROKEAHA.121.035564

86. Ostovan VR, Foroughi R, Rostami M, et al. Cerebral venous sinus
thrombosis associated with COVID-19: a case series and literature
review. \emph{J Neurol} . Oct 2021;268(10):3549-3560.
doi:10.1007/s00415-021-10450-8

87. Vayne C, Nguyen T-H, Rollin J, et al. Characterization of new
monoclonal PF4-specific antibodies as useful tools for studies on
typical and autoimmune heparin-induced thrombocytopenia.\emph{Thrombosis
and Haemostasis} . 2021;121(03):322-331.

88. Cines DB, Bussel JB. SARS-CoV-2 vaccine--induced immune thrombotic
thrombocytopenia {[}published correction appears in N Engl J Med. 2021
Jun 10;384(23):e92{]}. \emph{N Engl J Med} . 2021;384(23):2254-2256.
doi:10.1056/NEJMe2106315

89. Mehta PR, Apap Mangion S, Benger M, et al. Cerebral venous sinus
thrombosis and thrombocytopenia after COVID-19 vaccination - A report of
two UK cases. \emph{Brain Behav Immun} . Jul 2021;95:514-517.
doi:10.1016/j.bbi.2021.04.006

90. Hernandez AF, Calina D, Poulas K, Docea AO, Tsatsakis AM. Safety of
COVID-19 vaccines administered in the EU: Should we be
concerned?\emph{Toxicology Reports} . 2021;8:871-879.

91. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger
S. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination.\emph{N
Engl J Med} . Jun 3 2021;384(22):2092-2101. doi:10.1056/NEJMoa2104840

92. McCrae KR. Thrombotic thrombocytopenia due to SARS-CoV-2
vaccination. \emph{Cleveland Clinic Journal of Medicine} . 2021;

93. Sharifian-Dorche M, Bahmanyar M, Sharifian-Dorche A, Mohammadi P,
Nomovi M, Mowla A. Vaccine-induced immune thrombotic thrombocytopenia
and cerebral venous sinus thrombosis post COVID-19 vaccination; a
systematic review. \emph{J Neurol Sci} . Sep 15 2021;428:117607.
doi:10.1016/j.jns.2021.117607

94. Scully M, Singh D, Lown R, et al. Pathologic Antibodies to Platelet
Factor 4 after ChAdOx1 nCoV-19 Vaccination. \emph{N Engl J Med} . Jun 10
2021;384(23):2202-2211. doi:10.1056/NEJMoa2105385

95. Committee PRA. \emph{COVID-19 Vaccine AstraZeneca: benefits still
outweigh the risks despite possible link to rare blood clots with low
blood platelets} . 2021.

96. Oldenburg J, Klamroth R, Langer F, et al. Diagnosis and management
of vaccine-related thrombosis following AstraZeneca COVID-19
vaccination: guidance statement from the GTH. \emph{Hamostaseologie} .
2021;

97. Valeriani E, Riva N, Di Nisio M, Ageno W. Splanchnic Vein
Thrombosis: Current Perspectives. \emph{Vasc Health Risk Manag} .
2019;15:449-461. doi:10.2147/VHRM.S197732

98. Aalberg JJ, Collins TP, Dobrow EM. Axillary lymphadenopathy in a
renal cell carcinoma patient after COVID-19 Vaccination. \emph{Radiol
Case Rep} . Aug 2021;16(8):2164-2167. doi:10.1016/j.radcr.2021.05.031

99. Faermann R, Nissan N, Halshtok-Neiman O, et al. COVID-19 Vaccination
Induced Lymphadenopathy in a Specialized Breast Imaging Clinic in
Israel: Analysis of 163 cases. \emph{Acad Radiol} . Sep
2021;28(9):1191-1197. doi:10.1016/j.acra.2021.06.003

100. Mehta N, Sales RM, Babagbemi K, et al. Unilateral axillary
Adenopathy in the setting of COVID-19 vaccine. \emph{Clinical imaging} .
2021;75:12-15.

101. Eifer M, Eshet Y. Imaging of COVID-19 Vaccination at FDG
PET/CT.\emph{Radiology} . 2021;299(2):E248-E248.

102. Ozutemiz C, Krystosek LA, Church AL, et al. Lymphadenopathy in
COVID-19 vaccine recipients: diagnostic dilemma in oncology
patients.\emph{Radiology} . 2021:210275.

103. Keshavarz P, Yazdanpanah F, Rafiee F, Mizandari M. Lymphadenopathy
Following COVID-19 Vaccination: Imaging Findings Review. \emph{Acad
Radiol} . Aug 2021;28(8):1058-1071. doi:10.1016/j.acra.2021.04.007

104. Pereira MP, Flores P, Neto AS. Neck and supraclavicular
lymphadenopathy secondary to 9-valent human papillomavirus
vaccination.\emph{BMJ Case Rep} . Nov 5 2019;12(11):e231582.
doi:10.1136/bcr-2019-231582

105. Barouni AS, Augusto C, Queiroz MV, Lopes MT, Zanini MS, Salas CE.
BCG lymphadenopathy detected in a BCG-vaccinated infant. \emph{Braz J
Med Biol Res} . May 2004;37(5):697-700.
doi:10.1590/s0100-879x2004000500011

106. Katzir Z, Okon E, Ludmirski A, Sherman Y, Haas H. Generalized
lymphadenitis following BCG vaccination in an immunocompetent
12-year-old boy. \emph{European journal of pediatrics} .
1984;141(3):165-167.

107. Shlamovitz GZ, Johar S. A case of Evans' syndrome following
influenza vaccine. \emph{J Emerg Med} . Feb 2013;44(2):e149-51.
doi:10.1016/j.jemermed.2012.01.060

108. Toy H, Karasoy D, Keser M. Lymphadenitis caused by H1N1
vaccination: case report. \emph{Vaccine} . Mar 2 2010;28(10):2158-2160.
doi:10.1016/j.vaccine.2009.12.043

109. Sever JL, Brenner AI, Gale AD, et al. Safety of anthrax vaccine: an
expanded review and evaluation of adverse events reported to the Vaccine
Adverse Event Reporting System (VAERS). \emph{Pharmacoepidemiol Drug
Saf} . Dec 2004;13(12):825-40. doi:10.1002/pds.936

110. Hiller N, Goldberg SN, Cohen-Cymberknoh M, Vainstein V, Simanovsky
N. Lymphadenopathy Associated With the COVID-19 Vaccine. \emph{Cureus} .
Feb 23 2021;13(2):e13524. doi:10.7759/cureus.13524

111. Abou-Foul AK, Ross E, Abou-Foul M, George AP. Cervical
lymphadenopathy following COVID-19 vaccine: Clinical characteristics and
implications for head and neck cancer services. \emph{Authorea
Preprints} . 2021;

112. Singh B, Kaur P, Kumar V, Maroules M. COVID-19 vaccine induced
Axillary and Pectoral Lymphadenopathy on PET scan. \emph{Radiol Case
Rep} . Jul 2021;16(7):1819-1821. doi:10.1016/j.radcr.2021.04.053

113. Fernandez-Prada M, Rivero-Calle I, Calvache-Gonzalez A,
Martinon-Torres F. Acute onset supraclavicular lymphadenopathy
coinciding with intramuscular mRNA vaccination against COVID-19 may be
related to vaccine injection technique, Spain, January and February
2021. \emph{Eurosurveillance} . 2021;26(10):2100193.

114. Tandon S, Shahab R, Benton JI, Ghosh SK, Sheard J, Jones TM.
Fine-needle aspiration cytology in a regional head and neck cancer
center: comparison with a systematic review and meta-analysis.\emph{Head
Neck} . Sep 2008;30(9):1246-52. doi:10.1002/hed.20849

115. Edmonds CE, Zuckerman SP, Conant EF. Management of unilateral
axillary lymphadenopathy detected on breast MRI in the era of
coronavirus disease (COVID-19) vaccination. \emph{American Journal of
Roentgenology} . 2021;

116. Seely JM, Barry MH. The Canadian Society of Breast Imaging
Recommendations for the Management of Axillary Adenopathy in Patients
with Recent COVID-19 Vaccination - Update. \emph{Canadian Association of
Radiologists Journal} . 2021;72(4):601-602. doi:10.1177/0846537121998949

117. Lehman CD, D'Alessandro HA, Mendoza DP, Succi MD, Kambadakone A,
Lamb LR. Unilateral Lymphadenopathy After COVID-19 Vaccination: A
Practical Management Plan for Radiologists Across Specialties. \emph{J
Am Coll Radiol} . Jun 2021;18(6):843-852. doi:10.1016/j.jacr.2021.03.001

118. Hagen C, Nowack M, Messerli M, Saro F, Mangold F, Bode PK. Fine
needle aspiration in COVID-19 vaccine-associated
lymphadenopathy.\emph{Swiss Med Wkly} . Jul 19 2021;151:w20557.
doi:10.4414/smw.2021.20557

119. Al Soub H, Ibrahim W, Al Maslamani M, Abbas G, Ummer W.
Kikuchi-Fujimoto disease following SARS CoV2 vaccination: Case
report.\emph{IDCases} . 2021:e01253.

120. Kucukardali Y, Solmazgul E, Kunter E, Oncul O, Yildirim S, Kaplan
M. Kikuchi-Fujimoto Disease: analysis of 244 cases. \emph{Clin
Rheumatol} . Jan 2007;26(1):50-4. doi:10.1007/s10067-006-0230-5

121. Watanabe T, Hashidate H, Hirayama Y, Iinuma Y. Kikuchi-Fujimoto
disease following vaccination against human papilloma virus infection
and Japanese encephalitis. \emph{Eur J Pediatr} . Sep
2012;171(9):1409-11. doi:10.1007/s00431-012-1729-1

122. Podugu A, Kobe M. Kikuchi-Fujimoto Disease (KFD): A Rare Cause of
Fever and Lymphadenopathy Following Influenza Vaccination. \emph{Chest}
. 2013;144(4):230A.

123. Maleki A, Look-Why S, Manhapra A, Foster CS. COVID-19 Recombinant
mRNA Vaccines and Serious Ocular Inflammatory Side Effects: Real or
Coincidence? \emph{J Ophthalmic Vis Res} . Jul-Sep 2021;16(3):490-501.
doi:10.18502/jovr.v16i3.9443

124. Turbeville SD, Cowan LD, Gass JD. Acute macular neuroretinopathy: a
review of the literature. \emph{Surv Ophthalmol} . Jan-Feb
2003;48(1):1-11. doi:10.1016/s0039-6257(02)00398-3

125. Book BAJ, Schmidt B, Foerster AMH. Bilateral Acute Macular
Neuroretinopathy After Vaccination Against SARS-CoV-2. \emph{JAMA
Ophthalmol} . Jul 1 2021;139(7):e212471.
doi:10.1001/jamaophthalmol.2021.2471

126. Bohler AD, Strom ME, Sandvig KU, Moe MC, Jorstad OK. Acute macular
neuroretinopathy following COVID-19 vaccination. \emph{Eye (Lond)} . Jun
22 2021:1-2. doi:10.1038/s41433-021-01610-1

127. Scharf J, Freund KB, Sadda S, Sarraf D. Paracentral acute middle
maculopathy and the organization of the retinal capillary
plexuses.\emph{Prog Retin Eye Res} . Mar 2021;81:100884.
doi:10.1016/j.preteyeres.2020.100884

128. Pichi F, Aljneibi S, Neri P, Hay S, Dackiw C, Ghazi NG. Association
of Ocular Adverse Events With Inactivated COVID-19 Vaccination in
Patients in Abu Dhabi. \emph{JAMA Ophthalmol} . Sep 2
2021;doi:10.1001/jamaophthalmol.2021.3477

129. Semeraro F, Morescalchi F, Russo A, et al. Central Serous
Chorioretinopathy: Pathogenesis and Management. \emph{Clin Ophthalmol} .
2019;13:2341-2352. doi:10.2147/OPTH.S220845

130. Fowler N, Mendez Martinez NR, Pallares BV, Maldonado RS.
Acute-onset central serous retinopathy after immunization with COVID-19
mRNA vaccine. \emph{Am J Ophthalmol Case Rep} . Sep 2021;23:101136.
doi:10.1016/j.ajoc.2021.101136

131. Subramony R, Lin LC, Knight DK, Aminlari A, Belovarski I. Bilateral
Retinal Detachments in a Healthy 22-year-old Female Following Moderna
SARS-CoV-2 Vaccination. \emph{The Journal of Emergency Medicine} . 2021;

132. Renisi G, Lombardi A, Stanzione M, Invernizzi A, Bandera A, Gori A.
Anterior uveitis onset after bnt162b2 vaccination: is this just a
coincidence? \emph{International Journal of Infectious Diseases} .
2021;110:95-97.

133. Mudie LI, Zick JD, Dacey MS, Palestine AG. Panuveitis following
Vaccination for COVID-19. \emph{Ocul Immunol Inflamm} . May 19
2021;29(4):741-742. doi:10.1080/09273948.2021.1949478

134. Goyal M, Murthy SI, Annum S. Bilateral Multifocal Choroiditis
following COVID-19 Vaccination. \emph{Ocul Immunol Inflamm} . May 19
2021;29(4):753-757. doi:10.1080/09273948.2021.1957123

135. Saraceno JJF, Souza GM, Dos Santos Finamor LP, Nascimento HM,
Belfort R, Jr. Vogt-Koyanagi-Harada Syndrome following COVID-19 and
ChAdOx1 nCoV-19 (AZD1222) vaccine. \emph{Int J Retina Vitreous} . Aug 30
2021;7(1):49. doi:10.1186/s40942-021-00319-3

136. Hong J, Chopra S, Kahn J, Kim B, Khemichian S. Autoimmune hepatitis
triggered by COVID-19. \emph{Intern Med J} . 2021;51(7):1182-1183.
doi:10.1111/imj.15420

137. McShane C, Kiat C, Rigby J, Crosbie O. The mRNA COVID-19 vaccine -
A rare trigger of autoimmune hepatitis? \emph{J Hepatol} . Jul 8
2021;doi:10.1016/j.jhep.2021.06.044

138. Rela M, Jothimani D, Vij M, Rajakumar A, Rammohan A. Auto-immune
hepatitis following COVID vaccination. \emph{J Autoimmun} . Sep
2021;123:102688. doi:10.1016/j.jaut.2021.102688

139. Lu L, Liu M, Sun R, Zheng Y, Zhang P. Myocardial Infarction:
Symptoms and Treatments. \emph{Cell Biochem Biophys} . Jul
2015;72(3):865-7. doi:10.1007/s12013-015-0553-4

140. Chatterjee S, Ojha UK, Vardhan B, Tiwari A. Myocardial infarction
after COVID-19 vaccination-casual or causal? \emph{Diabetes Metab Syndr}
. May-Jun 2021;15(3):1055-1056. doi:10.1016/j.dsx.2021.04.006

141. Boivin Z, Martin J. Untimely Myocardial Infarction or COVID-19
Vaccine Side Effect. \emph{Cureus} . Mar 2 2021;13(3):e13651.
doi:10.7759/cureus.13651

142. Maadarani O, Bitar Z, Elzoueiry M, et al. Myocardial infarction
post COVID-19 vaccine--coincidence, Kounis syndrome or other
explanation--time will tell. \emph{JRSM open} .
2021;12(8):20542704211025259.

143. Oakley CM. Myocarditis, pericarditis and other pericardial
diseases. \emph{Heart} . Oct 2000;84(4):449-54.
doi:10.1136/heart.84.4.449

144. Singer ME, Taub IB, Kaelber DC. Risk of Myocarditis from COVID-19
Infection in People Under Age 20: A Population-Based
Analysis.\emph{medRxiv} . Jul 27 2021;doi:10.1101/2021.07.23.21260998

145. Luk A, Clarke B, Dahdah N, et al. Myocarditis and Pericarditis
following COVID-19 mRNA Vaccination: Practical Considerations for Care
Providers. \emph{Canadian Journal of Cardiology} . 2021;

146. Das BB, Moskowitz WB, Taylor MB, Palmer A. Myocarditis and
Pericarditis Following mRNA COVID-19 Vaccination: What Do We Know So
Far? \emph{Children} . 2021;8(7):607.

147. Ramirez-Garcia A, Lozano Jimenez S, Darnaude Ximenez I, Gil Cacho
A, Aguado-Noya R, Segovia Cubero J. Pericarditis after administration of
the BNT162b2 mRNA COVID-19 vaccine. \emph{Rev Esp Cardiol (Engl Ed)} .
Jul 16 2021;doi:10.1016/j.rec.2021.07.005

148. Diaz GA, Parsons GT, Gering SK, Meier AR, Hutchinson IV, Robicsek
A. Myocarditis and Pericarditis After Vaccination for
COVID-19.\emph{JAMA} . Sep 28 2021;326(12):1210-1212.
doi:10.1001/jama.2021.13443

149. Prasad A, Hurlburt G, Podury S, Tandon M, Kingree S, Sriwastava S.
A Novel Case of Bifacial Diplegia Variant of Guillain-Barre Syndrome
Following Janssen COVID-19 Vaccination. \emph{Neurol Int} . Aug 13
2021;13(3):404-409. doi:10.3390/neurolint13030040

150. Hasan T, Khan M, Khan F, Hamza G. Case of Guillain-Barre syndrome
following COVID-19 vaccine. \emph{BMJ Case Rep} . Jun 29
2021;14(6):e243629. doi:10.1136/bcr-2021-243629

151. Trimboli M, Zoleo P, Arabia G, Gambardella A. Guillain-Barre
syndrome following BNT162b2 COVID-19 vaccine. \emph{Neurol Sci} . Aug 4
2021:1-2. doi:10.1007/s10072-021-05523-5

152. Waheed S, Bayas A, Hindi F, Rizvi Z, Espinosa PS. Neurological
complications of COVID-19: Guillain-Barre syndrome following Pfizer
COVID-19 vaccine. \emph{Cureus} . 2021;13(2)

153. Introna A, Caputo F, Santoro C, et al. Guillain-Barre syndrome
after AstraZeneca COVID-19-vaccination: A causal or casual
association?\emph{Clin Neurol Neurosurg} . Sep 2021;208:106887.
doi:10.1016/j.clineuro.2021.106887

154. Scendoni R, Petrelli C, Scaloni G, Logullo FO.
Electromyoneurography and laboratory findings in a case of
Guillain-Barre syndrome after second dose of Pfizer COVID-19
vaccine.\emph{Hum Vaccin Immunother} . Aug 4 2021:1-4.
doi:10.1080/21645515.2021.1954826

155. McKean N, Chircop C. Guillain-Barre syndrome after COVID-19
vaccination. \emph{BMJ Case Rep} . Jul 30 2021;14(7):e244125.
doi:10.1136/bcr-2021-244125

156. ChC E, Zeller J, Stingele R. Stroke: causes and
classification.\emph{Hamostaseologie} . 2006;26(4):298-308.

157. Markus HS. Ischaemic stroke can follow COVID-19 vaccination but is
much more common with COVID-19 infection itself. \emph{Journal of
Neurology, Neurosurgery \& Psychiatry} .
2021;doi:10.1136/jnnp-2021-327057

158. Blauenfeldt RA, Kristensen SR, Ernstsen SL, Kristensen CCH,
Simonsen CZ, Hvas AM. Thrombocytopenia with acute ischemic stroke and
bleeding in a patient newly vaccinated with an adenoviral vector-based
COVID-19 vaccine. \emph{J Thromb Haemost} . Jul 2021;19(7):1771-1775.
doi:10.1111/jth.15347

159. Mason MC, Liaqat A, Morrow J, Basso R, Gujrati Y. Bilateral Facial
Nerve Palsy and COVID-19 Vaccination: Causation or
Coincidence?\emph{Cureus} . Aug 2021;13(8):e17602.
doi:10.7759/cureus.17602

160. Burrows A, Bartholomew T, Rudd J, Walker D. Sequential
contralateral facial nerve palsies following COVID-19 vaccination first
and second doses. \emph{BMJ Case Rep} . Jul 19 2021;14(7):e243829.
doi:10.1136/bcr-2021-243829

161. Gupta S, Jawanda MK, Taneja N, Taneja T. A systematic review of
Bell's Palsy as the only major neurological manifestation in COVID-19
patients. \emph{Journal of Clinical Neuroscience} . 2021;90:284-292.

162. Sato K, Mano T, Niimi Y, Toda T, Iwata A, Iwatsubo T. Facial nerve
palsy following the administration of COVID-19 mRNA vaccines: analysis
of a self-reporting database. \emph{Int J Infect Dis} . Sep 4
2021;111:310-312. doi:10.1016/j.ijid.2021.08.071

163. Soeiro T, Salvo F, Pariente A, Grandvuillemin A, Jonville-Bera A-P,
Micallef J. Type I interferons as the potential mechanism linking mRNA
COVID-19 vaccines to Bell's palsy. \emph{Therapie} . 2021;

164. Tahir N, Koorapati G, Prasad S, et al. SARS-CoV-2
Vaccination-Induced Transverse Myelitis. \emph{Cureus} . 2021;13(7)

165. Roman GC, Gracia F, Torres A, Palacios A, Gracia K, Harris D. Acute
Transverse Myelitis (ATM):Clinical Review of 43 Patients With
COVID-19-Associated ATM and 3 Post-Vaccination ATM Serious Adverse
Events With the ChAdOx1 nCoV-19 Vaccine (AZD1222). \emph{Front Immunol}
. 2021;12:653786. doi:10.3389/fimmu.2021.653786

166. Khan E, Shrestha AK, Colantonio MA, Liberio RN, Sriwastava S. Acute
transverse myelitis following SARS-CoV-2 vaccination: a case report and
review of literature. \emph{Journal of Neurology} . 2021:1-12.

167. Group TMCW. Proposed diagnostic criteria and nosology of acute
transverse myelitis. Neurology 2002; 59: 499--505. \emph{QJM: An
International Journal of Medicine} . 2020;

168. Pagenkopf C, Sudmeyer M. A case of longitudinally extensive
transverse myelitis following vaccination against Covid-19. \emph{J
Neuroimmunol} . Sep 15 2021;358:577606.
doi:10.1016/j.jneuroim.2021.577606

169. Notghi AA, Atley J, Silva M. Lessons of the month 1: Longitudinal
extensive transverse myelitis following AstraZeneca COVID-19
vaccination. \emph{Clin Med (Lond)} . Sep 2021;21(5):e535-e538.
doi:10.7861/clinmed.2021-0470

\textbf{Figure legend}

\textbf{Figure 1. Rare adverse events of COVID-19 vaccination.} The side
effects of the Covid-19 vaccines are different and can affect different
systems and tissues in the body. Vascular side effects have been seen in
the brain, vascular system of the limbs, abdomen, and heart, including
CVST/CVT, VITT, DIC, DVT, PTE, CLS, AHA, ITP, SVT, cardiac arrest, HF,
MI, pericarditis, and myocarditis, respectively. Ocular involvement
includes uveitis, bilateral retinal detachment, central serous
retinopathy, acute macular retinopathy, AAION and AZOOR, and paracentral
acute middle maculopathy. The thyroid gland can also cause thyroiditis.
Neurological side effects such as GBS, Bell's palsy, stroke, and
transverse myelitis have also been observed in patients. It causes
filler on the face. In addition to facial involvement, skin infections
such as erythema multiforme, chilblains, and cutaneous vasculitis have
also been reported. It causes autoimmune hepatitis in the liver and has
caused many complications for the kidneys. Symptoms of immune
rheumatologic events have also been observed in some patients.
Lymphadenitis is one of the immune complications in the lymph nodes. In
addition to the above, it also causes spontaneous abortion and menstrual
problems in women. Abbreviations: CVST/CVT, Cerebral venous sinus
thrombosis/Cerebral venous thrombosis; VITT, Vaccine-induced immune
thrombotic thrombocytopenia; DIC, Disseminated intravascular
coagulation; DVT, Deep vein thrombosis; PTE, Pulmonary
thromboendarterectomy; CLS, Capillary leak syndrome; AHA, Acquired
hemophilia A; ITP, Immune thrombocytopenic purpura; SVT,
Supraventricular tachycardia; HF, Heart failure; MI, Myocardial
infarction; AAION, Arteritic anterior ischemic optic neuropathy; AZOOR,
Acute zonal occult outer retinopathy; GBS, Guillain-Barre syndrome.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Table 1.docx`  available at \url{https://authorea.com/users/433057/articles/563161-rare-adverse-events-following-covid-19-vaccination-a-review}

\selectlanguage{english}
\FloatBarrier
\end{document}

