Discussion
Common adverse effects of COVID-19 vaccination including local
reactions, fever, myalgia, arthralgia and headache can be well tolerated
in outpatient setting, but some conditions need inpatient care and
somehow can be problematic or even fatal. Here in, we reported three
cases of serious events of post COVID-19 AstraZeneca vaccination that
hospitalized and managed successfully, including encephalopathy, CVST
and LCV.
Causality assessment of adverse drug reaction (ADR) with COVID-19
vaccination based on ADR scales including Naranjo Probability Scale(10)
and the WHO-UMC causality system(11) showed all discussed cases were
categorized as probable but not definite cases caused by COVID-19
vaccination. Severity of ADR by COVID-19 vaccination for presented cases
were evaluated by J Seigel and PJ Schneider study(12) and also Karch and
Lasanga study(13), post vaccination encephalitis and VITT were
classified as severe cases requiring intensive medical care which are
life threatening reactions, while LCV categorized with moderate severity
requiring special treatment with an increase in hospitalization by at
least one day.
Encephalitis/encephalopathy is defined as inflammation of brain tissue
provoked by an infection or an autoimmune response(14). The occurrence
of encephalitis, according to several publicly existing databases
(Welcome to GOV.UK (www.gov.uk),
European Medicines Agency |
(europa.eu),
Paul-Ehrlich-Institut -
Startseite (pei.de)), estimated to be 8 and 2 per 10 million injected
shots following AstraZeneca and Pfizer-Biontech vaccines,
respectively(15). Possible or confirmed diagnosis of encephalitis is
determined by combination of clinical manifestations, laboratory tests,
neuroimaging, and electroencephalographic studies(16). Our first case
had the major criteria of encephalitis according to Venkatesan et al.,
presenting to medical attention with altered mental status lasting ≥24 h
with no alternative cause stated, and one minor criteria of documented
fever within the 72 hours prior or after presentation(16). The patient
neuroimaging and CSF analysis weren’t compatible with encephalitis and
EEG wasn’t performed for her, so the complete criteria for encephalitis
cannot be fulfilled and encephalopathy after vaccination may be more
likely. However, it doesn’t seem to be a just fever-related delirium due
to patient’s age, past medical history and her clinical picture and a
CNS related dysfunction is highly probable.
Previously reported post vaccination encephalopathy cases were all older
than 50 years of age except for one 21 year old female, and were more
common following ChAdOx1 nCov-19 administration(15)(17)(18). Fever and
myalgia were commonly seen. Alike our patient, brain imaging was normal
in all of these reports and no remarkable finding was seen(15)(17)(18).
Two cases had abnormal findings in EEG, a 77years old male showed
moderate diffuse slowing and another 77year old male presented
generalized slow background in the theta range(17)(18). In terms of CSF
analysis, in contrast with our patient, pleocytosis was a common finding
being seen in 4 out of 5 cases and only one patient had normal WBC count
with an elevated protean level(15)(17)(18).
VITT is well established side effect of AZ and many studies reported the
post AZ vaccination VITT. A review by Franchini et al.(19) On previous
VITT cases due to AZ vaccine showed thrombotic complications occurred
5-25 days after first dose of AZ vaccination and in majority of cases
site of thrombosis was cerebral veins, while splenic vein thrombosis and
pulmonary embolism were in second and third place. Our patient showed
initial symptoms on first day after vaccination and admitted to hospital
but discharged due to improvement of patient’s conditions. But on second
admission, few days after discharge, CVST was detected on imaging and
laboratory data confirmed the VITT by positive HIPA, PIPA, and anti-PF4
IgG ELISA tests.
Although vaccine-induced thrombotic thrombocytopenia (VITT) was first
reported after AZ vaccination growing number of papers were recently
published reporting the VITT with Johnson&Johnson(20)(21),
Moderna(21)(22), and BioNTech/Pfizer(21)(23) vaccines. Due to positive
anti-PF4 antibodies in both mRNA-based vaccines and vector-based
vaccines it raises the question which component of vaccine is
responsible to elicit response to PF4 proteins and VITT phenomenon?
LCV is a cutaneous small vessel vasculitis of dermal capillaries and
venules and typically presents with a painful, burning rash
predominantly in lower extremities. It is often idiopathic but can be
associated with infections, neoplasms, or medications(24). However,
relation between vaccination or immunization with vasculitis is not well
determined, vasculitis precipitation has been reported secondary
multiple vaccines including influenza virus, hepatitis B virus (HBV),
Basil Calmette-Guerin (BCG), and Human papillomavirus (HPV)(25).
Skin vasculitis with cutaneous lesions have been reported during mild
and fulminant COVID-19 disease(26). On the other hand, vasculitis was
also reported after COVID-19 vaccination. A recent study by McMahon et
al. on 417 cases of cutaneous reaction after mRNA COVID-19 vaccines,
reported 0.7% and 2.9% of vasculitis after first dose of Moderna and
BioNTech/Pfizer vaccines, respectively(27). Several case reports were
also reported skin vasculitis following vector-based vaccines including
AZ(28) and Johnson Johnson(29).