COVID-19 vaccines and thrombosis with thrombocytopenia syndrome

Authors: Chih-Cheng Lai 1Wen-Chien Ko 2Chih-Jung Chen 3Po-Yen Chen 4Yhu-Chering Huang 3Ping-Ing Lee 5Po-Ren Hsueh 6 7


Introduction: To combat COVID-19, scientists all over the world have expedited the process of vaccine development. Although interim analyses of clinical trials have demonstrated the efficacy and safety of COVID-19 vaccines, a serious but rare adverse event, thrombosis with thrombocytopenia syndrome (TTS), has been reported following COVID-19 vaccination.

Areas covered: This review, using data from both peer-reviewed and non-peer-reviewed studies, aimed to provide updated information about the critical issue of COVID-19 vaccine-related TTS.

Expert opinion: : The exact epidemiological characteristics and possible pathogenesis of this adverse event remain unclear. Most cases of TTS developed in women within 2 weeks of the first dose of vaccine on the receipt of the ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines. In countries with mass vaccination against COVID-19, clinicians should be aware of the relevant clinical features of this rare adverse event and perform related laboratory and imaging studies for early diagnosis. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) and intravenous immunoglobulins are recommended for the treatment of TTS. However, further studies are required to explore the underlying mechanisms of this rare clinical entity.

Plain language summary: What is the context? Thrombosis with thrombocytopenia syndrome (TTS) usually develops within 2 weeks of the first doses of the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines. TTS mainly occurs in patients aged < 55 years and is associated with high morbidity and mortality. What is new? TTS mimics autoimmune heparin-induced thrombocytopenia and can be mediated by platelet-activating antibodies against platelet factor 4. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) should be considered as the treatment of choice if the platelet count is > 50 × 109/L and there is no serious bleeding. Intravenous immunoglobulins and glucocorticoids may help increase the platelet count within days and reduce the risk of hemorrhagic transformation when anticoagulation is initiated. What is the impact? TTS should be a serious concern during the implementation of mass COVID-19 vaccination, and patients should be educated about this complication along with its symptoms such as severe headache, blurred vision, seizure, severe and persistent abdominal pain, painful swelling of the lower leg, and chest pain or dyspnea. The incidence of TTS is low; therefore, maintenance of high vaccination coverage against COVID-19 should be continued.

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The Impact of COVID-19 on Developing Neurologic Disorders

Authors: Piotr Tekiela,  View ORCID ProfileJennifer J. Majersik

One of the greatest challenges of treating a new virus is the lack of information about it. When little is known about a virus, patients affected by it, as well as their families, are left with uncertainty. In an article appearing in this issue of Neurology®, Dr. Frontera and her team aimed to determine how often patients hospitalized with coronavirus disease 2019 (COVID-19) developed new neurologic disorders.1 They then compared several key outcomes in treatment between patients who developed a new neurologic disorder due to COVID-19 and those who did not. These included discharges to home, ventilator use, length of hospital stay, and in-hospital deaths. These findings can help us understand which groups of people may be more likely to develop more severe disease after having COVID-19, as well as what their prognosis is likely to be.

How Was the Study Done?

The study was run during the first wave of the COVID-19 pandemic, from March 10 through May 20, 2020, in 4 hospitals in the New York City metropolitan area. The researchers set strict guidelines for the type of patients they would include in the study. Patients had to be adults with a laboratory-confirmed severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. They also had to have been admitted to the hospital at some point during the duration of their illness. Patients who were only seen in an emergency department or at an outpatient clinic were not included in the study.

There are 3 major strengths of this study that set it apart from other studies. First, patients were excluded if they were not tested for SARS-CoV-2 or if they tested negative for the virus. Second, all of the neurologic diagnoses made during the study were determined by a neurologist. Lastly, only new diagnoses of neurologic disease were included in the study. If someone had a neurologic disorder that was known before hospitalization due to COVID-19, that diagnosis was not counted in the study results. This improved the accuracy of diagnosing new neurologic complications that appeared to be caused by COVID-19.

What Were the Results?

A total of 4,491 patients were hospitalized with COVID-19 at the 4 hospitals involved in the study. Of those patients, 606 (13.5%) developed a new neurologic disorder, as diagnosed by a neurologist. These disorders included a confused state in 51% (called a toxic-metabolic encephalopathy), stroke in 14%, seizures in 12%, and brain injury due to lack of oxygen or blood flow (called hypoxic or ischemic disorders) in 11% (see below to learn more about these disorders). The researchers did not find any infections in the brain (such as meningitis or encephalitis) or in the spinal cord (myelitis) in these patients. The patients at highest risk of developing a neurologic disease were older and more likely to be male, White, or diabetic.

For most patients (54%) who developed a neurologic disorder, the disorder appeared about 2 days after the initial COVID-19 symptoms (fever, cough, nausea, vomiting, or diarrhea) arose. In 43% of patients, neurologic problems developed at approximately the same time as their initial COVID-19 symptoms. Only 2% of patients developed neurologic symptoms before onset of the common COVID-19 symptoms.

Development of new neurologic disease was associated with worse outcomes overall. Patients who developed a neurologic disorder along with COVID-19 were 28% less likely to be discharged home from the hospital and 38% more likely to die (either from the illness or from the neurologic disorder). Further, they spent 6 more days on a ventilator and 4 more days in the hospital than patients who did not develop a new neurologic disorder.

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