key: cord-1007072-ijnrf8s4 authors: Sun, Minxian; Ruan, Xiaoyun; Li, Yuanyuan; Wang, Pei; Zheng, Shasha; Shui, Guiying; Li, Li; Zhang, Hongmei title: Clinical characteristics of 30 COVID-19 patients with epilepsy: a retrospective study in Wuhan date: 2020-10-02 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2020.09.1475 sha: f073564df0c5fc407a9b9c071fc317e620df0266 doc_id: 1007072 cord_uid: ijnrf8s4 Objective This study aims to present clinical characteristics of 30 hospitalized cases with epileptic seizure and coronavirus disease 2019(COVID-19). Methods This is a retrospective observational research. Clinical data were extracted from electronic medical records in 1550 patients with laboratory-confirmed diagnosis of COVID-19 who hospitalized in Wuhan Central Hospital, China, from 1 January to 31 April, 2020. 30 COVID-19 patients with the diagnosis of epilepsy were enrolled. The clinical characteristics, complications, treatments,and clinical outcomes of 30 cases were collected. Result Of 30 patients with diagnosis of epilepsy and COVID-19, 13 patients(43.4%) had new-onset epileptic seizure without epilepsy history(new-onset seizure group,NS group), 10 patients(33.3%) with epilepsy history had recurrent epileptic seizure(recurrent seizure group,RS group) and 7 patients(23.3%) with epilepsy history had no seizure during the course of COVID-19 (epilepsy history group,EH group). Patients in RS group had more other neurological disease history except for epilepsy than those in NS group and EH group(7/10[70%] VS 1/13 [7.7%]VS1/7[14.3%]), and the difference between RS group and NS group is significant (P < 0.05). Patients in NE group and RS group suffered more severe/critical COVID-19 infection than patients in EH group (10/13[76.9%] VS 6/10[60%] VS 1/7[14.3%]),and the difference between NS group and EH group is significant (P < 0.05). 36.7% of patients had 1 to 5 complications,and 46.4% of patients had 6-10 complications.The complications in patients with seizure(in RS group and NS group) seem to be more than those without seizure(in EH group), but it doesn’t have statistic difference. The proportion of antiepileptic drugs (AEDs) treatment before admission was higher in EH group than in RE group(7/7 [100%] VS 2/10 [20%], P < 0.05). The mortality of 30 patients with epilepsy and COVID-19 was 36.67%. The mortality of NS group(38.5%) and RS group(50%) were a little higher than in EH group(14.3%). None of convalescent patients had recurrent seizure, and there was no more death in the 3 month follow-up after discharge. Conclusions COVID-19 Patients with recurrent epileptic seizure had more underlying neurological diseases than patients who had epilepsy history but without seizure.Patients with new-onset and recurrent epileptic seizure suffered more sever/critical COVID-19, which may lead to a worse prognosis.If patients with epilepsy history continue using AEDs during COVID-19 pandemics, the risk of recurrent seizure may reduce, and a good prognosis for patients with epilepsy history could be expected. Since the end of December 2019, COVID-19, a new type of corona virus pneumonia began to spread rapidly in many countries and regions in the world, and has become a global public health emergency. Sever acute respiratory syndrome corona virus 2(SARS-CoV-2), the pathogen of COVID-19, mainly involves the human respiratory system,and causes fever,cough,shortness of breath,myalgia or fatigue 1 worth noticing that about 25%-36.4% of hospitalized patients with COVID-19 may appear neurological manifestations 2 .A few patients may appear more specific neurological symptoms, such as seizure (about 0.5%) 2 . Seizure is defined as a transient occurrence of signs and symptoms due to abnormal excessive or synchronous neuronal activity in the brain, which may produce a physical convulsion,minor physical signs, thought disturbance or a combination of symptoms. Epilepsy is a group of related disorders in the brain's electrical systems that are characterized by a tendency to cause recurrent seizure. Epilepsy is considered to be a systemic component with high prevalence of comorbidity, but not just a neurological condition 3 . About 2%-3% of patients who have new-onset seizure will go on to develop epilepsy 4 . Up to now, approximately over 70 million people are diagnosed with epilepsy worldwide 5 , and they deserve more attention while suffering from COVID- 19 . What's more, new-onset or recurrent seizures in COVID-19 patients may pose even more serious and costly problems,which may led to high mortality. However, since the onset of COVID-19 pandemic, in large retrospective multicenter J o u r n a l P r e -p r o o f 4 studies, they reported only one or two cases with COVID-19 suffered seizure 2, 6 ,and only a few case reports described about seizure of COVID-19 patients in detail 7, 8 .Therefore, seizures have not been widely and directly reported. It is not clear about the incidence, characteristics and pathogenesis in COVID-19 patients with seizure or epilepsy. We are interested to know which factors on earth cause seizure in COVID-19 patients, and whether the occur of seizure would affect the prognosis of COVID-19 patients. In this retrospective study, we reported the clinical characteristics of 30 COVID-19 patients with epileptic seizure who were hospitalized in the fever word from January to April 2020, looking forward to exploring the unknown mysteries. Clinical data of patients with the diagnosis of epilepsy at discharge were extracted from electronic medical records in 1550 hospitalized patients in Wuhan Central Hospital with laboratory-confirmed diagnosis of COVID-19 from 1 January to 31 April, 2020. COVID-19 is confirmed by one of the following etiological or serological evidence:a positive result of pharyngeal swab novel coronavirus nucleic acid by real time reverse transcriptase PCR; a positive result serum novel coronavirus specific IgM and IgG; or novel coronavirus specific IgG in the serum was changed from from negative to positive or increased by more than 4 times in the recovery period compared with the acute phase. The severity of disease was classified as mild/moderate and severe/critical. Patients with the diagnosis of epilepsy at discharge were confirmed by two neurological experts according the diagnosis and classification of International League Anainst Epilepsy 9 . Patients had an epileptic seizure without and with epileptic seizure history were respectively enrolled into new-onset seizure group (NS group) and recurrent seizure group (RS group) , while patients had no seizure but with an epilepsy history were in epilepsy history group (EH group). This study was approved by the Ethics Commission of the Central Hospital of J o u r n a l P r e -p r o o f designated hospital under the criteria of emerging infectious diseases. 30 hospitalized COVID-19 patients with epilepsy were enrolled. Data were extracted including demographic characteristics, past medical history, symptoms on admission, laboratory tests, complications, and treatments.Patients' complications besides COVID-19 and epilepsy were recorded according to the diagnosis at discharge. The clinical outcome at discharge was either rehabilitation or death. All participants were laboratory-confirmed COVID-19. All specimens were examined at the laboratory department. All data were analyzed using SPSS 20.0. Continuous variables were expressed as median (IQR) , and tested by non-parametric Mann-Whitney U test. Categorical variables were expressed as percentage(%), and tested by Fisher's exact test or X 2 test.P less than 0.05 was considered statistically significant. The onset symptoms and laboratory data of patients with epilepsy and COVID-19 on hospital admission were summarized in Table 2 .The most common symptoms were fever(60%),fatigue(43.3%),vomiting(36.7%). Special neurological symptoms include impaired consciousness(36.7%), language disorder or aphasia(33.3%), activity obstacle or paralysis(30%), and headache(26.7%). Three patients (10%) had seizure before hospital admission,one was in NS group, and the other two were in RS group. Twenty-six out of thirty (86.7%) patients had more than one compilations,while four patients(13.3%) had not any other complications beside COVID-19 and epilepsy. One of them was in RS group ,and the other three of them were in EH group. 36.7% of patients had 1 to 5 complications, and 46.4% of patients had 6-10 complications. The median number of complications in this study was 5.5 (3) (4) (5) (6) (7) (8) (9) .The complications in patients with seizure(median number was 7 NS group and 5 in RS group) were more than those without seizure(median number was 4 in EH group), but the difference was not statistically significant.The most common complications in this cohort were hypertension(18, 60%), the others were respiratory distress or fail (14, 46 .6%), cerebral hemorrhage(13,43.3%), gastrointestinal ulcer(13,43.3%),hepatic injury(10, 33.3%),cerebral infarction(6,20%),hypoproteinemia(6,20%),kidney failure(6, 20%),brain trauma(5,16.7%),cerebrovascular malformation(5,16.7%),and coronary heart disease(5,16.7%),and diabetes(5,16.7%) in sequence.In 13 patients with cerebral hemorrhage,ten patients had hypertension,two patients had brain trauma and cerebrovascular malformation.Two patients were accompanied with brain trauma,while three patients were accompanied with cerebrovascular malformation(cerebral aneurysm,or moyamoya disease ). Treatments, outcomes and 3 month follow-up of all patients were summarized in In 3 months follow-up, none of rehabilitation patients in NS group received AEDs, while all rehabilitation patients in EH group continued using AEDs after discharge.None of rehabilitation patients had recurrent seizure, and there was no more death in the 3 month follow-up after discharge. To our knowledge, this is the first report on detailed characteristic of hospitalized patients with COVID-19 and epileptic seizure, including COVID-19 patients with new-onset epileptic seizure,recurrent epileptic seizure and with epilepsy history. In 1550 hospitalized patients with COVID-19, the incidence of epileptic seizure was 1.49% (new-onset epileptic seizure and recurrent seizure were 0.84% and 0.65%,respectively),as low as previous studies 2, 6 . The incidence of COVID-19 patients with epilepsy history is also very low. Patients with epilepsy history have not been shown to be more susceptible to COVID-19. Epilepsy is a chronic disorder affecting all ages, and has a bimodal distribution according to age with peaks in the youngest individuals and in the elderly 10 There were some limitations in our study. Firstly,this is a retrospective study, sample size may not be large enough,and some bias may have occurred.Secondly,no routine or long-term electroencephalogram or cerebrospinal fluid examination was performed because of the risk of viral exposure to staff.Therefore,we can't find evidence to confirm the correlation between COVID-19 and seizure. China.COVID-19 patients with recurrent seizure had more neurological disease history except for epilepsy than those without seizure. New-onset and recurrent seizure patients accompanied with more sever and critical COVID-19 than patients who had epilepsy history but without seizure. Which may lead to a worse prognosis for COVID-19 patients.The recurrent individuals had an obviously lower proportion of AEDs treatment after before admission, a more complex past history, and more complications during hospitalization. If patients with epilepsy history continue using AEDs during COVID-19 pandemics, the risk rate of recurrent seizure may reduce,and a good prognosis for patients with epilepsy history may be expected. We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, This study was supported by the Health and Family Planning Commission of Wuhan City (WX18M02 and WX18C25). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. This study was approved by the Ethics Commission of the Central Hospital of Wuhan. Written informed consent was waived for retrospective study. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved. The data used to support the findings of this study are included within the article. Lupus nephritis 1(3.3%) 1(7.7%) 0(0%) 0(0%) 1 NS group: New-onset seizure group without epilepsy history; RS group: recurrent seizure with epilepsy history; EH group: epilepsy history group P less than 0.05 was considered statistcally significant a: differences between NS and RS group,P<0.05 ;b: differences between RS and EH group,P<0.05 ;c: differences between NS and EH group,P<0.05 . J o u r n a l P r e -p r o o f Use of AEDs after discharge(% in Rehabilitation) 11 (11/19，36 .67%) 0(0/8,0%) 5(5/5,100%) 6(6/6,100%) 0 Recurrent seizure recurrent 0(0%) 0(0%) 0(0%) 0(0%) NA Death 0(0%) 0(0%) 0(0%) 0(0%) NA NS group: New-onset seizure group without epilepsy history; RS group: recurrent seizure with epilepsy history; EH group: epilepsy history group AEDs:antiepileptic drugs; P less than 0.05 was considered statistcally significant a: differences between NS and RS group,P<0.05 ;b: differences between RS and EH group,P<0.05 ;c: differences between NS and EH group,P<0.05 . 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