Our aim was to clarify the incidence and risk of acute symptomatic seizures in people with coronavirus disease 2019 . This multicenter retrospective study enrolled people with COVID-19 from January 18 to February 18, 2020 at 42 government-designated hospitals in Hubei province, the epicenter of the epidemic in China; Sichuan province; and Chongqing municipality. Data were collected from medical records by 11 neurologists using a standard case report form. A total of 304 people were enrolled, of whom 108 had a severe condition. None in this cohort had a known history of epilepsy. Neither acute symptomatic seizures nor status epilepticus was observed. Two people had seizurelike symptoms during hospitalization due to acute stress reaction and hypocalcemia, and 84 (27%) had brain insults or metabolic imbalances during the disease course known to increase the risk of seizures. There was no evidence suggesting an additional risk of acute symptomatic seizures in people with COVID-19. Neither the virus nor potential risk factors for seizures seem to be significant risks for the occurrence of acute symptomatic seizures in COVID-19. K E Y W O R D Sacute symptomatic seizures, COVID-19, epilepsy, SARS-CoV-2 2 | LU et aL.

Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp) 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins.

Objective:To investigate new-onset neurologic impairments associated with coronavirus disease 2019 (COVID-19).Methods:A retrospective multicenter cohort study conducted between 18 January and 20 March 2020 including people with confirmed COVID-19 from 56 hospitals officially designated in three Chinese regions; data were extracted from medical records. New-onset neurologic events as assessed by neurology consultants based on manifestations, clinical examination and investigations, in which critical events included disorders of consciousness, stroke, CNS infection, seizures and status epilepticus.Results:We enrolled 917 people with average age 48.7 years and 55% were male. The frequency of new onset critical neurologic events was 3.5% (32/917) overall and 9.4% (30/319) among those with severe or critical COVID-19. These were impaired consciousness (n=25) or/and stroke (n=10). The risk of critical neurologic events was highly associated with age above 60 years and previous history of neurological conditions. Non-critical events were seen in less than 1% (7/917), including muscle cramp, unexplained headache, occipital neuralgia, tic and tremor. Brain CT in 28 people led to new findings in nine. Findings from lumbar puncture in three with suspected CNS infection, unexplained headache or severe occipital neuralgia were unremarkable.Conclusions:People with COVID-19 aged over 60 and neurologic comorbidities were at higher risk of developing critical neurologic impairment, mainly impaired consciousness and cerebrovascular accidents. Brain CT should be considered when new-onset brain injury is suspected, especially in people under sedation or showing an unexplained decline in consciousness. Evidence of direct acute insult of SARS-COV-2 to the CNS is still lacking.