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Table 1 Summary of COVID-19 cases identified involving anti-NMDAR encephalitis with neuropsychiatric symptoms

From: Molecular mimicry of NMDA receptors may contribute to neuropsychiatric symptoms in severe COVID-19 cases

Patient 1 Panariello et al., 2020 [10] Male (23 years-old). History drug abuse
  Reason for hospitalization Psychomotor agitation, anxiety, formal thought disorder, persecutory delusions and auditory hallucinations and global insomnia. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
  Respiratory (other) symptoms Fever, drop in O2 saturation, chest X-ray: bilateral milk glass opacities, chest CT: patchy bibasilar consolidation
  Neuropsychiatric symptoms Confusion, disorganization of speech, thought/behaviour, auditory hallucinations and insomnia. Week 2: mutistic/non-responsive. Week-3: dysphagia, dyskinesia, autonomic instability, fluctuations in body temperature, blood pressure, pulse and respiratory rate
  Blood test IL-6 not mentioned, no lymphopenia at anti-NMDAR encephalitis diagnosis, hyponatremia
  CSF examination SARS-CoV-2 negative. IL-6 elevated, NMDAR-antibodies positive. Virological and microbiological diagnostics negative. Elevated red and white cells
  EEG Theta activity, unstable, non-reactive to visual stimuli
  Therapy Seizure prophylaxis. No symptom improvement with antipsychotics. COVID-19 therapy with hydroxychloroquine and darunavir/cobicistat. Antibiotic prophylactic therapy. After anti-NMDAR encephalitis diagnosis, dexamethasone and intravenous immunoglobulin
  Course Clinical symptoms improved
Patient 2 Alvarez Bravo and Ramio, 2020 [11] Female (30 years-old). No previous medical history. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
  Reason for hospitalization Behavioral changes
  Respiratory (other) symptoms Fever, pneumonia, thrombosis of the left iliac vein, and bilateral pulmonary embolism attributed to SARS-CoV-2 infection
(Ovarian teratoma)
  Neuropsychiatric symptoms Psychomotor agitation, paranoid ideation, dysarthria with dysprosody, and visual hallucinations, focal and generalised seizures
  Blood test SARS-CoV-2 positive
  CSF examination Cells count and protein elevated. SARS-CoV-2 negative, NMDAR antibodies positive. Virological and microbiological diagnostics negative
  EEG Epileptic discharges in the left frontotemporal region
  Therapy After anti-NMDAR encephalitis diagnosis, 5 days of methylprednisolone and immunoglobulins administered
  Course Hypoprosexia, emotional lability and memory disorder, Stabilised systemic and respiratory symptoms
Patient 3 Allahyari et al., 2021 [12] Female (18 years-old). No previous medical history. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
  Reason for hospitalization Generalized tonic–clonic seizures
  Respiratory (other) symptoms Fever, pneumonia, hypotonia, tachycardia, tachypnea, oxygen saturation of 90%, bilateral pulmonary crackles in lower lung zones,
  Neuropsychiatric symptoms 3-week history of mood change as depression and anhedonia accompanied by lack of concentration, generalized tonic–clonic seizures
  Blood test Neutrophilia, lymphopenia, CRP normal
  CSF examination Cells count elevated. SARS-CoV-2 positive, NMDAR antibodies positive. Virological and microbiological diagnostics negative
  EEG Epileptic discharges in the left frontotemporal region
  Therapy Seizure prophylaxis. COVID-19 therapy with Remdesivir, Lopinavir/Ritonavir, and Interferon b1a (Resigen). Antibiotic prophylactic therapy. After anti-NMDAR encephalitis diagnosis, methylprednisolone and intravenous immunoglobulin
  Course After 2 months of hospitalization discharged with full recovery
Patient 4 McHattie et al., 2021 [13] Female (53 years-old). Ductal carcinoma of breast in remission. History of depression and psoriasis. Medications: sertraline, ciclosporin
  Reason for hospitalization 2-week confusion, fever and myalgias. SARS-CoV-2 negative on admission, positive on day-14 in nasopharyngeal swab RT-PCR testing
  Respiratory (other) symptoms Severe hypoxemia with O2 dependency. Chest X-ray: bilateral infiltrations
  Neuropsychiatric symptoms Day-5: catatonic symptoms of severe echolalia, palilalia, perseverations and echopraxia. Speech high-pitched and behavioural disinhibition. Left-side discrete hemiparesis, non-responsive to commands. Day-17: focal seizures, marked dysautonomia (increasingly hypotensive with bradycardia). Hyperkinetic movement disorder not present
  Blood test CRP elevated with lymphopenia. NMDAR antibodies negative
  CSF examination SARS-CoV-2 negative. Leukocytes high. Low glucose and high protein. Virological and microbiological diagnostics negative. NMDAR antibodies positive
  EEG Slow activity on admission. No evidence of epileptiform discharges
  Therapy Antiepileptic treatment. For suspected viral encephalitis, initial therapy with aciclovir and steroids. COVID-19 therapy with hydroxychloroquine, antibacterial and antifungal treatment. After anti-NMDAR encephalitis diagnosis, steroids, intravenous immunoglobulins and tocilizumab
  Course Worsening symptoms with steroids. 1-month therapy: neuropsychiatric symptoms improved but persistence of left-side weakness. Cardiac MRI day 70: regression of signal changes. Brain MRI: atrophy of left amygdala and left hippocampus
Patient 5 Monti et al., 2020 [14] Male (50 years-old). Moderate arterial hypertension
Reason for hospitalization Acute psychiatric symptoms. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
Respiratory (other) symptoms None. No diarrhoea. Fever present
Neuropsychiatric symptoms Confabulations and delirium. Day-4: focal motor seizures with reduced consciousness, orofacial dyskinesia, automatisms. Sudden refractory status epilepticus
Blood test IL-6 elevated. No CRP elevation or leukocytosis
CSF examination SARS-CoV-2 not mentioned. Third lumbar puncture: NMDAR antibodies positive, cell count and IL-6 elevated. Oligoclonal bands positive. Virological and microbiological diagnostics negative
EEG Diffuse delta activity with extreme delta brush pattern.Anterior subcontinuous periodic theta activity
Therapy Antiepileptics and anaesthetics. COVID-19 therapy with hydroxychloroquine and lopinavir/ritonavir. After diagnosis of anti-NMDAR encephalitis: corticosteroids, immunoglobulins and plasmapheresis
Course 4 months after symptom onset patient discharged in good condition with no neuropsychiatric symptoms
Patient 6 Burr et al., 2021 [15] Female (23 months-old). Vaccinated. No previous diseases. Family history unremarkable
Reason for hospitalization Fever, psychomotor agitation, sleep disturbances, constipation, decreased oral intake. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
Respiratory (other) symptoms None. Fever, dehydration present
Neuropsychiatric symptoms Agitation, poor sleep, mood swings, mutism, regular kicking/ flapping of extremities. Day-2: multiple epileptic seizures. Week 2: worsening encephalopathy with persistent hyperkinetic movements of extremities and head
Blood test CRP normal, NMDAR antibodies positive, IL-6 not mentioned
CSF examination SARS-CoV-2 negative. Mild elevation of leukocytes. Oligoclonal bands negative. Virological and microbiological diagnostics negative. NMDAR antibodies positive. IL-6 not mentioned
EEG Not mentioned
Therapy Antiepileptics. After anti-NMDAR encephalitis diagnosis, corticosteroid therapy for 5 days with no improvement, followed by intravenous immunoglobulin administration
Course Remission within one week after immunoglobulin therapy
Patient 7 Sanchez-Morales et al., 2021 [18] Male (14 years-old). No previous medical history. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
Reason for hospitalization Behavioral changes and neurological symptoms
Respiratory (other) symptoms None
Neuropsychiatric symptoms Altered behaviour and mental status, epileptic seizures, insomnia, orolingual dyskinesia
Blood test SARS-CoV-2 negative
CSF examination SARS-CoV-2 positive, NMDAR antibodies positive. Virological and microbiological diagnostics negative
EEG Not mentioned
Therapy After anti-NMDAR encephalitis diagnosis, methylprednisolone and immunoglobulins administered
Course Complete remission of neurological impairment. Control of epilepsy. Persistence of psychiatric symptoms
Patient 8 Sarigecili et al., 2021 [16] Male (7 years-old). Vaccinated. No previous diseases. No abnormal family history
Reason for hospitalization Gait disorder. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
Respiratory (other) symptoms None. No headache, fever, or cold symptoms. Day 8: tachycardia
Neuropsychiatric symptoms Ataxia and broad-based gait with poor muscle reflexes. Day-2: somnolence and epileptic seizures. Day 8: choreiform movements of extremities, tongue protrusion, bruxism, smacking, psychomotor agitation, catatonia, echolalia
Blood test CRP elevated, lymphopenia. IL-6 not mentioned
CSF examination No cells present. Oligoclonal bands negative. Virological and microbiological diagnostics negative. NMDAR antibodies positive. IL-6 not mentioned
EEG Encephalopathic pattern with disseminated delta waves
Therapy Antiepileptics after onset of seizures. Initial therapy with antibiotics/antivirals. After diagnosis of anti-NMDAR encephalitis: plasmapheresis three times, corticosteroid 7 days, immunoglobulins 5 days followed by corticosteroid again
Course Day 31: patient discharged walking but mildly ataxic with prednisolone and antiepileptic treatment. Possibility of repeat immunoglobulin administration