Intravenous immunoglobulin therapy in COVID-19-related encephalopathy

Abstract

Objective: To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy.

Methods: We retrospectively collected data on all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg.

Results: Five patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19-55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1-10 days). No adverse events related to IVIg were observed.

Conclusions: Our preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.

Fig. 1

Disease course in patient 1. Neurological manifestations, respiratory distress, temperature, IL-6 levels, timing of immunomodulatory treatments and diagnostic investigations during disease course. Neurological status severity was evaluated by treating neurologists. On the 15th day after disease onset, neurological evaluation was performed during temporary weaning of sedatives (red dot). Temperature and SpO2/FiO2 ratio were measured at least daily during hospitalization. Crosses on the IL-6 line represent the actual measurements. EEG electroencephalography, EMG electromyography, ICU intensive care unit, IVIg intravenous immunoglobulin treatment, LP lumbar puncture, MRI magnetic resonance imaging, S/F SpO2/FiO2 ratio