Long term clinical and lung function test assessment in critically ill covid-19 patients: a 1-year follow-up

Introduction: patients with severe interstitial Sars-CoV-2-related pneumonia may experience residual symptoms and impaired quality of life after being discharged. In our Hospital we planned a long-term follow-up protocol that has currently evaluated over 1400 inpatients. Aim(s): to monitor a subset of critical COVID-19 patients (need for ICU admittance or non-invasive ventilation) after discharge using clinical parameters and lung function tests (LFT) and evaluate long-term consequences on lung performance. Method(s): we monitored LFT, DLCO and 6MWT of 93 critically ill COVID-19 patients 1 month after discharge and up to 12 months later. No patient received any additional treatment. Follow-up is still ongoing. Result(s): we noted altered DLCO 1 month after discharge (T0). At T0 no patient showed desaturation at the 6MWT. Assessment of long-term follow-up (T1 - on average 10.2 months) showed significant improvement in LFT parameters, notably DLCO (table 1). 6MWT was not repeated. Conclusion(s): Altered LFT parameters are confirmed as consequences of severe ventilated Sars-CoV-2 pneumonia. Our work additionally demonstrates that these alterations are at least partially spontaneously reversible and do not seem to imply clinical consequences.

Encephalitis during first year of SARS-COV-2 pandemic– first results of the European ENCOVID registry

Background and aims: Objective: Several preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. No data about clinical, imaging and biomarkers presentations as well as long-term outcomes are available for SARS-CoV-2 encephalitis in comparison with infectious and autoimmune encephalitis. Methods: The ENCOVID European registry included patients with probable or definite diagnosis of encephalitis with and without SARS-CoV-2 infection admitted for hospitalization in the European recruiting centers between February 1st 2020 and March 30th, 2021. Each patient underwent a standardized assessment including full infectious screening, CSF, EEG, MRI data. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment and outcomes were recorded. Results: Results – Out of 155 cases screened, forty-five cases of encephalitis positive for SARS-CoV-2 infection and 63 without COVID-19 with full available data were included. SARS-CoV-2 encephalitis exhibited common presentation with aphasia and dysarthria compared to non-COVID- encephalitis and exhibited higher prevalence of patients with normal MRI but mild hyperproteinorracchia/pleocytosis. Most SARS-CoV-2 cases appeared during the onset of COVID-19 and exhibited different response to treatment and long-term outcomes compared to non COVID encephalitis. Conclusions: Conclusions –The registry identified a wide spectrum of encephalitis associated with COVID19 infection, with clinical characteristics and course different from classical infectious and autoimmune encephalitis. Biomarkers studies are warranted in order to evaluate the specific inflammatory pathways associated with SARS-Cov-2 encephalitis.

Clinical, neurophysiological and neuroradiological characteristics of 30 cases of SARS-COV-2-associated encephalitis in Lombardia

Background and aims: The number of cases of encephalitis in COVID-19 pandemic is increasing. We describe characteristics and outcome of encephalitis in COVID-19 (COV-ENC) patients in one of the most affected regions by COVID-19 of the world, Lombardia, during the first pandemic wave. Methods: A multi-center observational study on neurological complications in COVID-19 patients was conducted by the Italian society of Hospital Neuroscience (SNO). Adult patients admitted to 20 Neurological Departments in Lombardia between February-April 2020 with COV-ENC have been included. Results: 30 COV-ENC patients had a mean age of 66.5 years and male frequency of 56.6%. Altered consciousness was characterized by confusion in 86%, coma in 30%, delirium in 37.9% and alteration of personality traits in 27.6%. Epileptic seizures occurred in 74% of cases. One third of cases had hyperproteinorrachia, one third pleocytosis/hyperproteinorrachia, and remaining third had a normal CSF. PCR for SARS-CoV-2 was negative in all tested patients. EEG was altered in 82.7% of patients. Brain CT and MRI were normal in 9 patients, and among abnormal findings 9 patients had mesial temporal lesions, one of which confirmed with PET imaging. The course was favorable in 39.2% of patients, sequelae were few in 26.6% and moderate in 19.2%, while 20% of patients died. Conclusions: The outcome tends to be worse in male patients. PCR negativity seems to confirm an autoimmune etiology more than a direct invasion of the virus. However, a temporal lobe involvement, detected in 30% of patients with COV-ENC, suggests usual sites of encephalitis due to herpes virus.

SARS-CoV-2 infection: A potential trigger of inflammatory neurological disorders

Objective: To assess Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) specific IgA/G seropositivity in patients with suspected autoimmune central nervous system (CNS) disorders. Background: Inflammatory/autoimmune disorders can be triggered by viral infections, as described in patients with antibodies to neuronal surface proteins or myelin oligodendrocyte glycoprotein (MOG). Whether SARS-CoV-2 infection induces such conditions is unknown, although widely hypothesised. Design/Methods: We retrospectively analysed consecutive samples referred for antibody screening to the Neuropathology Laboratory, Verona, for SARS-COV-2 IgA and IgG testing, from March 1 2020 to August 31 2020. Clinical information of seropositive cases was extracted from clinical records or provided by referring physicians. Results: Among 332 patients referred for antibody testing, 26 showed either SARS-CoV-2 IgA and/or IgG (IgA n=12, IgG n=1, IgA and IgG n=13). Among 22/26 available CSF, 4 were positive (IgG n=3, IgG and IgA n=1). Median age of seropositive cases was 61 years (range 27- 82) and 16 were female. Clinical features, available in 23 cases, revealed encephalopathy (n=15) and seizures (n=8) as common manifestations and, in four cases, myelitis, predominantly with lower limbs weakness. 19/23 patients were systemically asymptomatic. Brain MRI showed FLAIR-T2 hyperintensities in 13/18 patients. EEG showed alterations including epileptic discharges (n=5) and/or generalized slowing (n=12). CSF pleocytosis (>5 cells/μL) was reported in 9/19 investigated cases. Autoimmune neurology screening revealed one patient with serum titin autoantibodies, one with limbic encephalitis and seizures had serum and CSF amphiphys in antibodies, and one presenting with acute disseminated encephalomyelitis had serum and CSF MOG antibodies. Conclusions: The incidence of SARS-CoV-2 IgG/IgA positivity in our referred cohort, which was higher (7.8%, 18% when considering only patients with suspected encephalitis) than that reported in the Italian population (2.5%) and the observed clinical spectrum of disorders suggest that SARS-CoV2 could trigger inflammatory CNS processes, usually not associated with wellknown autoantibodies. Case-control studies are now required.

COVID-19 and Guillain-Barré syndrome in early pandemia in Lombardia: Increased incidence or increased seroprevalence?

Background and aims: Several studies reported increased incidence of Guillain-Barre' Syndrome (GBS) after Zika epidemic, SARS-CoV and MERS, and more recently SARS-CoV-2 infection. We estimate incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients in one of the most affected regions by COVID-19 of the world, Lombardia. Methods: A multi-center observational study on neurological complications in COVID-19 patients was conducted in 20 Neurology Units by the Italian society of Hospital Neuroscience (SNO). Adult patients admitted to Neurological units between February-April 2020 with COVID19-GBS were included. Results: 38 COVID19-GBS patients had mean age of 60.7 years and male frequency of 86.8%. Mean interval between COVID-19 onset and GBS onset was 15.1 days. CSF albuminocytologic dissociation was detected in 71.4% of cases, PCR for SARS-CoV-2 negative in all 15 tested patients, and anti-ganglioside antibodies positive in 43.7%. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP diagnosis, 12.1% AMSAN and 6% AMAN. 29 patients have been treated with intravenous Immunoglobulin (IVIg), two with plasma exchange (PE), two with PE followed by IVIg and five untreated. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.1% worsened, of which three died. The estimated occurrence rate in Lombardia is 0.5 GBS cases per 1000 COVID-19 infections. Conclusion: We detected an increased incidence of GBS in COVID-19 patients which can reflect higher risk of GBS in COVID-19 patients or be secondary to an increase of prevalence of prior infection in that period.