Non-Invasive Intracranial Pressure in COVID-19 Individuals

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) is an infectious disease transmitted one person to another mainly from cough and sneeze aerosols as well as from contaminated surfaces. The most common respiratory symptoms are dry cough, fever, and dyspnea, but the Severe Respiratory Acute Syndrome (SARS) can be installed increasing disease´s mortality. In addition, neurological symptoms have been described according the increase of severity and age. Changes of intracranial pressure (ICP) can partially explain the Central Nervous System (CNS) impairment due to COVID-19. The ICP waveform can bring relevant information about intracranial compliance, and, nowadays, it can be measured by non-invasive technology. Clinically, non-invasive ICP waveform assessment would help to understand the repercussion of Invasive Mechanical Ventilation (IMV) on CNS in COVID-19 persons. AIMS: This study aims to evaluate the ICP waveform in intubated and non-intubated COVID-19 persons. Furthermore, the association between ICP and IMV parameters, level of sedation, heart rate variability, neurological symptoms, neuroimage, and final discharge will be investigated. . METHODS: At least 30 COVID-19 individuals will be included within 72h from admission and 14 days from symptoms onset. They will be divided into two groups: non-intubated (n=15) and intubated, paired with non-COVID-19 ones (non-intubated and intubated non-COVID-19 groups, respectively). The non-invasive ICP monitoring will be daily performed for 7 consecutive days. The Brain4Care's device and Analytic System will be used to assess the three pulse peaks (P1, 2 and 3) at the ICP waveform. The following variables will be investigated: P1 and P2 amplitude, P2/P1 ratio, time to peak and time percentage of P2 higher than P1. For statistics, all variables will be tested as to their normal or non-normal distribution through appropriate statical analyzes. For basic demographic and clinical variables, descriptive data analysis will be used. The repetitive measurement Anova will be used for ICP outcomes throughout the days. Pearson's or Spearman´s correlations will be applied according to data distribution.

Inclusion criteria

For COVID-19 group:

• Men and women (not pregnant) Older than 18 years old Diagnosis of COVID-19 confirmed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) Subjects intubated or non-intubated Time between admission and study inclusion ≤ 72h For intubated group time between IUC admission and study inclusion ≤ 72h Time between onset symptoms and study inclusion ≤ 14 days No neurological acute disease No cutaneous injury in the head to impossibility the ICP monitoring ICF signed by the participant or his/her legal representative*

No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. Subjects intubated or non-intubated For intubated group time between IUC admission and study inclusion ≤ 72h Time between admission and study inclusion ≤ 72h Time between onset symptoms and study inclusion ≤14 days No neurological acute disease

For Controls Group:

Men and women (not pregnant) Older than 18 years old No cutaneous injury in the head to impossibility the ICP monitoring • For intubated group: ICF signed by the participant or his/her legal representative* Intubated patients for others causes than COVID-19 or neurological diseases IUC admission and study inclusion ≤ 72h No symptoms of COVID-19 on the last 15 days

• For healthy group: No previous neurological disease No chronic disease as Diabetes Mellitus Type 2, Chronic Obstructive Pulmonary Disease (COPD), Heart Failure, hypertension or Chronic Kidney Disease (CKD)

No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously.

IUC admission and study inclusion ≤ 72h No neurological diseases

Exclusion criteria

• It will be excluded those who asked to stop their participation, and those with problems in acquiring ICP data.