COVID-19 is known to affect the respiratory system but may also have an impact on other organ systems, including the brain. A number of severely ill patients also presents neurological symptoms that may be the result of COVID-19 associated brain damage. The aim of this study is to investigate the presence, type, and severity of brain damage as well as the neurological and neuropsychological sequelae of COVID-19 infection. Further, the impact of this infection on daily life functioning, quality of life, and the emotional well-being of family members will be assessed. In this multicenter study, 6-9 months after hospital discharge patients will undergo a 3-T MRI scan and a neuropsychological examination. Additionally, both patients and their family members will answer several questionnaires at 6- 9 and 12-15 months after hospital discharge. COVID-19 patients previously admitted to a general hospital ward will be compared with patients previously admitted to the intensive-care unit. The proposed study will create a more comprehensive picture of the prolonged COVID-19 effects on the brain, mental, and cognitive well-being. The findings will aid patient care and rehabilitation.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2). COVID-19 primarily affects the respiratory system. However, in severely ill patients damage is also reported to other organ systems including the heart, the kidneys, the circulatory, and gastrointestinal system. Further, research indicates an impact of the virus on the brain and, thereby, on cognition. Patients experience neurological symptoms, MR imaging implies the presence of brain abnormalities, specifically in severely ill patients and studies on cognition suggest problems with memory, attention, information processing and executive function. Preliminary clinical data also show that COVID-19 is associated with neurological and neuropsychiatric illness.

Brain damage and therefrom resulting emotional and cognitive deficits in ICU-treated patients are not uncommon findings. Post-intensive care syndrome (PICS) summarizes physical, cognitive, and mental impairments associated with ICU admission. PICS is assumed to be induced by a combination of patient-specific (e.g., psychiatric history), disease-related (e.g., hypoxemia), and ICU factors (e.g., invasive procedures). These factors can cause a variety of pathophysiologic states including atrophy, encephalopathy, and neuropathy, eventually leading to impairment and reduced quality of life. Additionally, ICU-admission has been found to also affect the mental health of patients´ family members (PICS-F). Many of these PICS-inducing factors can be assumed to occur during severe COVID-19 illness and treatment. Therefore, it is likely that COVID-19 patients and their family members exhibit PICS symptoms.

To date, it is not known to what extend COVID-19 related brain injury and therewith associated symptoms are present after the (sub)acute stages of illness and whether this will lead to long-term deficits in function. Further, it is to be determined whether COVID-19 patients develop PICS syndrome and if so, whether the therewith associated symptoms are limited to ICU-treated patients or may generally affect the broader group of hospitalized COVID-19 patients.

The aim of this research is to fill these gaps in research through:

(1) the identification of COVID-19 related brain abnormalities, cognitive impairments, and emotional deficits after the (sub)acute stages of illness (i.e., 6-9 months post-hospital discharge), 2) a comparison of COVID-19 related brain abnormalities, cognitive impairments, and emotional deficits to historical PICS cohorts 3) a comparison between COVID-19 ICU survivors and COVID-19 non-ICU patients in order to assess a potential PICS gradient and 3) a follow-up examination of the aforementioned groups 6 months after the first assessment to gain insight into the persistence of deficits.

Inclusion Criteria:

Patients:

• Objectified COVID-19 infection for which ICU or non-ICU hospital admission was necessary at one of the participating hospitals
• Age > 18 years
• Sufficient command of the Dutch language to follow test instructions and understand questionnaires
• Informed consent.

Family members (if present):

Within the scope of this study, the term family member will be defined as a person who has good insight into the patient´s daily life functioning (before and after COVID-19 infection). This person can be the spouse, partner, adult child or, in some cases, another individual that plays the most significant role in the patient´s life. The patient will decide who this family member is. We will check the following criteria:

• Family member of a participant with COVID-19 infection as described above;
• Requires participation of the aforementioned family member as COVID-19 patient
• Age > 18 years
• Sufficient command of the Dutch language to understand questionnaires
• Informed consent.

Exclusion Criteria:

Patients:

• objectified cognitive impairments before the hospital admission for the COVID-19 infection
• an unexpected incident leading to severe neurological damage occurring after hospital discharge (such as stroke or traumatic brain injury)
• contra-indications for MRI scanning (e.g. metal implants, cardiac pacemaker, claustrophobia, pregnancy).

Family member: no exclusion criteria.

Former COVID-19 patients who were either admitted to the general hospital ward or the intensive care unit and their respective family members.