HCFI Dr KK Aggarwal Research Fund

Topic: Brain Fog: Understanding Neurocognitive symptoms in COVID19 & Country Updates

26^th June, 2021, Saturday, 9.30am-10.30am

Key points from the discussion

• #1. A presentation on “Brain Fog: Understanding Neurocognitive symptoms in COVID19” was given by Dr Kavita Sharma, Medical Director of Home and Palliative Hospice Care at Aurora Health Care, Wisconsin, USA
• Hospitalized Covid-19 patients, in particular critically ill ICU patients, commonly have neurologic complications. The most common neurological presentations are myalgias, headache, dizziness, encephalopathy, dysgeusia, anosmia. Uncommon presentations include stroke, movement disorders, ataxia, and seizures.
• Acute Covid-19 lasts for up to 4 weeks following onset of illness; ongoing symptomatic Covid-19 is symptoms from 4-12 weeks following onset of illness; post-covid-19 is when symptoms persist ≥12 weeks. These stages reflect only symptomatic recovery and not viral replication.
• Many hospitals in many parts of the world have developed acute care centers for the elderly. These centers address the unique needs of patients aged ≥ 65 years.
• The elderly patients are more at risk for severe Covid-19 as they have more cardiovascular and metabolic comorbidities.
• Delirium is a common presenting symptom of elderly with Covid-19. Delirum itself has high mortality. Dementia patients also have high mortality.
• Covid has affect management of hospitalized elderly patients. There are only few recommendations about caring for older, frail and multimorbid inpatients, or patients in long-term care, rehab and primary care.
• The neurologic injury results from systemic dysfunction and hypoxemia, RAS dysfunction, cytopathic effects (direct viral invasion of nervous system) and hyperactivation of the host immune response. The cytokine storm can damage the blood brain barrier, and then there are the para- and post-infectious triggers. Authoantibodies can result in thrombotic complications.
• The gray matter requires more than twice the oxygen as white matter. Time lost is brain lost.
• ACE2 receptors are highly expressed in the brain besides lungs, kidneys, gut. ACE2 receptor acts as a doorway to Covid19.
• The essential defense cells of brain are the microglial cells, which are activated by Covid-19 infection. This triggers T-killer cells migration resulting in neuroinflammation of brain stem.
• A proinflammatory state may be associated with thrombophilia, increasing risk of stroke and other thrombotic
• Loss of taste and smell are common early symptoms in Covid-19 patients, which can occur even in the absence of nasal discharge. The virus invades the brain through the olfactory epithelium and the neural-mucosal interface.
• Ischemic stroke, intracranial hemorrhage, cerebrovenous thrombosis have also been reported to occur 1-3 weeks after onset of Covid-19 symptoms.
• Neuromuscular disease has been reported – Guillain Barre syndrome, myositis, focal and multifocal neuropathies and peripheral nerve injuries after prone positioning.
• Case definition for multisystem inflammatory syndrome in children (MISC): Patient <21 years presenting with fever, lab evidence of inflammation and evidence of clinically severe illness requiring hospitalization with multisystem organ involvement AND no alternative plausible diagnosis AND positive for current or recent SARS-CoV-2 by RT PCR or Covid-19 exposure within the four weeks prior to the onset of symptoms.
• Encephalopathy is common in critically ill patients and also elderly patients with Covid-19. The predisposing risk factors include a history of any neurological disorder, cancer, CKD, diabetes, HT, heart failure. The risk is high in intubated patients in intensive care, use of vasopressor, benzodiazepenes or continuous opioid infusions.
• Patients with delirium have longer hospitalizations and worse functional impairment at the time of discharge; the 30-day mortality is also high vs those without delirium.
• Delirium can be characterised by a hyperactive/agitated state, hypoactive state or a combination of the two.
• Acute change in mentation and attention with disorganised thinking, easy distractibility or a waxing and waning level of consciousness is the hallmark of delirium. Illusions, delusions or hallucinations frequently co-occur.
• Terminal delirium means delirium in a patient in the final days of his/her life.
• CAM-ICU (Confusion Assessment Method-Intensive Care Unit) is a tool designed to assess delirium in non-verbal patients. It includes very specific assessment questions and is found online at icudelirium.org/delirium.html.
• The Intensive Care Delirium Screening Checklist (ICDSC) evaluates eight features of delirium: Altered level of consciousness, inattention, disorientation, hallucinations, psychomotor agitation/retardation, inappropriate mood/speech, sleep/wake cycle disturbance and symptom fluctuation.
• Non-pharmacologic treatments are the mainstay in delirium management and should be used regardless of the type of delirium.
• ABCDE (Awakening/Breathing Coordination, Delirium monitoring and Early exercise/mobility) bundle has been used to prevent and manage delirium in ICU settings.
• The underlying metabolic problems need correction along with fluid and electrolytes management.
• Benzodiazepenes (lorazepam) or antipsychotics (haloperidol) are indicated if non-pharmacological treatments have not helped or the patient is at risk for harm to himself or the staff.
• The FDA has issued a black box warning for atypical antipsychotics (olanzapine, risperidone, aripiprazole) about the need for monitoring QTc prolongation, when the patient is taking certain antibiotics or antinausea medications.
• In some patients “long haulers”, neurologic symptoms and cognitive dysfunction persist in the post-acute phase and constitute the syndrome of “post-acute sequelae of SARS-CoV-2 infection” (PASC).
• The 10 most frequent neurologic symptoms were non-specific cognitive complaints “brain fog”, headache, numbness, anosmia, dysgeusia, myalgia, dizziness, tinnitus, blurred vision.
• The prominent fatigue and cognitive complaints resemble those seen in patients with myalgic encephalopathy/chronic fatigue syndrome (ME/CFS).
• All patients with persistent symptoms should be evaluated in a specialized covid-19 recovery clinics or subspecialty clinics.
• The Society of Critical Care Medicine screening tools to detect long-term cognition are (Montreal Cognitive Assessment [MoCA]), anxiety (HADS), depression (HADS), PTSD (IES-R or the abbreviated IES-6) or physical function (6-min walk test and/or EuroOol-5D-5L)
• Vaccination may improve symptoms of long Covid as revealed in the largest survey to date of vaccinated people with long Covid; in this survey, 57% of respondents reported overall improvement in their symptoms after vaccination, while 19% reported an overall worsening of their symptoms. Patients reported complete clearing of the brain fog.
• Delirum can be considered a marker of acute brain dysfunction.

• Metabolic changes in the body when the patient is hypoxic or septic will cause delirium. Not all patients develop delirium, but those who develop delirium are at high risk of mortality. These patients need to be aggressively recognised.
• The brain fog is a transient state, but some patients have reported it lasting for several months. Probably residual virus may be causing an immune response.
• Ischemic stroke disease is mostly the small vessel disease, which are damaged by the Covid-19 infection. The ACE2 receptors are present in the capillaries, small vessels.
• Proximal myopathy is a common condition seen in post-Covid patients.
• A “glymphatic” (glial-lymphatic) pathway has been recently identified and it has a potential role in neurodegenerative diseases.

#2. Country Updates

• Bangladesh: The country will go for a strict nation-wide lockdown for 7 days to begin with. The number of cases and deaths are increasing, especially in the border areas. There is a shortage of vaccine in the country.
• India: The second wave is receding. The number of daily new cases has reduced to 40,000 per day. The number of vaccinations is around 8 million per day. The country hopes to complete its vaccination in the next 3-4 months. The side effects are very low 0.003%. Now there is a delta plus variant in the country; mostly disease with this variant has been mild to moderate, though two patients have died. Some studies have shown immune escape with the variant. Some states have been put on red alert because of the delta plus variant. Three principles for unlocking: have a test positivity rate (RT PCR) of less than 5% for 2 weeks, try to vaccinate 70% of geography with two doses of the vaccine and zero tolerance for non-adherence to Covid-appropriate behavior and protocols.
• South Africa: There is the third wave in the country and the numbers are high and rising. The hospitals are overcrowded so many patients are being treated at home.
• Pakistan: The positivity rate is between 1.5 and 2.5%; vaccination is very slow. Till now, only 4% of the population has been vaccinated. The fourth wave is anticipated in the month of July or August, which is a cause for concern.
• Japan: The fourth wave is ending; 50% of people aged 65 and older have been vaccinated. The country will be hosting the Olympics. It is preparing for the fifth wave.
• Singapore: About 80,000 vaccines are being given per day. More than 50% of the population is vaccinated; of these, 40% has had two doses, the rest have been given one dose. Delta variant in community spread – clusters in housing blocks. Singapore is also checking waste water to see for spread of the Covid-19 virus. Mass swabbing is done in blocks where the virus is detected in the waste water.

Participants

Member National Medical Associations

Dr Yeh Woei Chong, Singapore, Chair CMAAO

Dr Ravi Naidu, Malaysia, Immediate Past President CMAAO

Prof Ashraf Nizami, Pakistan, First Vice President CMAAO

Dr Alvin Yee-Shing Chan, Hong Kong Medical Association, Treasurer, CMAAO

Dr Marthanda Pillai, India Member World Medical Council

Dr Angelique Coetzee, South Africa

Dr Akhtar Hussain, South Africa

Dr Salma Kundi, Pakistan

Dr Qaiser Sajjad, Pakistan

Dr Md Jamaluddin Chowdhury, Bangladesh

Dr Marie Uzawa Urabe, Japan

 Invitees

 Dr Kavita Sharma

Dr Monica Vasudev, USA

Dr Brahm Vasudev, USA

Dr Shashank Joshi, Mumbai, India

Dr Mulazim Hussain Bukhari, Pakistan

Dr S Sharma, Editor IJCP Group

Moderator

Mr Saurabh Aggarwal