With inputs from Dr Monica Vasudev

9743: Minutes of Virtual Meeting of CMAAO NMAs on “COVID in children & COVID and Neurology”

11^th July, 2020, Saturday, 9.30am-10.30am

Participants, Member NMAs: Dr KK Aggarwal, President CMAAO, Dr Yeh Woei Chong, Singapore Chair CMAAO, Prof Ashraf Nizami, Pakistan, First Vice President CMAAO, Dr N Gnanabaskaran, President Malaysian Medical Association, Dr Marthanda Pillai, Member World Medical Council, Dr Alvin Yee-Shing Chan, Hong Kong, Treasurer CMAAO, Dr Koh Kar Chai, Malaysia Co Chair CMAAO, Dr Marie Uzawa Urabe, Japan Medical Association, Dr Qaisar Sajjad, Secretary Pakistan Medical Association, Dr Prakash Budhathoky, Nepal Medical Association

Invitees: Dr Russell D’Souza, UNESCO Chair in Bioethics, Australia, Dr Sanchita Sharma, Editor IJCP Group

Prof Ashraf Nizami and Dr Alvin Yee-Shing Chan spoke on COVID in children and COVID and Neurology, respectively.

Here are key points from each presentation:

COVID-19 in children and Pakistan

Prof Ashraf Nizami

First Vice President CMAAO, Immediate Past President PMA Center, President PMA Lahore

In his presentation, Prof Ashraf Nizami spoke on COVID-19 in children and also highlighted the role of government and particularly the Pakistan Medical Association (PMA) in dealing with COVID-19 in Pakistan. The first case was reported in Pakistan on 6^th February.

• There was a general perception that children are not affected by this pandemic. But the fact is that all children of all ages in all countries are affected. This is a universal crisis and will have lifelong impact for some children as it is not just a health issue. It is also a social and psychological issue.
• Clinical symptoms in children include abdominal pain, diarrhea and vomiting, red rash, cracked lips, red eyes, high fever, swollen glands on neck and swollen hands and feet.
• As per data on July 1, about 7.28% of the total reported cases in Pakistan are in people below 19 years of age. The mortality is 0.46% (16 out of 3501 under 15 years). Three suspected cases of Kawasaki disease have been reported in Lahore; also from Karachi, Rawalpindi and Islamabad.
• COVID has an impact on social growth. About 30% of industry is affected. Education is disturbed and only about 30% of children in Pakistan have access to technology in education (online). Healthcare services have been affected. COVID has also affected the physical and mental growth of children.
• The pandemic has led to anxiety and depression not only in children but also the parents. Incidence of domestic violence against women has increased due to lockdown, which has an impact on children and the family. Exploitation and child abuse have happened.
• COVID-19 has compromised access to health services due to lockdown; the basic health services are delayed due to SOPs in place. Polio vaccination has been affected; besides Pakistan and Afghanistan, recent outbreaks have been reported in Africa, East Asia and the Pacific.
• The government is creating awareness about the disease; special institutions have been designated for children. Special counters have been created in hospitals.
• According to UNICEF, adequate water, sanitation and hygiene services for households, schools and healthcare facilities are essential to prevent spread of infectious diseases, including COVID-19; 3 billion homes do not have soap and water; 900 million children do not have soap and water at schools.
• PMA is an active participant in COVID-19 activities. It was the first organization in Pakistan which spoke about COVID-19 and created awareness and raised an alarm about the outbreak. It also looks after coordination among doctors, government, social activities and people. A scientific meeting was organized for family physicians, who are considered as front liners. PMA is also developing guidelines with information derived from WHO, CMAAO, London School of Economics, etc.
• PMA is working on telemedicine facilities, analysis of government policies, plans and actions. It is playing an active role in advocacy and implementation of WHO recommendations as per local needs as well as international experiences.
• PMA is pressing upon the government that curative services should not be compromised, to start immunization services with all SOPs; it is critical for the government’s decision to reopen schools. Psychology and psychiatric teleconsultations are being planned.

COVID and Neurology

 Dr Alvin Yee-Shing Chan

Treasurer CMAAO, Vice Chairman, HKMA Charitable Foundation

• About 36.4% of COVID patients from Wuhan, China had neurological involvement; manifestations were more in cases of severe infection.
• Acute cerebrovascular diseases occurred in 5.7% of severe cases vs. 0.08% of milder cases.
• 14% of severe cases had impaired consciousness vs. 2.4% of mild cases.
• Musculoskeletal injury occurred in 19.3% of severe cases vs. 4.8% of mild cases.
• Neurological signs and symptoms are much higher in patients in intensive care: mental confusion and agitation (69%), diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, bilateral extensor plantar reflexes (67%).
• 33% of discharged patients had dysexecutive syndrome, consisting of inattention, disorientation, or poorly organized movements in response to command.
• MRI brain, in most of the patients, will show leptomeningeal enhancement, bilateral frontotemporal hypoperfusion, ischemic stroke; encephalopathic pattern on EEG.
• Clinically, these patients may have milder symptoms (hyperosmia, anosmia, headache, weakness, altered consciousness); patients with more severe infection have encephalitis with demyelination, neuropathy, and stroke.
• Invasion of the medullary cardiorespiratory center by the SARS-CoV-2 virus may cause refractory respiratory failure in ICU patients.
• The route of entry is mostly through olfactory bulbs – olfactory tracts in the brain.
• Human coronaviruses have neuroinvasive capability. Misdirected host immune responses can damage the CNS, which is associated with autoimmunity in the susceptible persons, resulting in virus induced neuro-immunopathology. The virus replication directly damages the CNS. ACE2 receptors occur in olfactory epithelium 70 times more than in tracheal or nasal epithelium. This is why anosmia occurs so frequently in this disease.
• The ACE2 receptor expression differs in neurons and glial cells and so, immunopathology differs in different persons.
• Since ACE2 receptors are present in brain cells, the BBB presents no problem to the new coronavirus. The virus has been detected in brain samples on autopsies and offers an explanation about the neurological sequelae even when the patients survive.
• Possible mechanism of direct neuronal damage: The trans-neuronal retrograde machinery is a possible route of neuronal invasion. The virus first infects peripheral neurons to invade the CNS via the axonal retrograde transport. It infects another neuron via synapses. The virus is released by exocytosis in the presynaptic terminal. It then binds to ACE2 receptor on the postsynaptic neuron. It gains entry into the neuroplasm via the receptor-mediated endocytosis. It causes cell death via apoptosis.
• COVID-19 induces anti-cardiolipin antibodies → endothelialitis → thrombosis (venous and arterial) → stroke, cerebrovascular accidents.
• The direct attack on neurons will cause milder cases, but if there is massive invasion of key neuronal cells, this may cause dysexecutive function. The vasculitis and endothelitis is instrumental in severe cases → stroke, and cell death due to ischemia.
• Hong Kong has very few pediatric patients and they have mild infection. There is resurgence in community spread with more than 40 cases with no obvious source. There are 7500 tests in a day, which is inadequate. No medical health staff has been infected through hospital or clinic. The silent cases in community are a cause of concern.

 Acute presentation

 Dr KK Aggarwal, President CMAAO

 Look for the following points in every patient who presents with onset of illness less than 3 months. Classifying patients accordingly makes it easier to manage them.

• Is the clinical presentation of COVID due to inflammation? There will be signs of inflammation like IL-6, ESR, CRP, ferritin → Give anti-inflammatory drugs; steroids are the most potent anti-inflammatory drugs.
• Can this be because of hypercoagulable state? e.g. thrombotic stroke/MI/appendicitis/gangrene/happy hypoxia (microclot formation in lung vessels): Do D-dimer; high D-dimers mean hypercoagulable state.  
• Is there any immunological reaction (immediate or delayed) - humoral? Vasculitis, look for rash, CRP is normal, high platelets.
• Is there cellular immunological response? Cytokine crisis.
• Except for hypercoagulable state, all will respond to steroids. So, combination of LMWH and steroids is standard treatment.
• Some patients may have simple viral response and illness will resolve spontaneously in 2-3 days; some will show a bacterial response with slightly high polymorphs – typhoid test may be falsely positive in such patients; some patients may have low CD4 count indicating HIV-like activity.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA