NEUROLOGY OF PANDEMIC INFECTIONS
Hadi Manji (United Kingdom)

Pandemics are not the exception but the rule throughout history - the Plague of Justinian in 541 AD, the cholera pandemics of the 18^th Century and the H1N1 Spanish flu pandemic in 1918 which was the ‘mother of all influenza pandemics’. 1981 was the start of HIV/AIDS and in 2020, the world was hit by COVID-19.

Most pathogens causing these pandemics have neurological consequences, directly or indirectly. These are frequently undiagnosed but can have significant mortality and long-term morbidity.

The pathophysiological mechanisms resulting in the neurological syndromes include neurotropism (direct viral invasion of neuronal and glial cells), neuro-invasion of the nervous system directly or via the Trojan Horse mechanism, triggering immune dysregulation of the innate and adaptive immune systems with cytokine storms, inflammatory cell invasion and antibody production and, in HIV, immunosuppression. Additional complications arise from the complications of sepsis, metabolic derangement and coagulopathies which were all very apparent during the early phase of COVID.

This lecture will focus on the 1918 influenza pandemic, HIV/AIDS, Zika virus in 2014 and the current COVID 19 outbreak which has had a seismic global effect in terms of mortality and morbidity. The lessons learnt from each will be highlighted.

An important issue to be addressed is the question of long-term consequence of these pandemic infections - for example, encephalitis lethargica following the 1918 influenza pandemic, the ongoing debate regarding HIV associated Neurocognitive Disorder (HAND) and now Long COVID. The postulated mechanisms include viral persistence, smouldering inflammation and antibody mediated disorders.