key: cord-331688-88veckbv
authors: Pavlakis, Steven; McAbee, Gary; Roach, E. Steve
title: Fear and Understanding in the Time of COVID-19
date: 2020-06-26
journal: Pediatr Neurol
DOI: 10.1016/j.pediatrneurol.2020.06.015
sha: 
doc_id: 331688
cord_uid: 88veckbv

nan

Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less.

New York City is now ravaged by COVID-19. An anesthesiologist friend tells us that, at State University of New York, Stony Brook, they are intubating about 18 patients per day for COVID-19 pulmonary disease. The authors have had five friends die due to COVID-19 complications in the last week, one a pediatric neurosurgeon and the others mostly from the theater world. The fear, uncertainty, and anxiety this pandemic provoke are reminiscent of the AIDS epidemic in the 1980s.

COVID-19 is a coronavirus that usually causes mild symptoms. However, some people die, in many cases abruptly. Anecdotally, many of our physicians suggest that critically ill patients are hypercoagulable, with intravenous lines that clot easily and associated kidney and liver disease. Chinese pathologists, anecdotally as well, note that pulmonary arteries and arterioles are involved with clotting. Furthermore the abruptness of the fatality in some cases is reminiscent of vascular disease. Stroke has been associated with COVID-19 as has heart disease; we treated one adult who experienced a concurrent stroke on our stroke service. To date there has not been a documented increase in stroke in either adults or children, but there are insufficient data to draw definitive conclusions. In a Chinese series comparing patients who died with those who survived, interleukin elevation, reactive protein elevation, and prolonged prothrombin time occurred more often among people who died. (1) The New York Times reported that some individuals with coronavirus experience brain dysfunction, (2) but this too is largely word-of-mouth. In children little is known about the neurological complications of COVID-19. One patient was reported with acute disseminated encephalomyelitis in 2004 who had a coronavirus (but not COVID-19) in cerebrospinal spinal fluid, suggesting that coronavirus may directly affect the central nervous system in children. (3) Similarly, we recently admitted a child with encephalitis and status epilepticus who was positive for COVID-19, possibly indicating a para-infectious process. Para-infectious here is used to describe a condition that is either infectious or post-infectious (without a direct infectious spread of the pathogen).

Do children die of this disease? Yes, children may die, although the disease course is generally milder in children than in older patients. (4) The Centers for Disease Control notes that the risk for severe disease in adults is aggravated by existing cardiovascular disease, diabetes and/or pulmonary disease. An artificial intelligence paradigm shows three features that are associated with severe pulmonary disease: high hemoglobin, elevated liver functions, and myalgia.

Premorbid pulmonary disease seems a reasonable predictor, high hemoglobin could be associated with chronic hypoxemia which may be a risk for stroke, and myalgia which is associated with inflammation. (5) Early anecdotal data from China and Italy note that patients with COVID-19 have a significant blood-clotting disorder, with the presence of small clots in the lungs and other organs.(6) Covid-19 infection is caused by binding of the surface spike protein to the human angiotensinconverting enzyme 2 (ACE2) receptor (7). ACE2 is highly expressed in the lung alveolar cells but also in the heart, intestinal epithelium, vascular endothelium, and kidneys, all tissues that have been affected by Covid-19 infection. (7) To summarize, many of the same risk factors for vascular disease are associated with poor prognosis in COVID-19, buttressing the concept that vascular disease may play a role for COVID-19 associated critical illness, at least in some patients.

Currently a study is planned to treat COVID-19 patients who are deteriorating with tPA by researchers at the University of Colorado. This could lyse clots that may be at play in this infection. The study is in the planning stages and outcome measures are likely to be pulmonary. (6) A small human trial conducted in 2001 noted a reduction in mortality from 100% to 70% in patients with severe respiratory distress who weren't expected to survive and were treated with tPA, albeit unrelated to COVID-19. (6) In summary, potential etiologies of neurological disease could include severe inflammation and upregulation of cytokines, clotting factors, macrophages, and the like (the "cytokine storm"). In addition, there may be direct infection based on the patient reported with coronavirus in the cerebrospinal fluid or possibly post-infectious changes based on our patient with encephalitis and seizures who was sent home. It has been said that coronavirus does not directly infect the brain, but that was also said about HIV-1 before an autopsy study determined that 25% of AIDS patients had human immunodeficiency virus in brain endothelial cells.

So what should we do? The incidence of COVID-19 in children is unknown because we have been testing too infrequently to know. Similarly, the population incidence of recent and chronic disease is unknown because IgG and IgM testing has not been completed in either adults or children. These are reasonable goals, but ones beyond the scope of pediatric neurology.

Pediatricians and pediatric neurologists should screen confirmed cases and obtain a good neurological history and examination including cognitive function. We have started this as a quality improvement project. This is important to do throughout the country and the child neurology associations throughout the world might take a lead on this. Blood tests should include coagulation factors as well as inflammatory markers to better understand the problem and, ultimately, to facilitate better treatment plans. Anecdotally steroids do not seem to help, but as with everything about this outbreak we are learning and making decisions on a day-by-day time frame. We and our adult colleagues need to obtain autopsy examinations of the brain and endothelial tissues. Stroke investigations in adult patients are planned and pediatric neurology should be investigating stroke associations as well.

Even amid the chaos of a pandemic, research is proceeding rapidly in multiple arenas. We need to know more about the manifestations of the virus, and we desperately need more effective treatment and prevention options. And as we emerge from the pandemic's devastation, we must learn the lessons that will help us manage the inevitable next pandemic. We need to turn this chaos around, and neurologists, as always, need to contribute.

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

Roni Rabin Some coronavirus patients show signs of brain ailments

Detection of Coronavirus in the Central Nervous System of a

COVID-19 in children: initial characterization of the pediatric disease

Towards an artificial intelligence framework for data-driven prediction of coronavirus clinical severity

Stroke drug could help covid-19 patients. WebMD

Covid-19) and Cardiovascular Disease