Newsweek - USA (2021-02-19)

28 NEWSWEEK.COM

MEDICINE

In this frenzy of viral reproduction, the infected cells

“sucked out all the oxygen” in the area, slowly starving

the surrounding neurons of essential nutrients and

sending them into a death spiral.

This “bystander” effect was also observed in ex-

periments in brain organoids conducted by Alysson

Muotri, a professor of pediatrics and cellular and

molecular medicine at the University of California,

San Diego. When he exposed his colonies of organ-

oids to SARS-CoV-2, he found that the virus infected

only a handful of neurons but had a dramatic im-

pact. Within 48 hours, it had killed off 50 percent

of the synaptic connections between various cells,

which could wreak havoc in a living brain.

Virus that hides in brain cells might account for

the delayed onset of some neurological symptoms.

These infected cells, he suspects, may release some

kind of neurotoxic or pro-inflammatory molecules

capable of damaging the cells around them.

The evidence for the brain-infection hypothesis

is inconsistent, however. In an autopsy of three pa-

tients with brain damage, Iwasaki and her collabora-

tors found, only one had clearly been infiltrated by

the pathogen. In the 63 brains that Bryce examined,

she found viral fragments in only one, belonging to

the initial Hispanic patient. And at NINDS, Nath has

so far been unable to find any signs of brain infec-

tions, an outcome he calls a “major mystery.”

“My expertise is in infection of the nervous system,

so every pandemic I have studied the brain,” Nath

says. “I was very surprised was there was no virus

that I could detect.”

Immune Systems Run Amok

nath suspects some long-haul symptoms might

be explained by a hypothesis he favors for the cause

of Chronic Fatigue Syndrome: The infection has left

its victims with a persistent activation of the im-

mune system, which has pushed the body into a

low-level state of war with itself. Indeed, the many

ways acute COVID-19 manifests in patients can be

explained by how each individual’s immune system

reacts to the disease. The same may well be true in

those suffering from chronic symptoms.

These two hypotheses for long-haul COVID-19—

autoimmunity and direct brain infection—are “not

mutually exclusive,” Yale’s Iwasaki notes.

She examined the impact of a special class of im-

mune cells called “autoantibodies”—molecular-level

cellular assassins that appear to be specially-de-

signed and directed to seek out and attack proteins

produced by the patient’s own body. After analyz-

ing autoantibodies based on blood samples culled

from 194 patients and healthcare workers infect-

ed with the virus, and comparing them to blood

drawn from 30 uninfected healthcare workers, she

found the COVID-19 patients exhibited “dramatic

increases” in autoantibody activity, with the spe-

cialized cells in many cases targeting other immune

cells. Of the 15 patients who died during the study,

all but one were found to have unleashed autoan-

tibodies on other elements of the immune system

needed to effectively fight off the disease. The au-

toantibodies also appeared to be attacking mole-

cules involved in blood clotting, connective tissue

and cells in the brain and central nervous system,

mistakenly identifying them as invading pathogens

that needed to be eliminated. Iwasaki published a

report in the British Medical Association’s flagship

journal in December.