veloping cardiovascular disease. They found
“COVID is an equal opportunity offender,”
Al-Aly says. “We found an increased risk of
cardiovascular problems in old people and
in young people, in people with diabetes
and without diabetes, in people with obe-
sity and people without obesity, in people
who smoked and who never smoked.”
COVID-19 boosted the risk of all 20 cardio-
vascular ailments studied, including heart
attacks, arrhythmias, strokes, heart failure,
cardiac arrest, pulmonary embolism, and
deep vein thrombosis.
For example, veterans who had
COVID-19 faced a 72% higher risk of heart
failure after 12 months than their pan-
demic-era peers who didn’t test positive.
That translated to nearly 12 more infected
people per 1000 developing heart failure
than controls. Overall, infection raised the
risk of developing any of the 20 conditions
by 63%, compared with pandemic-era con-
trols. But Miriam Merad, an immunologist
at the Icahn School of Medicine at Mount
Sinai, notes the researchers also found “a
clear correlation between the severity of
the [post–COVID-19] symptoms and the se-
verity of the initial disease.” The long-term
risks grew markedly from outpatients to
hospitalized patients to those in the inten-
sive care unit.
The team used statistical tools to try
to correct for the scarcity of women and
people of color, and their results are likely
to be relevant for those groups, too, says
Elizabeth Ofili, a preventive cardiologist at
Morehouse School of Medicine. “The correc-tion for gender and race goes a long way.”
One possible mechanism for long-term
damage is inflammation of the endothe-
lial cells that line the heart and blood
vessels, Al-Aly says; the virus is known to
directly attack such cells. But the research-
ers also include a list of other potential
mechanisms, including a greater tendency
of the blood to clot, persistent virus in
some sites, and elevated levels of proin-
flammatory chemical messengers called
cytokines. “The putative mechanistic path-
ways are still in the realm of speculation,”
Al-Aly says.The authors say their findings suggest
millions of COVID-19 survivors could suffer
long-term consequences, straining health
care delivery for years. “Governments and
health systems around the world should be
prepared to deal with the likely significant
contribution of the COVID-19 pandemic to
a rise in the burden of cardiovascular dis-
eases,” they write.
Al-Aly adds: “Some of these conditions
are chronic [and] will literally scar people
for a lifetime. It’s not like you wake up
tomorrow and suddenly no longer have
heart failure.” jCREDITS: (GRAPHIC K. FRANKLIN/
SCIENCE
; (DATA Y. XIE
ET AL
., NAT MED
(2022. DOI: 10.1038/S41591 022 01689
SCIENCE science.org 18 FEBRUARY 2022 • VOL 375 ISSUE 6582 707Any cardiovascular outcomeAbnormal heart rhythmBlood clotsHeart failureHeart attackStrokeMyocarditis0 25 125 225 325
Excess cases per 1000 COVID-19–infected peopleNonhospitalized
Hospitalized
Intensive care unitThe heartbreak of COVID-
One year later, veterans infected with COVID-19 faced higher risk of cardiovascular ailments, with risk rising
with the severity of initial disease and translating into many more affected people per thousand than in controls.T
he team that last week found elevated
long-term risks of cardiovascular
ailments among U.S. veterans who
got COVID-19 (see main story,
p. 706) is reporting more bad news.
According to a huge analysis published
this week in The BMJ, 1 year later the
veterans also faced higher risks of neuro-
psychiatric ailments, including brain fog,
than their uninfected peers.
“Most of us experienced some sort of
mental distress during the pandemic, but
this shows that people with COVID-19 had a
much higher risk of mental health disorders
than their contemporaries,” says senior
author Ziyad Al-Aly, a clinical epidemiologist
at Washington University in St. Louis and
chief of research at the VA St. Louis Health
Care system. “It’s a wake-up call.”
Many papers have used health records
to examine post– COVID-19 psychiatricoutcomes, but “The scale of ... this study
sets [it] apart, as well as the quality of the
statistical methods used,” says Alex
Charney, a neuroscientist and psychia-
trist at the Mount Sinai Health System.
Al-Aly and colleagues analyzed the elec-
tronic health records of nearly 154,
infected veterans (almost all unvaccinated
at the time) and 5.8 million uninfected
controls who used Affairs health system in
the first 10.5 months of the U.S. pandemic.
One year later, survivors of COVID-
were 46% more likely than controls
to have been diagnosed with any of
14 neuropsychiatric disorders. These
included depression, suicidal thoughts,
anxiety, sleep disturbance, opioid use
disorder, and neurocognitive decline
or “brain fog.” The risk of brain fog was
80% higher than in controls, which
translates to 10.75 more people in every1000 experiencing the condition. People
hospitalized with coronavirus infections
had the highest risk of developing any of
the disorders—343% more than controls.
Outpatients faced 40% higher risk.
The study has limitations, including
that its population was 71% to 76% white,
90% male, and on average 63 years old.
“This is a Veterans Affairs cohort and
not generalizable,” says Sung-Min Cho, a
neurointensivist and physician-scientist
at Johns Hopkins University’s School
of Medicine.
Neuroimmunologist Cecilie Bay-
Richter of Aarhus University adds that
just how infection could damage mental
health is unclear. She says animal stud-
ies will be needed “to be able to truly
disentangle the direct, biological causes
from the indirect causes” of long-term
neuropsychiatric conditions. — M .W.Lasting impact of infection extends to the brain