I think that this anticoagulation trial in critically ill patients is way too late. As soon as you are diagnosed you should be getting anticoagulation. But I'm not medically trained so I obviously know nothing useful.
Physicians give first comprehensive review of COVID-19's effects outside the lung
MedicalXpress Breaking News-and-Events|July 13, 2020
After
only a few days caring for critically ill COVID-19 patients at the
start of the outbreak in New York City, Aakriti Gupta, MD, realized that
this was much more than a respiratory disease.
"I
was on the front lines right from the beginning. I observed that
patients were clotting a lot, they had high blood sugars even if they
did not have diabetes, and many were experiencing injury to their hearts
and kidneys," says Gupta, one of the first Columbia cardiology fellows
to be deployed to the COVID intensive care units at Columbia University
Irving Medical Center.
In early March, there
wasn't much clinical guidance on the non-respiratory effects of
COVID-19, so Gupta decided to coalesce findings from studies that were
just beginning to appear in the literature with what the physicians were
learning from experience.
Gupta,
along with senior author Donald Landry, MD, Ph.D., chair of medicine at
Columbia University Vagelos College of Physicians and Surgeons,
organized senior co-authors, and Gupta, along with two other colleagues,
Mahesh Madhavan, MD, a cardiology fellow at CUIMC, and Kartik Sehgal,
MD, a hematology/oncology fellow at Beth Israel Deaconess Medical
Center/Harvard Medical School, mobilized clinicians at Columbia,
Harvard, Yale, and Mount Sinai Hospital, among other institutions, to
review the latest findings on COVID-19's effect on organ systems outside the lungs and provide clinical guidance for physicians.
Their review—the first extensive review of COVID-19's effects on all affected organs outside the lungs—was published today in Nature Medicine.
"Physicians
need to think of COVID-19 as a multisystem disease," Gupta says.
"There's a lot of news about clotting but it's also important to
understand that a substantial proportion of these patients suffer
kidney, heart, and brain damage, and physicians need to treat those conditions along with the respiratory disease."
Blood Clots, Inflammation, and an Immune System in Overdrive
"In
just the first few weeks of the pandemic, we were seeing a lot of
thrombotic complications, more than what we would have anticipated from
experience with other viral illnesses," says Sehgal, "and they can have
profound consequences on the patient."
Scientists
think these clotting complications may stem from the virus's attack on
cells that line the blood vessels. When the virus attacks blood vessel
cells, inflammation increases, and blood begins to form clots, big and
small. These blood clots can travel all over the body and wreak havoc on
organs, perpetuating a vicious cycle of thromboinflammation.
To
combat clotting and its damaging effects, clinicians at Columbia, many
of whom are co-authors on this review, are conducting a randomized
clinical trial to investigate the optimal dose and timing of
anticoagulation drugs in critically ill patients with COVID-19.
The untempered inflammation can also overstimulate the immune system,
and though doctors initially shied away from using steroids to globally
suppress the immune system, a recent clinical trial has found that at
least one steroid, dexamethasone, reduced deaths in ventilated patients
by one-third. Randomized clinical trials are underway to target specific components of thromboinflammation and the immune system, such as interleukin-6 signaling.
"Scientists
all over the world are working at an unprecedented rate towards
understanding how this virus specifically hijacks the normally
protective biological mechanisms. We hope that this would help in the
development of more effective, precise, and safer treatments for
COVID-19 in the near future," says Sehgal.
Straight to the Heart
Clots can cause heart attacks, but the virus attacks the heart in other ways, one author says.
"The
mechanism of heart damage is currently unclear, as the virus has not
been frequently isolated from the heart tissue in autopsy cases," says
Gupta.
The heart muscle may be damaged by
systemic inflammation and the accompanying cytokine release, a flood of
immune cells that normally clears up infected cells but can spiral out
of control in severe COVID-19 cases.
Despite
the degree of heart damage, physicians were not able to utilize the
diagnostic and therapeutic strategies, including heart biopsies and
cardiac catheterizations, that they would normally use during the early
stages of the pandemic given the need to protect personnel and patients
from viral transmission. This has changed as the disease prevalence has
gone down in New York CIty.
Kidney Failure
Another surprising finding was the high proportion of COVID-19 patients in the ICU with acute kidney damage.
The
ACE2 receptor used by the virus to gain entry into the cells is found
in high concentrations in the kidney and could likely be responsible for
the renal damage. Studies in China reported renal complications, but in
New York City, clinicians saw renal failure in up to 50% of patients in
the ICU.
"About 5 to 10% of patients needed dialysis. That's a very high number," Gupta says.
Data
regarding long-term renal damage are currently lacking, but a
significant proportion of patients will likely go on to require
permanent dialysis.
"Future studies following
patients who experienced complications during hospitalizations for
COVID-19 will be crucial," notes Madhavan.
Neurological Effects
Neurological symptoms, including headache, dizziness, fatigue, and loss of smell, may occur in about a third of patients.
More concerning, strokes caused by blood clots occur in up to 6% of severe cases and delirium in 8% to 9%.
"COVID-19 patients can be intubated for two to three weeks; a quarter require ventilators for 30 or more days," Gupta says.
"These
are very prolonged intubations, and patients need a lot of sedation.
'ICU delirium' was a well known condition before COVID, and the
hallucinations may be less an effect of the virus and more an effect of
the prolonged sedation."
"This virus is
unusual and it's hard not to take a step back and not be impressed by
how many manifestations it has on the human body," says Madhavan.
"Despite
subspecialty training as internists, it's our job to keep all organ
systems in mind when caring for the patients in front of us. We hope
that our review, observations, and recommendations can help other
clinicians where cases are now surging."
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The paper is titled, "Extrapulmonary manifestations of COVID-19."
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