The Impact of COVID-19 on Developing Neurologic Disorders

Authors: Piotr Tekiela,  View ORCID ProfileJennifer J. Majersik

One of the greatest challenges of treating a new virus is the lack of information about it. When little is known about a virus, patients affected by it, as well as their families, are left with uncertainty. In an article appearing in this issue of Neurology®, Dr. Frontera and her team aimed to determine how often patients hospitalized with coronavirus disease 2019 (COVID-19) developed new neurologic disorders.1 They then compared several key outcomes in treatment between patients who developed a new neurologic disorder due to COVID-19 and those who did not. These included discharges to home, ventilator use, length of hospital stay, and in-hospital deaths. These findings can help us understand which groups of people may be more likely to develop more severe disease after having COVID-19, as well as what their prognosis is likely to be.

How Was the Study Done?

The study was run during the first wave of the COVID-19 pandemic, from March 10 through May 20, 2020, in 4 hospitals in the New York City metropolitan area. The researchers set strict guidelines for the type of patients they would include in the study. Patients had to be adults with a laboratory-confirmed severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. They also had to have been admitted to the hospital at some point during the duration of their illness. Patients who were only seen in an emergency department or at an outpatient clinic were not included in the study.

There are 3 major strengths of this study that set it apart from other studies. First, patients were excluded if they were not tested for SARS-CoV-2 or if they tested negative for the virus. Second, all of the neurologic diagnoses made during the study were determined by a neurologist. Lastly, only new diagnoses of neurologic disease were included in the study. If someone had a neurologic disorder that was known before hospitalization due to COVID-19, that diagnosis was not counted in the study results. This improved the accuracy of diagnosing new neurologic complications that appeared to be caused by COVID-19.

What Were the Results?

A total of 4,491 patients were hospitalized with COVID-19 at the 4 hospitals involved in the study. Of those patients, 606 (13.5%) developed a new neurologic disorder, as diagnosed by a neurologist. These disorders included a confused state in 51% (called a toxic-metabolic encephalopathy), stroke in 14%, seizures in 12%, and brain injury due to lack of oxygen or blood flow (called hypoxic or ischemic disorders) in 11% (see below to learn more about these disorders). The researchers did not find any infections in the brain (such as meningitis or encephalitis) or in the spinal cord (myelitis) in these patients. The patients at highest risk of developing a neurologic disease were older and more likely to be male, White, or diabetic.

For most patients (54%) who developed a neurologic disorder, the disorder appeared about 2 days after the initial COVID-19 symptoms (fever, cough, nausea, vomiting, or diarrhea) arose. In 43% of patients, neurologic problems developed at approximately the same time as their initial COVID-19 symptoms. Only 2% of patients developed neurologic symptoms before onset of the common COVID-19 symptoms.

Development of new neurologic disease was associated with worse outcomes overall. Patients who developed a neurologic disorder along with COVID-19 were 28% less likely to be discharged home from the hospital and 38% more likely to die (either from the illness or from the neurologic disorder). Further, they spent 6 more days on a ventilator and 4 more days in the hospital than patients who did not develop a new neurologic disorder.

For More Information: https://n.neurology.org/content/96/4/e647

COVID and the brain: researchers zero in on how damage occurs

Authors: Michael Marshall

Growing evidence suggests that the coronavirus causes ‘brain fog’ and other neurological symptoms through multiple mechanisms.

How COVID-19 damages the brain is becoming clearer. New evidence suggests that the coronavirus’s assault on the brain could be multipronged: it might attack certain brain cells directly, reduce blood flow to brain tissue or trigger production of immune molecules that can harm brain cells.

Infection with the coronavirus SARS-CoV-2 can cause memory loss, strokes and other effects on the brain. The question, says Serena Spudich, a neurologist at Yale University in New Haven, Connecticut, is: “Can we intervene early to address these abnormalities so that people don’t have long-term problems?”

With so many people affected — neurological symptoms appeared in 80% of the people hospitalized with COVID-19 who were surveyed in one study1 — researchers hope that the growing evidence base will point the way to better treatments.

For More Information: https://www.nature.com/articles/d41586-021-01693-6

Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition

Authors: Jia YuXuan YuanHang ChenShruti ChaturvediEvan M. BraunsteinRobert A. Brodsky

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious respiratory virus that can lead to venous/arterial thrombosis, stroke, renal failure, myocardial infarction, thrombocytopenia, and other end-organ damage. Animal models demonstrating end-organ protection in C3-deficient mice and evidence of complement activation in humans have led to the hypothesis that SARS-CoV-2 triggers complement-mediated endothelial damage, but the mechanism is unclear. Here, we demonstrate that the SARS-CoV-2 spike protein (subunit 1 and 2), but not the N protein, directly activates the alternative pathway of complement (APC). Complement-dependent killing using the modified Ham test is blocked by either C5 or factor D inhibition. C3 fragments and C5b-9 are deposited on TF1PIGAnull target cells, and complement factor Bb is increased in the supernatant from spike protein–treated cells. C5 inhibition prevents the accumulation of C5b-9 on cells, but not C3c; however, factor D inhibition prevents both C3c and C5b-9 accumulation. Addition of factor H mitigates the complement attack. In conclusion, SARS-CoV-2 spike proteins convert nonactivator surfaces to activator surfaces by preventing the inactivation of the cell-surface APC convertase. APC activation may explain many of the clinical manifestations (microangiopathy, thrombocytopenia, renal injury, and thrombophilia) of COVID-19 that are also observed in other complement-driven diseases such as atypical hemolytic uremic syndrome and catastrophic antiphospholipid antibody syndrome. C5 inhibition prevents accumulation of C5b-9 in vitro but does not prevent upstream complement activation in response to SARS-CoV-2 spike proteins.

For More Information: https://ashpublications.org/blood/article/136/18/2080/463611/Direct-activation-of-the-alternative-complement

The Thorny Problem Of COVID-19 Vaccines And Spike Proteins

Authors: W. Glen Pyle

Almost since the beginning of the COVID-19 pandemic, a piece of the SARS-CoV2 virus called the “spike protein” has drawn interest from researchers and healthcare professionals.

New research by Yuyang Lei and colleagues published in the journal Circulation Research sheds new light on how the spike protein might play a critical role in the widespread damage caused by SARS-CoV2, and offers insight into treating the complications of COVID-19.

Vaccine skeptics have seized on the study to cast doubt on the safety of vaccines. But a review of the study’s findings shows that the concerns raised by vaccine doubters are much ado about nothing.

The Study

The vascular endothelium is an important player in the illness and death associated with COVID-19. The endothelium is a system of cells that line and protect the inside of blood vessels. SARS-CoV2 injures the endothelium leading to blood clots, heart attack, pulmonary embolism, and stroke. Despite the established link between COVID-19 and these cardiovascular complications, the mechanism by which they develop is unknown.

Researchers from Jiaotong University; the University of California, San Diego; and the Salk Institute used a pseudovirus coated with spike protein to investigate the effects of the viral protein on endothelial cells. Pseudoviruses – which were first developed over 50 years ago – contain the outer shell of the virus, but they lack the viral genes needed to reproduce.

Hamsters treated with the spike protein coated pseudovirus showed lung damage similar to that seen in humans infected with SARS-CoV2. When researchers added pseudovirus to cultured endothelial cells they found that the mitochondria inside the cells were injured. Since mitochondria are responsible for providing energy to cells, their dysfunction can cause cell death.

When isolated pulmonary arteries were exposed to the spike protein carrying pseudovirus there was some disruption in the ability of the blood vessels to dilate. The decreased ability to expand blood vessels that serve the lungs could impair the ability of the body to take up oxygen from lungs that are damaged by the virus.

The novelty of this study was the discovery that the spike protein itself causes damage, and that the pathway triggered by the spike protein could explain the widespread cardiovascular complications that develop in COVID-19 patients.

For More Information: https://www.science20.com/w_glen_pyle/the_thorny_problem_of_covid19_vaccines_and_spike_proteins-254373

Evidence Shows that COVID-19 Attacks Blood Vessels

Authors: Carolyn Crist

As researchers learn more about COVID-19, they’ve seen reports from patients about unusual rashes, blood clots, and strokes, which could all be linked to damaged blood vessels.

Scientists are now looking at the vascular system, which includes arteries, veins, and capillaries, to monitor the various ways that the coronavirus attacks the body, according to NPR.

In particular, they’ve found that the virus seems to attack the endothelium, or the single layer of cells that line the inside of blood vessels. These cells prevent clotting, control blood pressure, and protect the body from invading pathogens.

“When the virus damages the inside of the blood vessel and shreds the lining, that’s like the ice after a hockey game,” William Li, a vascular biologist at the Angiogenesis Foundation, told NPR.

Li and a group of international researchers published a study this July that found lung tissue damage in COVID-19 patients. As compared with patients who died from the flu, the lung tissue of coronavirus patients had nine times as many small blood clots. They also saw what’s classified as “severe endothelial injury.”

“The surprise was that this respiratory virus makes a beeline for the cells lining blood vessels, filling them up like a gumball machine and shredding the cell from the inside out,” Li says. “We found blood vessels are blocked and blood clots are forming because of that lining damage.”

For More Information: https://www.webmd.com/lung/news/20201109/evidence-shows-that-covid-19-attacks-blood-vessels