COVID-19 neurological symptoms investigated

• COVID-19 has been linked to neurological problems.
• More study is needed to determine how COVID-19 affects neurological symptoms.
• These findings were presented at Neuroscience 2021, the Society for Neuroscience’s annual meeting.

COVID-19 impacts a person’s nervous system, creating neurological symptoms, according to researchers.

They presented their findings at Neuroscience 2021 this week. This is the Society for Neuroscience‘s annual conference, which is the world’s biggest gathering of scientists and clinicians interested in brain and nervous system health.

The results reveal how the virus that causes COVID-19, SARS-CoV-2, acquires entry to a person’s brain. They also give information on the impact it has once it reaches this area of the body.

Symptoms of the nervous system

COVID-19 causes respiratory symptoms in the majority of persons. The most frequent symptoms of COVID-19, according to the World Health Organization (WHO), are fever, cough, fatigue, and loss of taste or smell.

The severity of these and other, less frequent symptoms can range from moderate to life-threatening. Some patients who get SARS-CoV-2 may show no signs or symptoms.

In addition to respiratory symptoms, COVID-19 has been linked to a variety of neurological problems, according to doctors and researchers.

According to research, COVID-19 has been associated with headaches, brain inflammation, muscular weakness or discomfort, and numbness or paralysis in the hands, feet, or limbs.

However, further study is needed to fully comprehend how COVID-19 impacts the neural system.

Access to the brain

A number of papers presented at Neuroscience 2021 revealed studies on how SARS-CoV-2 is expected to impact a person’s brain.

Dr. Ashutosh Kumar, an assistant professor in the Department of Anatomy at the All India Institute of Medical Sciences in Patna, India, presented research that revealed a potential receptor for SARS-CoV-2 entry to the brain.

SARS-CoV-2 enters cells in different sections of the body through attaching to the protein angiotensin converting enzyme 2 (ACE2) with the aid of transmembrane serine protease 2  (TMPRSS2). ACE2 and TMPRSS2, on the other hand, are not found in large amounts in a person’s brain.

“We know that COVID-19 patients have substantial neuropsychiatric symptoms, and [that] virus-induced damage — including indications of the replicating virus in brain tissue — have been detected in postmortem investigations,” Dr. Kumar told Medical News Today. The lack of expression of the ACE2 and TMPRSS2 genes, on the other hand, left a fundamental issue unanswered: “How can SARS-CoV-2 access brain cells?”

“By the middle of last year, another receptor — neuropilin-1 precursor (NRP1), a cell surface protein involved in brain development and cancer etiology — had been demonstrated to bind to furin-cleaved SARS-CoV-2 spike protein[s].” Uniquely, binding to the NRP1 didn’t require TMPRSS2.”

“By curiosity, we checked the expressions of NRP1 and furin in the postmortem human brain tissue, which [revealed] that both of these molecules are abundant in all key brain regions — chiefly, the olfactory and hippocampus.”

“Olfactory nerves present a way for the entry of the virus into the brain through the nose, and their infection can also explain the loss of smell as a key symptom in COVID-19. Further, the involvement of the hippocampus can explain the prominence of psychiatric symptoms in COVID-19 patients during and after recovery from acute illness,” said Dr. Kumar.

Dr. Kumar believes that his discoveries will aid in the development of future medications to prevent or cure COVID-19’s neurological effects.

“Our findings are important in the sense that they indicate the putative drug targets for preventing and treating neuropsychiatric symptoms in COVID-19. The binding sites of NRP1 and furin at the SARS-CoV-2 spike protein can be targeted with various approaches, such as with monoclonal antibodies or decoy receptors,” said Dr. Kumar.

Both the Journal of Neuroscience Research and Frontiers in Immunology have published the findings.

Monkey models

Prof. John H. Morrison, director of the University of California, Davis’ California National Primate Research Center, presented findings from a rhesus monkey study. These findings further imply that SARS-CoV-2 may get entry to the brain through the olfactory system.

Prof. Morrison told MNT: “The monkeys were infected both through the nose and the trachea and sacrificed [7] days after infection. We were particularly interested in whether or not aged type 2 diabetic (T2D) monkeys were more vulnerable to neuroinvasion by the virus than young monkeys, given that aging and T2D are key comorbidities in humans.”

“We studied the brains of four groups: 1) young [with neither the infection nor diabetes], 2) young [with the infection but without diabetes], 3) aged [with neither the infection nor diabetes], and 4) aged [with both the infection and diabetes]. The following are the key findings:

1. SARS-CoV-2 proteins and evidence of productive viral infection were present in multiple brain areas 7 days after infection.
2. The primary affected regions were the cortical regions that receive direct olfactory input, suggesting that the virus enters through the olfactory system in the nose.
3. Neurons were the main cell type that became infected.
4. Pathology is also seen in cortical regions that receive input from the primary olfactory regions, demonstrating that the virus can transmit across circuits and connections.
5. SARS-CoV-2 infection led to neuroinflammation, as well as neurodegeneration.
6. Aged T2D monkeys have far more widespread and more aggressive brain infection.”

According to Prof. Morrison, the data show that COVID-19 is both a neurological and a respiratory disease.

Prof. Morrison stated, “There has been an ongoing discussion about whether SARS-CoV-2 may infect neurons.” “These findings demonstrate unequivocally that neurons can be infected in our monkey model of COVID-19 and that the virus appears to enter the brain through olfactory connections from the nose.”

“The direct entry through [the] olfactory system, productive infection of neurons, and transport to multiple brain regions by SARS-CoV-2 is the likely cause of neurological complications in COVID-19, such as anxiety, memory loss, and ‘brain fog.’ The heightened vulnerability of aged T2D monkeys suggests that such comorbidities in humans may also lead to more extensive neurological complications.”

“As a result, COVID-19 might be a brain issue as well as a pulmonary disease, and COVID-19 prevention and therapy should focus on preserving the brain as well as the heart and lungs in individuals with long-term symptoms.” Furthermore, because the infection happened in [7] days, such medications must be administered as soon as possible following infection.”

Prof. Morrison believes that a better knowledge of COVID-19’s neurological consequences would aid researchers’ comprehension of long COVID.

“Many of the symptoms associated with ‘long COVID’ are neurologic in nature and likely to be caused by neuroinvasion and infection of neurons. We do not know if such symptoms are linked to ongoing infection of neurons linked through circuits or through damage that occurred early and outlasts the infection,” said Prof. Morrison.

Prof. Morrison pointed out that studies in humans corroborated the findings that older T2D monkeys had more serious neurological illnesses.

“Clinical studies have shown that [older people] are far more likely to display neurological symptoms. In addition, the virus is getting to some brain regions that are highly vulnerable to Alzheimer’s disease as well, but we don’t know if such an infection leaves a patient more vulnerable to Alzheimer’s disease in the future,” said Prof. Morrison.

Nervous system of the periphery

SARS-CoV-2 is also likely to be able to acquire access to a person’s brain via neurons that transmit touch and pain, according to another study.

Jonathan Joyce, a graduate student in Dr. Andrea S. Bertke’s laboratory at Virginia Tech’s Department of Population Health Sciences in Blacksburg, VA, employed a mouse model to see if SARS-CoV-2 might infect peripheral nerves. Throughout the investigation, Dr. Bertke collaborated closely with Joyce.

“While most of the attention paid to assessing the ability of SARS-CoV-2 to invade the nervous system has focused on the central nervous system — for example, the brain,” Joyce told MNT. “[w]hile most of the attention paid to assessing the ability of SARS-CoV-2 to invade the nervous system has focused on the central nervous system — for example, the brain,” Joyce added.

“Previous research has demonstrated that SARS-CoV-2 may infect neurons in the peripheral nervous system, but those studies only looked at scent nerves.”

“We have shown that SARS-CoV-2 is capable of infecting additional nerves of the peripheral nervous system in the head, neck, and body responsible for carrying out automatic bodily — for example, superior cervical ganglion — functions and relaying sensory information, particularly those that convey touch and pain, to the brain and spinal cord — for example, trigeminal ganglion and dorsal root ganglion.”

“We also found that various regions of the brain, impacted in COVID-19, are capable of being infected by SARS-CoV-2. It is worth noting that these findings are based on a mouse model of infection and will have to be repeated in other animal models for verification,” said Joyce.

The finding is valuable because it shows that SARS-CoV-2 is not limited to infecting the central nervous system, but can also infect the peripheral nervous system at several locations, according to Joyce.

“Many studies that investigate how SARS-CoV-2 enters the nervous systems focus on how it enters the brain using neurons in the nose responsible for smell,” said Joyce.

“Our findings show that the virus can infect the peripheral nervous system at multiple points, particularly among nerves that convey touch and pain, and that some of these points have connections to regions of the brain impacted by COVID-19.”

“The presence of the virus in these nerves may have a role in the symptoms [that] COVID-19 patients [experience].”

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