In a recent review published in the Cell Death Discovery Journal, researchers elucidated the mechanisms underlying the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on the brain and recall.
They also identified risk factors for long-term coronavirus disease (COVID) and discussed ways to prevent the post-COVID 2019 (COVID-19) condition.
Study: Long-term effects of SARS-CoV-2 infection on human brain and memory. Image Credit: Justlight/Shutterstock.com
Background
Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic waves have occurred. SARS-CoV-2 has evolved with great transmissibility and immunological evasiveness from the ancestral Wuhan-Hu-1 strain to the Omicron variant.
Long COVID can result in persistent symptoms such as tiredness, frequent headaches, breathlessness, motor dysfunction, and concentration and memory difficulties.
Long COVID exposure may cause pathological alterations in the brain and impair human memory.
About the review
In the present review, researchers present the mechanisms by which SARS-CoV-2 could infect the brain and affect memory. They also discussed long COVID risk factors and prevention strategies.
SARS-CoV-2 infects the human brain and affects human memory, facilitated by host receptors
Long-term COVID-19 patients may develop latent cognitive deficits, with dementia after acute COVID-19 treatment being a major risk factor. SARS-CoV-2 may infect the nasal passages and transmit directly to the brain's olfactory bulb via the olfactory nerves.
SARS-CoV-2 infection in the respiratory tract with high viral titers, on the other hand, might produce considerable pathological alterations, allowing the virus to penetrate the circulatory system and disseminate to other organs, aided by angiotensin-converting enzyme 2 (ACE2) production by different cell types.
SARS-CoV-2 might also infect the eyes and proceed to the occipital brain via the optic nerve. SARS-CoV-2 can break the tight connections between the blood-brain barrier (BBB) and intracellular cargo, allowing it to infiltrate different organs.
Persistent SARS-CoV-2 replication and SARS-CoV-2 spike protein-host ACE2 receptor interactions might lead to syncytia development and increase cytokine and autoantibody synthesis, thereby affecting brain function and memory in the long run.
ACE2, a crucial receptor for SARS-CoV-2 to infiltrate the host, is expressed in various tissues, including the lungs, liver, heart, kidney, brain, and gut. The cluster of differentiation (CD147), the tyrosine-protein kinase receptor UFO (ALX), neuropilin 1 (NRP1), and C-Type lectins are potential SARS-CoV-2 receptors that are expressed in various cell types.
Structural investigations have revealed a decrease in the dimension of the parahippocampal gyrus, orbitofrontal region, and olfactory cortex of the brain. Increased production of cytokines such as interleukin-1 (IL-1) and IL-6, as well as tumor necrosis factor-alpha (TNF) via toll-like receptor (TLR) signaling and microglial activation induced by SARS-CoV-2, may have a negative influence on memory and cognition.
Post-COVID-19 condition risk factors and prevention
Infection with SARS-CoV-2 could result in immunological disorders and cause cellular death, which are direct sources of long-term influences on the body's tissues. SARS-CoV-2 may stimulate the immunological system, enabling it to release cytokines and cause cell lysis.
Dysregulated cytokine production can result in cytokine storms, leading to serious illnesses that increase COVID symptoms.
SARS-CoV-2 spike protein fusion with cells of the host can result in hyperimmune reactions, cell death, and prolonged symptoms after SARS-CoV-2 recovery.
Autoantibodies to type I interferon (IFN) enhance the chances of developing severe SARS-CoV-2 infections, resulting in acquired immunodeficiencies that may extend COVID symptoms. Microclots may trigger autoantibodies to form in diseased organs, which may affect COVID-19 recovery.
Persistent COVID-19 can stimulate host immune system reactions and SARS-CoV-2 protein expression indefinitely. Spike protein alone has the potential to cause behavioral and neuroinflammatory alterations. COVID-19 symptomatology is connected with emotional stress in certain individuals, which may be linked to the biological and psychosocial consequences of the disease.
Biopsychosocial variables can add to COVID-19 dread and impact long COVID recovery.
SARS-CoV-2 vaccinations can efficiently alleviate symptoms but are unable to avoid SARS-CoV-2 infections. Non-pharmaceutical measures, including mask use and social isolation, have reduced SARS-CoV-2 transmission.
However, new medications that can restrict viral spread are urgently required to restrict viral transmission and, as a result, reduce the number of protracted COVID patients.
Cytokine-blocking medications administered in the initial stages of COVID-19 may help prevent the later emergence of symptoms of depression. Cognitive remediation treatment may help COVID-19 patients with cognitive impairments.
Furthermore, optimum health can protect against SARS-CoV-2 infections. Regular physical activity, regular sleep schedules, and a balanced diet (especially rich in vegetables, vitamins, magnesium, and zinc) are all vital components of overall health.
Conclusion
Overall, the review findings revealed potential pathways of brain damage associated with COVID-19, including direct infection with SARS-CoV-2, immune dysfunction, and persistent SARS-CoV-2 infections.
Prevention strategies, such as vaccinations, antiviral therapies, masks, exercise, regular sleep, and a balanced diet, are crucial in decreasing the risk of cognitive impairments from COVID-19.
Long-term consequences, such as memory loss, can significantly lower self-confidence and study efficiency among children, especially during the initial developmental phases. Further research is required to improve our understanding of long COVID pathophysiology.
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