In a recent Life Sciences study, researchers analyze the available scientific evidence supporting vitamin D as a neuroprotective agent against the neurological sequelae of coronavirus disease 2019 (COVID-19).
Study: COVID-19 and neurological sequelae: Vitamin D as a possible neuroprotective and/or neuroreparative agent. Image Credit: Komarina / Shutterstock.com
The infectious capacity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not limited to the respiratory system. In fact, SARS-CoV-2 can also invade other vital organs, including the central nervous system (CNS), which can result in several neurological consequences.
Some of the neurological manifestations of SARS-CoV-2 infection can include immune-mediated demyelinating disease, anxiety, stroke, depression, and neurodegeneration. Two possible reasons why SARS-CoV-2 attacks the CNS include its ability to remain latent within cells for long periods, as well as its association with inducing the cytokine storm.
These neurological medical conditions can be worsened in COVID-19 patients with underlying chronic medical conditions such as hypertension, diabetes, or coronary heart diseases. As a result, this subset of COVID-19 patients is more likely to experience neurovascular sequelae of this disease.
There is considerable scientific evidence that vitamin D down-modulates the effects of neuroinflammatory cytokines, thus weakening adverse consequences of COVID-19. Notably, vitamin D also has other anti-inflammatory/immunomodulatory effects.
In the current meta-analysis covering 54 independent studies examining the literature on COVID-19 and vitamin D, researchers found that patients with low 25-hydroxyvitamin D levels exhibited higher susceptibility to SARS-CoV-2 infection and related hospitalization. These patients were also at an increased risk of acute respiratory disease, hospital admission, and SARS-CoV-2-related mortality.
Neuroinflammation and neurodegeneration in COVID-19
Due to the cytokine storm, some COVID-19 patients have reported acute necrotizing hemorrhagic encephalopathy. During SARS-CoV-2 invasion of dendritic cells, monocytes, macrophages, and proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1, and 6 (IL-1 and IL-6), are overexpressed.
As these biomarkers are associated with increased COVID-19 severity and its derived neurological pathologies, monitoring these biomarkers could help categorize the most severely ill patients and select appropriate therapeutic options.
In one study on more than 30,000 healthy individuals, autoantibody titers directed against type-1 interferon (IFN) increased with age. This finding demonstrates why older people tend to have a worse prognosis against COVID-19 and its neuropathological consequences.
As brain cells act as latent reservoirs of SARS-CoV-2 in some cases, such latency could be associated with delayed apoptosis and oxidative stress pathways in the nervous system cells, leading to neurodegenerative pathologies such as Alzheimer’s disease (AD). Other reports suggest that SARS-CoV-2 increases alpha-synuclein synthesis, which triggers the release of various cytokines and chemokines that are characteristic of Parkinson’s disease (PD).
The SARS-CoV-2-induced neuroinflammatory response is associated with a marked reduction in human angiotensin-converting enzyme 2 (hACE2) activity. The hACE2 regulates neuroprotective and neuroimmunomodulatory functions in the host and potentially neutralizes cellular inflammation and oxidative stress.
Furthermore, the SARS-CoV-2-ACE2 binding alters gamma-aminobutyric acid (GABA) neurotransmission in the amygdala and possibly in other parts of the brain. Alternatively, it might produce alterations in dopaminergic neurotransmission, thus representing other neurodegenerative sequelae associated with COVID-19.
Antibodies against SARS-CoV-2 epitopes have also been found to react with receptors at the neuromuscular junction, including the nicotinic acetylcholine. This activity could thus accelerate COVID-19-linked neurodegenerative pathologies, such as myasthenia gravis.
Vitamin D supplementation minimizes COVID-19-related neurological sequelae
Several studies have explored vitamin D and 25-hydroxyvitamin D3 (calcifediol) as novel therapeutic options for COVID-19-related neurological conditions. In fact, this type of supplementation has been shown to enhance innate immunity, such as early macrophage reaction to mucosal-invading viruses and bacteria, thereby reducing the incidence and severity of acute respiratory infections.
A sufficient plasma level of 25-hydroxyvitamin D converts into the hormone 1,25-dihydroxyvitamin D, which activates genes encoding antimicrobial substances against fungi, bacteria, and viruses, including SARS-CoV-2.
In their study, Durrant et al. showed that vitamin D3 supplementation efficiently induced gene expression associated with type I and type II IFN activity, which is critical to the innate response to bacterial and viral infections. Similarly, 1,25(OH)2D contributes to inhibiting the action of renin by increasing hACE2 production, while also reducing the cellular immune response induced by the cytokine storm during SARS-CoV-2-induced pneumonia.
Several clinical studies are also in the process of evaluating the possible optimization of SARS-CoV-2 vaccine efficacy by vitamin D supplementation.
Taken together, data from several studies support the use of vitamin D supplementation, as well as its role in improving disease prognosis and preventing fatal consequences.
In the future, longitudinal studies should follow up with COVID-19 patients to gather the data needed to evaluate the diagnosis, prognosis, and treatment of COVID-19-related neurological sequelae. Meanwhile, studies should also monitor vitamin D supplementation in current COVID-19 patients and in those who have recovered from the disease.
To conclude, vitamin D could be a valuable addition to the current therapeutic arsenal against COVID-19 neurological sequelae.