As of April 13, 2022, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 501 million worldwide and caused over 6.2 million deaths. Many of the individuals who have recovered from the acute illness have reported persistent symptoms that are commonly known as ‘long coronavirus disease 2019 (COVID-19)’.
A new Biomolecules journal study discusses the possible mechanism of long COVID in children and how they might relate to their dietary intake of important vitamins and elements.
Study: Long COVID-19 in Children: From the Pathogenesis to the Biologically Plausible Roots of the Syndrome. Image Credit: Oksana Kuzmina / Shutterstock.com
Introduction
Children have largely been spared by the severe effects of COVID-19. However, many children have reported long-term or chronic tiredness, headache, numbness, depression, altered smell and taste, or poor appetite after clinical resolution of the initial infection and viral clearance.
While currently available COVID-19 vaccines significantly reduce the risk of severe and fatal outcomes of COVID-19, they may not completely prevent long COVID in the event that a breakthrough infection occurs. Thus, the current study investigates long COVID in children in order to better understand its impact on this patient population.
Long COVID, which is also referred to as post-COVID-19, is defined by the World Health Organization (WHO) as “a condition which occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months that cannot be explained by an alternative diagnosis.”
The underlying processes responsible for long COVID remain unknown, with little information available on which organs are primarily targeted by this condition. Some of the other questions surrounding long COVID include:
- What is the role of inflammation?
- Is it an autoimmune process or due to endothelial dysfunction?
- What part does gut dysbiosis play?
Vitamins and COVID-19
The current study explores the role of diet in immunity against SARS-CoV-2, both in acute illness and against its long-term sequelae. One possible explanation is the deficiency of anti-inflammatory and anti-oxidant factors in the diet. This may indicate that a given patient’s diet is an inadequate source of immunomodulation and antiviral activity, which predisposes them to more severe disease following SARS-CoV-2 infection.
Fermented cabbage and other Brassica vegetables have been identified as staples of populations that had very low mortality rates related to COVID-19. Another set of hypotheses linked vitamin D, zinc, selenium, and magnesium deficiencies to more severe forms of COVID-19 and/or higher mortality rates. These studies indicate the potentially significant impact of nutritional support for COVID-19 patients by reducing inflammation and oxidative stress.
In addition, supplementing these factors could block viral replication, reduce clotting tendencies, and protect host cells against injury due to the presence of SARS-CoV-2, thereby limiting tissue damage while also preventing gut dysbiosis. Gut dysbiosis, for example, is reflected in disease severity, as well as the levels of cytokines, inflammatory chemicals, biomarkers of tissue injury, and the presence of persistent symptoms.
Vitamin B complex plays a major role in energy metabolism, as well as the synthesis of nucleic acids and proteins. These vitamins, which are also required for immunoregulation, also form part of the cofactors for many mitochondrial and protein enzymes, play a role in antioxidant activity, and regulate inflammatory pathways.
Thiamine (B1) deficiency causes neuropathy and neuroinflammation, while B6 in its active form is depleted during inflammation. B12 (cobalamine) is an antioxidant that spares glutathione while removing reactive oxygen species (ROS) from tissues and also regulating cytokine levels. Methyl folate enhances endothelial functioning.
Together, these vitamins are also important in maintaining the health of the gut microbiome. Their supplementation, in concert with vitamin D and magnesium, has been associated with the clinical mildness of COVID-19. Vitamin D modulates the immune response and its presence at adequate levels in plasma is associated with a reducing propensity to infection.
Vitamin D has been reported to reduce the mortality due to COVID-19 in hospitalized patients by protecting these individuals against lung and endothelial damage associated with this disease. Furthermore, vitamin D may also prevent autoimmune diseases related to SARS-CoV-2 and protect the gut against dysbiosis. Its daily supplementation, rather than monthly dosing, is highly preferable, according to these researchers.
Like Vitamin E, Vitamin C is a major antioxidant and participates in energy metabolism and various biosynthetic pathways including those of several neurotransmitters. Vitamin C is also an important molecule in immunity and its deficiency is associated with tiredness, pain, and brain fog.
Magnesium
Magnesium is the most abundant of divalent cations in cells and plays an important role in the cell cycle in dividing and differentiating cells. This element is essential for heart function, and vascular tone, preventing vasoconstriction and clotting, as well as preventing atherosclerosis.
Magnesium deficiency acts on hundreds of pathways in the body and can promote hypertension, metabolic syndrome, and type 2 diabetes, as well as cardiovascular disease and low-grade inflammation. Oxidative stress due to low magnesium levels may account for the tiredness and muscle pain associated with long COVID.
The platelet adhesion and aggregation effects of low magnesium levels could be responsible for microthrombotic complications of this condition as well. Finally, its deficiency impacts the biological availability and activity of vitamin D. Conversely, supplementing magnesium along with selenium and coenzyme Q10 improved thyroid structure and function, which is significant considering the prevalence of thyroiditis as a feature of long COVID in some patients.
Selenium
Selenium also has a host of biological functions, as it modulates stress-induced inflammatory pathways and reduces ROS levels. This not only prevents hyper-inflammatory responses to SARS-CoV-2 infection but could prevent the emergence of ROS-induced viral mutations that enhance viral pathogenicity.
As seen with the infamous Keshan disease in China, selenium deficiency can be deadly; however, its supplementation may resolve these issues. Both thyroid and gut microbiome function is enhanced by selenium, and perhaps mental health as well.
Zinc
Zinc supplementation is also important, as this element mediates cellular signaling and is an essential component of hundreds of transcription factors and thousands of enzymes. Moreover, zinc is essential for growth and development, as well as for the biosynthesis of DNA and transcription of RNA. Zinc also reduces oxidative stress and modulates immunity by promoting T- and B-cell formation.
Zinc deficiency is linked to autoimmune disease and endothelial dysfunction, as well as increased numbers of T-helper Th17 cells, which can predispose individuals to inflammation.
Phytochemicals
Phytochemicals are likely to be useful in limiting viral propagation and the host response to SARS-CoV-2, thus preventing hyper-inflammatory responses and autoimmunity. These chemicals bind to SARS-CoV-2 particles extra- and intra-cellularly, thereby preventing receptor binding as well as replication and virion secretion from the infected cell.
Most phytochemicals also oppose platelet activation and thrombosis, while stabilizing heart rhythms. The most studied phytochemicals include resveratrol, quercetin, curcumin, and sulforaphane.
Implications
Further research should focus on the dietary patterns among children and their impact on inflammation, coagulation, and illnesses, in addition to the COVID-19 status. Measurement of the levels of these potentially protective nutraceuticals is an essential step in understanding their true contribution to immunity against SARS-CoV-2 and future outbreaks.
In the absence of any effective treatment for long COVID, supplementation with these substances appears to be a logical way to help these patients experience some relief from their symptoms.
Journal reference:
- Piazza, M., Di Cicco, M., Pecoraro, L., et al. (222). Long COVID-19 in Children: From the Pathogenesis to the Biologically Plausible Roots of the Syndrome. Biomolecules. doi:10.3390/biom12040556.
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