Prevention of COVID-19 and/or Alleviation of

Its Symptoms by Vitamin Supplementation

(Until 2021)

Department of Nutrition and Food Technology, School of Agriculture

The University of Jordan, Amman, Jordan
Vitamins in Nutrition (653753)
Supervised by: Dr. Hamed Takruri
Presented by: Nour Gammoh (8210485)
Table of Contents

1. Introduction
2. COVID-19 pathophysiology
3. Recommendations
According to: Coronavirus Disease 2019 (COVID-19) Treatment Guidelines
4. Potential roles of vitamins
a. Potential mechanisms
b. Evidence about each vitamin regarding respiratory infections & COVID-19
5. Conclusion
6. References
COVID-19
Coronavirus Disease
‣ Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2
virus.
‣ The clinical spectrum of COVID-19 is wide, since disease manifestations in the
respiratory tract might be lacking (asymptomatic patients), mild, moderate, or severe.
‣ Most people infected with the virus will experience mild to moderate respiratory
illness and recover without requiring special treatment.
‣ However, some will become seriously ill and require medical attention.
‣ Older people and those with underlying medical conditions like cardiovascular
disease, diabetes, chronic respiratory disease, or cancer are more likely to develop
serious illness.
‣ Anyone can get sick with COVID-19 and become seriously ill or die at any age.
COVID-19 Infection Symptoms

‣ The most frequent symptoms are cold-like or mild influenza-like, including fever, coughing,
chills, fatigue, and shortness of breathing.
‣ However, severe cases are characterized by respiratory and extra-respiratory complications
that include ARDS, acute cardiac and vascular complications, multiple organ disfunction,
septic shock, and respiratory failure, which frequently require ventilatory support.

‣ On average it takes 5–6 days from when someone is infected with the virus for symptoms to
show, however it can take up to 14 days.

(WHO, 2021), (Toledano et al., 2021)

‣ These complications are believed to be associated with uncontrolled inflammation owing to the
abnormally strong release of cytokines triggered by viral replication.
‣ This response might result in pulmonary tissue damage, reduced lung capacity, and functional
impairment.

Two phases of immune response have been described during SARS-CoV-2 infection.
1. The first one is characterized by a defense-based protective activity.
2. The second one is represented by broad inflammation.

‣ Therefore, therapeutic management should be oriented toward strategies that enhance immunity in
the first phase and suppress it in the second one.
‣ Stimulating the immune system in mild stages of the disease can be advisable; however, in contrast,
once lung impairment and other complications have already appeared, immunosuppression would be
required instead. (Toledano et al., 2021)
‣ In this context, nutritional and lifestyle factors should be taken into consideration as a complement
to vaccination or treatment, and to enhance immunity before exposure to the virus.
‣ Optimal dietary patterns and healthy nutritional status are neglected during this stressful time of
restrictions. However, an adequate provision of several nutrients (even beyond the classic essential
requirements) provided by both a balanced diet and supplementation, is fundamental for a suitable
immune response and an optimal modulation of inflammation and oxidative stress. Among these
nutrients, vitamins should be specially taken into consideration, as they exert several mechanisms
related to immune function and oxidative stress that could be beneficial during SARS-CoV-2
infection.

(Toledano et al., 2021)

‣ In order to enter the organism, microbes need to go through natural barriers that protect the body
against them. This is why adequate membrane state and junction integrity in epithelia is so
important to prevent pathogens from invading tissues, i.e., something that can be enhanced by
vitamins such as D or C. Mucosal IgA also has a major implication in protecting these physical
barriers against viruses, to the extent that an increased IgA response has been observed in severe
cases of COVID-19.
‣ Once pathogens manage to overcome this first line of defense, they must face both innate and
adaptive immunity, which tries to neutralize them. Although the precise interactions between
SARS-CoV-2 and the immune system have not been fully explained yet, the cells involved in it seem
to have a completely relevant role in the clinical symptoms and severity of the disease.
‣ This assumption is also based on previous studies performed with its closest relative, SARS-CoV.
‣ This is supported by currently available scientific evidence related to similar respiratory infectious
diseases and, in some cases, to COVID-19 itself, which will be addressed in the following sections.
(Toledano et al., 2021)
COVID-19 pathophysiology
In short, what does COVID-19 do to
the body?
 If SARS-CoV-2 virus could go through the natural barriers, the immune system will respond
against it by:
1. The primary inflammatory response by releasing several inflammatory cytokines ( IL-6, IL-1β,
TNF-α)
• With the purpose of getting an optimal immune response, a certain level of inflammation is
physiologically required after the exposure to a microbe.
• But, a chronic state of low-grade systemic inflammation is associated with a dysregulation of the
immune system, and, as a result, an increased risk of infection.
• This situation is a common feature of several illnesses, such as CVD, T2D, metabolic syndrome,
overweight/obesity, arthritis, or cancer. All of them are considered as comorbidities for COVID-19
patients.

(Toledano et al., 2021)

2. Excessive inflammation
• Due to viral replication
• Is considered the main cause of complications associated with the severe pneumonia
produced by coronaviruses
o In this case, body releases several cytokines, chemokines, and other related molecules, such as IL-
1β, IL-10, IL-4, IFN-γ, IP-10, MCP-1, TNFα, IL-2, IL-7, and G-CSF, which is specially observed
in patients hospitalized in ICU.
o Furthermore, it has been reported that bronchial epithelial cells react to SARS-CoV and SARS-
CoV-2 infection by generating an increased number of NF-κB-mediated cytokines, such as IL-6
and IL-8; IL-6 is associated with a deterioration in patients’ recovery.
o This situation, known as “cytokine-storm”, results in hyper-inflammation, immune cell
infiltration, edema, and excessive reactions, which can lead to life-threatening complications, such
as hyperpyrexia, immune exhaustion, thrombosis, ARDS, and multiple organ failure.
(Toledano et al., 2021)
3. Exhausting and reduced activity of:
• NK cells (natural killers – limiting microbial spread and subsequent tissue damage).
• Cytotoxic CD8+ T cells, CD4+ T cells, and regulatory T cells ( are very important for immune
defense against intracellular pathogens, including viruses)
The reduction in their activity happens at the first stages of the infection. Leading to a more severe disease
progression.
4. Downregulating major histocompatibility complex (MHC), which decreases T-cell-mediated
immune responses.
5. SARS-CoV-2 has an immunosuppressive activity on the adaptive immune system.

(Toledano et al., 2021)

Recommendations
According to: Coronavirus Disease 2019 (COVID-19)
Treatment Guidelines
According to: Coronavirus Disease 2019 (COVID-19) Treatment Guidelines
‣ Ongoing studies are evaluating the use of vitamin and mineral supplements
for both the treatment and prevention of SARS-CoV-2 infection.

‣ COVID-19 Treatment Guidelines Panel (until the end of 2021), reported the
recommendations for using vitamin C, and D in the treatment of COVID-19:
‣ There is insufficient evidence for the COVID-19 Treatment Guidelines
Panel to recommend either for or against the use of vitamin C for the
treatment of COVID-19.
‣ There is insufficient evidence for the Panel to recommend either for or
against the use of vitamin D for the treatment of COVID-19.
COVID-19 Treatment Guidelines Panel, 2022
Although there is insufficient evidence for or
against the use of vitamins to prevent or treat
COVID-19 infection, there are potential
benefits of using vitamins supplementation
in reducing the risk of COVID-19 and
treating it.
Potential roles of vitamins
 Potential mechanisms
 Evidence about each vitamin regarding
respiratory infections & COVID-19
Vitamin D
 Potential Mechanisms of Vitamin D
in Prevention of COVID-19 and/or Alleviation of
Its Symptoms
(Toledano et al., 2021)
Evidence about Vitamin D Regarding
Respiratory Infections and COVID-19
• Elderly are the group of population most severely affected by SARS-CoV-2 infection
• Due to reduced epidermal synthesis of vitamin D, increased time indoors, reduced food intake and
impairment in vitamin D metabolism due to drugs.
• COVID-19 is higher in black people compared to the rest of population.
• Increased pigmentation complicates the penetration of UV light needed for epidermal synthesis
(which represent the man source of vitamin D)
• This pandemic has also increased the risk for general population to develop a vitamin D deficiency,
due to lockdown or “staying at home” mitigation strategies, which are adopted to prevent the virus
spread.
• Another noteworthy fact is that countries have experimented on a more complicated situation
regarding to the pandemic during and right after seasons with less sun exposure (autumn and winter),
rather than after seasons with more sun hours (spring and summer). This might be connected to the
lower vitamin D concentrations that the population has in those periods of time.
(Toledano et al., 2021), (Rhodes et al., 2020)
Vitamin C
 Potential Mechanisms of Vitamin C
in Prevention of COVID-19 and/or Alleviation of
Its Symptoms
(Toledano et al., 2021)
Evidence about Vitamin C Regarding
Respiratory Infections and COVID-19
• A decrease in the duration of hospital stay for those receiving earlier and higher doses of vitamin C has been
reported.
• For individuals (suffering from burns, ARDS, sepsis, and septic shock), intravenous administration of ascorbic
acid has been tested, and results highlight lower mortality according to a meta-analysis.
• These patients have higher vitamin C requirements than the general population in order to normalize their
blood levels, which have been seriously reduced by their pathology.
• Vitamin C has been included in the treatment of some COVID-19 ICUs patients, which have shown to
improve mortality rate. Intravenous administration of high doses in China and the USA exhibited promising
results in patients with moderate to severe disease, as it attenuated cytokine storm during the late stage of the
infection, just as lung inflammation and injury.
• There are some case reports of COVID-19 patients that described less mortality, mechanical ventilation need,
and a decrease in inflammatory markers when using intravenous vitamin C.
• Despite these positive results, the intravenous use of vitamin C should be performed cautiously, as in some
cases and depending on dosage, it might exert a pro-oxidant effect rather than antioxidant.
(Toledano et al., 2021), (Hiedra et al., 2020)
Vitamin A
 Potential Mechanisms of Vitamin A
in Prevention of COVID-19 and/or Alleviation of
Its Symptoms
(Toledano et al., 2021)
Evidence about Vitamin A Regarding
Respiratory Infections and COVID-19
• Systematic reviews and meta-analyses have reported that retinoid administration
improves symptoms related to acute pneumonia.
• A correlation between the lower concentration of vitamin A and host susceptibility to
influenza and COVID-19 has been found.
• Therefore, and even though there is still no clinical evidence regarding vitamin A and
COVID-19, in the light of its roles in lung function and immunity, the vitamin is
currently been investigated for the treatment of SARS-CoV-2 infection alongside with
other antioxidants.

(Toledano et al., 2021), (Jovic et al., 2020)

Vitamin E
 Potential Mechanisms of Vitamin E
in Prevention of COVID-19 and/or Alleviation of
Its Symptoms
(Toledano et al., 2021)
Evidence about Vitamin E Regarding
Respiratory Infections and COVID-19
• A recent study in which adult volunteers received either tocopherol or tocotrienol
supplementation showed a rise in the expression of several genes related to immunity, although
the specific affected genes were different in each group.
• Vitamin E supplementation in the elderly was associated with an important reduction in re-
hospitalization rate within 90 days after a first hospitalization due to pneumonia.
• The existence of a negative association between plasma vitamin E levels has also been
demonstrated, as well as a risk of infection in healthy adults over 60 years.
• Results appear to be contradictory in some way, as some studies have reported a decrease in the
risk of upper (but not lower) respiratory tract infections in the elderly due to vitamin E
supplementation, though others have not observed a significant effect on the incidence, duration,
or severity of infections in this group of population.

(Toledano et al., 2021), (Meydani et al., 2004)

B Vitamins
 Potential Mechanisms of B Vitamins
in Prevention of COVID-19 and/or Alleviation of
Its Symptoms
 Constitutes an important
antioxidant pathway

Helping in prevent A marker of oxidative stress

the access of
SARS-CoV-2 virus
to host cells
Which increases the levels
of plasma lymphocytes

(Toledano et al., 2021)

Evidence about B Vitamins Regarding
Respiratory Infections and COVID-19
• Vitamin B1 has demonstrated its relevance when administered to critically ill patients, reducing
mortality rates in those with septic shock.
• There are several trials that show the benefits of a combination of thiamine, vitamin C, and
hydrocortisone during sepsis, thus improving organ failure, severe pneumonia, time for shock
reversal, and mortality rates.
• There is an inverse relationship between vitamin B6 intake and inflammatory signaling, which has
been widely reviewed before. However, a clear correlation for this nutrient with epidemiologic
COVID-19 indicators has not been found.
• It has been reported that some of the countries less affected by the COVID-19 pandemic are the
ones with the highest B12 intake.

(Toledano et al., 2021), (Galmés et al., 2020)

Vitamin K
 Potential Mechanisms of Vitamin K
in Prevention of COVID-19 and/or Alleviation of
Its Symptoms
Further research is needed to further
investigate its potential

(Kudelko et al., 2021)

Evidence about Vitamin K Regarding
Respiratory Infections and COVID-19
• Inhibition of TNF, IL-1, and IL-6 by vitamin K has been demonstrated.

• Administrating of vitamin K may help reduce cytokine levels as well as preserve the

integrity of alveolar-capillary membranes thereby reducing the risk of developing ARDS

in COVID-19 patients.

• Vitamin K is thought to promote blood vessel health and reduce the risk of developing

pulmonary fibrosis during COVID-19

(Kudelko et al., 2021)

Keep Yourself and Others Safe: Do It All!
‣ Get vaccinated.
‣ Keep physical distance of at least 1 meter from others, even if they don’t appear to be
sick. Avoid crowds and close contact.
‣ Wear a properly fitted mask when physical distancing is not possible and in poorly
ventilated settings.
‣ Clean your hands frequently with alcohol-based hand rub or soap and water.
‣ Cover your mouth and nose with a bent elbow or tissue when you cough or
sneeze. Dispose of used tissues immediately and clean hands regularly.
‣ If you develop symptoms or test positive for COVID-19, self-isolate until you
recover.
Supplementing with vitamins A, B, C, D, and E may improve
inflammatory response and reduce disease severity in COVID-
19 patients. The rate of prolonged hospitalization and
mortality rates were lower in patients who received the
supplements. Further studies are needed to know exactly what
role each vitamin plays in the pathological pathway of
COVID19.
References
COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health.
Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed [Jan 5,2022].
Galmés, S., Serra, F., & Palou, A. 2020, Current state of evidence: influence of nutritional and nutrigenetic factors on immunity in the
COVID-19 pandemic framework. Nutrients, 12(9), 2738. https://doi.org/10.3390/nu12092738
Hiedra, R., Lo, K. B., Elbashabsheh, M., Gul, F., Wright, R. M., Albano, J., Azmaiparashvili, Z., & Patarroyo Aponte, G. 2020, The use of IV
vitamin C for patients with COVID-19: a case series. Expert Review of Anti-Infective Therapy, 18(12), 1259–1261.
https://doi.org/10.1080/14787210.2020.1794819
Jovic, T. H., Ali, S. R., Ibrahim, N., Jessop, Z. M., Tarassoli, S. P., Dobbs, T. D., Holford, P., Thornton, C. A., & Whitaker, I. S. 2020, Could
vitamins help in the fight against COVID-19? Nutrients, 12(9), 2550. https://doi.org/10.3390/nu12092550
Kudelko, M., Yip, T. F., Hei Law, G. C., & Lee, S. M. Y. 2021, Potential beneficial effects of vitamin K in SARS-CoV-2 induced vascular
disease? the American Association of Immunologists, 1(1), 17–29.
Meydani, S. N., Leka, L. S., Fine, B. C., Dallal, G. E., Keusch, G. T., Singh, M. F., & Hamer, D. H. 2004, Vitamin E and respiratory tract
infections in elderly nursing home residents. The Journal of the American Medical Association, 292(7), 828.
https://doi.org/10.1001/jama.292.7.828
Rhodes, J. M., Subramanian, S., Laird, E., & Kenny, R. A. 2020, Editorial: low population mortality from COVID-19 in countries south of
latitude 35 degrees North supports vitamin D as a factor determining severity. Alimentary Pharmacology & Therapeutics, 51(12),
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Toledano, J. M., Moreno-Fernandez, J., Puche-Juarez, M., Ochoa, J. J., & Diaz-Castro, J. 2021, Implications of vitamins in COVID-19
prevention and treatment through immunomodulatory and anti-oxidative mechanisms. Antioxidants, 11(1), 5.
https://doi.org/10.3390/antiox11010005
World Health Organization. 2021, Coronavirus disease (COVID-19): symptoms. Retrieved from
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