A Hypothesis for the Possible Role of Zinc in the Immunological Pathways Related to COVID-19 Infection
Front. Immunol. 11:1736. doi: 10.3389/fimmu.2020.01736
Ander Mayor-lbarguren1*t, Carmen Busca-Arenzana22 andAngel Robles-Marhuenda2t
1 Department of Dermatology, La Paz University Hospital, Madrid, Spain,
2 Department of Internal Medicine, La Paz University Hospital, Madrid, Spain
KEY POINTS
- Zinc deficiency may be common and associated with severe infection.
- Zinc helps to enhance the interferon type 1 response to the virus and participates in many regulatory pathways.
- Low levels of zinc have been associated with higher IL-6 responses.
- IL-6 plays an important role in severe lung injury due to COVID-19 infection.
- Zinc inhibits SARS-CoV RNA polymerase, and thus its replication capacity.
- Zinc may increase the efficacy of antimalarial agents, since they are zinc ionophores.
- Differences in mortality due to COVID-19 infection may be explained to some degree by-174 IL-6 gene polymorphism.
Zinc (Zn) is the second most abundant trace metal in the human body after iron. However, unlike iron, there is no specialized zinc store (1). Zinc's functions can be classified as catalytic, structural, and regulatory (2). For example, important zinc metalloenzymes include alkaline phosphatase, RNA polymerases, and alcohol dehydrogenase (3). Zinc deficiency can precipitate an immune system imbalance, exemplified in severe deficiency by high susceptibility to infections, skin disorders, gastrointestinal disorders, weight loss, growth retardation and male hypogonadism, amongst other symptoms (4).
While severe zinc deficiency is rare, mild to moderate deficiency is more common worldwide ⑸.There are very low levels of free zinc in plasma, since it is mostly bound to proteins such as albumin, alpha-2-macroglobulin (A2M), and transferrin. Plasma zinc levels are therefore only around 1 ug/ml, equal to 0.1% of total body zinc, but are still the most important reservoir for zinc homeostasis, which requires “free” or “labile” zinc mobilization (6, 7). Kinetic studies suggest that only a small proportion of total body zinc (10%) represents the “functional pool” of zinc, located within the liver and other tissues, that exchanges rapidly with that found in the plasma (8, 9).
When this functional pool is depleted, zinc deficiency ensues (8). Intracellular zinc is distributed in zinc-storing vesicles called zincosomes, the nucleus and other organelles. In cytoplasm, zinc mostly binds zinc-chelating proteins called metallothioneins (MTs). Zinc homeostasis is understood to be the correct balance of zinc distribution. Internal zinc homeostasis is regulated by the cooperative activities of two metal transporter protein families. One family consists of 10 solute-linked carrier 30 (SLC30 or ZnT) exporters, and the other family consists of 14 solute-linked carrier 39 (SLC39 or ZIP) importers (10, 11). For instance, most labile zinc in the body is absorbed by intestinal epithelial cells via SLC39a4 protein, and excessive zinc is excreted through the kidneys, and the intestine via SLC39a5 (12).
Download the PDF from VitaminDWiki
Items in both categories Zinc and Virus are listed here:
- COVID was associated with low Vitamin D or Zinc – umbrella review Feb 2023
- 23 COVID mitigation strategies: at least 6 of which increase Vitamin D in cells - Sept 2022
- COVID and Zinc - many studies
- Surviving COVID with vitamins and minerals is not a myth – June 2022
- Vitamin D, Zinc, Magnesium etc. are needed to fight COVID – April 2022
- How vitamins D, C, Zinc, and Selenium might fight COVID - Dec 2021
- Nutritional supplementation during COVID hospitalization helped - RCT - Jan 2022
- COVID-19 decreased risk if add Vitamin D, A, C, NAC, Se, Zn, or Omega-3 – Dec 2021
- COVID-19 patients had low levels of Zinc, Vitamin A, Vitamin D, and Vitamin C – Sept 2021
- COVID-19 risk reduced 4X by each of: Vitamin D, Omega-3, Curcumin, Zinc (each increases D in cells)
- Vitamin D, C, A, and E, as well as Iron, Se, and Zinc each augment vaccine response – July 2021
- How Vitamin D, Magnesium, Omega-3 and Zinc prevent and treat COVID-19 and many other health problems – June 2021
- COVID-19 treatment outside of hospital – Vitamin D, zinc, etc. – May 2021
- Important Role of Micronutrients during COVID-19 (Zinc, Vitamin D, C, Folate) – May 5, 2021
- Many supplements appear to fight COVID-19 – vitamin D cited 52 times – May 2021
- Zinc therapy for COVID-19 – Feb 2021
- COVID-19 alternative treatments - real-time database
- Overview of reviews of COVID-19 and vitamin D, etc. – April 2021
- COVID-19 what it is, prevention by Functional Nutrition doctor - Feb 2021
- Vitamin D, Zinc, etc. look promising for COVID-19 (Holick) - Jan 25, 2021
- Less than 10 dollars of Vitamin D per COVID-19 life saved in Myanmar - Jan 2021
- Micronutrients for COVID-19: Vitamin D, Vitamin C, Melatonin, Zinc, Se, etc. - Dec 2020
- Zinc (which increases vitamin D in tissues) may both prevent and treat COVID-19
- COVID-19 possible therapies: Vitamin D, Selenium, Zinc, Vitamin C, Potassium, Resveratrol , etc.– Aug 5, 2020
- 7 reasons to think that Zinc should fight COVID-19 – July 2020
- Observations that Vitamin D, Zinc, and Selenium separately reduce COVID-19 – Aug 7, 2020
- Mild COVID-19 quickly treated by Zinc lozenges in 4 people – June 6, 2020
- Zinc, respiratory tract infections and COVID-19 – July 2020
- Fight COVID-19 with Vitamin D, Vitamin C, Zinc, Selenium, Resveratrol, etc. - Sardi May 12, 2020
- Common cold prevented and treated by Vitamin D, Vitamin C, Zinc, and Echinacea – review April 2018
- Loss of smell may be related to low Zinc or perhaps low vitamin D
- Dengue fever immune response and micronutrients (vitamins D, E, A, and Zinc, Iron, Chromium) – Nov 2015
- Overview Colds and flu and Vitamin D
Items in both categories Zinc and Immune System are listed here:
- Mild COVID-19 quickly treated by Zinc lozenges in 4 people – June 6, 2020
- Deficiencies in nutrients needed for a healthy immune system (Vitamin D, etc.) – June 2020
- Vitamins and Metals needed by the Immune System – Jan 2020
- Common cold prevented and treated by Vitamin D, Vitamin C, Zinc, and Echinacea – review April 2018
- Dengue fever immune response and micronutrients (vitamins D, E, A, and Zinc, Iron, Chromium) – Nov 2015
- Zinc and Vitamin D
VitaminDWiki had previously proposed a Vitamin and Mineral Concentrate to prevent and treat COVID-19 which included Zinc
Both Zinc and Vitamin C need to be taken multiple times a day
Items in both categories Vitamin D Receptor and Virus are listed here:
- COVID in hospital stopped by Vitamin D Receptor activators (curcumin, quercetin) – RCT June 2023
- Children with COVID 4X more likely to have poor Vitamin D Receptors (Note: COVID deactivates VDR) – April 2023
- COVID variants protect themselves by deactivating different VDR variants– March 2023
- COVID kids were more likely to have a poor VDR (4.3 X), than low Vitamin D (2.6 X) – Sept 2022
- Cancers are associated with low vitamin D, poor vaccination response and perhaps poor VDR – July 2022
- COVID 3X more likely if a poor Receptor (cells get less Vitamin D from the blood) – July 2022
- Long-COVID is now the biggest COVID concern - many studies
- COVID death 12X more likely if poor Vitamin D Receptor (less D gets to cells) -several studies
- COVID severity, ICU, and mortality all associated with poor vitamin D receptor (but not D, everyone had low D) -Dec 2021
- Different Vitamin D Receptor problems cause different COVID problems - Dec 2021
- COVID-19 severity associated with 3 vitamin D genes – Oct 2021
- Poor Vitamin D receptor blocked Vitamin D from fighting avian influenza viruses (in mice) – July 2021
- Epstein-Barr is yet another virus that deactivates the Vitamin D receptor (COVID later suspected as well)– 2010
- COVID-19 symptoms and comorbidities associated with the type of Vitamin D Receptor – Oct 2021
- Enveloped virus infection (RSV, coronavirus, HIV, etc.) 1.5X more likely if poor Vitamin D Receptor – meta-analysis Dec 2018
- COVID-19 outpatients getting Quercetin nanoemulsion had excellent outcomes (Q increased Vitamin D in cells) – RCT – June 2021
- A virus that most adults have (Cytomegalovirus) decreases the amount of Vitamin D which gets to the cells – Jan 2017
- COVID virus alters the activation of 100 vitamin D related genes in the lung – April 2021
- Common sense COVID-19 risk reduction - masks, social distancing, vitamin D - Oct 2020
- AI is examining 170,000 potential COVID-19 treatments, Vitamin D is one of only 6 found – Sept 4, 2020
- Vitamin D Receptor activation should reduce ARDS associated with COVID-19 - June 2020
- Dengue viral production decreased 1000X if activate Vitamin D Receptor (in lab) – July 2020
- Vitamin D, Quercetin, and Estradiol all increase vitamin D in cells and increase genes which reduce COVID-19 – May 21, 2020
- Quercetin and Vitamin D - Allies Against COVID-19
- Risk of enveloped virus infection is increased 50 percent if poor Vitamin D Receptor - meta-analysis Dec 2018
- Hand, foot, and Mouth disease is 14X more likely if poor Vitamin D Receptor – Oct 2019
- Treating herpes reduced incidence of senile dementia by 10 X (HSV1 reduces VDR by 8X) – 2018
- Severe hand, foot, and mouth virus is 2.9 X more likely if poor Vitamin D receptor – Oct 2018
- Hepatitis B virus reduced by 5X the Vitamin D getting to liver cells in the lab – Oct 2018
- Some enveloped virus are 1.2 X more likely if have a poor Vitamin D Receptor -Aug 2018
- Severe Pertussis is 1.5 times more likely if poor vitamin D receptor – Feb 2016
- Dengue Fever associated with poor vitamin D receptor – July 2002
- Dengue virus 2X to 4X more likely if vitamin D receptor gene problems