Evidence suggests that zinc could protect against Covid-19 — how?

Shin Jie Yong

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Sep 23, 2020 · 6 min read

Evidence is growing that shows nutritional status plays a part in how Covid-19 would turn out — whether a person recovers or progresses into a more severe condition. For example, many human studies back the anti-Covid-19 effects of vitamin D, including a randomized controlled trial (RCT). Notably, the second most important nutrient next to vitamin D that could fight Covid-19 is perhaps zinc — why and how?

Zinc as an antiviral and immunomodulator

Zinc has long been known to be an enemy of viruses. Zinc could block the replication of coronaviruses by disrupting its enzyme that makes its genes. For instance, there was an over 50% reduction in SARS-1 replication in cells with healthy zinc levels.

And the antiviral spectrum of zinc is broad, including herpes simplex virus, hepatitis virus, human papillomavirus, respiratory syncytial virus, rhinovirus, HIV, and many more. Many studies have also supported the efficacy of zinc therapy against both upper and lower respiratory tract infections, as compiled by a 2020 research review.

Another review, published in 2020, ranked zinc as the top three most vital nutrients for immunological health, alongside vitamins C and D. In general, the review noted that zinc is involved in the:

• Enhancement of immune cells’ activities in the recognition and killing of foreign invaders.
• Production of antibodies and antimicrobial peptides.
• Recruitment of immune cells to the site of infection.
• Suppression of excessive inflammation and oxidative stress.
• Maintenance of the organs (e.g., skin, lung, gut) integrity.
• Prevention of autoimmunity.

With a solid antiviral and immunological background, it should not come as a surprise that clinical studies have started favoring zinc as anti-Covid-19.

Further, zinc deficiency has ties to various cancers and chronic diseases of the kidney, liver, gut, or pancreas. So, Covid-19 need not be the only reason to be aware of one’s zinc status or any nutrient for that matter.

Zinc deficiency as a risk factor for Covid-19

In a study published in September, scientists in Japan measured zinc levels in the blood of 29 Covid-19 patients upon hospitalization. They identified zinc deficiency in 14% of patients who remained with mild-to-moderate Covid-19 and 86% of patients who later progressed into severe Covid-19.

Another September study out of India did similar research with a sample of 49 Covid-19 and 45 healthy participants. At hospitalization, the patients had overall lower zinc levels than the healthy group. And a subset of patients with zinc deficiency was more likely to suffer greater Covid-19 severity and more extended hospitalization than those with higher levels.

And both these results were not attributed to confounding factors such as age, sex, or comorbidities, although the small sample size remains a caveat.

In a larger study of 249 Covid-19 patients presented in a conference this week, researchers in Spain calculated that each unit increase in blood zinc levels at admission decreased the risk of death by 7%. And zinc deficiency at admission increased the risk of death by 2.3-times. Interestingly, this study also found a correlation between healthy zinc status and lower systemic inflammation. And these findings were also adjusted for confounders.

This shows that zinc deficiency may not be apparent in every Covid-19 cohort. So, zinc status can be considered as a risk, but not causal, factor for severe Covid-19.

An earlier study, however, found a higher prevalence of vitamin D and selenium deficiencies — but not vitamin B, folate, or zinc — in a group of 50 Covid-19 patients compared to healthy people. But this study did not test if the baseline nutritional status would affect the clinical outcomes of Covid-19. Anyhow, this shows that zinc deficiency may not be apparent in every Covid-19 cohort. So, zinc status can be considered as a risk, but not causal, factor for severe Covid-19.

Zinc as a therapeutic for Covid-19

In a study published in September, titled “Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients,” researchers collected Covid-19 patient data from hospitals across New York. The study wanted to see if the addition of zinc helped Covid-19 patients fared better. So, they then identified two groups of patients:

• 521 patients received standard care, which was hydroxychloroquine (HCQ) and azithromycin (AZI) at that time.
• 441 patients received standard care plus zinc sulfate.

Both groups had similar baseline features — such as age, sex, ethnicity, tobacco use, Covid-19 severity, and comorbidities (i.e., hypertension, diabetes, cancer, obesity, or diseases of the heart, lungs, or kidneys).

And, comparing the two groups, the results are as follows:

• After adjusting for confounders, zinc+ therapy lowered the odds of death by 44% and increased the odds of hospital discharge by 53%. The treatment did not affect rates of intensive care unit (ICU) admission or the need for ventilators.
• After excluding non-ICU patients, zinc+ therapy no longer reduced mortality. This means that Covid-19 patients at the ICU level of severity did not benefit much from the treatment.
• After excluding ICU patients, zinc+ therapy halved the odds of death (i.e., 55% reduction) compared to standard care. In other words, zinc+ therapy is most effective in mild-to-moderate cases of Covid-19.

Note that this study is retrospective in design, where researchers look back at how the patients were treated and their respective health outcomes. Retrospective studies are inferior to the gold-standard prospective randomized controlled trial (RCT), where none of the participants had the disease at enrollment, and data collection begins after treatment. Hence, the authors cautioned that RCTs are still needed to verify their findings.

In other words, zinc+ therapy is most effective in mild-to-moderate cases of Covid-19.

And, indeed, there are (at least) four on-going RCTs looking at zinc + vitamin D3, zinc + vitamins D and C and HCQ, zinc + HCQ and AZI, and zinc + HCQ. The commonality of HCQ in these trials is that HCQ acts as a zinc ionophore, which means it helps shuttle zinc inside the cell — a zinc booster. While many studies do not support HCQ as a remedy for Covid-19, HCQ plus zinc has been largely overlooked.

Short abstract and thoughts

Zinc has antiviral and immunological properties, so it is not a surprise to see recent studies backing its relevance in Covid-19. In particular, zinc deficiency has been noted as a risk factor for greater Covid-19 severity. And zinc therapy managed to reduce Covid-19 mortality in a retrospective study, which awaits further support from on-going prospective RCTs.

As zinc cannot be stored and must be regularly replenished with foods or supplements, about 17–20% of the global population is estimated to be zinc deficient. Further, zinc deficiency has ties to various cancers and chronic diseases of the kidney, liver, gut, or pancreas. So, Covid-19 need not be the only reason to be aware of one’s zinc status or any nutrient for that matter.