Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can have a variety of outcomes, from asymptomatic to mild symptoms and severe pathologies such as pneumonia and acute respiratory distress that can potentially be fatal. This makes it very crucial that we identify the biomarkers that predict severe disease in the early stages of infection. Finding the biomarkers for predicting coronavirus disease 2019 (COVID-19) outcomes will help improve prognosis and treatment.

A team of researchers from various universities and institutes in Spain recently published a paper on the preprint server medRxiv,* in which they hypothesize that serum zinc levels have a significant influence on COVID-19 progression and thus may be a useful biomarker in predicting severe disease in early stages of COVID-19 infection.

Study: Low zinc levels at clinical admission associates with poor outcomes in COVID-19. Image Credit: Fida Olga / Shutterstock

Role of zinc in our immune system

Zinc is a trace element in our body that plays various roles essential for maintaining various basic biological processes. Zinc acts as a signaling molecule, cofactor, and structural element. One of the most critical roles of zinc in the human body is its effect on our immune system. Zinc levels affect both innate and adaptive immunity. Zinc balances our immune responses and drives a direct antiviral action against some viruses.

Zinc deficiency is caused by low zinc intake or malabsorption of zinc. It is common in the elderly population, and individuals with underlying diseases, two groups that are more prone to severe COVID-19. Consequently, zinc deficiency causes an immune imbalance that can ultimately lead to a major public health concern that affects at-risk individuals even more.

Study finds strong correlation between serum zinc levels and severe COVID-19

The team of researchers ran a retrospective, observational study involving 249 COVID-19 patients admitted to Hospital del Mar. They studied severity of COVID-19 and disease progression in the admitted patients. They also parallelly analyzed the replication of the SARS-CoV-2 virus in the Vero E6 cell line at various concentrations of zinc.

The findings of their study showed a correlation between COVID-19 outcome and serum zinc levels. Patients with serum zinc levels less than 50 mcg/dl, which defines the cutoff for zinc deficiency and development of related clinical symptoms, at the time of admission exhibited worse clinical presentation, took longer to attain stability, and also had higher mortality. In vitro results of the study show that lower levels of zinc favor viral expansion in cells infected with SARS-CoV-2.

“These results would support that the poor clinical outcome observed in low SZC patients is caused by the effect of ZD on both, inducing immune imbalance and increasing viral load via promoting viral expansion in the infected cell.”

Zinc supplementation in at-risk groups may help reduce COVID-19 severity

The association between serum zinc levels and human health is well known. Zinc deficiency remains a major nutritional concern in many countries due to poor nutrition leading to low zinc intake. Moreover, even in developed countries, zinc deficiency is prevalent in 15 to 31% of the elderly population.

According to the authors, their work is aimed at bringing clinical attention to serum zinc concentrations in COVID-19 patients. Their analysis shows a strong correlation between low serum zinc levels and severity COVID-19 and mortality. They think that the reason behind this could be a combination of immune system imbalance and improved viral replication in patients with zinc deficiency. Hence, they propose serum zinc levels as a new biomarker that can help predict COVID-19 outcomes.

The researchers believe that there is an urgent need to begin supplementing patients having zinc deficiency with zinc during admission to bring their zinc levels to normal range. They also recommended prophylactic zinc supplementation in at-risk groups, such as the elderly, to mitigate COVID-19 severity.

The authors encourage future studies that perform randomized clinical trials to assess the effects of zinc supplementation as potential prophylaxis and also as a therapeutic approach in people who are at risk of zinc deficiency.

“It should be also recommended to promote zinc supplementation programs targeted to people at risk of zinc deficiency, such as elderly, in order to reduce COVID-19 severity.”