Zinc Supplementation Impact in Acute COVID-19 Clinical Outcomes (MARZINC)

Zinc-based Nutritional Immunity to Lower Inflammation, Viral Load and COVID-19 Mortality During SARS-CoV-2 Infection.

Infections with SARS-CoV-2 result in a systemic disease with a variety of outcomes, from no symptoms to severe and diverse pathologies. Therefore, it is important to identify risk factors determining COVID-19 severity, especially if those factors might be adjusted, allowing early and effective therapeutic interventions. Zinc is a trace element essential for human health. Zinc deficiency is common in old adults, vegetarians and patients with chronic inflammatory diseases. This condition causes immune dysfunction leading to increased risk of inflammatory and infectious diseases, including acquired immune deficiency syndrome, measles, malaria, tuberculosis, and pneumonia. Besides, zinc has a direct antiviral activity against specific viruses like rhinovirus, HCV, herpes simplex virus. In this scenario, it has been shown that zinc supplementation has benefits on the recurrence and persistence of acute and chronic viral infections like common cold or HCV, HBV. Moreover, our team has recently done an observational study with 249 COVID-19 patients that showed how COVID-19 patients with lower plasma zinc content had worse prognosis, increased time of hospitalization and mortality.

Therefore, the main aim of the project is to explore the therapeutic benefit of zinc supplementation for COVID-19 patients and to determine the cellular and molecular basis of the effect of Zn levels on SARS CoV-2 infections. For that purpose the investigators will run a clinical trial supplementing with zinc COVID-19 patients. Moreover, the investigators will carry out experiments to understand the association between zinc nutritional status and SARS-Cov-2 infection progression in cellular and animal models.

Given the current knowledge about zinc supplementation toxicity and dosage, the investigators expect that recommendations derived from this study will be rapidly applied by physicians and public health decision makers. The results of these studies will be used as a guideline to administer zinc supplements in COVID-19 patients in order to reduce disease severity and mortality. Moreover, the experiments will clarify whether zinc supplementation as a prophylaxis strategy is useful to protect the population at risk of zinc deficiency, more than 20% worldwide. Finally, considering the new knowledge that this project will generate about the role of zinc in immune responses and viral expansion, the investigators expect that our results will help researchers and physicians to design novel strategies to boost specific immune cell subpopulations against SARS-CoV2 infection. Thus, this knowledge could be used long-term for designing medicines against SARS-CoV-2 and other viral infections.

Study Overview

• Status: Completed
• Conditions: Zinc Deficiency; Sars-CoV-2 Infection
• Intervention / Treatment: Dietary supplement: Zinc Acetate

Detailed Description

Background: The essential micronutrient zinc balances immune responses to infections and additionally directly inhibits some viruses. The investigators have recently shown a robust correlation between serum zinc levels (SZL)and COVID-19 outcome in patients and a direct effect of zinc levels on SARS-CoV-2 expansion in cell culture.These results suggest that SZL might represent an important risk factor for COVID-19 severity whose adjustment would constitute an early and cost-effective therapeutic intervention.

Objectives: To explore the therapeutic benefit of zinc supplementation for COVID-19 patients and to determine the cellular and molecular basis of the effect of zinc levels on SARS-CoV-2 infections.

Methodology: A randomized clinical trial supplementing COVID-19 patients with zinc will be carried out and viral loads, inflammatory and novel zinc-related clinical markers and SARS-CoV-2-specific T- and B-cell Responses monitored. Humanized-ACE2-mice models will be used to address causal-effect associations between zinc levels and SARS-CoV-2 infection. Infections of human Calu-3 cells will be used to decipher the direct antiviral action of zinc on SARS-CoV-2 life cycle. Expected results: The investigators will generate a clear insight into zinc functioning in COVID-19 patients that might provide a therapeutic guideline immediately applicable to reduce the severity of SARS-CoV-2 pathogenicity and possibly other virus infections.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• SARS-CoV-2 infection requiring hospital admission.

Exclusion Criteria:

• Previous immunization against SARS-CoV-2
• <18 years
• pregnancy/breastfeeding
• oral intolerance
• life expectancy <72h on admission.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standars of Care; Standard of Care of treatment for SARS-coV-2 infection
Experimental: Zinc Supplementation +Standard of Care; Standard of care + ( 240mg zinc acetate Zinc (75mg Zn element) +NM QD) during 14 days	Dietary supplement: Zinc Acetate; Each participant allocated in the intervention arm will be treated as Standard of Care and will be supplemented with 240mg of Zinc Acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of progression	progression to severe forms of SARS-Cov-2 disease, assessed by a combined outcome that includes mortality and/or need for ICU admission	day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to clinical stability	time until clinical stability (defined as basal saturation >94%, HR <100l/min, SBP>90mm Hg and afebrile)	day 14
hospital length of stay	days of hospital stay	day 14 and day 28
Adverse Effects	Adverse Effects	Day 14 and Day 28

Collaborators and Investigators

• Sponsor: Parc de Salut Mar
• Collaborators: Universitat Pompeu Fabra
• Investigators: Principal Investigator: Robert Güerri-Fernández, M.D. Ph.D., PsMar

Publications and helpful links

General Publications

• Vogel-Gonzalez M, Tallo-Parra M, Herrera-Fernandez V, Perez-Vilaro G, Chillon M, Nogues X, Gomez-Zorrilla S, Lopez-Montesinos I, Arnau-Barres I, Sorli-Redo ML, Horcajada JP, Garcia-Giralt N, Pascual J, Diez J, Vicente R, Guerri-Fernandez R. Low Zinc Levels at Admission Associates with Poor Clinical Outcomes in SARS-CoV-2 Infection. Nutrients. 2021 Feb 9;13(2):562. doi: 10.3390/nu13020562.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Actual): February 23, 2022
• Study Completion (Actual): May 25, 2022

Study Registration Dates

• First Submitted: March 4, 2023
• First Submitted That Met QC Criteria: March 18, 2023
• First Posted (Actual): March 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: March 18, 2023
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections
• Other Study ID Numbers: 2021/9673/I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will shared on demand and under reasonable basis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No