Zinc and Coronavirus Disease 2019: Causal or Casual Association?

Abstract

We read with interest the article by Yao et al1Yao J.S. Paguio J.A. Dee E.C. C et al.The minimal effect of zinc on the survival of hospitalized patients with COVID-19: an observational study.Chest. 2021; 159: 108-111Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar this issue of CHEST whereby they have studied the effect of zinc supplementation in hospitalized patients of coronavirus disease 2019 (COVID-19) infection.1Yao J.S. Paguio J.A. Dee E.C. C et al.The minimal effect of zinc on the survival of hospitalized patients with COVID-19: an observational study.Chest. 2021; 159: 108-111Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar In reference to the patient assessment parameters and results, one very important aspect needs attention. Although the authors have evaluated in detail the baseline clinical and treatment characteristics, they have no data pertaining to serum zinc levels before or after zinc supplementation. We do understand because this was a retrospective analysis with waiver of consent, but one should be cautious about the interpretation of results in this scenario. Before concluding that zinc supplementation did not lead to a statistically significant decrease in mortality or other outcome parameters, we should have data clarifying which patients were zinc deficient and which were not before receiving zinc supplementation. This could have been done by measuring serum zinc levels. It is well mentioned in literature that patients with certain respiratory illnesses, for example, asthma, have decreased serum zinc levels. Ibraheem et al2Ibraheem R.M. Johnson A.B. Abdulkarim A.A. Biliaminu S.A. Serum zinc levels in hospitalized children with acute lower respiratory infections in the north-central region of Nigeria.Afr Health Sci. 2014; 14: 136-142Crossref Scopus (16) Google Scholar recorded the prevalence of 98.3% for low serum zinc levels in children with acute lower respiratory tract infection than that in control subjects of 64.2%.2Ibraheem R.M. Johnson A.B. Abdulkarim A.A. Biliaminu S.A. Serum zinc levels in hospitalized children with acute lower respiratory infections in the north-central region of Nigeria.Afr Health Sci. 2014; 14: 136-142Crossref Scopus (16) Google Scholar Rerksuppaphol and Rerksuppaphol3Rerksuppaphol S. Rerksuppaphol L. A randomized controlled trial of zinc supplementation in the treatment of acute respiratory tract infection in Thai children.Pediatr Rep. 2019; 11: 7954Crossref PubMed Scopus (32) Google Scholar have also shown that zinc supplementation reduces the number of hospital days in children with acute lower respiratory tract infection, and their results were substantiated by measuring pre and post supplementation serum zinc levels. Serum zinc level is also the recommended modality to estimate dietary zinc status in individuals.4McDonald C.M. Suchdev P.S. Krebs N.F. et al.Adjusting plasma or serum zinc concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.Am J Clin Nutr. 2020; 111: 927-937Crossref Scopus (31) Google Scholar Also, in COVID-19 disease, C-reactive protein has emerged as one of the key inflammatory markers, and serum zinc levels also have been found to be inversely proportional to C-reactive protein levels in some surveys.4McDonald C.M. Suchdev P.S. Krebs N.F. et al.Adjusting plasma or serum zinc concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.Am J Clin Nutr. 2020; 111: 927-937Crossref Scopus (31) Google Scholar This further highlights the importance of getting serum zinc levels before making any conclusions about zinc therapy in such patients. The work done by the authors is worth appreciation; however, a prospective cohort study with pre and post zinc supplementation zinc levels would probably yield better or probably different answers. The Minimal Effect of Zinc on the Survival of Hospitalized Patients With COVID-19: An Observational StudyCHESTVol. 159Issue 1PreviewZinc is an investigational agent against coronavirus disease 2019 (COVID-19) and has known preventative and therapeutic roles in other infections.1-3 Zinc deficiency is associated with lower survival among older patients with pneumonia and predisposes to other viral infections.3 Established risk factors for critical COVID-19, including older age, diabetes mellitus, and cardiovascular disease, are also associated with zinc deficiency.2 Full-Text PDF ResponseCHESTVol. 159Issue 1PreviewWe thank Dr Khurana et al for their thoughtful response to our letter1 and for pointing out the value of serum zinc levels. Our study assessed the association between zinc supplementation and survival among hospitalized patients with coronavirus disease 2019 (COVID-19), using a causal inference approach to retrospective data. Our institutions do not routinely measure serum zinc levels. Although our study population consisted of patients admitted to a single hospital, our study assessed the effect of zinc in the contexts in which it was routinely used in the inpatient setting at the peak of the COVID-19 pandemic in the United States. Full-Text PDF