Low Levels of Few Micronutrients May Impact COVID-19 Disease Progression: An Observational Study on the First Wave

Abstract

We report an observational study performed between March and May 2020 in a Spanish university hospital during the SARS-CoV-2 pandemic. The main objective was to analyse the association between the levels of micronutrients in severe Covid-19 patients and their outcome. Adult patients with a positive polymerase-chain-reaction (PCR) for SARS-CoV-2 in the nasopharyngeal swab or in tracheal aspirate culture in the case of intubation were included. Micronutrient data were obtained from plasma analysis of a standard nutritional assessment performed within the first 24 h of hospital admission. Vitamins A, B6, C and E were analysed with HPLC methods; 25-OH-vitamin D by immunoassay and zinc by colorimetric measurements. One hundred and twenty patients were included. We found that 74.2% patients had low levels of zinc (normal levels >84 µg/dL) with a mean value of 63.5 (SD 13.5); 71.7% patients had low levels of vitamin A (normal levels >0.3 mg/L) with a mean value of 0.17 (SD 0.06); 42.5% patients had low levels of vitamin B6 (normal levels >3.6 ng/mL) with a mean value of 2.2 (SD 0.9); 100% patients had low levels of vitamin C (normal levels >0.4 mg/dL) with a mean value of 0.14 (SD 0.05); 74.3% patients had low values of vitamin D (normal levels >20 ng/mL) with mean value of 11.4 (SD 4.3); but only 5.8% of patients had low levels of vitamin E (normal levels >5 mg/L) with a mean value of 3.95 (SD 0.87). The variables associated with the need for ICU admission were low levels of zinc (standard error 0.566, 95% CI 0.086 to 0.790, p = 0.017), low levels of vitamin A (standard error 0.582, 95% CI 0.061 to 0.594, p = 0.004), age over 65 (standard error 0.018, 95% CI 0.917 to 0.985, p = 0.005) and male gender (standard error 0.458, 95% CI 1.004 to 6.040, p = 0.049). The only variable that was independently associated with the need for orotracheal intubation was low levels of vitamin A (standard error 0.58, 95% CI 0.042 to 0.405, p = 0.000). Conclusions: Low levels of vitamin A and zinc are associated with a greater need for admission to the ICU and orotracheal intubation. Patients older than 65 years had higher mortality. Randomized clinical trials are needed to examine whether micronutrient supplementation could be beneficial as an adjunctive treatment in COVID-19.

Integration of omics data to generate and analyse COVID-19 specific genome-scale metabolic models

“…Both tINIT and GIMME models predicted downregulation of retinol metabolism in different datasets, which is in line with the observations in COVID-19 patients. Low levels of vitamin A in plasma of COVID-19 patients was observed and this was significantly associated with the severity of the disease [ 73 , 74 ]. High-throughput screening of natural compounds found that all-trans retinoic acid inhibited 3C-like protease of SARS-CoV-2 and by this exhibited antiviral effect [ 75 ].…”

“…However, a meta-analysis of studies on vitamin A supplements in children did not confirm the effect on respiratory tract infection [ 77 ]. Both tINIT and GIMME models predicted also downregulation of vitamin E metabolism in different datasets, however, only one study so far measured the vitamin E level in COVID-19 patients, which was found unchanged [ 73 ].…”

Gustatory and Saliva Secretory Dysfunctions in COVID-19 Patients with Zinc Deficiency

“…Although a blood zinc level does not necessarily reflect the zinc status of an individual, zinc serum (or plasma) concentrations can be used as an indicator for the populational zinc status [ 133 ]. Table 1 summarizes serum zinc concentrations of COVID-19 patients reported by 15 studies [ 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 ], together with comorbidities such as diabetes mellitus, hypertension, respiratory disease, and cardiovascular disease that potentially induce zinc deficiency. Serum zinc concentrations ranged from 73 μg/dL to 106 μg/dL in controls or healthy subjects [ 135 , 136 , 141 , 145 , 146 , 148 ], whereas they ranged from 57 μg/dL to 80 μg/dL in COVID-19 patients [ 135 , 136 , 139 , 140 , 141 , 142 , 143 , 145 , 146 , 147 , 148 ].…”

“…In a German cohort, serum zinc concentration was 71.7 ± 24.6 μg/dL and 97.6 ± 29.4 μg/dL for COVID-19 patients and healthy subjects, respectively, which were significantly different ( p < 0.0001), and the ratio of zinc deficiency in non-survivors (dead) was higher than that in survivors discharged from hospital (73.5% vs. 40.9%, p < 0.0001) [ 136 ]. When serum zinc of Spanish COVID-19 patients was measured within the first 24 h of hospital admission, 74.2% of the patients showed lower concentration (63.5 ± 13.5 μg/dL) compared with normal subjects (> 84 µg/dL) [ 144 ]. Serum zinc concentrations of Iranian COVID-19 patients (68.4 ± 14.3 μg/dL for females and 66.7 ± 16.2 μg/dL for males) were significantly lower than controls (86.7 ± 11.8 μg/dL) ( p < 0.001 for both) [ 141 ].…”

Impact of the Coronavirus Disease on Micronutrient Search Trends and Interest in Global Population: A Worldwide Google Trend Analysis

“…An ecological study has reported correlation of the suboptimal consumption of Vitamin D, Vitamin C, Vitamin B12, and iron with either COVID-19 incidence or mortality indicators; highlighting the importance of Vitamin D and iron for the immune system as well as for the prevention and fight against COVID-19 [19]. One of the observational study have reported low levels of multiple micronutrients in most patients with severe COVID-19 pneumonia-especially low level Vitamin A and zinc [20].…”