Summary
Background & aims Nutritional predisposition to severe coronavirus disease 2019 (COVID-19) remains unclear. Zinc deficiency could be critical since it is associated with a higher susceptibility to infections. We evaluated the prevalence of hypozincemia in the early stage of COVID-19, its association with risk factors for severe COVID-19, and its prognostic value for hospitalization for respiratory complications within 10 days. Methods For 152 COVID-19 patients and 88 non-COVID-19 patients admitted to COVID-19 screening centers, national early warning score for COVID-19 (NEWS) and laboratory analyses were performed to identify the risk for severe COVID-19. Multivariable logistic regression analysis assessed whether hypozincemia was an independent predictor of hospitalization for respiratory complications within 10 days (primary judgment criterion). The secondary judgment criteria were high NEWS score (≥7), comorbidities, and biomarkers associated with severe COVID-19.
Hypozincemia was more frequent in COVID-19 patients compared to non-COVID-19 patients (27.6% vs 11.4%; p = 0.003). Older patients (≥65 years) and medically assisted nursing home residents were at higher risk of hypozincemia (p < 0.01). Hypozincemia was associated with a worse NEWS score (p < 0.01) and lymphopenia (p < 0.001). Hypozincemia was independently associated with hospitalization for respiratory complications within 10 days (OR = 10.9, 95% CI = 2.3–51.6, p = 0.002). Conclusions In the early stage of COVID-19, the prevalence of hypozincemia exceeded 20%. Hypozincemia was an independent predictor of hospitalization for respiratory complications within 10 days. This may suggest the importance of early detection and treatment of zinc deficiency in the nutritional management of COVID-19, especially in older people. Therefore, intervention and adjuvant treatment trials are strongly needed.
Results
The prevalence of hypozincemia was significantly higher in COVID-19 patients compared to non-COVID-19 patients (27.6% vs 11.4%; p = 0.003) whereas hyposelenemia was not (5.3% vs 11.4%; p = 0.08). Compared to the French middle-aged population [[6] ], the prevalence of hypozincemia was significantly higher in COVID-19 middle-aged women (28.2% vs 10.0%; p < 0.001) and men (25.0% vs 10.0%; p = 0.03). In patients with low CRP levels, COVID-19 patients presented a higher prevalence of hypozincemia compared to non-COVID-19 patients (21.8% vs 11.1%; p < 0.05). In COVID-19 patients, inflammation significantly increased this prevalence (73.3% vs 21.8%; p = 0.001) (Fig. 1). Moreover, COVID-19 patients presented more hypozincemia alone than combined hyposelenemia and hypozincemia (23.7 vs 3.9; p < 0.001), especially when CRP levels were low (20.3 vs 0.8; p < 0.001).Fig. 1Distribution of hypozincemia and hyposelenemia (%) according to CRP levels and COVID-19 status. Qualitative variables were expressed as no. (%) or no./total no (%) where total no. is the total number with available data, and compared using Chi-square test or Fisher's exact test, as appropriate. CRP cutoffs were determined to take count of potential inflammation impact in order to get reliable clinical interpretation of zinc and selenium levels. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001.
According to COVID-19 status (Table 1), hypozincemia in COVID-19 patients was mainly related to gender (p = 0.01) and older age (65 and over) (p < 0.05). It was not influenced by hypoalbuminemia, obesity, BMI <18.5 kg/m2, or digestive manifestations. In patients with lymphopenia and low CRP levels, hypozincemia was significantly marked in COVID-19 patients compared to non-COVID-19 patients (p = 0.01). Furthermore, in patients with hypozincemia and low CRP levels, lymphopenia was also more frequent in COVID-19 patients (p = 0.02) (Table 1).
Discussion
Our study reported a 2.4-fold higher prevalence of hypozincemia in the 152 COVID-19 patients compared to the 88 non-COVID-19 patients assessed in our COVID-19 screening centers. In COVID-19 patients, hypozincemia was not significantly combined with hyposelenemia or associated with BMI <18.5 kg/m2. In COVID-19 patients, while inflammation increased hypozincemia, hypozincemia was marked without a potential inflammation impact. We also showed that hypozincemia was associated with a worse risk score of clinical deterioration (NEWS ≥ 7). Finally, we showed that hypozincemia in the early stage of COVID-19 was an independent predictor of hospitalization for severe COVID-19 within 10 days.
In a smaller cohort of hospitalized patients, Heller et al. also showed that hypozincemia was higher in COVID-19 patients, and more particularly in non-survivors ]. Consistently, Carlucci et al. showed that zinc supplementation increased the frequency of discharge and reduced mortality of COVID-19 [ ]. Furthermore, Zhao et al. showed that NRS score (Nutritional Risk Screening 2002) over 5 was associated with a massive increase in mortality ]. Consequently, because nutritional assessment is essential, further studies might be of interest in order to compare plasma zinc status according to the presence or absence of malnutrition.
We reported the first evidence linking hypozincemia with lymphopenia and inflammation in the early stage of COVID-19. Our results are consistent with the pleiotropic effects of zinc on the immune system and inflammation ]. Zinc deficiency is known to increase interleukin IL-6 and to impair immunity by producing lymphopenia, especially in older people [ ]. Conversely, inflammation reduces plasma zinc concentration during the acute phase of infection ]. In the interrelationship between zinc and COVID-19, hypozincemia could reflect a primary zinc deficiency or a reversible status due to COVID-19-related inflammation which recovered in response to medical care [ ]. Our results in non-hospitalized COVID-19 patients were consistent with both hypotheses. Indeed, while inflammation increased hypozincemia, COVID-19 patients with hypozincemia were mainly associated with low CRP levels. Therefore, if our results are confirmed, and because nutrition status could be impaired during COVID-19, it would be cost-effective to detect early and correct zinc deficiency in the nutritional management of COVID-19.
Conclusions
The prevalence of hypozincemia defined by WHO criteria exceeded 20% in the early stage of COVID-19 even without a potential inflammation impact. Hypozincemia was associated with a worse risk score of clinical deterioration (NEWS ≥ 7) and was an independent predictor of hospitalization for respiratory complications within 10 days. This may suggest the importance of early detection and treatment of zinc deficiency in the nutritional management of COVID-19, especially in older people. Therefore, intervention and adjuvant treatment trials are strongly needed.
Credited to Julian
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