COVID-19 has the most impact on people with comorbidities likely due to a higher inflammatory state. Zinc (Zn) is known for its substantial involvement in immune response as an antioxidant and anti-inflammatory agent. Zn plasma levels’ clinical significance at COVID diagnosis is not yet established. We investigated the effects of Zn deficiency and inflammation on COVID-19 outcomes.
Plasma Zn levels were collected from patients during the acute phase of a confirmed COVID-19 diagnosis. Data was dichotomized into Zn deficient (Zn<75 µg/dL) and Zn sufficient (Zn ?75 µg/dL). Soluble tumor necrosis factor alpha receptor II (sTNF-RII) and intestinal fatty-acid binding protein (I-FABP) were also measured. COVID-19 outcomes were classified according to the WHO clinical progression scale (0-10), then stratified into 3 groups [grp 1= (WHO score 0-4) asymptomatic or mild disease; moderate grp 2= (WHO 5-6), and severe grp 3= (7-10)]. Hazard ratios (AHRs) and 95% Confidence Intervals (CIs) were computed using cumulative logit regression and adjusted for demographics, BMI, comorbidities, inflammation markers, and laboratory data.
We included 149 patients with a confirmed COVID-19 diagnosis. The median age (interquartile range [IQR]) was 53 years (38.0, 63.0); 42% of the patients were female, 52% non-white, and 86% had at least one comorbidity. Overall, 50% of patients were in grp 1= asymptomatic or mild, whereas 8.5% had the worse outcome (grp 3). More than half of the participants (54%) had sufficient zinc levels. There was not enough evidence to suggest any differences regarding age, gender, body mass index (BMI), hemoglobin, white blood cells, transaminases enzymes, I-FABP, and sTNF-RII between the Zn- sufficient and deficient arms (p>0.05). However, 21% of the Zn sufficient arm were non-White compared to 31% in the deficient arm (p= 0.0004). Patients with zinc deficiency had a median BMI of 31.96 kg/m2 (IQR: 26.69, 36.44) and a median sTNF-RII of 3027.00 (IQR: 2446.00, 4468.00). In adjusted models, as zinc levels decreased, the risk of severe COVID-19 outcomes increased [AHR: 0.24 (95% CI: 0.06, 0.93)]. As sTNF-RII increases, but not I-FABP, the risk of severe COVID-19 outcomes rises two-fold [AHR: 2.17 (95% CI: 1.10, 4.31)].
Zinc deficiency and higher levels of sTNF-RII during acute COVID-19 presentation are independently associated with worse outcomes, suggesting a potential relationship between these 2 variables in COVID-19 progression.