Zinc Deficiency and Post-acute Outcomes in Patients With COVID-19: A Six-Month Retrospective Cohort Analysis of 3,726 Patients

Background Previous studies have suggested that zinc deficiency (ZD) may increase the risk of short-term mortality in patients with coronavirus disease 2019 (COVID-19). However, the relationship between zinc status and post-acute COVID-19 outcomes remains unclear. This study aimed to determine the association between ZD and long-term outcomes in patients with COVID-19. Methodology We conducted a retrospective cohort study using the TriNetX database, including patients aged 18 years or older diagnosed with COVID-19 between January 1, 2022, and July 31, 2023. Patients had documented serum or plasma zinc levels within three months before COVID-19 diagnosis and were not deceased or hospitalized in the first month of infection. They were categorized into ZD (zinc levels <70 μg/dL) and control (zinc levels ≥70 μg/dL) groups. After 1:1 propensity score matching for demographic and clinical variables, outcomes were assessed from 30 to 180 days post-diagnosis, including all-cause hospitalization, all-cause mortality, and four subphenotypes of post-acute COVID-19. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results After matching, each group included 1,863 patients with balanced baseline characteristics. The ZD group had a higher incidence of all-cause hospitalization (25.3% vs. 20.3%; HR = 1.314; 95% CI = 1.148-1.505; p < 0.001) and all-cause mortality (3.8% vs. 2.2%; HR = 1.735; 95% CI = 1.180-2.551; p = 0.045) compared to the control group during the follow-up period. Among the four subphenotypes, only the cardiac and renal subphenotype showed a significantly higher risk in the ZD group (HR = 1.099; 95% CI = 1.002-1.205; p = 0.004). Conclusions ZD is associated with increased risks of long-term hospitalization, mortality, and increased risk in COVID-19 patients with cardiac and renal comorbidities. Monitoring and managing zinc levels may be important for improving long-term outcomes. Further research is warranted to explore the potential benefits of zinc supplementation in COVID-19 patients with ZD.