4. Discussion
infection, critically ill, bacterial superinfections
CRITICALLY ILL, ACUTE RESPIRATORY INFECTIONS, PCT, DISEASE, ADVERSE EFFECTS, SECONDARY, INFECTION, VITAMIN D DEFICIENCY, SUPERINFECTION
In our study, vitamin D supplementation in patients with severe COVID-19 treated in an intensive care unit (ICU) for invasive or non-invasive respiratory support did not reduce the number of days on respiratory support compared to patients who did not receive vitamin D supplementation. Furthermore, there were no differences in the number of days spent in the ICU, hospital length of stay or rate of bacterial superinfections. Regarding the survival, there were no differences in 14-, 28-day or 60-day survival rates. However, the study findings should be interpreted with caution due to inadequate study power for primary outcome. With this caveat, the trial should be viewed as a contribution to a still under-researched body of evidence about the effect of vitamin D supplementation in critically ill patients with COVID-19. The results of this RCT should be pooled in a systematic review, since a single trial can seldom provide a definitive answer [Vitamin D supplementation was shown to have benefits regarding acute respiratory infections [In this study, vitamin D supplementation was administered in daily doses of 10,000 IU of cholecalciferol. This dosage increased mean values of vitamin D concentrations from 27.2 to 56.2 nmol/L over a 14-day period, and no adverse effects were recorded. Studies showed that these doses are safe, and the cumulative dose for patients included in our study is considered low [Results for the primary outcome in our study show that vitamin D supplementation did not reduce the number of days on respiratory support (median number of days 10 (IQR 6–15) in the intervention group and 8 (IQR 6–15) in the control group). These results are in concordance with the results published by Lan et al. in their systematic review [Regarding secondary outcomes, we found no significant differences in the number of days spent in the ICU nor in hospital length of stay. Most of the published studies showed similar results [In this study, there was no difference in the 14-, 28- or 60-day survival rate between the intervention and control group. Bassatne et al. showed in their systematic review increased mortality rates in COVID-19 patients with vitamin D deficiency [A systematic review by D’Ecclesiis et al. included 38 studies that assessed the association of vitamin D levels or vitamin D supplementation with SARS-CoV2 infection, severity and mortality [The results of our study show different trends in disease severity markers between patients who received vitamin D supplementation and those who did not receive supplementation. Many of the patients from our study had increases in inflammatory and disease severity markers 7–10 days after ICU admission. This can be explained by the fact that more than 70% of patients from both groups had bacterial superinfection during their ICU stay. There was no significant difference between the two groups. Similar results were reported in a rapid review where authors report that supplementing vitamin D did slightly improve fibrinogen levels but did not influence D-dimer, CRP or PCT levels [