and clinical adverse events in children with COVID ‐

To the Editor, Hypoalbuminemia is considered a predictor of adverse outcomes in critically ill children and in adults affected by COVID‐19. In particular, former studies reported that hypoalbuminemia is a predictor of vascular disease and death. Hypoalbuminemia has been reported in children with a severe form of COVID‐19. Conversely, it is unclear whether children with moderate/mild form of COVID‐19 have reduced albumin values and if there is an association with inflammatory or infective events. Thus, we wanted to explore this issue in this study. This study was performed at Bambino Gesù Children's Hospital located in Rome (Italy) and in the dedicated COVID unit. Methods are described in Supporting Information data. Sixty‐three children affected by mild/moderate COVID‐19 were consecutively recruited at the Bambino Gesù Children's Hospital in Rome. Clinical characteristics and symptoms at admission are reported in Table 1. The median in‐hospital stay was 7 days (interquartile range [IQR] =5–11). Sixteen patients experienced clinical events: seven multisystem inflammatory syndromes, four pneumonia, three myocardial involvement (troponin increased with ST‐segment elevation (n=1), troponin increase alone (n=1), pericarditis (n=1)), and two urinary tract infections. All these clinical events occurred in symptomatic children. Compared to patients who did not experience clinical events, those with clinical events had lower serum albumin (Figure 1A), higher high‐ sensitivity C reactive protein (hs‐CRP) and presence of fever at admission (see Table 1). Furthermore, serum albumin correlated with hs‐ CRP levels (R= −0.616, p < .001) in all the population. The highest and lowest levels of hs‐CRP and serum albumin were detected in the children with multisystem inflammatory syndrome. Compared to the other children who manifested a clinical event (n = 9), those with multisystem inflammatory syndrome (n = 7) had lower serum albumin (median = 4.2, IQR = 3.9–4.3 g/dl vs. median = 2.7 g/dl, IQR = 2.5–4.1 g/dl, p = .04, respectively) (Figure 1B) and higher, even if not significant, hs‐CRP levels (median = 0.25 mg/L, IQR = 0.07–4.94mg/L vs. median = 5.3 mg/L, IQR = 0.66–14.5mg/L, p = .07, respectively). A significant difference for albumin and hs‐CRP values was also observed when children with multisystem inflammatory syndrome were compared to children without clinical events (albumin:median = 2.7g/dl, IQR = 2.5–4.1 g/dl vs. median = 4.6 g/dl, IQR = 4.2–4.8 g/dl, p = .001 [Figure 1B] and hs‐ CRPmedian = 5.3 mg/L, IQR = 0.66–14.5mg/L vs. median = 0.06 mg/L, IQR = 0.03–0.26mg/L, p < .001, respectively). Furthermore, compared to children without clinical events, those who experienced clinical events without multisystem inflammatory syndrome had lower serum albumin (p = .04, Figure 1B) and higher hs‐CRP (p = .03) levels. In this study, we showed that among children with moderate/mild COVID‐19 those with clinical complications involving lungs and other organs had lower albumin serum levels compared to those without clinical events. Furthermore, children with COVID‐19 and multisystem inflammatory syndrome have the lowest values of serum albumin. These values could be a precocious marker of this potentially lethal condition. COVID‐19 infection is characterized by a cytokine storm, which entails systemic inflammation and eventually vascular damage predisposing to thrombosis and death. Albumin is an acute‐phase protein, which is reduced during infections because of its anti‐inflammatory and antioxidant properties. Its reduction, however, hampers the body's anti‐ inflammatory defense, thus promoting inflammation and eventually leading to multiorgan damage. In this context, it is interesting to note that TABLE 1 Clinical and laboratory characteristics on admission in patients selected according to the presence of clinical events or not during hospitalization