Long-term effects of Omicron BA.2 breakthrough infection on immunity-metabolism balance: a 6-month prospective study.

There have been reports of long coronavirus disease (long COVID) and breakthrough infections (BTIs); however, the mechanisms and pathological features of long COVID after Omicron BTIs remain unclear. Assessing long-term effects of COVID-19 and immune recovery after Omicron BTIs is crucial for understanding the disease and managing new-generation vaccines. Here, we followed up mild BA.2 BTI convalescents for six-month with routine blood tests, proteomic analysis and single-cell RNA sequencing (scRNA-seq). We found that major organs exhibited ephemeral dysfunction and recovered to normal in approximately six-month after BA.2 BTI. We also observed durable and potent levels of neutralizing antibodies against major circulating sub-variants, indicating that hybrid humoral immunity stays active. However, platelets may take longer to recover based on proteomic analyses, which also shows coagulation disorder and an imbalance between anti-pathogen immunity and metabolism six-month after BA.2 BTI. The immunity-metabolism imbalance was then confirmed with retrospective analysis of abnormal levels of hormones, low blood glucose level and coagulation profile. The long-term malfunctional coagulation and imbalance in the material metabolism and immunity may contribute to the development of long COVID and act as useful indicator for assessing recovery and the long-term impacts after Omicron sub-variant BTIs.

Comparison of four markers of hepatic fibrosis and hepatic function indices in patients with liver cirrhosis and hepatoma.

BACKGROUND: The present study aimed to compare four hepatic fibrosis markers [i.e., hyaluronic acid (HA), laminin (LN), procollagen III N-terminal peptide (PIIINP), and collagen type IV (CIV)] and 16 hepatic function indices in patients with liver cirrhosis of varying etiology. METHODS: The hepatic function indices and hepatic fibrosis markers were measured in 108 patients with liver cirrhosis and hepatoma using an automatic biochemical analyzer and luminescent immune analyzer. Twenty healthy controls were enrolled to compare the differences between liver cirrhosis and hepatoma of varying etiology and to analyze the correlations between the hepatic function indices and fibrosis markers. RESULTS: There was no correlation between alanine aminotransferase (ALT), total protein (TP), alkaline phosphatase (ALP), or the four markers of hepatic fibrosis in liver cirrhosis caused by hepatitis B (P>0.05). Aspartate aminotransferase (AST) was positively correlated with HA (r=0.428, P=0.007), LN (r=0.458, P=0.004), and CIV (r=0.374, P=0.021). Total bilirubin (TBIL) and direct bilirubin (DBIL) were positively correlated with LN (TBIL: r=0.480, P=0.002; DBIL: r=0.457, P=0.004), PIIINP (TBIL: r=0.380, P=0.017; DBIL: r=0.406, P=0.011), and CIV (TBIL: r=0.415, P=0.010; DBIL: r=0.400, P=0.013). Total bile acid (TBA) and γ-glutamyltranspeptidase (GGT) were positively correlated with PIIINP (TBA: r=0.363, P=0.025; GGT: r=0.353, P=0.029) and CIV (TBA: r=0.419, P=0.009; GGT: r=0.335, P=0.040). Leucine aminopeptidase (LAP) was positively correlated with LN (r=0.482, P=0.002). Cholinesterase (CHE) (HA: r=-0.452, P=0.004, LN: r=-0.336, P=0.039; PIIINP: r=-0.468, P=0.003; CIV: r=-0.485, P=0.002), prealbumin (PA) (HA: r=-0.575, P=0.000, LN: r=-0.413, P=0.010; PIIINP: r=-0.344, P=0.035; CIV: r=-0.371, P=0.022), albumin (ALB) (HA: r=-0.541, P=0.000, LN: r=-0.373, P=0.021; PIIINP: r=-0.353, P=0.030; CIV: r=-0.415, P=0.010), and superoxide dismutase (SOD) (HA: r=-0.334, P=0.040, LN: r=-0.347, P=0.033; PIIINP: r=-0.487, P=0.002; CIV: r=-0.536, P=0.001) were negatively correlated with the four markers of hepatic fibrosis. There was no correlation between ALT, AST, TBIL, TP, ALP, GGT, or the four hepatic fibrosis markers in hepatoma caused by hepatitis B (P>0.05). Meanwhile, DBIL and TBA were positively correlated with CIV (DBIL: r=0.519, P=0.023; TBA: r=0.563, P=0.012), while CHE (r=-0.604, P=0.006), ALB (r=-0.564, P=0.012), and SOD (r=-0.489, P=0.034) were negatively correlated with CIV. Moreover, PA was negatively correlated with LN (r=-0.510, P=0.026) and CIV (r=-0.696, P=0.001). CONCLUSIONS: The concentrations of the serological indices differed significantly based on the specific liver cirrhosis etiology. There was a strong correlation between the hepatic function indices and four hepatic fibrosis markers. Thus, the detection of these markers might improve the diagnosis and treatment of hepatoma.