Objectives To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre‐eclampsia (PE) in pregnancies with COVID‐19, and to assess their accuracy to differentiate between PE and the PE‐like features associated with COVID‐19. Design A prospective, observational study. Setting Tertiary referral hospital. Participants Singleton pregnancies with COVID‐19 at >20+0 weeks. Methods Forty‐two consecutive pregnancies were recruited and classified into two groups: severe and non‐severe COVID‐19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms‐like tyrosine kinase‐1/placental growth factor [sFlt‐1/PlGF]) were assessed in women with suspected PE. Main outcome measures Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt‐1/PlGF. Results Thirty‐four cases were classified as non‐severe and 8 as severe COVID‐19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID‐19 cases (62.5%). However, abnormal sFlt‐1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE‐like syndrome. Conclusions Pregnant women with severe COVID‐19 can develop a PE‐like syndrome that might be distinguished from actual PE by sFlt‐1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre‐eclampsia with caution. Tweetable abstract This study shows that a pre‐eclampsia‐like syndrome could be present in some pregnancies with severe COVID‐19.

AIMTo detect hyper-conserved regions in the hepatitis B virus (HBV) X gene (HBX) 5’ region that could be candidates for gene therapy.METHODSThe study included 27 chronic hepatitis B treatment-naive patients in various clinical stages (from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeAg-negative and HBeAg-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/mL, the HBX 5’ end region [nucleotide (nt) 1255-1611] was PCR-amplified and submitted to next-generation sequencing (NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences (haplotypes) obtained by NGS. Conservation at the HBx protein amino acid (aa) level was also analyzed.RESULTSNGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample (2487-9279, IQR 2817). In 14/27 patients (51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper-conserved nucleotide regions, one in the HBX upstream non-coding region (nt 1255-1286) and the other in the 5’ end coding region (nt 1519-1603). This last region coded for a conserved amino acid region (aa 63-76) that partially overlaps a Kunitz-like domain.CONCLUSIONTwo hyper-conserved regions detected in the HBX 5’ end may be of value for targeted gene therapy, regardless of the patients’ clinical stage or HBV genotype.

Liver disease is frequently asymptomatic, challenging early identification in the primary care setting. The fibrosis 4 (FIB4) index is a liver fibrosis biomarker that is a potential alternative to liver biopsy for diagnosing and managing liver disease. This study aimed to calculate the FIB4 index for screening individuals at high risk of liver disease at the community level. This was a retrospective real-world study analyzing blood and serum test results from a central laboratory. The primary outcome was the number of individuals within each risk category for hepatic fibrosis: high risk (FIB4 ≥ 3.25) and low risk (FIB4 < 1.3). The analysis included samples from 31,753 patients, of which 18,102 were aged 40 to 75 years. In these patients, the FIB4 index had been explicitly requested in 1852 (10.2%) cases and estimated ad hoc in the rest. Of the 263 (1.5%) cases with FIB4 ≥ 3.25, the FIB4 index was requested in 46 (17.5%), and 52 (19.8%) showed evidence of liver fibrosis in their medical records, while the rest did not report any data regarding liver fibrosis. FIB4 is a simple score that can play a role as a “red flag” for early identification of patients at high risk of advanced liver fibrosis and their referral to specialized care.

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