The long-term follow-up of COVID-19 related liver injury

IntroductionAcute COVID-19 infection is well-known to cause abnormalities in liver blood tests (LBTs). This study aimed to identify what are the long-term implications of COVID-19 on LBTs.MethodsThis is a retrospective cohort study that examined the impact of COVID-19 infection on LBTs both during acute infection and for up to one year following hospital admission in 373 patients. Data analysis was done using Python using the SciPy and NumPy library. R factor was used to identify type of liver injury;hepatocellular, cholestatic or mixed. χ² test and Fisher exact was used for statistical analysis with p<0.05 being considered significant.ResultsDuring acute infection, 57.5% of patients showed LBT abnormalities with at least one raised liver blood test (ALT, ALP and/or bilirubin). Male patients were significantly more likely to develop LBT abnormalities than were female patients (74.5% versus 25.5%;p<0.001). The rate of LBT abnormalities was significantly correlated with severity of COVID-19 infection, such that patients requiring ITU admission were more likely to have abnormal LBTs compared to those treated on a general ward (87% versus 51% respectively;p<0.001). During short term follow-up (1-5 months post discharge), LBT abnormalities persisted in 31.3% of patients. LBT abnormalities persisted for up to 12 months in 24.0% of patients. In both the acute setting and long-term follow-up, cholestatic or mixed injury types were most commonly seen (acute;41.1%, 41.6% respectively, long-term;50.0%, 44.4% respectively).ConclusionOur data suggests that up to one in four patients have persistent LBT abnormalities up to one year following COVID-19 infection. Future research is needed to investigate what the clinical significance of this LBT abnormalities is and whether there are interventions, pharmacological or otherwise, that could reduce COVID-19 related liver injury, both in the acute setting, and longer-term.KeywordsCOVID-19, coronavirus, hepatology, liver function

Innate Immune Responses to Acute Viral Infection During Pregnancy.

Immunological adaptations in pregnancy allow maternal tolerance of the semi-allogeneic fetus but also increase maternal susceptibility to infection. At implantation, the endometrial stroma, glands, arteries and immune cells undergo anatomical and functional transformation to create the decidua, the specialized secretory endometrium of pregnancy. The maternal decidua and the invading fetal trophoblast constitute a dynamic junction that facilitates a complex immunological dialogue between the two. The decidual and peripheral immune systems together assume a pivotal role in regulating the critical balance between tolerance and defense against infection. Throughout pregnancy, this equilibrium is repeatedly subjected to microbial challenge. Acute viral infection in pregnancy is associated with a wide spectrum of adverse consequences for both mother and fetus. Vertical transmission from mother to fetus can cause developmental anomalies, growth restriction, preterm birth and stillbirth, while the mother is predisposed to heightened morbidity and maternal death. A rapid, effective response to invasive pathogens is therefore essential in order to avoid overwhelming maternal infection and consequent fetal compromise. This sentinel response is mediated by the innate immune system: a heritable, highly evolutionarily conserved system comprising physical barriers, antimicrobial peptides (AMP) and a variety of immune cells-principally neutrophils, macrophages, dendritic cells, and natural killer cells-which express pattern-receptors that detect invariant molecular signatures unique to pathogenic micro-organisms. Recognition of these signatures during acute infection triggers signaling cascades that enhance antimicrobial properties such as phagocytosis, secretion of pro-inflammatory cytokines and activation of the complement system. As well as coordinating the initial immune response, macrophages and dendritic cells present microbial antigens to lymphocytes, initiating and influencing the development of specific, long-lasting adaptive immunity. Despite extensive progress in unraveling the immunological adaptations of pregnancy, pregnant women remain particularly susceptible to certain acute viral infections and continue to experience mortality rates equivalent to those observed in pandemics several decades ago. Here, we focus specifically on the pregnancy-induced vulnerabilities in innate immunity that contribute to the disproportionately high maternal mortality observed in the following acute viral infections: Lassa fever, Ebola virus disease (EVD), dengue fever, hepatitis E, influenza, and novel coronavirus infections.