Background: Cases of excessive neutrophil counts in the blood in severe coronavirus disease (COVID-19) patients have drawn significant attention. Neutrophil infiltration was also noted on the pathological findings from autopsies. It is urgent to clarify the pathogenesis of neutrophils leading to severe pneumonia in COVID-19. Methods: A retrospective analysis was performed on 55 COVID-19 patients classified as mild (n = 22), moderate (n = 25), and severe (n = 8) according to the Guidelines released by the National Health Commission of China. Trends relating leukocyte counts and lungs examined by chest CT scan were quantified by Bayesian inference. Transcriptional signatures of host immune cells of four COVID19 patients were analyzed by RNA sequencing of lung specimens and BALF. Results: Neutrophilia occurred in 6 of 8 severe patients at 7–19 days after symptom onset, coinciding with lesion progression. Increasing neutrophil counts paralleled lesion CT values (slope: 0.8 and 0.3–1.2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular trap (NET)-associated genes in COVID-19 patients, which was related to innate immunity and interacted with T/NK/B cells, as supported by a protein–protein interaction network analysis. Conclusion: Excessive neutrophils and associated NETs could explain the pathogenesis of lung injury in COVID-19 pneumonia.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an imminent threat to humanity. SARS-CoV-2 invades host cells, causing a failure of host immune recognition. Instead of an effective antiviral immunological response after SARS-CoV-2 invasion, the cascading pathological syndrome of COVID-19, especially in severe disease, is exacerbated by an overt inflammatory response and the suppression of SARS-CoV-2–specific immune responses. As is known, excessive inflammation leads to pathophysiological changes in virus-infected tissues or organs, manifested by imbalanced immune responses, cytokine storm, and aggressive neutrophil activation, ultimately leading to lung damage, such as alveolar damage, endotheliitis, and fluid overload. However, the triggers and consequences of a disruption to immune system homeostasis and the underlying mechanisms of uncontrolled immunopathology following viral infection remain unclear. Here, we review the dynamic and systemic immune progression from an imbalance in cell-mediated immune responses to COVID-19 lung injury. Our understanding of key mechanisms involved in pathogenesis is critical for the development of therapeutic agents and to optimize therapeutic strategies.

Acute-on-chronic liver failure (ACLF) is an acute syndrome accompanied with decompensation of cirrhosis, organ failure with high 28-day mortality rate. Systemic inflammation is the main feature of ACLF, and poor outcome is closely related with exacerbated systemic inflammatory responses. It is well known that severe systemic inflammation is an important event in chronic hepatitis B (CHB)-ACLF, which eventually leads to liver injury. However, the initial CHB-ACLF events are unclear; moreover, the effect of these events on host immunity as well as that of immune imbalance on CHB-ACLF progression are unknown. Here, we investigate the initial events of ACLF progression, discuss possible mechanisms underlying ACLF progression, and provide a new model for ACLF prediction and treatment. We review the characteristics of ACLF, and consider its plausible immune predictors and alternative treatment strategies.

Background: The upper limits of normal (ULNs) for alanine aminotransferase (ALT) are different among international guidelines for chronic hepatitis B (CHB). We aimed to investigate the proportion of significant histological disease in Asian patients with CHB with detectable hepatitis B virus (HBV) DNA under diverse ALT ULNs. Methods: Consecutive patients with CHB and detectable HBV DNA who underwent liver biopsy were retrospectively included from four tertiary hospitals. Above grade 2 inflammation and stage 2 fibrosis were defined as significant inflammation and significant fibrosis, respectively. Significant histological disease was defined as above grade 2 inflammation or stage 2 fibrosis. Results: Among the 414 patients with detectable HBV DNA and normal ALT, the proportion of those with significant histological disease was lower (59.7%) according to the ULN for ALT at 30/19 U/L (male/female), while the corresponding proportions were 66.7% and 62.3% according to the ULNs of 40 U/L and 35/25 U/L (male/female), respectively. In patients with detectable HBV DNA and normal ALT levels without significant fibrosis, the proportions of significant inflammation were comparable among different ULNs of ALT at 40 U/L (30.7%), 35/25 U/L (27.3%) and 30/19 U/L (25.0%). The proportion of significant histological disease was significantly lower in patients with normal ALT for 2 determinations at least 6 months apart compared to patients with normal ALT once. Conclusions: Although a more stringent ALT ULN may reduce the risk of the presence of significant histological disease in patients with detectable HBV DNA, the rates of significant histological disease remain high. Persistently normal ALT levels are more important for excluding patients with CHB with a high probability of significant histological disease.

The molecular properties of the circulating causative agents of hand, foot and mouth disease (HFMD) in Wuxi remain unclear, posing diagnostic and prevention challenges. Additionally, in several regions of mainland China, the EV71 immunisation drastically reduced related cases and altered the HFMD pathogen spectrum, while the precise situation in Wuxi remained unknown. To address these issues, paediatric HFMD cases diagnosed in the clinic were enrolled and anal swabs were acquired in the spring of 2019. The 5′-UTR and VP1 genes were interpreted using RT-nPCR with degenerate primers to confirm their genotypes. Following that, the entire genome sequences of each viral type were recovered, allowing for the interpretation of several molecular properties. A total of 249 clinically confirmed HFMD cases had their anal swabs taken for viral identification, from which the genome sequences of seven genotypes were recovered. Coxsackievirus A16 is the most prevalent type, followed by Coxsackievirus A6, A10, A2, A4, A5 and Echovirus 11, all of which were genetically determined for the first time in Wuxi. Phylogenetic and recombination analyses were used to evaluate their evolutionary relationships with other strains found in other regions. Noticeably, a CVA16 subtype, responsible for a large proportion of the observed cases, phylogenetically clustered within clade B1a along with some strains from other countries, was the first one to be reported in China. Furthermore, some recombination events were inferred from strains detected in sporadic cases, particularly the recombination between CVA2 and CVA5 strains. Our investigation elucidated the multiple molecular characteristics of the HFMD causal enterovirus strains in Wuxi, underlining the potential hazards associated with these circulating viral types in the population and aiding in future surveillance and prevention of this disease.

Normal serum transaminases and immunoglobulin G (IgG) levels are surrogate markers for hepatic histologic disease activity in autoimmune hepatitis (AIH). This study aimed to evaluate liver inflammation in patients with AIH with normal serum alanine aminotransferase (ALT) and IgG levels. Two hundred and five AIH patients who underwent liver biopsy in four medical centers were included. Logistic regression analysis was used to identify risk factors associated with advanced inflammation. One hundred and thirty-one (63.9 %) AIH patients had advanced liver inflammation, and 108 (52.7 %) patients had advanced liver fibrosis. 60.0 % of patients with normal ALT and 51.7 % of patients with normal ALT and IgG had advanced inflammation. However, 76.7 % and 35.0 % of patients with or without advanced fibrosis with normal ALT had advanced inflammation, while the corresponding proportions of advanced inflammation were 78.6 % and 26.7 % in patients with normal ALT and IgG, respectively. Moreover, 81.0 % and 44.8 % of patients with and without cirrhosis with normal ALT had advanced inflammation, while the corresponding proportions were 83.3 % and 29.4 % in patients with normal ALT and IgG, respectively. Red cell distribution width (OR = 1.325, 95%CI 1.045–1.681, P = 0.020) and PT (OR = 1.514, 95%CI 1.138–2.014, P = 0.004) were independent factors associated with advanced inflammation. High proportion of advanced inflammation was found in AIH patients with normal ALT and IgG levels despite without advanced fibrosis. Although using non-invasive methods may contribute to rule out liver fibrosis in AIH patients with normal ALT and IgG levels, liver biopsy is encouraged to assess liver inflammation.