Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection.

The ongoing global pandemic of Coronavirus disease 2019 (COVID-19) poses a serious threat to human health, with patients reportedly suffering from thrombus, vascular injury and coagulation in addition to acute and diffuse lung injury and respiratory diseases. Angiotensin converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 entry, is also an important regulator of renin-angiotensin system (RAS) homeostasis, which plays an unsettled role in the pathogenesis of COVID-19. Here, we demonstrated that SARS-CoV-2 Spike protein activated intracellular signals to degrade ACE2 mRNA. The decrease of ACE2 and higher level of angiotensin (Ang) II were verified in COVID-19 patients. High dose of Ang II induced pulmonary artery endothelial cell death in vitro, which was also observed in the lung of COVID-19 patients. Our finding indicates that the downregulation of ACE2 potentially links COVID-19 to the imbalance of RAS.

TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection.

Limited understanding of T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impeded vaccine development and drug discovery for coronavirus disease 2019 (COVID-19). We found that triggering receptor expressed on myeloid cells 2 (TREM-2) was induced in T cells in the blood and lungs of patients with COVID-19. After binding to SARS-CoV-2 membrane (M) protein through its immunoglobulin domain, TREM-2 then activated the CD3ζ/ZAP70 complex, leading to STAT1 phosphorylation and T-bet transcription. In vitro stimulation with M protein-reconstituted pseudovirus or recombinant M protein, and TREM-2 promoted the T helper cell 1 (TH1) cytokines interferon-γ and tumor necrosis factor. In vivo infection of CD4­TREM-2 conditional knockout mice with murine coronavirus mouse hepatitis virus A-59 showed that intrinsic TREM-2 in T cells enhanced TH1 response and viral clearance, thus aggravating lung destruction. These findings demonstrate a previously unidentified role for TREM-2 in SARS-CoV-2 infection, and suggest potential strategies for drug discovery and clinical management of COVID-19.

Analysis of pathological changes in the epithelium in COVID-19 patient airways.

Severe COVID-19 patient airways plugged by MUC5AC-containing mucus exhibit hyperplasia of goblet cells, and hypoplasia of multiciliated cells and club cells, as well as significantly reduced CC16 and MUC5B levels, and increased IL-13 levels https://bit.ly/2M2NcdO.

Longitudinal changes of liver function and hepatitis B reactivation in COVID-19 patients with pre-existing chronic hepatitis B virus infection.

AIM: With the current coronavirus disease (COVID-19) pandemic and high endemic levels of chronic hepatitis B virus (HBV) infection worldwide, it is urgent to investigate liver function changes of COVID-19 patients with chronic HBV infection, and how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in turn affects the course of chronic HBV infection. METHOD: We undertook a retrospective study based on 347 COVID-19 patients (21 vs. 326 with vs. without chronic HBV infection). With the propensity score matching (PSM) method, we yielded 20 and 51 matched patients for the HBV group and the non-HBV group, respectively. RESULTS: At the end of follow-up, all of these 71 patients achieved SARS-CoV-2 clearance (P = 0.1). During the follow-up, 30% versus 31.4% in the HBV group versus non-HBV group progressed to severe COVID-19 (P = 0.97). After PSM, the longitudinal changes of median values for liver biochemistries were not significantly different between the two groups. In the HBV group versus non-HBV group, 35% (7/20) versus 37.25% (19/51) (P = 0.86) had abnormal alanine aminotransferase at least once during hospitalization, 30% (6/20) versus 31.37% (16/51) had abnormal aspartate aminotransferase (P = 0.91), 40% (8/20) versus 37.25% (19/51) had abnormal γ-glutamyltransferase (P = 0.83), and 45% (9/20) versus 39.22% (20/51) had abnormal total bilirubin levels (P = 0.91). Moreover, three patients in the HBV group had hepatitis B reactivation. CONCLUSIONS: Liver dysfunction presented in COVID-19 patients with/without chronic HBV. Moreover, those COVID-19 patients co-infected with chronic HBV could have a risk of hepatitis B reactivation. It is necessary to monitor liver function of COVID-19 patients, as well as HBV-DNA levels for those co-infected with HBV during the whole disease course.

COVID-19: Abnormal liver function tests.

BACKGROUND & AIMS: Recent data on the coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has begun to shine light on the impact of the disease on the liver. But no studies to date have systematically described liver test abnormalities in patients with COVID-19. We evaluated the clinical characteristics of COVID-19 in patients with abnormal liver test results. METHODS: Clinical records and laboratory results were obtained from 417 patients with laboratory-confirmed COVID-19 who were admitted to the only referral hospital in Shenzhen, China from January 11 to February 21, 2020 and followed up to March 7, 2020. Information on clinical features of patients with abnormal liver tests were collected for analysis. RESULTS: Of 417 patients with COVID-19, 318 (76.3%) had abnormal liver test results and 90 (21.5%) had liver injury during hospitalization. The presence of abnormal liver tests became more pronounced during hospitalization within 2 weeks, with 49 (23.4%), 31 (14.8%), 24 (11.5%) and 51 (24.4%) patients having alanine aminotransferase, aspartate aminotransferase, total bilirubin and gamma-glutamyl transferase levels elevated to more than 3× the upper limit of normal, respectively. Patients with abnormal liver tests of hepatocellular type or mixed type at admission had higher odds of progressing to severe disease (odds ratios [ORs] 2.73; 95% CI 1.19-6.3, and 4.44, 95% CI 1.93-10.23, respectively). The use of lopinavir/ritonavir was also found to lead to increased odds of liver injury (OR from 4.44 to 5.03, both p <0.01). CONCLUSION: Patients with abnormal liver tests were at higher risk of progressing to severe disease. The detrimental effects on liver injury mainly related to certain medications used during hospitalization, which should be monitored and evaluated frequently. LAY SUMMARY: Data on liver tests in patients with COVID-19 are scarce. We observed a high prevalence of liver test abnormalities and liver injury in 417 patients with COVID-19 admitted to our referral center, and the prevalence increased substantially during hospitalization. The presence of abnormal liver tests and liver injury were associated with the progression to severe pneumonia. The detrimental effects on liver injury were related to certain medications used during hospitalization, which warrants frequent monitoring and evaluation for these patients.