Progress on the protective effect of heme oxygenase-1 in viral infection

Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the conversion of heme to CO, biliverdin, and iron, which together protect cells from oxidative and inflammatory damage and play an important role in maintaining cell homeostasis. In recent years, HO-1 has also been found to have antiviral biological effects, and the induced expression of HO-1 inhibits the replication of various viruses such as hepatitis C virus, hepatitis B virus, human immunodeficiency virus, dengue virus, ebolavirus, influenza A virus, Zika virus, severe acute respiratory syndrome coronavirus 2, human respiratory syncytial virus, hepatitis A virus and enterovirus 71. The inhibitory effect of HO-1 on these viruses involves three mechanisms, including direct inhibition of virus replication by HO-1 and its downstream products, enhancement of type I interferon responses in host cell, and attenuation of inflammatory damage caused by viral infection. This review focuses on the recent advances in the antiviral effect of HO-1 and its mechanism, which is expected to provide evidence for HO-1 as a potential target for antiviral therapy.

[Analysis of differences and influencing factors of liver injury associated with different strains of 2019-nCoV infection].

Objective: To analyze whether there are differences and related influencing factors in liver injury associated with different strains of 2019-nCoV/SARS-CoV-2 infection. Methods: Data of epidemiology, clinical symptoms, laboratory tests, and treatment outcomes of patients with COVID-19 infection confirmed with Alpha and Delta virus strain in Zhejiang Province were retrospectively collected. Statistical analysis was performed using independent samples t-test or Mann-Whitney U test, χ2 test or Fisher's exact test, and logistic regression analysis. Results: A total of 788 and 381 cases with Alpha and Delta virus strain were included. Vaccination ratio was 0% in Alpha and 85.30% in Delta group (P<0.001), The proportion of patients with fever (80.71% vs. 40.94%, P<0.001) was significantly higher in Alpha than Delta strain group. The proportion of critical ill patients was significantly higher in Delta group (9.90% vs. 1.57%, respectively, P<0.001). The virus negative conversion time was significantly longer in Delta than Alpha group (22 d vs. 11 d, P<0.001), but the incidence of liver injury was significantly higher in Alpha than Delta group (20.05% vs. 13.91%, P=0.011). Univariate analysis showed that Alpha virus strain infection, male sex, body mass index, chronic liver disease, fever, diarrhea, shortness of breath, severe/critical illness, elevated creatine kinase (CK), elevated international normalized ratio (INR) and an elevated neutrophil/lymphocyte ratio was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced. Multivariate analysis showed that shortness of breath [OR, 2.667 (CI: 1.389-5.122); P=0.003], increased CK [OR, 2.544 (CI: 1.414-4.576); P=0.002] and increased INR [OR, 1.721] (CI: 1.074-2.758); P=0.024] was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced [OR, 0.424 (CI: 0.254-0.709); P=0.001]. Conclusion: Although the virulence of the Delta is stronger than Alpha strain, most patients infected with Delta strain vaccinated against COVID-19 in Zhejiang province had milder clinical symptoms and a lower incidence and degree of liver injury. Notably, the infection risk even remains after vaccination; however, symptoms and the incidence of severe and critical illness can be significantly reduced.

The Course of Mild and Moderate COVID-19 Infections-The Unexpected Long-Lasting Challenge

Background. The course of disease in mild and moderate COVID-19 has many implications for mobile patients, such as the risk of spread of the infection, precautions taken, and investigations targeted at preventing transmission. Methods. Three hundred thirty-one adults were hospitalized from January 21 to February 22, 2020, and classified as severe (10%) or critical (4.8%) cases;1.5% died. Two hundred eighty-two (85.2%) mild or moderate cases were admitted to regular wards. Epidemiological, demographic, clinical, chest computed tomography (CT) scan, laboratory, treatment, and outcome data from patient records were analyzed retrospectively. Results. Patients were symptomatic for 9.82 +/- 5.75 (1-37) days. Pulmonary involvement was demonstrated on a chest CT scan in 97.9% of cases. It took 16.81 +/- 8.54 (3-49) days from the appearance of the first symptom until 274 patients tested virus-negative in naso- and oropharyngeal (NP) swabs, blood, urine, and stool, and 234 (83%) patients were asymptomatic for 9.09 +/- 7.82 (1-44) days. Subsequently, 131 patients were discharged. One hundred sixty-nine remained in the hospital;these patients tested virus-free and were clinically asymptomatic because of widespread persisting or increasing pulmonary infiltrates. Hospitalization took 16.24 +/- 7.57 (2-47) days;the time interval from the first symptom to discharge was 21.37 +/- 7.85 (3-52) days. Conclusions. With an asymptomatic phase, disease courses are unexpectedly long until the stage of virus negativity. NP swabs are not reliable in the later stages of COVID-19. Pneumonia outlasts virus-positive tests if sputum is not acquired. Imminent pulmonary fibrosis in high-risk groups demands follow-up examinations. Investigation of promising antiviral agents should heed the specific needs of mild and moderate COVID-19 patients.