Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing coronavirus disease 2019 pandemic. How SARS-CoV-2 regulates cellular responses to escape clearance by host cells is unknown. Autophagy is an intracellular lysosomal degradation pathway for the clearance of various cargoes, including viruses. Here, we systematically screened 28 viral proteins of SARS-CoV-2 and identified that ORF3a strongly inhibited autophagic flux by blocking the fusion of autophagosomes with lysosomes. ORF3a colocalized with lysosomes and interacted with VPS39, a component of the homotypic fusion and protein sorting (HOPS) complex. The ORF3a–VPS39 interaction prohibited the binding of HOPS with RAB7, which prevented the assembly of fusion machinery, leading to the accumulation of unfused autophagosomes. These results indicated the potential mechanism by which SARS-CoV-2 escapes degradation; that is, the virus interferes with autophagosome–lysosome fusion. Furthermore, our findings will facilitate strategies targeting autophagy for conferring potential protection against the spread of SARS-CoV-2.

In this study, we demonstrated an essential function of the hexosamine biosynthesis pathway (HBP)–associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in influenza A virus (IAV)–induced cytokine storm. O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, mediated IAV-induced cytokine production. Upon investigating the mechanisms driving this event, we determined that IAV induced OGT to bind to interferon regulatory factor–5 (IRF5), leading to O-GlcNAcylation of IRF5 on serine-430. O-GlcNAcylation of IRF5 is required for K63-linked ubiquitination of IRF5 and subsequent cytokine production. Analysis of clinical samples revealed that IRF5 is O-GlcNAcylated, and higher levels of proinflammatory cytokines correlated with higher levels of blood glucose in IAV-infected patients. We identified a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates IRF5 function during IAV infection, highlighting the importance of glucose metabolism in IAV-induced cytokine storm.

Background: We aim to investigate the profile of acute antibody response in COVID-19 patients, and provide proposals for the usage of antibody test in clinical practice. Methods: A multi-center cross-section study (285 patients) and a single-center follow-up study (63 patients) were performed to investigate the feature of acute antibody response to SARS-CoV-2. A cohort of 52 COVID-19 suspects and 64 close contacts were enrolled to evaluate the potentiality of the antibody test. Results: The positive rate for IgG reached 100% around 20 days after symptoms onset. The median day of seroconversion for both lgG and IgM was 13 days after symptoms onset. Seroconversion of IgM occurred at the same time, or earlier, or later than that of IgG. IgG levels in 100% patients (19/19) entered a platform within 6 days after seroconversion. The criteria of ‘IgG seroconversion’ and ‘> 4-fold increase in the IgG titers in sequential samples’ together diagnosed 82.9% (34/41) of the patients. Antibody test aided to confirm 4 patients with COVID-19 from 52 suspects who failed to be confirmed by RT-PCR and 7 patients from 148 close contacts with negative RT-PCR. Conclusion: IgM and IgG should be detected simultaneously at the early phase of infection. The serological diagnosis criterion of seroconversion or the ‘>; 4-fold increase in the IgG titer’ is suitable for a majority of COVID-19 patients. Serologic test is helpful for the diagnosis of SARS-CoV-2 infection in suspects and close contacts.

To date, it remains unclear if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection exacerbates liver injury in patients with chronic hepatitis B virus (HBV) infection. In this study, we present a retrospective study of 133 hospitalized confirmed mild coronavirus disease 2019 (COVID-19) cases, including 116 patients with COVID-19 with negative serum hepatitis B antigen and 17 HBV inactive carriers with COVID-19. We found that there were no significant differences for the discharge rate or duration of hospitalization between the two groups. However, inactive HBV carriers with SARS-CoV-2 co-infection are at a higher risk of abnormal liver function tests. The enhanced liver injury induced by SARS-CoV-2 and HBV co-infection was identified as the hepatocyte type rather than the cholangiocyte type. Moreover, the inflammatory response, including abnormal lactate dehydrogenase, D-dimer and interleukin-6 production, may contribute to this injury following SARS-CoV-2 co-infection. Collectively, SARS-CoV-2 and HBV co-infection exacerbates liver function of the patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic that poses a great threat to human health worldwide. As the humoral immune response plays essential roles in disease occurrence and development, understanding the dynamics and characteristics of virus-specific humoral immunity in SARS-CoV-2-infected patients is of great importance for controlling this disease. In this review, we summarize the characteristics of the humoral immune response after SARS-CoV-2 infection and further emphasize the potential applications and therapeutic prospects of SARS-CoV-2-specific humoral immunity and the critical role of this immunity in vaccine development. Notably, serological antibody testing based on the humoral immune response can guide public health measures and control strategies; however, it is not recommended for population surveys in areas with very low prevalence. Existing evidence suggests that asymptomatic individuals have a weaker immune response to SARS-CoV-2 infection, whereas SARS-CoV-2-infected children have a more effective humoral immune response than adults. The correlations between antibody (especially neutralizing antibody) titers and protection against SARS-CoV-2 reinfection should be further examined. In addition, the emergence of cross-reactions among different coronavirus antigens in the development of screening technology and the risk of antibody-dependent enhancement related to SARS-CoV-2 vaccination should be given further attention.