Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection.

Coronavirus disease 2019 is a respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence on the pathogenesis of SARS-CoV-2 is accumulating rapidly. In addition to structural proteins such as Spike and Envelope, the functional roles of non-structural and accessory proteins in regulating viral life cycle and host immune responses remain to be understood. Here, we show that open reading frame 8 (ORF8) acts as messenger for inter-cellular communication between alveolar epithelial cells and macrophages during SARS-CoV-2 infection. Mechanistically, ORF8 is a secretory protein that can be secreted by infected epithelial cells via both conventional and unconventional secretory pathways. Conventionally secreted ORF8 is glycosylated and loses the ability to recognize interleukin 17 receptor A of macrophages, possibly due to the steric hindrance imposed by N-glycosylation at Asn78. However, unconventionally secreted ORF8 does not undergo glycosylation without experiencing the ER-Golgi trafficking, thereby activating the downstream NF-κB signaling pathway and facilitating a burst of cytokine release. Furthermore, we show that ORF8 deletion in SARS-CoV-2 attenuates inflammation and yields less lung lesions in hamsters. Our data collectively highlights a role of ORF8 protein in the development of cytokine storms during SARS-CoV-2 infection.

Functional studies of HLA and its role in SARS-CoV-2: Stimulating T cell response and vaccine development.

In the biological immune process, the major histocompatibility complex (MHC) plays an indispensable role in the expression of HLA molecules in the human body when viral infection activates the T-cell response to remove the virus. Since the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2019, how to address and prevent SARS-CoV-2 has become a common problem facing all mankind. The T-cell immune response activated by MHC peptides is a way to construct a defense line and reduce the transmission and harm of the virus. Presentation of SARS-CoV-2 antigen is associated with different types of HLA phenotypes, and different HLA phenotypes induce different immune responses. The prediction of SARS-CoV-2 mutation information and the design of vaccines based on HLAs can effectively activate autoimmunity and cope with virus mutations, which can provide some references for the prevention and treatment of SARS-CoV-2.

Implication of COVID-19 on the mental health of Egyptian dermatologists: A cross-sectional study.

BACKGROUND: Major epidemic outbreaks create an increased demand for healthcare workers (HCWs) and pose increased health risk and psychological distress to them as well. AIM: The aim of this cross sectional study was to find out the prevalence of depression, anxiety and stress among Egyptian dermatologists and their possible predictor factors. PATIENTS/METHODS: A cross sectional study was designed and data were collected using structured self-administered online depression, anxiety, and stress scale (DASS-21). RESULTS: The depression scale of DASS was 18.98 ± 9.56 among which 38% of dermatologists had either severe or extremely severe depression and 34.2% complained of moderate depression. Meanwhile, the anxiety scale was 12.92 ± 7.75 and 35.4 % of surveyed dermatologists had either severe or extremely severe anxiety. Thirty three percent of dermatologists were normal on stress score. Female dermatologists possessed more significant depression and stress than males (19.70 ± 9.71 vs. 16.62 ± 8.68, p = 0.003; 21.42 ± 9.53 vs. 17.40 ± 8.49, p <0.001 respectively). On the contrary, male dermatologists expressed more anxiety than female dermatologists however this was not statistically significant (13.26 ± 7.99 vs. 12.82 ± 7.69, p = 0.625). CONCLUSION: To our knowledge, this is the first study to explore the differential impacts of the COVID-19 pandemic on Egyptian dermatologists. Mental health care and support are of extreme importance to physicians mid this pandemic.