ABSTRACT
SARS-CoV-2 infection induces interferon-stimulated genes, one of which encodes Tetherin, a transmembrane protein inhibiting the release of various enveloped viruses from infected cells. Previous studies revealed that SARS-CoV encodes two Tetherin antagonists: the Spike protein (S) inducing lysosomal degradation of Tetherin, and ORF7a altering its glycosylation. SARS-CoV-2 ORF7a has also been shown to antagonize Tetherin. Therefore, we here investigated whether SARS-CoV-2 S is also a Tetherin antagonist and compared the abilities and mechanisms of S and ORF7a in counteracting Tetherin. SARS-CoV and SARS-CoV-2 S reduced Tetherin cell surface levels in a cell type-dependent manner, possibly related to the basal protein levels of Tetherin. In HEK293T cells, under conditions of high exogenous Tetherin expression, SARS-CoV-2 S and ORF7a reduced total Tetherin levels much more efficiently than the respective counterparts derived from SARS-CoV. Nevertheless, ORF7a from both strains was able to alter Tetherin glycosylation. The ability to decrease total protein levels of Tetherin was conserved among S proteins from different SARS-CoV-2 variants (D614G, Cluster 5, , {gamma}, {delta}, o). While SARS-CoV-2 S and ORF7a both colocalized with Tetherin, only ORF7a directly interacted with the restriction factor. Despite the presence of two Tetherin antagonists, however, SARS-CoV-2 replication in Caco-2 cells was further enhanced upon Tetherin knockout. Altogether, our data show that endogenous Tetherin restricts SARS-CoV-2 replication, and that the antiviral activity of Tetherin is partially counteracted by two viral antagonists with differential and complementary modes of action, S and ORF7a.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
Background Pre-hospitalisation, hospitalisation and post-hospitalisation factors may significantly affect depression, anxiety and post-traumatic growth (PTG) among COVID-19 survivors. Objective Our study investigated depression, anxiety and PTG and their correlates among COVID-19 survivors. Method A cross-sectional telephone survey recruited 199 COVID-19 patients (Mean age = 42.7;53.3% females) at six-month follow-up after hospital discharge in five Chinese cities (i.e. Wuhan, Shenzhen, Zhuhai, Dongguan and Nanning). Their demographic information, clinical records and experiences during (e.g. severity of covid-19 symptoms, treatment and exposure to other patients’ suffering) and after hospitalisation (e.g. perceived impact of covid-19, somatic symptoms after hospitalisation), and psychosocial factors (e.g. perceived discrimination, self-stigma, affiliate stigma, resilience and social support) were investigated. Depressive and anxiety symptoms were measured by the Patient Health Questionnaire (PHQ-9) and the Generalised anxiety disorder (GAD-7) scale, respectively. PTG was examined by the Post-traumatic Growth Inventory (PTGI) instrument. Results The proportion of depressive symptoms <5, ≥5 and <10, ≥10 were 76.9%, 12.0% and 11.1%, respectively. The proportion of anxiety symptoms <5, ≥5 and <10, ≥10 were 77.4%, 15.1% and 7.5%, respectively. Multivariate logistic regression showed that receiving mental health care services during hospitalisation, somatic symptoms after discharge, perceived affiliate stigma and perceived impact of being infected with COVID-19 were significantly and positively associated with probable depression. Significant correlates of probable anxiety also included permanent residents of the city, somatic symptoms after discharge, perceived impact of being infected with COVID-19 and self-stigma. Social support, self-stigma and receiving mental health care services during hospitalisation were positively associated with PTG. Conclusions: The results suggest that post-hospitalisation and psychosocial factors had relatively stronger associations with depression, anxiety and PTG than pre-hospitalisation and hospitalisation factors. Promoting social support and social inclusion may be useful strategies to improve the mental health of COVID-19 survivors. HIGHLIGHTS • Post-hospitalisation and psychosocial factors had relatively stronger associations with depression, anxiety and PTG than pre-hospitalisation and hospitalisation factors, promoting social support and social inclusion may be useful strategies to improve mental health of COVID-19 survivors.
ABSTRACT
Background: Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular features, which may be deteriorated in cancer patients.Methods: We retrospectively assessed 1,244 COVID-19 patients from February 1st to August 31st (140 cancer and 1104 non-cancer patients). Clinical data and laboratory findings were obtained and compared between cancer and non-cancer groups. Risk factors for in-hospital mortality were identified by multivariable COX regression models.Findings: The median age of cancer group was older than that in non-cancer patients [61 (57-67) vs. 56 (40-68), p < 0.001]. For cancer group, 56% were in severe and critical status, while the proportion was 10% for non-cancer group. Cancer patients had increased levels of leukocyte, neutrophil count and BUN (all p < 0.01), while lymphocyte count was significantly lower (p < 0.001). The most common solid tumor types were gastrointestinal cancer (26%), lung cancer (21%), breast and reproductive cancer (both 19%). There is a rising for cardiac biomarkers, including Pro-BNP, cTnI, MYO, CK-MB, and D-Dimer in COVID-19 cancer population, especially in deceased cancer subjects. The 30-day in hospital mortality in cancer group was dramatically raised than that in non-cancer group (12.9% vs. 4.0%, p<0.01). In multivariable COX regression models, fever, disease severity status, underlying diseases were risk factors for mortality. The Pro-BNP and D-Dimer levels were significantly increased in cancer subjects with cardiovascular disease.Interpretation: COVID-19 cancer patients relate to deteriorating conditions, increased risk of admission to intensive care units and in-hospital mortality. They display severely impaired myocardium, damaged heart function and imbalanced homeostasis of coagulation, which warrants more aggressive treatment. Funding: The current work was supported by the National Natural Science Foundation Project of China (Grant No. 81670304) and the Fundamental Research Funds for the Central Universities of China (NO.2042019kf0058).Declaration of Interests: All authors report no relationship or conflict of interest to disclose.Ethics Approval Statement: This study was approved by the National Health Commission of China and the institutional review board at Renmin Hospital of Wuhan University (Wuhan, China).