The rapid change of mental health in college students after on-campus quarantine in Shanghai 2022 Covid lockdown (preprint)

Importance: Social isolation during outbreaks of epidemics always challenge psychological resilience profoundly. However, it still remains unclear how students’ mental health would be affected by strict o n-campus quarantine, which means students stayed at dormitories or on-campus for quarantine. We analyzed the data from one of the earliest universities releasing strict on-campus quarantine to prevent the Omicron spread-out in Shanghai, to evaluate the time course of the psychological resilience in the influence of an unexpected change in the living space in university students. Objectives: ： The campus was locked down on 9 th March. From 9 th to 23 rd , all students on campus were asked to stay in their dormitries, and teachers sent food supplies three times a day. From 24 th March to early April, students were gradually allowed to enter the campus for necessary activities. We quantify dynamic changes in depression severity during the campus locked down. Method: All participants were undergraduate or graduate students. The survey was released on 5th, April. All survey was dropped a public link on www.wjx.cn and administered from April 5th to 7th, 2022. Following the schedule of quarantine area, we assessed depressive symptoms in SJTU students from Period 1 (two weeks before 9 th , March), Period 2 (9 th to 23 rd , March), and Period 3 (24 th March to 5 th April). 274 students completed the online survey, and two incomplete data were excluded for further analysis. All these participants aged range from 18 to 25 years old and were quarantined in dormitories since 9 th March 2022. Findings: A remarkable increase in depression was observed in university students after stringent quarantine. The portion of students with depression started at 9.1% before quarantine and rapidly increased to 36.1% right after quarantine. No more increase in depressive symptoms was observed with time though quarantine was ongoing, which can be predicted by the food supplement satisfaction and the duration of physical fitness per day. Interestingly, the impact of a sudden change in living space on the psychological resilence was more evident in students who have a romatic relationship than singles.

Rapid increase in depression within the first month of the Shanghai Covid lockdown in 2022 (preprint)

In the global efforts to combat Covid-19, researchers have increasingly recognized the profound impacts of society lockdown on population mental health. However, the fine temporal evolution of negative psychological consequences induced by lockdowns remains poorly understood. Here we report a rapid and systematic increase in depression due to the Shanghai Covid lockdown in March 2022. Measured by Beck Depression Inventory-2, 10% of the participants experienced at least mild depression before the official citywide lockdown started, and two and four weeks later this number increased to 21% and 36 %, respectively. Regression analyses show that lockdown duration and physical restriction jointly contribute to worsening depression. Furthermore, the time of sleep and social communication during the lockdown are associated with the severity of depression symptoms. These results highlight the fast development of depression during lockdowns and call for special attention to early psychological interventions once a lockdown is initiated.

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity (preprint)

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.

Targeting heparan sulfate proteoglycan-assisted endocytosis as a COVID-19 therapeutic option (preprint)

Drugs capable of blocking the infectious cycle of the coronavirus SARS-CoV-2 are urgently needed to tackle the ongoing COVID-19 pandemic. To this end, the cell entry of SARS-CoV-2, initiated by the binding of the viral Spike (S) protein to human ACE2, has emerged as an attractive drug repurposing target. Here we use murine leukemia viruses pseudotyped with Spike from SARS-CoV or SARS-CoV-2 to demonstrate that ACE2-mediated coronavirus entry can be mitigated by heparin, a heparan sulfate-related glycan, or by genetic ablation of biosynthetic enzymes for the cell surface heparan sulfate proteoglycans (HSPGs). A drug repurposing screen targeting HSPG-dependent endocytosis identifies pharmacologically active endocytosis inhibitors that also abrogate coronavirus cell entry. Among them, Mitoxantrone (EC50=~10 nM) targets HSPGs directly, whereas Sunitinib and BNTX disrupt the actin network to impair HSPG-assisted viral entry. Gene expression profiling suggests potential combination regimens that optimally target HSPG-dependent viral entry. Altogether, our study establishes HSPGs as an assisting factor for ACE2 in endocytosis-mediated coronavirus entry and identifies drugs that can be repurposed to target this important stage in the viral life cycle.