Network pharmacology- and molecular simulation-based exploration of therapeutic targets and mechanisms of heparin for the treatment of sepsis/COVID-19.

Critically infected patients with COVID-19 (coronavirus disease 2019) are prone to develop sepsis-related coagulopathy as a result of a robust immune response. The mechanism underlying the relationship between sepsis and COVID-19 is largely unknown. LMWH (low molecular weight heparin) exhibits both anti-inflammatory and anti-coagulating properties that result in a better prognosis of severely ill patients with COVID-19 co-associated with sepsis-induced coagulopathy or with a higher D-dimer value. Heparin-associated molecular targets and their mechanism of action in sepsis/COVID-19 are not well understood. In this work, we characterize the pharmacological targets, biological functions and therapeutic actions of heparin in sepsis/COVID-19 from the perspective of network pharmacology. A total of 38 potential targets for heparin action against sepsis/COVID-19 and 8 core pharmacological targets were identified, including IL6, KNG1, CXCL8, ALB, VEGFA, F2, IL10 and TNF. Moreover, enrichment analysis showed that heparin could help in treating sepsis/COVID-19 through immunomodulation, inhibition of the inflammatory response, regulation of angiogenesis and antiviral activity. The pharmacological effects of heparin against these targets were further confirmed by molecular docking and simulation analysis, suggesting that heparin exerts effective binding capacity by targeting the essential residues in sepsis/COVID-19. Prospective clinical practice evaluations may consider the use of these key prognostic indicators for the treatment of sepsis/COVID-19.Communicated by Ramaswamy H. Sarma.

Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.

Chest CT Images for COVID-19: Radiologists and Computer-Based Detection.

BACKGROUND: Characteristic chest computed tomography (CT) manifestation of 2019 novel coronavirus (COVID-19) was added as a diagnostic criterion in the Chinese National COVID-19 management guideline. Whether the characteristic findings of Chest CT could differentiate confirmed COVID-19 cases from other positive nucleic acid test (NAT)-negative patients has not been rigorously evaluated. PURPOSE: We aim to test whether chest CT manifestation of 2019 novel coronavirus (COVID-19) can be differentiated by a radiologist or a computer-based CT image analysis system. METHODS: We conducted a retrospective case-control study that included 52 laboratory-confirmed COVID-19 patients and 80 non-COVID-19 viral pneumonia patients between 20 December, 2019 and 10 February, 2020. The chest CT images were evaluated by radiologists in a double blind fashion. A computer-based image analysis system (uAI System, Lianying Inc., Shanghai, China) detected the lesions in 18 lung segments defined by Boyden classification system and calculated the infected volume in each segment. The number and volume of lesions detected by radiologist and computer system was compared with Chi-square test or Mann-Whitney U test as appropriate. RESULTS: The main CT manifestations of COVID-19 were multi-lobar/segmental peripheral ground-glass opacities and patchy air space infiltrates. The case and control groups were similar in demographics, comorbidity, and clinical manifestations. There was no significant difference in eight radiologist identified CT image features between the two groups of patients. There was also no difference in the absolute and relative volume of infected regions in each lung segment. CONCLUSION: We documented the non-differentiating nature of initial chest CT image between COVID-19 and other viral pneumonia with suspected symptoms. Our results do not support CT findings replacing microbiological diagnosis as a critical criterion for COVID-19 diagnosis. Our findings may prompt re-evaluation of isolated patients without laboratory confirmation.

Assessment of Coronavirus Disease 2019 Community Containment Strategies in Shenzhen, China.

Importance: A new outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 in Wuhan, China, is spreading rapidly around the globe. Limited information on control in community settings is available. Objective: To detail measures enacted within a community to prevent the spread of coronavirus disease 2019 (COVID-19) and to evaluate the spread of COVID-19 associated with implementation of the program. Design, Setting, and Participants: This case series study details the implementation of prevention measures in a specific community setting among community-dwelling individuals exposed to or at risk of COVID-19 in Haiyu, Shenzhen, China, from January 23 to April 10, 2020. Exposures: Community containment strategies for tracking, quarantine, and management were strictly, cooperatively, and effectively implemented by a team that included a general practitioner, a community manager, and public safety bureau officials. Main Outcomes and Measures: Number of locally acquired cases with indirect links to confirmed COVID-19 cases. Diagnosis with COVID-19 was confirmed when throat swab samples tested positive for severe acute respiratory syndrome coronavirus 2 on reverse transcription-polymerase chain reaction. Results: Approximately 34 686 individuals live in Haiyu, including 2382 residents aged 65 years or older. Seven individuals with COVID-19 acquired outside the community (age, 20-70 years; 3 [42%] women) were moved from quarantine to a hospital for standard isolation treatment. A total of 20 people who were asymptomatic and who had had direct contact with these individuals were closely observed by health care workers at a nearby hotel. Additionally, 800 individuals considered to be at higher risk were moved from quarantine to home isolation for 14 days. There were no locally acquired cases of COVID-19 with indirect links reported in the Haiyu community from the time that the study began on January 23, 2020, to April 10, 2020. Conclusions and Relevance: These findings suggest that cooperation among the authorities of multiple sectors allowed for the implementation of preventive measures that were associated with limited community transmission.