Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2.

Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 µM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 µM (EC50). In comparison with vehicle-treated animals, rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals. At necropsy, nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nelfinavir and control groups, showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever time by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients, together with its well-established good safety profile in almost all ages and during pregnancy, indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.

Burnout in nurses during the COVID-19 pandemic in China: New challenges for public health.

During the COVID-19 pandemic, frontline nurses have faced extraordinary personal and professional challenges. These challenges have had mental health consequences, and concerning reports of burnout have emerged globally. We conducted a cross-sectional survey at a designated COVID-19 hospital in Shanghai at the peak of the pandemic, i.e. about 2 months after the onset of the outbreak from February to April 2020. Findings revealed burnout in 6.85% of nurses. Of 336 respondents, 87 (25.89%) had a high level of emotional exhaustion, 61 (18.15%) had a high level of depersonalization, and 100 (29.76%) had a low level of personal accomplishment. Burnout can be prevented by offering more support from families and supervisors, paying attention to health monitoring and personal protection, and creating a rational human resource allocation and shift management system. Specific training on infection control and self-protection, mental health guidance, and stress coping techniques must be implemented. As the current health crisis ultimately abates, moving the focus from mental health issues to public health issues, more attention and support at the national and organizational levels are needed to reduce occupational discrimination, nurse autonomy and status need to be promoted, and public health emergency teams need to be created. A positive and fair working environment is essential to effective healthcare delivery.

Epidemiology and clinical course of COVID-19 in Shanghai, China.

Background: Novel coronavirus pneumonia (COVID-19) is prevalent around the world. We aimed to describe epidemiological features and clinical course in Shanghai. Methods: We retrospectively analysed 325 cases admitted at Shanghai Public Health Clinical Center, between January 20 and February 29, 2020. Results: 47.4% (154/325) had visited Wuhan within 2 weeks of illness onset. 57.2% occurred in 67 clusters; 40% were situated within 53 family clusters. 83.7% developed fever during the disease course. Median times from onset to first medical care, hospitalization and negative detection of nucleic acid by nasopharyngeal swab were 1, 4 and 8 days. Patients with mild disease using glucocorticoid tended to have longer viral shedding in blood and feces. At admission, 69.8% presented with lymphopenia and 38.8% had elevated D-dimers. Pneumonia was identified in 97.5% (314/322) of cases by chest CT scan. Severe-critical patients were 8% with a median time from onset to critical disease of 10.5 days. Half required oxygen therapy and 7.1% high-flow nasal oxygen. The case fatality rate was 0.92% with median time from onset to death of 16 days. Conclusion: COVID-19 cases in Shanghai were imported. Rapid identification, and effective control measures helped to contain the outbreak and prevent community transmission.

A simple algorithm helps early identification of SARS-CoV-2 infection patients with severe progression tendency.

OBJECTIVES: We aimed to develop a simple algorithm to help early identification of SARS-CoV-2 infection patients with severe progression tendency. METHODS: The univariable and multivariable analysis were computed to identify the independent predictors of COVID-19 progression. The prediction model was established in a retrospective training set of 322 COVID-19 patients and was re-evaluated in a prospective validation set of 317 COVID-19 patients. RESULTS: The multivariable analysis identified age (OR = 1.061, p = 0.028), lactate dehydrogenase (LDH) (OR = 1.006, p = 0.037), and CD4 count (OR = 0.993, p = 0.006) as the independent predictors of COVID-19 progression. Consequently, the age-LDH-CD4 algorithm was derived as (age × LDH)/CD4 count. In the training set, the area under the ROC curve (AUROC) of age-LDH-CD4 model was significantly higher than that of single CD4 count, LDH, or age (0.92, 0.85, 0.80, and 0.75, respectively). In the prospective validation set, the AUROC of age-LDH-CD4 model was also significantly higher than that of single CD4 count, LDH, or age (0.92, 0.75, 0.81, and 0.82, respectively). The age-LDH-CD4 ≥ 82 has high sensitive (81%) and specific (93%) for the early identification of COVID-19 patients with severe progression tendency. CONCLUSIONS: The age-LDH-CD4 model is a simple algorithm for early identifying patients with severe progression tendency following SARS-CoV-2 infection, and warrants further validation.