Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro.

The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC50 values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment.

COVID-19 pandemic impact on ocular trauma in a tertiary hospital.

AIM: To analyze the impact of the coronavirus disease-2019 (COVID-19) pandemic on the presentation and characteristics of patients hospitalized for ocular trauma in a tertiary hospital in China between 2019 and 2020. METHODS: A retrospective case study was designed to collect information on all cases of ocular trauma in a tertiary hospital from 2019 to 2020 and compare differences in inpatients' data (age, sex, admission vision acuity, type of diagnosis, hospital stays, mechanism of injury and location of injury). RESULTS: The total number of patients admitted to the Ophthalmology Department was 883 (mean 73.58±11.25 patients per month) in 2019 and 714 (59.50±17.92 patients per month) in 2020. The injury number of in work was also the most within the four types of location in this two year (42.36% in 2019, 43.84% in 2020). The mean hospital stays were 12.66d in 2019 and 10.81d in 2020. The highest incidence of ocular trauma was the middle-aged (41-65y) groups in 2019 and 2020. The most common cause of ocular trauma was sharp object in 2019 (47.34%) and 2020 (47.58%). The mechanical ocular trauma reaches 98.98% in 2019 and 99.72% in 2020. CONCLUSION: The number of patients with ocular trauma decreased in 2020, but middle-aged (41-65y) are still high incident groups. Mechanical ocular trauma remains the leading cause of hospitalization for ocular trauma patients and the proportion of patients injured at home increases. It is necessary to arouse social attention and the public's awareness of eye trauma protection should be strengthened during the pandemic.

The Epidemiological, Clinical Features and Outcomes of Imported Chinese COVID-19 Patients Following Inactivated Vaccines Injection.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination had been demonstrated as an effective way to reduce the risk of coronavirus disease 2019 (COVID-19), and only a few vaccines suffered from SARS-CoV-2 infection. However, limited data concerning the clinical features of these vaccines infected with SARS-CoV-2 can be identified. Methods: We retrospectively collected and analyzed epidemiological and clinical characteristics data of the imported COVID-19 cases who received Chinese inactivated vaccines abroad. Data were extracted from electronic medical records from a designated hospital in the Shaanxi Province of China between March 22 and May 17, 2021. Results: Totally, 46 confirmed SARS-CoV-2 infection patients were enrolled. The mean age was 40.5 years (range 20-61), 41 (89.1%) are male. Eighteen (39.1%) patients were from Pakistan. Fourteen (30.4%) patients had at least one comorbidity. Forty (87.0%) and 6 cases were fully vaccinated and partly vaccinated. The time interval between vaccination and infection was 88 days (IQR, 33-123), 31 (67.4%) and 15 (32.6%) were asymptomatic and symptomatic cases, respectively. Fever (3/46, 6.5%) was the most common symptom; however, none had a body temperature higher than 38.0°C, and no severe case was observed. Notably, the rate of SARS-CoV-2 shedding discontinuation at 7 days after hospitalization in asymptomatic cases was higher than symptomatic one (93.5% vs 40%, P < 0.0001). Conclusion: Individuals who received Chinese inactivated vaccines abroad remain to have the probability of being infected with SARS-CoV-2, but all the vaccines infected with SARS-CoV-2 were asymptomatic or had mild symptoms with favorable clinical outcomes.

A Case Series of Olfactory Dysfunction in Imported COVID-19 Patients: A 12-Month Follow-Up Study.

Objective: The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases. Methods: A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up. Results: Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases. Conclusions: Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.

Mental status of patients with chronic insomnia in China during COVID-19 epidemic.

AIM: To study the sleep and mental health of chronic insomnia patients in China during coronavirus disease in 2019 (COVID-19) epidemic. METHODS: A total of 764 patients with chronic insomnia were included in this study. From 17 January 2020 to 24 January 2020, insomnia, anxiety and physical symptoms were evaluated online, and they were followed up for 4 and 8 weeks. Main outcomes and indicators were assessed using the Pittsburgh Sleep Quality Index (PSQI) and each factor score, the General Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-15 (PHQ-15), respectively. In addition, insomnia, anxiety and physical symptoms were assessed at baseline and at the end of fourth and eighth weeks. Wilcoxon signed rank test was used to compare the changes in patients' scale scores at different time points. RESULTS: Among the 764 participants, there were 755 and 738 evaluators who completed the fourth and eighth weeks, respectively, and the questionnaire completion rates were 98.82% and 96.60%, respectively. Among them, there are 459 (60.0%) aged 41-60 years old, 546 (71.5%) women, 218 (28.5%) men and 313 (41%) college degrees. After 8 weeks of follow-up, the differences in sleep status, anxiety symptoms and physical symptoms were statistically significant. Among the factors of PSQI, there were differences in subjective sleep quality, sleep latency, sleep duration, sleep disturbance (disorder), sleep efficiency and daytime function. At 4 weeks of follow-up, there was a statistically significant difference in the use of hypnotic drugs; at 8 weeks of follow-up, there was no statistically significant difference in the use of hypnotic drugs. CONCLUSION: Under the influence of the COVID-19, the sleep status and anxiety of patients with chronic insomnia are affected by the epidemic.