Cytoplasmic domain and enzymatic activity of ACE2 are not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells.

The recent COVID-19 pandemic poses a global health emergency. Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2 (ACE2). Here, by using lentivirus based pseudotypes bearing spike protein, we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis, and phosphoinositides played essential roles during this process. In addition, we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry. Finally, we showed that the current predominant Delta variant, although with high infectivity and high syncytium formation, also entered cells through clathrin-mediated endocytosis. These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.

Pathogenesis process and vaccine-design strategies for severe acute respiratory syndromes Coronavirus 2

In December 2019, infection by a novel coronavirus that was subsequently named "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-Z) by the International Committee for Taxonomy of virus (ICTV) broke out in Wuhan (Hubei Province, China). Severe acute respiratory syndromes coronavirus 2 (SARS-CoV-Z) causing human infections broke out in China. Clinical manifestation mainly presents with fever, cough and dyspnea, whereas some cases may can progress to acute respiratory distress syndrome. The pathogenesis process of SARS-CoV-Z-infected includes cross-species infection and host-cells infection, as well as interactions between SARS-CoV-Z and the host immune system. It is key to know about the pathogenesis process of SARS-CoV-Z for new medicine research and vaccine design. This review focuses on the summary of the pathogenesis process and vaccine design strategies forof SARS-CoV-Z.

Impact of COVID-19 Pandemic on Mechanical Reperfusion in ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Multicenter Retrospective Study From a Non-epicenter Region.

Objective: The COVID-19 pandemic placed heavy burdens on emergency care and posed severe challenges to ST-segment-elevation myocardial infarction (STEMI) treatment. This study aimed to investigate the impact of COVID-19 pandemic on mechanical reperfusion characteristics in STEMI undergoing primary percutaneous coronary intervention (PPCI) in a non-epicenter region. Methods: STEMI cases undergoing PPCI from January 23 to March 29 between 2019 and 2020 were retrospectively compared. PPCI parameters mainly included total ischemic time (TIT), the period from symptom onset to first medical contact (S-to-FMC), the period from FMC to wire (FMC-to-W) and the period from door to wire (D-to-W). Furthermore, the association of COVID-19 pandemic with delayed PPCI risk was further analyzed. Results: A total of 14 PPCI centers were included, with 100 and 220 STEMI cases undergoing PPCI in 2020 and 2019, respectively. As compared to 2019, significant prolongations occurred in reperfusion procedures (P < 0.001) including TIT (420 vs. 264 min), S-to-FMC (5 vs. 3 h), FMC-to-W (113 vs. 95 min) and D-to-W (83 vs. 65 min). Consistently, delayed reperfusion surged including TIT ≥ 12 h (22.0 vs.3.6%), FMC-to-W ≥ 120 min (34.0 vs. 6.8%) and D-to-W ≥ 90 min (19.0 vs. 4.1%). During the pandemic, the patients with FMC-to-W ≥ 120 min had longer durations in FMC to ECG completed (6 vs. 5 min, P = 0.007), FMC to DAPT (24 vs. 21 min, P = 0.001), catheter arrival to wire (54 vs. 43 min, P < 0.001) and D-to-W (91 vs. 78 min, P < 0.001). The pandemic was significantly associated with high risk of delayed PPCI (OR = 7.040, 95% CI 3.610-13.729, P < 0.001). Conclusions: Even in a non-epicenter region, the risk of delayed STEMI reperfusion significantly increased due to cumulative impact of multiple procedures prolongation.

Stress and psychological impact of the COVID-19 outbreak on the healthcare staff at the fever clinic of a tertiary general hospital in Beijing: a cross-sectional study.

BACKGROUND: It is important to maintain the psychological well-being of front-line healthcare staff during the coronavirus disease 2019 (COVID-19) pandemic. AIMS: To examine COVID-19-related stress and its immediate psychological impact on healthcare staff. METHOD: All healthcare staff working in the fever clinic, from 20 January 2020 to 26 March 2020, of a tertiary general hospital were enrolled. Stress management procedures were in place to alleviate concerns about the respondents' own health and the health of their families, to help them adjust their work and to provide psychological support via a hotline. Qualitative interviews were undertaken and the Sources of Distress and the Impact of Event Scale-Revised (IES-R) were administered. RESULTS: Among the 102 participants (25 males; median age 30 years, interquartile range (IQR) = 27-36), the median IES-R total score was 3 (IQR = 0-8), and 6 participants (6.0%) scored above the cut-off on the IES-R (≥20). Safety and security were acceptable or better for 92 (90.2%) participants. The top four sources of distress were worry about the health of one's family/others at 0.88 (IQR = 0.25-1.25), worry about the virus spread at 0.50 (IQR = 0.00-1.00), worry about changes in work at 0.50 (IQR = 0.00-1.00) and worry about one's own health at 0.25 (IQR = 0.25-0.75). There was a moderate correlation between the IES-R score and the Sources of Distress score (rho = 0.501, P = 0.001). CONCLUSIONS: The stress levels of healthcare staff in the fever clinic during the COVID-19 epidemic were not elevated. Physio-psychosocial interventions, including fulfilment of basic needs, activation of self-efficacy and psychological support, are helpful and worth recommending in fighting COVID-19.

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) may be safe for COVID-19 patients.

BACKGROUND: To investigate the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARBs) administration to hypertension patients with the coronavirus disease 2019 (COVID-19) induced pneumonia. METHODS: We recorded the recovery status of 67 inpatients with hypertension and COVID-19 induced pneumonia in the Raytheon Mountain Hospital in Wuhan during February 12, 2020 and March 30, 2020. Patients treated with ACEI or ARBs were categorized in group A (n = 22), while patients who were not administered either ACEI or ARBs were categorized into group B (n = 45). We did a comparative analysis of various parameters such as the pneumonia progression, length-of-stay in the hospital, and the level of alanine aminotransferase (ALT), serum creatinine (Cr), and creatine kinase (CK) between the day when these patients were admitted to the hospital and the day when the treatment ended. RESULTS: These 67 hypertension cases counted for 33.17% of the total COVID-19 patients. There was no significant difference in the usage of drug treatment of COVID-19 between groups A and B (p > 0.05). During the treatment, 1 case in group A and 3 cases in group B progressed from mild pneumonia into severe pneumonia. Eventually, all patients were cured and discharged after treatment, and no recurrence of COVID-2019 induced pneumonia occurred after the discharge. The length of stays was shorter in group A as compared with group B, but there was no significant difference (p > 0.05). There was also no significant difference in other general parameters between the patients of the groups A and B on the day of admission to the hospital (p > 0.05). The ALT, CK, and Cr levels did not significantly differ between groups A and B on the day of admission and the day of discharge (p > 0.05). CONCLUSIONS: To treat the hypertension patients with COVID-19 caused pneumonia, anti-hypertensive drugs (ACEs and ARBs) may be used according to the relative guidelines. The treatment regimen with these drugs does not need to be altered for the COVID-19 patients.

Clinical Characteristics and Eosinophils in Young SARS-CoV-2-Positive Chinese Travelers Returning to Shanghai.

Background: The COVID-19 outbreak, which was first reported in Wuhan, China, in December 2019, began to spread throughout the world, and now involves over 200 countries. Methods: A total of 37 overseas young and middle-aged people, who tested as SARS-CoV-2 positive upon their return to Shanghai, were enrolled for an analysis of their clinical symptoms, blood routine indexes, and lung CT images. Results: The clinical symptoms were characterized by fever (51.4%), dry cough (13.5%), expectoration (27.0%), hypodynamia (21.6%), pharyngalia (10.8%), pharynoxerosis (8.1%), rhinobyon (13.5%), rhinorrhea (8.1%), muscular soreness (16.2%), and diarrhea (2.7%). In 16.2% of cases, no symptoms were reported. Fever was the most common symptom (51.40%). The pneumonic changes referred to the latticed ground glass imaging and similar white lung imaging accompanied by consolidated shadows. The rate of pneumonia was high (81.10%). We found that the exclusive percent of eosinophils was abnormally low. By analyzing the correlation of eosinophils, fever, and pneumonia, we found that the percentage of eosinophils was low in the COVID-19 patients afflicted with fever or pneumonia (P < 0.01). Additionally, pneumonia and fever were negatively correlated with the percentage of eosinophils and eosinophils/neutrophils ratio (P < 0.01, respectively), but not associated with pneumonia severity (P > 0.05). Fever was not correlated with pneumonia (P > 0.05). Conclusion: A low percentage of eosinophils may be considered as a biomarker of pneumonia of COVID-19, but not as a biomarker of pneumonia severity.

Optimization of the Working Procedure of Radionuclide Treatment Ward during 2019-nCoV Prevention

Since the end of 2019, Novel Coronavirus Pneumonia (2019-nCov) has appeared and spread rapidly in the world. During the epidemic period, how to control the infection in the working procedure of radionuclide treatment ward is a clinical protection problem that must be solved. If a novel coronavirus pneumonia (NCP) is suspected or diagnosed, the most important thing is to isolate the relevant doctors and patients on the spot in time and initiate relevant NCP clinical emergency plans and procedures. When the radioactive infected medical waste is disinfected, it should be treated as radioactive waste. Therefore, it is necessary to optimize the working procedures of radionuclide therapy ward.

Cardiovascular Implications of the COVID-19 Pandemic: A Global Perspective

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased use of health care services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.

SARS-CoV-2 infection-induced immune responses: Friends or foes?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that belongs to the ß-genus, causing the outbreak of coronavirus disease 19 (COVID-19). SARS-CoV-2 infection can stimulate a pronounced immune response in the host, which embodies in the decrease of lymphocytes and aberrant increase of cytokines in COVID-19 patients. SARS-CoV-2 RNA and proteins interact with various pattern recognition receptors that switch on antiviral immune responses to regulate viral replication and spreading within the host in vivo. However, overactive and impaired immune responses also cause immune damage and subsequent tissue inflammation. This article focuses on the dual roles of immune system during SARS-CoV-2 infection, providing a theoretical basic for identifying therapeutic targets in a situation with an unfavourable immune reaction.