Corrigendum: Prevalence and outcomes of pancreatic enzymes elevation in patients with COVID-19: a meta-analysis and systematic review.

[This corrects the article DOI: 10.3389/fpubh.2022.865855.].

Progress in research on SARS-CoV-2 vaccine and drugs

Since 2019, SARS-CoV-2 has caused a large number of infections and deaths worldwide. Vaccines and drugs treating SARS-CoV-2 have played an important role in pandemic control. After the infection peak, the society has returned to its normal status recently. However, with variants of the virus still being prevalent both in China and abroad, the research on vaccines and anti-SARS-CoV-2 drugs are still indispensable. This article summarized the characteristics and clinical trial results of inactivated vaccine, live attenuated vaccine, recombinant protein vaccine, viral vector vaccine, nucleic acid vaccine, virus-like particle vaccine, and reviewed the progress in research on anti-SARS-CoV-2 drugs both at home and abroad.

Excessive IL-10 and IL-18 trigger hemophagocytic lymphohistiocytosis-like hyperinflammation and enhanced myelopoiesis.

BACKGROUND: Hyperinflammation is a life-threatening condition associated with various clinical disorders characterized by excessive immune activation and tissue damage. Multiple cytokines promote the development of hyperinflammation; however, the contribution of IL-10 remains unclear despite emerging speculations for a pathological role. Clinical observations from hemophagocytic lymphohistiocytosis (HLH), a prototypical hyperinflammatory disease, suggest that IL-18 and IL-10 may collectively promote the onset of a hyperinflammatory state. OBJECTIVE: We aimed to investigate the collaborative roles of IL-10 and IL-18 in hyperinflammation. METHODS: A comprehensive plasma cytokine profile for 87 secondary HLH patients was first depicted and analyzed. We then investigated the systemic and cellular effects of coelevated IL-10 and IL-18 in a transgenic mouse model and cultured macrophages. Single-cell RNA sequencing was performed on the monocytes/macrophages isolated from secondary HLH patients to explore the clinical relevance of IL-10/IL-18-mediated cellular signatures. The therapeutic efficacy of IL-10 blockade was tested in HLH mouse models. RESULTS: Excessive circulating IL-10 and IL-18 triggered a lethal hyperinflammatory disease recapitulating HLH-like phenotypes in mice, driving peripheral lymphopenia and a striking shift toward enhanced myelopoiesis in the bone marrow. IL-10 and IL-18 polarized cultured macrophages to a distinct proinflammatory state with pronounced expression of myeloid cell-recruiting chemokines. Transcriptional characterization suggested the IL-10/IL-18-mediated cellular features were clinically relevant with HLH, showing enhanced granzyme expression and proteasome activation in macrophages. IL-10 blockade protected against the lethal disease in HLH mouse models. CONCLUSION: Coelevated IL-10 and IL-18 are sufficient to drive HLH-like hyperinflammatory syndrome, and blocking IL-10 is protective in HLH models.

Prevalence and Outcomes of Pancreatic Enzymes Elevation in Patients With COVID-19: A Meta-Analysis and Systematic Review.

Background: Although coronavirus disease 2019 (COVID-19) is considered to be a disease that mainly involves the respiratory system, an increasing number of studies have reported that COVID-19 patients had pancreatic enzymes (PE) elevation and even pancreatic injury. The study aims to determine the prevalence of PE elevation, and the relationship between elevated PE and prognosis in COVID-19 patients. Methods: A comprehensive literature search was conducted according to the PRISMA guideline in PubMed, Embase, Scopus, Web of Science, and Google Scholar for studies reporting PE elevation in patients with COVID-19 from 1st January 2020 to 24th November 2021. Results: A total of 13 studies (24,353 participants) were included in our review. The pooled prevalence of PE elevation in COVID-19 patients was 24% (18%-31%), the pooled odds ratio (OR) of mortality was 2.5 (1.7-3.6), the pooled OR of ICU admission was 4.4 (2.8-6.8), and the pooled OR of kidney injury, respiratory failure and liver injury were 3.5 (1.6-7.4), 2.0 (0.5-8.7), and 2.3 (1.4-3.9) respectively. In addition, the subgroup analysis revealed that although PE elevated to > 3 × upper normal limit (ULN) was significantly related to the mortality (OR = 4.4, 2.1-9.4), it seemed that mild elevation of PE to 1-3 ULN also had a considerable risk of mortality (OR = 2.3, 1.5-3.5). Conclusions: PE elevation was a common phenomenon in patients with COVID-19, and was associated with poor clinical outcomes. However, due to the limited numbers of included studies, the result of our study still needed to be validated. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=295630, identifier: CRD42021295630.

Identification of potential target endoribonuclease NSP15 inhibitors of SARS-COV-2 from natural products through high-throughput virtual screening and molecular dynamics simulation.

SARS-CoV-2 wreaks havoc around the world, triggering the COVID-19 pandemic. It has been confirmed that the endoribonuclease NSP15 is crucial to the viral replication, and thus identified as a potential drug target against COVID-19. The NSP15 protein was used as the target to conduct high-throughput virtual screening on 30,926 natural products from the NPASS database to identify potential NSP15 inhibitors. And 100 ns molecular dynamics simulations were performed on the NSP15 and NSP15-NPC198199 system. In all, 10 natural products with high docking scores with NSP15 protein were obtained, among which compound NPC198199 scored the highest. The analysis of the binding mode between NPC198199 and NSP15 found that NPC198199 would form H-bond interactions with multiple key residues at the catalytic site. Subsequently, a series of post-dynamics simulation analyses (including RMSD, RMSF, PCA, DCCM, RIN, binding free energy, and H-bond occupancy) were performed to further explore inhibitory mechanism of compound NPC198199 on NSP15 protein at the molecular level. The research strongly indicates that the 10 natural compounds screened can be used as potential inhibitors of NSP15, and provides valuable information for the subsequent drug discovery of anti-SARS-CoV-2. PRACTICAL APPLICATIONS: Natural products play an important role in the treatment of many difficult diseases. In this study, high-throughput virtual screening technology was used to screen the natural product database to obtain potential inhibitors against endoribonuclease NSP15. The binding mechanism between natural products and NSP15 was investigated at the molecular level by molecular dynamics technology so that it is expected to become candidate drugs for the treatment of SARS-CoV-2. We hope that our research can provide new clue to combat COVID-19 and overcome the epidemic situation as soon as possible.

Management Strategies for COVID-19 in the General Ward of Cardiovascular Surgery: Experience From a Single Tertiary Hospital in China.

Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease that threatens global health. During the pandemic period of COVID-19, the task for prevention in the general ward of cardiovascular surgery is fairly arduous. The present study intends to summarize our experience with infection control, including ward setting, admission procedures, personnel management, health education, and so on, to provide references for clinical management.

The post-traumatic stress disorder impact of the COVID-19 pandemic

On March 11, the World Health Organization (WHO) announced that the novel coronavirus disease 2019 (COVID-19) outbreak had become a global pandemic. The symptoms of COVID-19 are well known, and a range of treatments have been used to save lives. However, those who have recovered from COVID-19 may be struggling to mentally cope with what they have experienced physically. They may even develop signs and symptoms of an acute stress response, or post-traumatic stress disorder (PTSD). A question we face in the coming months is how to help survivors of severe COVID-19 recover. Although patients with confirmed or suspected cases of COVID-19, health care workers, and other people are showing signs of psychological problems related to the disease, survivors of previous diseases, health care workers, and front-line employees face a higher risk of infection and are more likely to be depressed, anxious, or even diagnosed with PTSD. Exposure, fear, isolation, loss of income, reduced autonomy, and the inability of health care professionals to cure coronavirus infections contribute to this increased stress. As everyone is vulnerable to COVID-19, providing mental health support will help people maintain their mental health and return to a heathy life more quickly. The objective of this paper is to explore the research progress of post-traumatic stress disorder (PTSD) related to COVID-19. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

A snapshot of public knowledge of novel coronavirus disease 2019: a web-based national survey.

BACKGROUND: Although the number of existing cases of coronavirus disease 2019 (COVID-19) in China has been decreasing since late February 2020, the number of confirmed cases abroad is surging. Improving public knowledge of COVID-19 is critical to controlling the pandemic. This study aimed to determine China's public knowledge of COVID-19 and the attitudes towards control measures. METHODS: A cross-sectional study was conducted over 48 h from 22:30 29 February 2020 to 22:30 2 March 2020 based on a self-administered web-based questionnaire. The survey was conducted on the WeChat network. Exponential non-discriminative snowball sampling was applied. The questionnaire was voluntarily completed by WeChat users. The questionnaire covered basic demographic information, public knowledge of the epidemiological and clinical characteristics of COVID-19, psychological state, and attitudes towards the overall control measures. The primary outcome was the China's public knowledge of COVID-19 and the attitudes towards control measures and secondary outcome was the psychological state of the public during this pandemic. RESULTS: The study included 10,905 participants and 10,399 valid questionnaires were included for analysis. Participants with tertiary education, younger participants and healthcare workers had better overall knowledge than other participants (all P < 0.05). Approximately 91.9% of the participants believed in person-to-person transmission and 39.1% believed in animal-to-person transmission. No significant correlation between anxiety and the number of regional existing confirmed cases was found, while participants in Hubei were more anxious than those in other regions. In general, 74.1% of the participants acknowledged the effectiveness of the overall control measures, and the percentage of participants with agreement with the overall control measures was negatively correlated with the number of regional existing confirmed cases (r = - 0.492, P = 0.007). CONCLUSIONS: In conclusion, the survey revealed that the Chinese public had overall good knowledge of COVID-19 except for those indeterminate knowledges. With dynamic changes in the global pandemic situation and more research, further studies should be conducted to explore changes in public knowledge and attitudes towards COVID-19 in the future. The media could be used in a strict and regular manner to publicize knowledge of such pandemics to halt their spread.

Emergency reconstruction of large general hospital under the perspective of new COVID-19 prevention and control.

OBJECTIVE: To summarize the successful experience of timely crisis management, correct measures, and successful display of the hospital image in the First Affiliated Hospital of Zhejiang University (FAHZU), to improve the ability of emergency response. METHODS: The FAHZU, as the earliest designated hospital, accomplished the transformation from general hospital to infectious disease hospital under the guiding ideology of centralized patients, centralized experts, centralized resources, and centralized treatment with measures to transfer the Zhijiang campus hospitalized patients quickly, complete the space layout, create diagnosis and treatment space, streamline logistics, and transform logistics facilities within 48 h. As of 5 March, the hospital had admitted 104 patients. RESULTS: Of the severe cases in Zhejiang province 95% underwent centralized treatment with the goal of zero deaths for severely ill patients, zero misdiagnoses for infected patients, and zero infections for medical staff, and this served as a reference for large medical institutions regarding how to manage such a public health emergency. CONCLUSION: The successful cases of FAHZU provided a valuable experience for large medical institutions on how to address public health emergencies and how to carry out diagnosis and treatment and streamline the layout and related facilities in emergency reconstruction.

CT features and outcomes of newly developed pulmonary lesions in patients with Coronavirus Disease 2019 (COVID-19).

Background: In patients with coronavirus disease 2019 (COVID-19) pneumonia, whether new pulmonary lesions will continue to develop after treatment was unknown. This study aimed to determine whether new pulmonary lesions will develop after treatment in patients with COVID-19 pneumonia, and investigate their CT features and outcomes. Methods: This retrospective study included 56 consecutive patients with confirmed COVID-19 pneumonia from January 20 to March 5, 2020. Their initial and follow-up CT images and clinical data were reviewed. The CT manifestations of primary and newly developed pulmonary lesions and their changes after treatment were mainly evaluated. Results: Among the 56 patients (mean age: 48±15 years, 35 men) with COVID-19 pneumonia, 42 (75.0%) patients developed new pulmonary lesions during treatment. All new lesions developed before the nucleic acid test turned negative. Patients with new lesions were more likely to have lymphopenia (P=0.041) or increased C-reactive protein (CRP) levels (P<0.001) than those without new lesions. Of the 42 patients, 30 (71.4%) patients developed new lesions once, and 12 (28.6%) twice or thrice, which usually appeared when primary lesions were progressing (37, 88.1%) and 1-15 days after treatment. The newly developed lesions were usually multiple (38, 90.5%), distributed in the previously involved (39, 92.9%) or uninvolved (27, 64.3%) lobes, and manifested as ground-glass opacities (GGOs) with consolidation (23, 54.8%) or pure GGOs (19, 45.2%). After their occurrence, the new lesions in most patients (32, 76.2%) showed direct absorption, whereas those in some patients (10, 23.8%) progressed before absorption. Conclusion: During treatment, most patients with COVID-19 pneumonia will develop new pulmonary lesions, which usually manifest as multiple GGOs distributed around the primary lesions or in previously uninvolved lobes, and are subsequently absorbed directly.

SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19.

BACKGROUND: Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk. Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear. METHODS: Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients. We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo. RESULTS: We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count. Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients. Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming. SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo. Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation. SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates. Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation. CONCLUSIONS: Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2. SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients.

Epidemiology and Clinical Characteristics of COVID-19.

Since December 2019, there has been an outbreak of a novel coronavirus (COVID-19) infection in Wuhan, China. Meanwhile, the outbreak also drew attention and concern from the World Health Organization (WHO). COVID-19 is another human infectious disease caused by coronavirus. The transmission of COVID-19 is potent and the infection rate is fast. Since there is no specific drug for COVID-19, the treatment is mainly symptomatic supportive therapy. In addition, it should be pointed out that patients with severe illness need more aggressive treatment and meticulous care. Recently, accurate RNA detection has been decisive for the diagnosis of COVID-19. The development of highly sensitive RT-PCR has facilitated epidemiological studies that provide insight into the prevalence, seasonality, clinical manifestations and course of COVID-19 infection. In this review, we summarize the epidemiology and characteristics of COVID-19.