[Clinical features of 23 neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2]. / æ–°ç”Ÿå„¿æ–°åž‹å† çŠ¶ç— æ¯’Omicronå˜å¼‚æ ªæ„ŸæŸ“23例临床分析.

OBJECTIVES: To summarize the clinical features of neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The medical data of 23 neonates with Omicron variant of SARS-CoV-2 infection admitted to the City North Campus of Urumqi First People's Hospital from October to December 2022 were retrospectively reviewed. RESULTS: All 23 infants had a history of exposure to confirmed caregivers with SARS-CoV-2 infection after birth, and none of them was vertically transmitted. Clinical classification: 5 cases of asymptomatic infection, 18 cases of mild infection, and no cases of moderate, severe, or critically ill. The first symptoms were fever in 13 cases, cough in 3 cases, nasal congestion in 1 case, and diarrhea in 1 case. Blood white blood cell counts decreased in 2 cases, and C-reactive protein increased in 1 case. Seven infants underwent chest X-ray examination due to cough or shortness of breath, and one of which showed focal exudative changes, while the rest showed no abnormal changes. All infants were discharged after symptomatic treatment and the median hospital stay was 6 days. The duration of nucleic acid positivity of SARS-CoV-2 was negatively correlated with N gene Ct values and ORF1ab gene Ct values (rs=-0.719 and -0.699, respectively; P<0.05). One month after discharge, all infants had no symptoms or signs of nucleic acid re-positivity. CONCLUSIONS: The clinical manifestations are usually mild or asymptomatic in neonates infected with SARS-CoV-2 Omicron variant. The lower the Ct values of the N and ORF1ab genes of SARS-CoV-2, the longer the duration of nucleic acid positivity. Neonates infected with SARS-CoV-2 Omicron variant can have a good prognosis after symptomatic treatment.

Autocrine, Paracrine, and Endocrine Signals That Can Alter Alveolar Macrophages Function.

Alveolar macrophages (AMs) are extremely versatile cells with complex functions involved in health or diseases such as pneumonia, asthma, and pulmonary alveolar proteinosis. In recent years, it has been widely identified that the different functions and states of macrophages are the results from the complex interplay between microenvironmental signals and macrophage lineage. Diverse and complicated signals to which AMs respond are mentioned when they are described individually or in a particular state of AMs. In this review, the microenvironmental signals are divided into autocrine, paracrine, and endocrine signals based on their secreting characteristics. This new perspective on classification provides a more comprehensive and systematic introduction to the complex signals around AMs and is helpful for understanding the roles of AMs affected by physiological environment. The existing possible treatments of AMs are also mentioned in it. The thorough understanding of AMs signals modulation may be contributed to the development of more effective therapies for AMs-related lung diseases.

Apatinib combined with camrelizumab in advanced acral melanoma patients: An open-label, single-arm phase 2 trial.

BACKGROUND: At present, immune monotherapy and combination therapy has not shown satisfactory effects on acral melanoma, and still no standard treatment is available for advanced acral melanoma. Here, a phase II trial was performed to explore the safety and efficacy of apatinib combined with camrelizumab in advanced acral melanoma patients as first-line therapy (NCT03955354). METHODS: Patients with pathologically confirmed, locally unresectable or metastatic treatment native acral melanoma received 250 mg apatinib once daily and camrelizumab 200 mg once every two weeks intravenously every 28-day cycle. The primary end-point was objective response rate and the secondary end-points were disease control rate, overall survival, progression-free survival and safety. RESULTS: Thirty patients were recruited between January 2015 and January 2022. Among them, 21 (70.0%) had stage IV, and a median tumour burden was 50 mm (range: 11-187). Objective response rate was 24.1%, and 7 of 29 patients had an anti-tumour response, including partial response (n = 5) and complete response (n = 2). Disease control rate was 82.8%, median progression-free survival was 7.39 months (confidence interval: 3.65-9.92), and median overall survival was 13.4 months (confidence interval: 1.9-25.0). Grade 3-4 treatment-related toxicity (grade 3 50.5%; grade 4 3.3%) included transaminase elevations, proteinuria, leukocytopenia, vomiting, diarrhea and drug-induced liver injury. No treatment-related mortality occurred. The mutations of TTN, MUC16, VPS13D, ALPK2 and SCUBE1 showed significant alterations with survival outcome. CONCLUSIONS: Apatinib combined with camrelizumab showed manageable safety profile and reasonable anti-tumour activity in advanced acral melanoma patients as first-line therapy.

Classification of Coronavirus Spike Proteins by Deep-Learning-Based Raman Spectroscopy and its Interpretative Analysis.

The outbreak of COVID-19 has spread worldwide, causing great damage to the global economy. Raman spectroscopy is expected to become a rapid and accurate method for the detection of coronavirus. A classification method of coronavirus spike proteins by Raman spectroscopy based on deep learning was implemented. A Raman spectra dataset of the spike proteins of five coronaviruses (including MERS-CoV, SARS-CoV, SARS-CoV-2, HCoVHKU1, and HCoV-OC43) was generated to establish the neural network model for classification. Even for rapidly acquired spectra with a low signal-to-noise ratio, the average accuracy exceeded 97%. An interpretive analysis of the classification results of the neural network was performed, which indicated that the differences in spectral characteristics captured by the neural network were consistent with the experimental analysis. The interpretative analysis method provided a valuable reference for identifying complex Raman spectra using deep-learning techniques. Our approach exhibited the potential to be applied in clinical practice to identify COVID-19 and other coronaviruses, and it can also be applied to other identification problems such as the identification of viruses or chemical agents, as well as in industrial areas such as oil and gas exploration.

Classification of Coronavirus Spike Proteins by Deep-Learning-Based Raman Spectroscopy and its Interpretative Analysis

The outbreak of COVID-19 has spread worldwide, causing great damage to the global economy. Raman spectroscopy is expected to become a rapid and accurate method for the detection of coronavirus. A classification method of coronavirus spike proteins by Raman spectroscopy based on deep learning was implemented. A Raman spectra dataset of the spike proteins of five coronaviruses (including MERS-CoV, SARS-CoV, SARS-CoV-2, HCoVHKU1, and HCoV-OC43) was generated to establish the neural network model for classification. Even for rapidly acquired spectra with a low signal-to-noise ratio, the average accuracy exceeded 97%. An interpretive analysis of the classification results of the neural network was performed, which indicated that the differences in spectral characteristics captured by the neural network were consistent with the experimental analysis. The interpretative analysis method provided a valuable reference for identifying complex Raman spectra using deep-learning techniques. Our approach exhibited the potential to be applied in clinical practice to identify COVID-19 and other coronaviruses, and it can also be applied to other identification problems such as the identification of viruses or chemical agents, as well as in industrial areas such as oil and gas exploration.

Prevalence of Post-traumatic Stress Disorder Status Among Healthcare Workers and Its Impact on Their Mental Health During the Crisis of COVID-19: A Cross-Sectional Study.

Objective: After the unprecedented coronavirus disease 2019 (COVID-19) outbreak, the health status of the general population has suffered a huge threat, and the mental health of front-line healthcare providers has also encountered great challenges. Therefore, this study aims to: (1) investigate the prevalence and influencing factors of post-traumatic stress disorder (PTSD) among healthcare providers, and (2) verify the moderating role of self-efficacy in the influence of PTSD on mental health. Methods: A cross-sectional study was conducted using an online survey of 1993 participants. The presence of depression, anxiety, self-efficacy, and PTSD was evaluated using screening tests from March 1. Sociodemographic and COVID-19-related data were also collected. A data analysis was performed using descriptive statistics, Pearson's correlation coefficient, and multiple linear regression. Results: The prevalence of PTSD among healthcare providers was 9.3%. PTSD was negatively correlated with self-efficacy (r = -0.265, P < 0.01), anxiety (r = -0.453, P < 0.01), and depression (r = 0.708, P < 0.01). Profession, daily working hours, maximum continuous working days, and daily sleep time were influencing factors of PTSD. A binary logistic regression analysis showed that physicians (OR = 2.254, 95% CI = 1.298, 3.914) and nurses (OR = 2.176, 95% CI = 1.337, 3.541) were more likely to experience PTSD than other healthcare providers. Conclusion: Self-efficacy has a moderating effect on the influence of PTSD on anxiety and depression. This suggests that health managers need to respond to the current psychological crisis of healthcare providers, implement appropriate psychological interventions, and minimize the psychological harm caused by COVID-19.

Urban park use and self-reported physical, mental, and social health during the COVID-19 pandemic: An on-site survey in Beijing, China.

The COVID-19 pandemic created unprecedented challenges for people's health. Studies have demonstrated the positive impact of urban green spaces, particularly urban parks, on physical and mental health. However, few studies have evaluated social health, which is a component of human health, and more understanding of the relationship between urban parks and human health during the COVID-19 pandemic is required. This study examined the effects of urban parks on people's health using a canonical correlation model. Physical, mental, and social health were the dependent health variables, and five factors related to urban parks were the independent variables. This study investigated 22 urban parks inside the Forth Ring Road in Beijing, China using a questionnaire survey. The results demonstrated a positive association between urban parks and human health during the pandemic. Distance to the parks, park area, and park size were positively correlated with physical, mental, and social health. Furthermore, frequency and duration of visits to urban parks were positively associated with mental health and contact with neighbors. The health effects of urban park use varied with park types and locations' urbanization background. These findings can provide insights for health-oriented urban park planning and construction.

Development and application of ribonucleic acid therapy strategies against COVID-19.

The Coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2), remaining a global health crisis since its outbreak until now. Advanced biotechnology and research findings have revealed many suitable viral and host targets for a wide range of therapeutic strategies. The emerging ribonucleic acid therapy can modulate gene expression by post-transcriptional gene silencing (PTGS) based on Watson-Crick base pairing. RNA therapies, including antisense oligonucleotides (ASO), ribozymes, RNA interference (RNAi), aptamers, etc., were used to treat SARS-CoV whose genome is similar to SARV-CoV-2, and the past experience also applies for the treatment of COVID-19. Several studies against SARS-CoV-2 based on RNA therapeutic strategy have been reported, and a dozen of relevant preclinical or clinical trials are in process globally. RNA therapy has been a very active and important part of COVID-19 treatment. In this review, we focus on the progress of ribonucleic acid therapeutic strategies development and application, discuss corresponding problems and challenges, and suggest new strategies and solutions.

Current situation of construction and management of infectious diseases department and fever clinics in medical institutions in Jiangsu Province

OBJECTIVE: To analyze theconstruction of infectious diseases departments and fever clinics in medical institutions at all levels in Jiangsu Province after the COVID-19 epidemic, and to provide a basis for promoting their standardized construction. METHODS: A questionnaire survey was conducted on the construction of infectious diseases departments and fever clinics in 429 medical institutions of Jiangsu Province from July to December 2020, including the overview of medical institutions, the construction status of infectious diseases departments, the construction status and future construction plans of fever clinics, etc. RESULTS: The construction rate of infectious diseases department and fever clinics in medical institutions of Jiangsu province were 33.3% and 75.3% respectively. Ventilation by opening window for was the main form of airflow organization in infectious diseases department and fever clinics, and independent ICUs and negative pressure wards were not set up in most of infectious diseases departments. The setting rate of "three zones and two channels" in fever clinics was high(96.9%), but most of them were not equipped with special CT for fever clinics patients. The proportion of air conditioning and ventilation system without air disinfection devices in the of fever clinics of medical institutions at all levels was higher than 90%. Considering the both hardware construction and quality management, the situation in tertiary medical institutions were superior to secondary medical institutions, and secondary medical institutions were superior to primary medical institutions. Various construction indicators and management systems failed to fully meet the requirements of documents and standards. CONCLUSION: Jiangsu province actively promotes the construction of infectious diseases department and fever clinic layout, but there is still a gap with the construction standard, which is necessary to further promote standardized construction. We should mend the shortages, strengthen the weakness, expand the bases, comprehensively improve the service and anti-epidemic capacity of infectious diseases departments, fever clinics and even the entire medical and health system, so as to better serve the health and life safety of the people.

SARS-CoV-2 hijacks macropinocytosis to facilitate its entry and promote viral spike-mediated cell-to-cell fusion.

Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike-mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike-mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T-angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike-mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike-mediated cell-to-cell fusion.

Development and application of ribonucleic acid therapy strategies against COVID-19

The Coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2), remaining a global health crisis since its outbreak until now. Advanced biotechnology and research findings have revealed many suitable viral and host targets for a wide range of therapeutic strategies. The emerging ribonucleic acid therapy can modulate gene expression by post-transcriptional gene silencing (PTGS) based on Watson-Crick base pairing. RNA therapies, including antisense oligonucleotides (ASO), ribozymes, RNA interference (RNAi), aptamers, etc., were used to treat SARS-CoV whose genome is similar to SARV-CoV-2, and the past experience also applies for the treatment of COVID-19. Several studies against SARS-CoV-2 based on RNA therapeutic strategy have been reported, and a dozen of relevant preclinical or clinical trials are in process globally. RNA therapy has been a very active and important part of COVID-19 treatment. In this review, we focus on the progress of ribonucleic acid therapeutic strategies development and application, discuss corresponding problems and challenges, and suggest new strategies and solutions.

Prevalence of Post-traumatic Stress Disorder Status Among Healthcare Workers and Its Impact on Their Mental Health During the Crisis of COVID-19: A Cross-Sectional Study

Objective After the unprecedented coronavirus disease 2019 (COVID-19) outbreak, the health status of the general population has suffered a huge threat, and the mental health of front-line healthcare providers has also encountered great challenges. Therefore, this study aims to: (1) investigate the prevalence and influencing factors of post-traumatic stress disorder (PTSD) among healthcare providers, and (2) verify the moderating role of self-efficacy in the influence of PTSD on mental health. Methods A cross-sectional study was conducted using an online survey of 1993 participants. The presence of depression, anxiety, self-efficacy, and PTSD was evaluated using screening tests from March 1. Sociodemographic and COVID-19-related data were also collected. A data analysis was performed using descriptive statistics, Pearson's correlation coefficient, and multiple linear regression. Results The prevalence of PTSD among healthcare providers was 9.3%. PTSD was negatively correlated with self-efficacy (r = −0.265, P < 0.01), anxiety (r = −0.453, P < 0.01), and depression (r = 0.708, P < 0.01). Profession, daily working hours, maximum continuous working days, and daily sleep time were influencing factors of PTSD. A binary logistic regression analysis showed that physicians (OR = 2.254, 95% CI = 1.298, 3.914) and nurses (OR = 2.176, 95% CI = 1.337, 3.541) were more likely to experience PTSD than other healthcare providers. Conclusion Self-efficacy has a moderating effect on the influence of PTSD on anxiety and depression. This suggests that health managers need to respond to the current psychological crisis of healthcare providers, implement appropriate psychological interventions, and minimize the psychological harm caused by COVID-19.

Spatial Humanities and Geo-computation for Social Sciences:Advances and Applications

Humanities and Social Sciences (HSS) are undergoing the transformation of spatialization and quantification. Geo-computation, with geoinformatics (including RS: Remote Sensing;GIS: Geographical Information System;GNSS: Global Navigation Satellite System), provides effective computational and spatialization methods and tools for HSS. Spatial Humanities and Geo-computation for Social Sciences (SH&GSS) is a field coupling geo-computation, and geoinformatics, with HSS. This special issue accepted a set of contributions highlighting recent advances in methodologies and applications of SH&GSS, which are related to sentiment spatial analysis from social media data, emotional change spatial analysis from news data, spatial analysis of social media related to COVID-19, crime spatiotemporal analysis, “double evaluation” for Land Use/Land Cover (LUCC), Specially Protected Natural Areas (SPNA) analysis, editing behavior analysis of Volunteered Geographic Information (VGI), electricity consumption anomaly detection, First and Last Mile Problem (FLMP) of public transport, and spatial interaction network analysis for crude oil trade network. Based on these related researches, we aim to present an overview of SH&GSS, and propose some future research directions for SH&HSS.

The COVID‐19 vaccine: Attitudes and vaccination in patients with autoimmune inflammatory rheumatic diseases

Background We examined attitudes toward the COVID‐19 vaccine, potential factors underlying these attitudes, and ways to increase vaccination willingness in autoimmune inflammatory rheumatic diseases (AIIRD) patients. Methods A multicenter, web‐based, observational survey using an online questionnaire was conducted among AIIRD patients aged ≥18 years from May 24, 2021, to June 3, 2021. Participants were 3104 AIIRD patients (2921 unvaccinated and 183 vaccinated). Results Of the unvaccinated patients, 32.9% were willing to receive the COVID‐19 vaccine, 45.0% were uncertain, and 14.8% were unwilling. When vaccination was recommended by physicians, patients' willingness increased to 93.8%. Participants' main concerns were that the vaccine may aggravate AIIRD disease (63.0%) and may cause vaccine‐related adverse events (19.9%). Female patients were less likely to be vaccinated. However, patients who had children aged ≤18 years were more willing to be vaccinated. In addition, vaccination willingness was higher in patients with trust in the safety and efficacy of the COVID‐19 vaccine. Notably, 183 (5.9%) patients were vaccinated. The major vaccination side effects were injection reaction, myalgia, and fatigue. At a median follow‐up of 88 (38, 131) days, patients' disease activities were stable. Conclusions The findings show that AIIRD patients were unwilling to receive the COVID‐19 vaccine because of fears of potential disease exacerbation and additional adverse events. Sociodemographic characteristics and concerns about COVID‐19 disease and vaccines had a significant effect on vaccination willingness. Key points The percentage of patients willing to receive the COVID‐19 vaccine greatly increased when vaccination was recommended by a physician. Gender, marital status, age of the patients' children, smoking, trust in the safety and efficacy of the vaccine, and previous vaccinations had significant effects on the willingness of patients with AIIRDs to receive the COVID‐19 vaccine. The data from vaccinated patients indicated no aggravation of AIIRD or additional adverse events. The population characteristics of AIIRD patients with different attitudes towards COVID‐19 vaccine.

Constructing high-accuracy theoretical Raman spectra of SARS-CoV-2 spike proteins based on a large fragment method.

In order to control COVID-19, rapid and accurate detection of the pathogenic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an urgent task. The target spike proteins of SARS-CoV-2 have been detected experimentally via Raman spectroscopy. However, there lacks high-accuracy theoretical Raman spectra of the spike proteins to as a standard reference for the clinic diagnostic purpose. In this paper, we propose a large fragment method to construct the high-precision Raman spectra for the spike proteins. The large fragment method not only reduces the calculation error but also improves the accuracy of the protein Raman spectra by completely calculating the interactions within the large fragment. The Pearson correlation coefficient of theoretical Raman spectra is greater than 0.929 or more. Compared with the experimental spectra, the characteristic patterns are easily visible. This work provides a detection standard for the spike proteins which shall bring a step closer to the fast recognition of SARS-CoV-2 via Raman spectroscopy method.

Supervised learning-based assessment of office layout satisfaction in academic buildings

Employee satisfaction significantly affects health, well-being and productivity, and office layout plays a dominant role in office psychological satisfaction. However, existing studies have not yet proposed a quantitative evaluation method for office layout satisfaction to assist design decisions. This study conducts a post-occupancy evaluation (POE) process of office layout satisfaction from 1,317 staff members at 3 universities in the Yangtze River Delta, China. The proposed office layout feature network supports the questionnaire design and environmental measurement. Based on the survey data, multiple resampling methods are considered to face the imbalanced dataset problem, and feature selection integrates statistical analysis methods and machine learning algorithms. Nine supervised learning algorithms are tested for office layout satisfaction prediction, and the final predictive model is established based on the random forest algorithm. The predictive model explanation is further integrated with original data analysis to extract the quantified impacts of various building characteristics. The workstation adjustment under the background of COVID-19 in an actual staff office is chosen to be an application scenario of the predictive model. The results show that the workstation distance, room depth and room width-depth ratio are dominant in the evaluation of office layout satisfaction. The proposed predictive model achieves 64.5% accuracy, and the prediction results are interpretable, which promotes its application in office design practice. The data processing methods in this study respond to the common data problems in the POE based opinion collection process. The extracted influence mechanisms of building characteristics can directly support user-centered office design.

The COVID-19 vaccine: Attitudes and vaccination in patients with autoimmune inflammatory rheumatic diseases.

Background: We examined attitudes toward the COVID-19 vaccine, potential factors underlying these attitudes, and ways to increase vaccination willingness in autoimmune inflammatory rheumatic diseases (AIIRD) patients. Methods: A multicenter, web-based, observational survey using an online questionnaire was conducted among AIIRD patients aged ≥18 years from May 24, 2021, to June 3, 2021. Participants were 3104 AIIRD patients (2921 unvaccinated and 183 vaccinated). Results: Of the unvaccinated patients, 32.9% were willing to receive the COVID-19 vaccine, 45.0% were uncertain, and 14.8% were unwilling. When vaccination was recommended by physicians, patients' willingness increased to 93.8%. Participants' main concerns were that the vaccine may aggravate AIIRD disease (63.0%) and may cause vaccine-related adverse events (19.9%). Female patients were less likely to be vaccinated. However, patients who had children aged ≤18 years were more willing to be vaccinated. In addition, vaccination willingness was higher in patients with trust in the safety and efficacy of the COVID-19 vaccine. Notably, 183 (5.9%) patients were vaccinated. The major vaccination side effects were injection reaction, myalgia, and fatigue. At a median follow-up of 88 (38, 131) days, patients' disease activities were stable. Conclusions: The findings show that AIIRD patients were unwilling to receive the COVID-19 vaccine because of fears of potential disease exacerbation and additional adverse events. Sociodemographic characteristics and concerns about COVID-19 disease and vaccines had a significant effect on vaccination willingness.

Dynamic SARS-CoV-2-specific B-cell and T-cell responses following immunization with an inactivated COVID-19 vaccine.

OBJECTIVE: The dynamic adaptive immune responses elicited by the inactivated virus vaccine CoronaVac remain elusive. METHODS: In a prospective cohort of 100 healthcare professionals naïve for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who received two doses of CoronaVac, we analysed SARS-CoV-2-specific humoral and cellular responses at four different timepoints, including before vaccination (T1), 2 weeks after the first dose (T2), 2 weeks after the booster dose (T3), and 8-10 weeks after the booster dose (T4). SARS-CoV-2-specific antibodies, serum neutralizing activities, peripheral B cells, CD4+ and CD8+ T cells and their memory subsets were simultaneously measured in this cohort. RESULTS: SARS-CoV-2 spike-specific IgG responses reached a peak (geometric mean titre (GMT) 54827, 30969-97065) after two doses and rapidly declined (GMT 502, 212-1190) at T4, whereas suboptimal IgA responses were detected (GMT 5, 2-9). Spike-specific circulating B cells (0.60%, 0.46-0.73% of total B cells) and memory B cells (1.18%, 0.92-1.44% of total memory B cells) were effectively induced at T3 and sustained over time (0.33%, 0.23-0.43%; 0.87%, 0.05-1.67%, respectively). SARS-CoV-2-specific circulating CD4+ T cells (0.57%, 0.47-0.66%) and CD8+ T cells (1.29%, 1.04-1.54%) were detected at T3. At T4, 0.78% (0.43-1.20%) of memory CD4+ T cells and 0.68% (0.29-1.30%) of memory CD8+ T cells were identified as SARS-CoV-2-specific, while 0.62% (0.51-0.75%) of CD4+ T cells and 0.47% (0.38-0.58%) of CD8+ T cells were SARS-CoV-2-specific terminally differentiated effector memory cells. Furthermore, age and interval between doses affected the magnitude of CoronaVac-induced immune responses. SARS-CoV-2 memory CD4+ T cells were strongly associated with both receptor binding domain (RBD)-specific memory B cells (r 0.87, p <0.0001) and SARS-CoV-2-specific memory CD8+ T cells (r 0.48, p <0.0001). CONCLUSIONS: CoronaVac induced robust circulating and memory B cell and T cell responses. Our study offers new insight into the underlying immunobiology of inactivated virus vaccines in humans and may have implications for vaccine strategies in the future.

Discovery of Small-Molecule Inhibitors of SARS-CoV-2 Proteins Using a Computational and Experimental Pipeline.

A rapid response is necessary to contain emergent biological outbreaks before they can become pandemics. The novel coronavirus (SARS-CoV-2) that causes COVID-19 was first reported in December of 2019 in Wuhan, China and reached most corners of the globe in less than two months. In just over a year since the initial infections, COVID-19 infected almost 100 million people worldwide. Although similar to SARS-CoV and MERS-CoV, SARS-CoV-2 has resisted treatments that are effective against other coronaviruses. Crystal structures of two SARS-CoV-2 proteins, spike protein and main protease, have been reported and can serve as targets for studies in neutralizing this threat. We have employed molecular docking, molecular dynamics simulations, and machine learning to identify from a library of 26 million molecules possible candidate compounds that may attenuate or neutralize the effects of this virus. The viability of selected candidate compounds against SARS-CoV-2 was determined experimentally by biolayer interferometry and FRET-based activity protein assays along with virus-based assays. In the pseudovirus assay, imatinib and lapatinib had IC50 values below 10 µM, while candesartan cilexetil had an IC50 value of approximately 67 µM against Mpro in a FRET-based activity assay. Comparatively, candesartan cilexetil had the highest selectivity index of all compounds tested as its half-maximal cytotoxicity concentration 50 (CC50) value was the only one greater than the limit of the assay (>100 µM).