Erratum: Inhaled ACE2-engineered microfluidic microsphere for intratracheal neutralization of COVID-19 and calming of the cytokine storm.

[This corrects the article DOI: 10.1016/j.matt.2021.09.022.].

The preclinical and clinical progress of cell sheet engineering in regenerative medicine.

Cell therapy is an accessible method for curing damaged organs or tissues. Yet, this approach is limited by the delivery efficiency of cell suspension injection. Over recent years, biological scaffolds have emerged as carriers of delivering therapeutic cells to the target sites. Although they can be regarded as revolutionary research output and promote the development of tissue engineering, the defect of biological scaffolds in repairing cell-dense tissues is apparent. Cell sheet engineering (CSE) is a novel technique that supports enzyme-free cell detachment in the shape of a sheet-like structure. Compared with the traditional method of enzymatic digestion, products harvested by this technique retain extracellular matrix (ECM) secreted by cells as well as cell-matrix and intercellular junctions established during in vitro culture. Herein, we discussed the current status and recent progress of CSE in basic research and clinical application by reviewing relevant articles that have been published, hoping to provide a reference for the development of CSE in the field of stem cells and regenerative medicine.

Potential of conserved antigenic sites in development of universal SARS-like coronavirus vaccines.

Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.

Doing good or looking good: how socially responsible human resource management practices influence employees' CSR-specific performance

PurposeThis study examines whether, how and when socially responsible human resource management (SRHRM) practices increase employees' in-role and extra-role corporate social responsibility (CSR) performance.Design/methodology/approachThis study uses data from 422 employees of 68 companies.FindingsSRHRM improves employees' in-role CSR-specific performance via impression management motivation and enhance extra-role CSR-specific performance via prosocial motivation. Moral identity symbolization strengthens the relationship between SRHRM and impression management motivation, and moral identity internalization reinforces the relationship between SRHRM and prosocial motivation. The authors also propose mediated moderation models.Practical implicationsThis study indicates that company can adopt SRHRM practices to improve employees' in-role and extra-role CSR-specific performance.Originality/valueThis study reveals how and when SRHRM practices influence employees' CSR-specific performance and sheds light on the social impacts of SRHRM.

The Impact of The COVID-19 Pandemic On SLE.

Little is known about the association between coronavirus disease 2019 [COVID-19] and autoimmune diseases, especially for systemic lupus erythematosus [SLE]. SLE patients meet with a throng of questions during the pandemic, including minimize the risk of infection, the complex pathological features and cytokine profiles, diagnosis and treatment, rational choice of drugs and vaccine, good nursing and psychological supervision, etc. In this study, we review and discuss the multifaceted effects of the COVID-19 pandemic on patients living with SLE using the available literatures. Cross-talk was existed in implicated inflammatory pathways/mechanisms between SLE and SARS-CoV-2 infection, and SARS-CoV-2 infection shares similarities with SLE in clinical characters and immuno-inflammatory responses. Current epidemiological data inadequate assess the risk and severity of COVID-19 in SLE. More evidences supported that HCQ and CQ unable prevent COVID-19. During the pandemic, patients with SLE had a higher rate of hospitalization. Vaccination helps to reduce the risk of infection. Several therapies for patients with SLE infected COVID-19 were discussed. The cases in the study can provide meaningful information for clinical diagnosis and management. Our mainly aim is to help the prevention and treatment of patients with SLE infected COVID-19.

Worry and fear during the COVID-19 epidemic normalization: Analyzing prevalence and risk factors among 182,991 high school students in China.

It is worth paying attention to the level of worry and fear of students during the normalization of the epidemic. We conducted the cross-sectional study that included 182,991 high school students using an online survey to assess worry and fear levels and its influencing factors in three cities in Henan Province, China, from May 21 to May 27, 2021. Worry and fear levels were measured using a five-item Likert-type scale. Multinomial logistic regression was used to analyze the risk factors. Approximately 65.42% of students reported being high worry about the coronavirus disease 2019 (COVID-19) epidemic, and about 41.44% of students reported being high fear about the COVID-19 epidemic. In addition, compared with female, male had lower odds of suffering from a high worry, and compared with senior high school students, junior high school students were more likely to suffer from a high worry. Students lived in rural had highest odds increased likelihood of high worry. Similar results in fear levels. During the normalization period of the COVID-19 epidemic, many students have high levels of worry and fear. This study has implications for potential influencers of worry and fear levels in follow-up work.

The safety of digestive tract cancer surgery during COVID-19: A living systematic review and meta-analysis.

Surgery is the primary curative treatment of solid cancers. However, its safety has been compromised by the outbreak of COVID-19. Therefore, it is necessary to evaluate the safety of digestive tract cancer surgery in the context of COVID-19. We used the Review Manager software (v.5.4) and Stata software (version 16.0) for meta-analysis and statistical analysis. Sixteen retrospective studies involving 17,077 patients met the inclusion criteria. The data indicates that performing digestive tract cancer surgery during the COVID-19 pandemic led to increased blood loss(MD = -11.31, 95%CI:-21.43 to -1.20, P = 0.03), but did not increase postoperative complications(OR = 1.03, 95%CI:0.78 to1.35, P = 0 0.86), anastomotic leakage (OR = 0.96, 95%CI:0.52 to1.77, P = 0 0.89), postoperative mortality (OR = 0.65, 95%CI:0.40 to1.07, P = 0 0.09), number of transfusions (OR = 0.74, 95%CI:0.30 to 1.80, P = 0.51), number of patients requiring ICU care(OR = 1.37, 95%CI:0.90 to 2.07, P = 0.14), postoperative 30-d readmission (OR = 0.94, 95%CI:0.82 to 1.07, P = 0 0.33), total hospital stay (MD = 0.11, 95%CI:-2.37 to 2.59, P = 0.93), preoperative waiting time(MD = - 0.78, 95%CI:-2.34 to 0.79, P = 0.33), postoperative hospital stay(MD = - 0.44, 95%CI:-1.61 to 0.74, P = 0.47), total operation time(MD = -12.99, 95%CI:-28.00 to 2.02, P = 0.09) and postoperative ICU stay (MD = - 0.02, 95%CI:-0.62 to 0.57, P = 0.94). Digestive tract cancer surgery can be safely performed during the COVID-19.

Current thoughts on cellular functions of numb-associated kinases.

Members of the Numb-associated kinase family of serine/threonine kinases play an essential role in many cellular processes, such as endocytosis, autophagy, dendrite morphogenesis, osteoblast differentiation, and the regulation of the Notch pathway. Numb-associated kinases have been relevant to diverse diseases, including neuropathic pain, Parkinson's disease, and prostate cancer. Therefore, they are considered potential therapeutic targets. In addition, it is reported that Numb-associated kinases have been involved in the life cycle of multiple viruses such as hepatitis C virus (HCV), Ebola virus (EBOV), and dengue virus (DENV). Recently, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten global health. Studies show that Numb-associated kinases are implicated in the infection of SARS-CoV-2 which can be suppressed by Numb-associated kinases inhibitors. Thus, Numb-associated kinases are proposed as potential host targets for broad-spectrum antiviral strategies. We will focus on the recent advances in Numb-associated kinases-related cellular functions and their potential as host targets for viral infections in this review. Questions that remained unknown on the cellular functions of Numb-associated kinases will also be discussed.

Retrospective Study of Aging and Sex-Specific Risk Factors of COVID-19 with Hypertension in China.

Background: Coronavirus disease 2019 (COVID-19) has been a global threat that pushes healthcare to its limits. Hypertension is one of the most common risk factors for cardiovascular complications in COVID-19 and is strongly associated with disease severity and mortality. To date, clinical mechanisms by which hypertension leads to increased risk in COVID-19 are still unclear. Furthermore, additional factors might increase these risks, such as the consideration of age and sex, which are of interest when in search of personalized treatments for hypertensive COVID-19 patients. Methods: We conducted a retrospective cohort study of 543 COVID-19 patients in seven provinces of China to examine the epidemiological and clinical characteristics of COVID-19 in this population and to determine risk factors of hypertensive COVID-19 patients. We also used univariable and multivariable logistic regression methods to explore the risk factors associated with hypertensive COVID-19 patients in different age and sex subgroups. Results: Among the enrolled COVID-19 patients, the median age was 47 years (interquartile range (IQR) 34.0-57.0), and 99 patients (18.23%) were over 60 years old. With regard to comorbidities, 91 patients (16.75%) were diagnosed with hypertension, followed by diabetes, coronary disease, and cerebrovascular disease. Of the hypertensive COVID-19 patients, 51 (56.04%) were male. Multivariable analysis showed that old age, comorbid diabetes or coronary heart disease on admission, increased D-dimer, increased glucose, and decreased lymphocyte count were independent risk factors associated with hypertensive COVID-19 patients. Elevated total bilirubin (odds ratio [OR]: 1.014, 95% confidence interval [CI]: 0.23-1.05; p = 0.043) and triglycerides (OR: 1.173, 95% CI: 0.049-1.617; p = 0.007) were found to be associated with elderly hypertensive COVID-19 patients. In addition, we found that decreased lymphocytes, basophil, high-density lipoprotein, and increased fibrinogen and creatinine were related to a higher risk of disease severity in male patients. The most common abnormal clinical findings pertaining to female hypertensive COVID-19 patients were hemoglobin, total bile acid, total protein, and low-density lipoprotein. Conclusions: Factors associated with increased risk of hypertensive COVID-19 patients were identified. Results to the different age and sex subgroups in our study will allow for better possible personalized care and also provide new insights into specific risk stratification, disease management, and treatment strategies for COVID-19 patients with hypertension in the future.

Redemption from SRHRM under COVID‐19: How business threat due to COVID‐19 affects employee insomnia via hope and workplace anxiety

Existing studies show that the COVID‐19 pandemic influences employee outcome in the work domain. However, the impact of business threat due to COVID‐19 on employee daily insomnia remains unexplored. Addressing this research gap can help scholars understand the risks of COVID‐19 in the non‐work domain. Drawing on appraisal theories of emotion, we explore how and when business threat due to COVID‐19 triggers employee insomnia. Using an experience sampling methodology where 89 employees are surveyed for 7 workdays, our multilevel analyses show that employee daily hope and workplace anxiety mediate the effects of business threat due to COVID‐19 on employee insomnia. Furthermore, socially responsible human resource management (SRHRM) practices weaken the negative relationship between business threat due to COVID‐19 and employees' hope and mitigate the positive relationship between business threat due to COVID‐19 and their workplace anxiety. We also find that SRHRM practices influence the indirect effect of business threat due to COVID‐19 on employee insomnia via workplace anxiety. Our study helps understand the underlying mechanisms in the relationship between business threat due to COVID‐19 and employee insomnia and further sheds light on the role of SRHRM in mitigating the destructive effect of business threat due to COVID‐19. [ FROM AUTHOR]

Association between attitudes toward the COVID-19 vaccines and mental health among 140,259 college students in China.

Background: With the launch of the COVID-19 vaccines, the vaccination rate has become a hot issue of concern. However, the evidence for the relationship between college students' attitudes toward vaccines and anxiety and depressive symptoms has been limited. Methods: In total, 140,259 college students were recruited using a cluster sampling method in Zhengzhou, Xinxiang, Xinyang city of Henan Province, China, May 21-27, 2021. Anxiety symptoms were determined by the Generalized Anxiety Disorder tool (GAD-7) and depressive symptoms were determined by the Patient Health Questionnaire (PHQ-9). Multiple logistic regression was performed to estimate the association between students' attitudes toward the vaccines and anxiety and depressive symptoms. Results: The results indicate that 22.45% of students are unclear whether the vaccine can protect them from infection and 45.57% are unclear whether the vaccine is safe and has no side effects. In addition, after adjusting, the model showed that students who think vaccines can protect them and are safe had 0.128 (95%CI 0.110-0.150; Ptrend < 0.001) times lower risk of anxiety compared to their counterparts who think vaccines can neither protect them nor are safe. Similar ORs were found in depression (aOR = 0.157; 95%CI 0.137-0.180). Conclusion: This large-scale study has shown an association between symptoms of anxiety and depression and reluctance to obtain vaccination. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01830-7.

PSTCNN: Explainable COVID-19 diagnosis using PSO-guided self-tuning CNN

Since 2019, the coronavirus disease-19 (COVID-19) has been spreading rapidly worldwide, posing an unignorable threat to the global economy and human health. It is a disease caused by severe acute respiratory syndrome coronavirus 2, a single-stranded RNA virus of the genus Betacoronavirus. This virus is highly infectious and relies on its angiotensin-converting enzyme 2-receptor to enter cells. With the increase in the number of confirmed COVID-19 diagnoses, the difficulty of diagnosis due to the lack of global healthcare resources becomes increasingly apparent. Deep learning-based computer-aided diagnosis models with high generalisability can effectively alleviate this pressure. Hyperparameter tuning is essential in training such models and significantly impacts their final performance and training speed. However, traditional hyperparameter tuning methods are usually time-consuming and unstable. To solve this issue, we introduce Particle Swarm Optimisation to build a PSO-guided Self-Tuning Convolution Neural Network (PSTCNN), allowing the model to tune hyperparameters automatically. Therefore, the proposed approach can reduce human involvement. Also, the optimisation algorithm can select the combination of hyperparameters in a targeted manner, thus stably achieving a solution closer to the global optimum. Experimentally, the PSTCNN can obtain quite excellent results, with a sensitivity of 93.65% ± 1.86%, a specificity of 94.32% ± 2.07%, a precision of 94.30% ± 2.04%, an accuracy of 93.99% ± 1.78%, an F1-score of 93.97% ± 1.78%, Matthews Correlation Coefficient of 87.99% ± 3.56%, and Fowlkes-Mallows Index of 93.97% ± 1.78%. Our experiments demonstrate that compared to traditional methods, hyperparameter tuning of the model using an optimisation algorithm is faster and more effective. [ FROM AUTHOR]

Association of Workplace Bullying with Suicide Ideation and Attempt Among Chinese Nurses During the COVID-19 Pandemic.

Nurses experience a high incidence of workplace bullying and are at a higher risk of suicide than the general population. However, there is no empirical evidence on how exposure to workplace bullying is associated with suicide ideation and attempts among nurses. Nurses were recruited from tertiary hospitals in Shandong Province, China, using stratified cluster sampling. Suicide ideation and attempts were assessed using two items, and the Workplace Psychologically Violent Behaviors Instrument was used to measure subtypes of workplace bullying. The prevalence of workplace bullying, suicide ideation, and suicide attempts was 30.6%, 16.8%, and 10.8%, respectively. After adjusting for covariates, victims of workplace bullying were at a high risk of suicide ideation and attempts. Among workplace bullying subtypes, individuals' isolation from work and direct negative behaviors were predictors of both suicide ideation and attempts; attack on personality only predicted suicide attempts. The more bullying subtypes experienced by nurses, the greater their likelihood of suicide ideation and attempts. These findings suggested that workplace bullying was associated with an increased risk of suicide ideation and attempts in nurses, with both independent and cumulative risks. Interventions should focus on prevention and managing the effects of workplace bullying among nurses.

Immunotherapy for Sepsis Induced by Infections: Clinical Evidence and Potential Targets.

Sepsis is a life-threatening organ dysfunction caused by the maladjustment of the body's response to infection. Abnormal immune response plays an important role in the progression of sepsis, and immunomodulatory therapy is a promising therapeutic strategy for sepsis. Great efforts have been made recently to elucidate the mechanism by which immune dysfunction contributes to sepsis, and identify potential biomarkers and targets for the diagnosis and therapy of sepsis induced by emerging pathogens, especially for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)that causes COVID-19. In this review, we summarize recent progress on the understanding of immune dysregulation involved in sepsis, and highlight potential biomarkers and targets to evaluate immune status of the patients with sepsis for individualized and precise immunotherapy.

The safety of esophageal cancer surgery during COVID-19.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic has drastically challenged the safety of on esophageal cancer (EC) surgery during COVID-19. The study aimed to evaluate the safety of EC surgery during the COVID-19 pandemic. METHODS: This systematic review was performed in accordance with the PRISMA-P 2015 guidelines and registered in PROSPERO (registration number: CRD42022335164). A systematic search of PubMed, Embase, Cochrane Library, Web of Science, Medline, Chinese National Knowledge Infrastructure database, Chinese Scientific Journal database, and Wan Fang database was conducted to identify potentially relevant publications from January 2020 to May 2022. All data were independently extracted by two researchers. We will apply a fixed-effect model or random effect model basis on the heterogeneity test and employ with RevMan 5.4.1 software for data synthesis. The dichotomous surgical outcomes used risk ratios or risk differences, and for continuous surgical outcomes, mean differences (MD) or standardized MD, both with 95% confidence intervals were used. The primary outcomes were postoperative complications, anastomotic leaks, and mortality. The secondary outcomes were total hospital stay, postoperative stay, preoperative waiting, operation time, blood loss, transfusion, postoperative intensive care unit (ICU) stay, number of patients needing ICU stay, and 30-day readmission. RESULTS: This study will comprehensively summarize the high-quality trials to determine the safety of EC surgery during COVID-19. CONCLUSION: Our systematic review and meta-analysis will present evidence for the safety of EC surgery during COVID-19.

Potential of conserved antigenic sites in development of universal SARS-like coronavirus vaccines

Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.

Prevalence and risk factors of depressive symptoms among 140,259 college students during the COVID-19 epidemic normalization in China: A cross-sectional survey.

Objective: College students are one of the most vulnerable populations to the COVID-19 pandemic's mental health effects. During the coronavirus disease 2019 (COVID-19) outbreak, we wanted to see how common depressive symptoms were among college students and what factors contributed to that. Methods: Between 21 and 27 May 2021, 140,259 college students from three cities in Henan Province, China, were involved. The Patient Health Questionnaire-9 was used to determine depressive symptoms (PHQ-9). Multiple logistic regression analysis was used to calculate odds ratios (ORs) and 95% CIs for potential depressive symptom factors. Results: Mild depressive symptoms and above are present in 21.12% of college students. Women had a higher prevalence of mild depressive symptoms than men (61.38 vs. 59.75%), and depressive symptoms were most prevalent among rural students and least prevalent among city students (21.44 vs. 20.29%). Participants with depressive symptoms are also more likely to have a poor-behavioral status. From none-to-severe depressive symptoms, 78.88, 15.78, 2.80, 1.67, and 0.88% had them. Gender, residential location, and behavioral status were found to be associated with depressive symptoms after adjusting for potential confounders. Conclusion: This cross-sectional study identified the factors that influence the prevalence of depression in college students. It found that the government should pay more attention to mental health issues affecting college students in combating the COVID-19 epidemic normalization.

Attitude toward COVID-19 vaccines and its association with depressive symptoms in 386,924 Chinese primary school students during COVID-19 epidemic normalization.

AIM: Before Chinese primary school students were generally vaccinated against the COVID-19 vaccine, this study evaluated the willingness of this population and its influencing factors before vaccination, and evaluate its association between attitudes toward the vaccine and depressive symptoms. METHODS: A cross-sectional study involved 386,924 primary school students using a cluster sampling method during May 21-27, 2021. The Chinese version of the Children Depression Inventory (CDI) was used to assess depressive symptoms. Multiple logistic regression analysis models were used to estimate the relationship between attitudes toward COVID-19 vaccines and depressive symptoms. RESULTS: Among the participants, the prevalence of depressive symptoms was higher in higher grades. The prevalence was higher in fifth and sixth grade students than third and fourth grade students and first and second grades (10.22% vs. 6.07% vs. 3.04%). In addition, 20.79% of students do not know whether the vaccine can protect him from the COVID-19 infection, and 40.60% of students do not know whether the vaccine is safe. Of note, in terms of attitudes toward COVID-19 vaccines, students with more positive attitudes have a lower risk of depressive symptoms (adjusted odds ratio (aOR) = 0.151; 95% confidence interval (CI): 0.140-0.164). CONCLUSION: Based on these findings, it is necessary for the government and schools to promote vaccine safety and reliability information in a timely manner to increase vaccination uptake.

Diagnostic accuracy of CRISPR technology for detecting SARS-CoV-2: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of CRISPR-Cas technology for SARS-CoV-2. METHODS: RT-qPCR is defined as the reference standard. Data was collected and assessed by Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. A bivariate model for pooling was employed and subgroups analysis was used to explore heterogeneity. RESULTS: 2264 samples from 28 articles were extracted for evaluating the accuracy of CRISPR technology for diagnosing SARS-CoV-2. The pooled sensitivity and specificity of CRISPR technology were 0.98 (95% CI: 0.95-0.99) and 1.0 (95% CI: 0.98-1.00), respectively. High risks in patient selection bias and unclear risk of index test bias may affect accuracy. Subgroup analysis showed that CRISPR-Cas12 is applicable for molecular diagnostics for its active editing characteristics. RT-LAMP and RT-RPA are usually used for pre-amplification and fluorescence detection to output results quantitatively. Nasopharyngeal swabs and dual-genes perform greatly in our study. CONCLUSION: The results concluded from all studies showed that CRISPR technology is a promising molecular method for detecting SARS-CoV-2. Standard methods including comparable sample material, patient selection, operating procedure and operators should be established.

Online Hydrophilic Interaction Chromatography (HILIC) Enhanced Top-Down Mass Spectrometry Characterization of the SARS-CoV-2 Spike Receptor-Binding Domain.

SARS-CoV-2 cellular infection is mediated by the heavily glycosylated spike protein. Recombinant versions of the spike protein and the receptor-binding domain (RBD) are necessary for seropositivity assays and can potentially serve as vaccines against viral infection. RBD plays key roles in the spike protein's structure and function, and thus, comprehensive characterization of recombinant RBD is critically important for biopharmaceutical applications. Liquid chromatography coupled to mass spectrometry has been widely used to characterize post-translational modifications in proteins, including glycosylation. Most studies of RBDs were performed at the proteolytic peptide (bottom-up proteomics) or released glycan level because of the technical challenges in resolving highly heterogeneous glycans at the intact protein level. Herein, we evaluated several online separation techniques: (1) C2 reverse-phase liquid chromatography (RPLC), (2) capillary zone electrophoresis (CZE), and (3) acrylamide-based monolithic hydrophilic interaction chromatography (HILIC) to separate intact recombinant RBDs with varying combinations of glycosylations (glycoforms) for top-down mass spectrometry (MS). Within the conditions we explored, the HILIC method was superior to RPLC and CZE at separating RBD glycoforms, which differ significantly in neutral glycan groups. In addition, our top-down analysis readily captured unexpected modifications (e.g., cysteinylation and N-terminal sequence variation) and low abundance, heavily glycosylated proteoforms that may be missed by using glycopeptide data alone. The HILIC top-down MS platform holds great potential in resolving heterogeneous glycoproteins for facile comparison of biosimilars in quality control applications.