Structural and componential design: new strategies regulating the behavior of lipid-based nanoparticles in vivo.

Lipid-based nanoparticles have made a breakthrough in clinical disease as delivery systems due to their biocompatibility, thermal and long-term stability, high loading ability, simplicity of preparation, inexpensive production costs, and scalable manufacturing production. In particular, during the COVID-19 pandemic, this delivery system served as a vital vaccine component for virus confrontation. To obtain effective drug delivery, lipid-based nanoparticles should reach the desired sites with high efficiency, enter target cells, and release drugs. The structures and compositions of lipid-based nanoparticles can be modified to regulate these behaviors in vivo to enhance the therapeutic effects. Herein, we briefly review the development of lipid-based nanoparticles, from simple self-assembled nanovesicle-structured liposomes to multifunctional lipid nanoparticles. Subsequently, we summarize the strategies that regulate their tissue distribution, cell internalization, and drug release, highlighting the importance of the structural and componential design. We conclude with insights for further research to advance lipid-based nanotechnology.

Real-time updating of dynamic social networks for COVID-19 vaccination strategies.

Vaccination strategy is crucial in fighting the COVID-19 pandemic. Since the supply is still limited in many countries, contact network-based interventions can be most powerful to set an efficient strategy by identifying high-risk individuals or communities. However, due to the high dimension, only partial and noisy network information can be available in practice, especially for dynamic systems where contact networks are highly time-variant. Furthermore, the numerous mutations of SARS-CoV-2 have a significant impact on the infectious probability, requiring real-time network updating algorithms. In this study, we propose a sequential network updating approach based on data assimilation techniques to combine different sources of temporal information. We then prioritise the individuals with high-degree or high-centrality, obtained from assimilated networks, for vaccination. The assimilation-based approach is compared with the standard method (based on partially observed networks) and a random selection strategy in terms of vaccination effectiveness in a SIR model. The numerical comparison is first carried out using real-world face-to-face dynamic networks collected in a high school, followed by sequential multi-layer networks generated relying on the Barabasi-Albert model emulating large-scale social networks with several communities.

Real-time updating of dynamic social networks for COVID-19 vaccination strategies

Vaccination strategy is crucial in fighting the COVID-19 pandemic. Since the supply is still limited in many countries, contact network-based interventions can be most powerful to set an efficient strategy by identifying high-risk individuals or communities. However, due to the high dimension, only partial and noisy network information can be available in practice, especially for dynamic systems where contact networks are highly time-variant. Furthermore, the numerous mutations of SARS-CoV-2 have a significant impact on the infectious probability, requiring real-time network updating algorithms. In this study, we propose a sequential network updating approach based on data assimilation techniques to combine different sources of temporal information. We then prioritise the individuals with high-degree or high-centrality, obtained from assimilated networks, for vaccination. The assimilation-based approach is compared with the standard method (based on partially observed networks) and a random selection strategy in terms of vaccination effectiveness in a SIR model. The numerical comparison is first carried out using real-world face-to-face dynamic networks collected in a high school, followed by sequential multi-layer networks generated relying on the Barabasi-Albert model emulating large-scale social networks with several communities.

Long-term Consequences of COVID-19: Chemosensory Disorders.

PURPOSE OF REVIEW: A number of sequelae after acute coronavirus disease 2019 (COVID-19) significantly affect the quality of life of patients. The chemosensory disorders including olfactory dysfunction (OD) and gustatory dysfunction (GD) are two of the commonest symptoms complained by patients with COVID-19. Although chemosensory function has been reported improved in over 60% of COVID-19 patients in a short time after acute infection, it may last as a major symptom for patients with long COVID-19. This narrative review discussed current literatures on OD and GD in long COVID-19 including the prevalence, risk factors, possible mechanisms, and potential therapies. RECENT FINDINGS: Although the prevalence of OD and GD has declined continuously after acute COVID-19, a considerable number of patients had persistent chemosensory disorders 3 months to 2 years after symptom onset. Female gender, initial severity of dysfunction, nasal congestion, emotional distress and depression, and SARS-CoV-2 variants have been identified as risk factors for persistent OD and GD in long COVID-19. The pathogenesis of OD and GD in long COVID-19 remains unknown, but may be analogous to the persistent OD and GD post common respiratory viral infection. Corticosteroids and olfactory training might be a potential choice regarding the treatment of lasting OD and GD after SARS-CoV-2 infection; however, more studies are needed to prove it. OD and GD are common long-term consequences of COVID-19 and influenced by gender, initial severity of dysfunction, emotional distress and depression, and SARS-CoV-2 variants. More studies are needed to illustrate their pathogenesis and to establish therapeutic strategies.

Neutralization sensitivity, fusogenicity, and infectivity of Omicron subvariants.

BACKGROUND: The emergence of SARS-CoV-2 Omicron subvariants has raised questions regarding resistance to immunity by natural infection or immunization. We examined the sensitivity of Delta and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) to neutralizing antibodies from BBIBP-CorV-vaccinated and BBIBP-CorV- or ZF2001-boosted individuals, as well as individuals with Delta and BA.1 breakthrough infections, and determined their fusogenicity and infectivity. METHODS: In this cross-sectional study, serum samples from two doses of BBIBP-CorV-vaccinated individuals 1 (n = 36), 3 (n = 36), and 7 (n = 37) months after the second dose; BBIBP-CorV- (n = 25) or ZF2001-boosted (n = 30) individuals; and fully vaccinated individuals with Delta (n = 30) or BA.1 (n = 26) infection were collected. The serum-neutralizing reactivity and potency of bebtelovimab were assessed against D614G, Delta, and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) through a pseudovirus neutralization assay. The fusogenicity and infectivity of D614G, Delta, and Omicron subvariants were determined by cell-cell fusion assay and pseudovirus infection assay, respectively. RESULTS: Omicron subvariants markedly escaped vaccine-elicited neutralizing antibodies after two doses of BBIBP-CorV with comparable efficiency. A third dose vaccination of BBIBP-CorV or ZF2001 increased neutralizing antibody titers and breadth against Delta and three Omicron subvariants. Delta and BA.1 breakthrough infections induced comparable neutralizing antibody titers against D614G and Delta variants, whereas BA.1 breakthrough infections elicited a stronger and broader antibody response against three Omicron subvariants than Delta breakthrough infections. BA.2.12.1 and BA.4/5 are more resistant to immunity induced by breakthrough infections. Bebtelovimab had no significant loss of potency against the Delta and Omicron subvariants. Cell culture experiments showed Omicron subvariants to be less fusogenic and have higher infectivity than D614G and Delta with comparable efficiency. CONCLUSIONS: These findings have important public health implications and highlight the importance of repeated exposure to SARS-CoV-2 antigens to broaden the neutralizing antibody response against Omicron subvariants.

Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle-immunized mice (preprint)

The COVID-19 pandemic continues to threaten human health worldwide, as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around K417 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC50 values that range from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on a broadly neutralizing chimeric antibody to create K-RBD-hAb-62, which still retains excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.

Dysregulated liver function in SARS-CoV-2 infection: Current understanding and perspectives.

Since it was first reported in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread rapidly around the world to cause the ongoing pandemic. Although the clinical manifestations of SARS-CoV-2 infection are predominantly in the respiratory system, liver enzyme abnormalities exist in around half of the cases, which indicate liver injury, and raise clinical concern. At present, there is no consensus whether the liver injury is directly caused by viral replication in the liver tissue or indirectly by the systemic inflammatory response. This review aims to summarize the clinical manifestations and to explore the underlying mechanisms of liver dysfunction in patients with SARS-CoV-2 infection.

Distinct effects of asthma and COPD comorbidity on disease expression and outcome in patients with COVID-19.

BACKGROUND: The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood. OBJECTIVE: To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients. METHODS: A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines. RESULTS: In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135; P < .01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461-267.369; P = .025) than asthmatics. COPD patients, particularly those with severe COVID-19, had lower counts of CD4+ T and CD8+ T cells and B cells and higher levels of TNF-α, IL-2 receptor, IL-10, IL-8, and IL-6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL-4 and IL-13 downregulated, but TNF-α, IL-12, and IL-17A upregulated ACE2 expression in BEAS-2B cells. CONCLUSION: Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.

Real-time Updating of Dynamic Social Networks for COVID-19 Vaccination Strategies (preprint)

Vaccination strategy is crucial in fighting against the COVID-19 pandemic. Since the supply is limited, contact network-based interventions can be most powerful to set an optimal strategy by identifying high-risk individuals or communities. However, due to the high dimension, only partial and noisy network information can be available in practice, especially for dynamical systems where the contact networks are highly time-variant. Furthermore, numerous mutations of SARS-CoV-2 impact considerably the current infectious probability, requiring real-time network updating algorithms. In this study, we propose a sequential network updating approach based on data assimilation techniques to combine different sources of temporal information. We then prioritise the individuals with high-degree or high-centrality, obtained from the assimilated networks, for vaccination. The assimilation-based approach is compared with the standard method (based on partially observed networks) and a random selection strategy in terms of vaccination effectiveness in a SIR model. The numerical comparison is first carried out using real-world face-to-face dynamical networks collected in a high school, following by sequential multi-layer networks, generated relying on the Barabasi-Albert model emulating the department of Computing at Imperial College London in the UK as an example.

Self-reported Taste and Smell Disorders in Patients with COVID-19: Distinct Features in China.

Last December 2019, a cluster of viral pneumonia cases identified as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19. In this retrospective study, 1206 laboratory-confirmed COVID-19 patients were included and followed up by telephone one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. From patients (n=1172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. 20.6% COVID-19 patients had loss of taste (median score=6), while 11.4% had loss of smell (median score=5). Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels were positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks. In this cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out of 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.

Self-Reported Taste and Smell Disorders in Patients with COVID-19: Distinct Features in China (preprint)

Background: Last December 2019, a cluster of viral pneumonia cases identified as coronavirus disease 2019 (COVID-19), was reported in Wuhan, China. We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19.Methods: In this retrospective study, 1,206 laboratory-confirmed COVID-19 patients were included and followed-up by telephone call one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. Results: From COVID-19 patients (N = 1,172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. The most common nasal symptom was loss of taste (20.6%, median score = 6), while 11.4% had loss of smell (median score = 5). The incidence of nasal symptom including loss of smell and loss of taste as the first onset symptom was <1% in COVID-19 patients. Loss of smell or taste scores showed no correlation with the scores of other nasal symptoms. Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks.Conclusions: In the Wuhan COVID-19 cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.

Self-reported taste and smell disorders in patients with COVID-19: distinct features in China (preprint)

ObjectivesWe aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19. MethodsIn this retrospective study, 1,206 laboratory-confirmed COVID-19 patients were included and followed-up by telephone call one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. ResultsFrom COVID-19 patients (N = 1,172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. The most common nasal symptom was loss of taste (20.6%, median score = 6), while 11.4% had loss of smell (median score = 5). The incidence of nasal symptom including loss of smell and loss of taste as the first onset symptom was <1% in COVID-19 patients. Loss of smell or taste scores showed no correlation with the scores of other nasal symptoms. Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks. ConclusionIn the Wuhan COVID-19 cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.