Risk factors associated with indoor transmission during home quarantine of COVID-19 patients.

Purpose: The study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves. Methods: A retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. Results: A total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p < 0.001), and had higher rates of symptoms (p = 0.003) or shared living room (p < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40-2.48, p < 0.001), symptoms development (OR = 1.86, 95%CI 1.34-2.58, p < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09-1.96, p = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41-0.92, p = 0.018). Conclusion: Patients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19.

Working from anywhere: yin-yang cognition paradoxes of knowledge sharing and hiding for developing careers in China.

Digital technology coupled with the quarantines caused by the COVID-19 pandemic has made working from anywhere (WFA)-a modern form of remote working-a widespread phenomenon. Given that WFA brings new career challenges to and engenders paradoxes of knowledge exchange among employees, this research aims to examine how the interactions of remote work time (RWT), knowledge sharing (KS), and knowledge hiding (KH) affect career development (CD) from a culturally grounded paradoxical framing of yin-yang harmonizing. The data were collected from Chinese manufacturing employees, and a moderated hierarchical regression analysis was used to examine the hypotheses. The results show an inverted U-shaped relationship between RWT and CD. The interaction of KS and KH is significantly related to CD, and the inverted U-shaped RWT-CD relationship is moderated by the interaction term, in which RWT exerts the most substantial positive impact on CD when KS is high and KH is low. This study offers valuable implications for coping with perplexing employment relationships and increasing career challenges in volatile work environments. The primary originality is to adopt a novel cognitive frame of yin-yang harmonizing to examine the nonlinear effect of remote working and the symbiotic impact of KS and KH on CD, which not only enriches the understanding of flexible work arrangements in the digital economy but also provides novel insights into the interconnectedness of KS and KH and their interacting effects on HRM-related outcomes.

Innate and Adaptive Immune Responses Induced by Aspergillus fumigatus Conidia and Hyphae.

Previous research indicated that hyphae of Aspergillus fumigatus (A. fumigatus) rather than conidia could successfully build a pulmonary aspergillosis model in immunocompetent mice. In this study, we compared the immune responses induced by hyphae and conidia to explore the possible mechanism of this striking phenomenon. Herein, a novel method was designed and adopted to quantify hyphal fragments. Murine macrophages RAW264.7 and human peripheral blood mononuclear cells were stimulated by A. fumigatus hyphae and conidia in vitro, respectively, and then immunological reactions were measured. Male C57BL/6 mice were challenged with conidia and hyphae through intratracheal inoculation. Dynamic conditions of mice were recorded, and RNA-seq measured corresponding immune responses. The results of the study confirmed that hyphae could induce more intensive inflammation than conidia in vitro and in vivo. However, macrophages revealed a higher production of ROS and M1 polarisation in response to conidia stimuli. Additionally, conidia could promote Th1 cell differentiation, while hyphae could increase the CD4/CD8 ratio. RNA-seq validated the fact that those multiple immunologically relevant pathways were more strongly activated by hyphae than conidia, which also promoted Th2 cell differentiation and suppressed Th1 signalling. Both hyphae and conidia could activate Th17 signalling. In general, conidia and hyphae induced distinctly different host immune responses, and the immune responses induced by conidia played a better protective effect. Therefore, the unique function of hyphae in the spread and infection of Aspergillus should be emphasised, and more research is required to clarify the underlying mechanisms for better understanding and management of aspergillosis.

Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (Mpro), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.

Viral contamination on the surfaces of the personal protective equipment among health care professionals working in COVID-19 wards: A single-center prospective, observational study.

OBJECTIVE: To evaluate potential viral contamination on the surfaces of personal protective equipment (PPE) in COVID-19 wards. METHODS: Face shields, gloves, the chest area of PPE and shoe soles were sampled at different time points. The samples were tested for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR, and the cycle threshold (CT) values were recorded. RESULTS: The positive rate was 74.7% (239/320) for all PPE specimens. The CT values of the samples were ranked in the following order: face shields > chests > gloves > shoe soles (37.08±1.38, 35.48±2.02, 34.17±1.91 and 33.52±3.16, respectively; P for trend < .001). After disinfection, the CT values of shoe soles decreased compared with before disinfection (32.78±3.47 vs. 34.3±2.61, P = .037), whereas no significant effect of disinfection on the CT values of face shields, chests and gloves was observed. After disinfection, the CT values of specimens collected from shoe soles gradually increased; before disinfection, the CT values of shoe sole specimens were all less than 35. CONCLUSIONS: SARS-CoV-2 can attach to the surfaces of the PPE of healthcare professionals in COVID-19 wards, especially the shoe soles and undisinfected gloves. Shoe soles had the highest SARS-CoV-2 loads among all tested PPE items.

Reduced B cell antigenicity of Omicron lowers host serologic response.

The SARS-CoV-2 Omicron variant evades most neutralizing vaccine-induced antibodies and is associated with lower antibody titers upon breakthrough infections than previous variants. However, the mechanism remains unclear. Here, we find using a geometric deep-learning model that Omicron's extensively mutated receptor binding site (RBS) features reduced antigenicity compared with previous variants. Mice immunization experiments with different recombinant receptor binding domain (RBD) variants confirm that the serological response to Omicron is drastically attenuated and less potent. Analyses of serum cross-reactivity and competitive ELISA reveal a reduction in antibody response across both variable and conserved RBD epitopes. Computational modeling confirms that the RBS has a potential for further antigenicity reduction while retaining efficient receptor binding. Finally, we find a similar trend of antigenicity reduction over decades for hCoV229E, a common cold coronavirus. Thus, our study explains the reduced antibody titers associated with Omicron infection and reveals a possible trajectory of future viral evolution.

Reduced B-cell antigenicity of Omicron lowers host serologic response

The SARS-CoV-2 Omicron variant evades most neutralizing vaccine-induced antibodies and is associated with lower antibody titers upon breakthrough infections than previous variants. However, the mechanism remains unclear. Here, we find using a geometric deep-learning model that Omicron's extensively mutated receptor binding site (RBS) features reduced antigenicity compared to previous variants. Mice immunization experiments with different recombinant Receptor Binding Domains (RBD) variants confirm that the serological response to Omicron is drastically attenuated and less potent. Analyses of serum cross-reactivity and competitive ELISA reveal a reduction in antibody response across both variable and conserved RBD epitopes. Computational modeling confirms that the RBS has a potential for further antigenicity reduction while retaining efficient receptor binding. Finally, we find a similar trend of antigenicity reduction over decades for hCoV229E, a common cold coronavirus. Thus our study explains the reduced antibody titers associated with Omicron infection and reveals a possible trajectory of future viral evolution. Graphical SARS-CoV-2 Omicron variant evades most neutralizing vaccine-induced antibodies and is associated with lower antibody titers upon breakthrough infections than previous variants. Tubiana et al. investigate the underlying mechanism using geometric deep learning, mice immunization experiments and biochemical assays. Mutations reduce antigenicity of the receptor binding site, leading to lower antibody response.

Skin-Attachable Sensors for Biomedical Applications

With the growing concern about human health issues, especially during the outbreak of the COVID-19 pandemic, the demand for personalized healthcare regarding disease prevention and recovery is increasing. However, tremendous challenges lie in both limited public medical resources and costly medical diagnosis approaches. Recently, skin-attachable sensors have emerged as promising health monitoring platforms to overcome such difficulties. Owing to the advantages of good comfort and high signal-to-noise ratio, skin-attachable sensors enable household, real-time, and long-term detection of weak physiological signals to efficiently and accurately monitor human motion, heart rate, blood oxygen saturation, respiratory rate, lung and heart sound, glucose, and biomarkers in biomedical applications. To further improve the integration level of biomedical skin-attachable sensors, efforts have been made in combining multiple sensing techniques with elaborate structural designs. This review summarizes the recent advances in different functional skin-attachable sensors, which monitor physical and chemical indicators of the human body. The advantages, shortcomings, and integration strategies of different mechanisms are presented. Specially, we highlight sensors monitoring pulmonary function such as respiratory rate and blood oxygen saturation for their potential usage in the COVID-19 pandemic. Finally, the future development of skin-attachable sensors is envisioned.

Human infection of avian influenza A H3N8 virus and the viral origins: a descriptive study.

BACKGROUND: The H3N8 avian influenza virus (AIV) has been circulating in wild birds, with occasional interspecies transmission to mammals. The first human infection of H3N8 subtype occurred in Henan Province, China, in April, 2022. We aimed to investigate clinical, epidemiological, and virological data related to a second case identified soon afterwards in Hunan Province, China. METHODS: We analysed clinical, epidemiological, and virological data for a 5-year-old boy diagnosed with H3N8 AIV infection in May, 2022, during influenza-like illness surveillance in Changsha City, Hunan Province, China. H3N8 virus strains from chicken flocks from January, 2021, to April, 2022, were retrospectively investigated in China. The genomes of the viruses were sequenced for phylogenetic analysis of all the eight gene segments. We evaluated the receptor-binding properties of the H3N8 viruses by using a solid-phase binding assay. We used sequence alignment and homology-modelling methods to study the effect of specific mutations on the human receptor-binding properties. We also conducted serological surveillance to detect the H3N8 infections among poultry workers in the two provinces with H3N8 cases. FINDINGS: The clinical symptoms of the patient were mild, including fever, sore throat, chills, and a runny nose. The patient's fever subsided on the same day of hospitalisation, and these symptoms disappeared 7 days later, presenting mild influenza symptoms, with no pneumonia. An H3N8 virus was isolated from the patient's throat swab specimen. The novel H3N8 virus causing human infection was first detected in a chicken farm in Guangdong Province in December, 2021, and subsequently emerged in several provinces. Sequence analyses revealed the novel H3N8 AIVs originated from multiple reassortment events. The haemagglutinin gene could have originated from H3Ny AIVs of duck origin. The neuraminidase gene belongs to North American lineage, and might have originated in Alaska (USA) and been transferred by migratory birds along the east Asian flyway. The six internal genes had originated from G57 genotype H9N2 AIVs that were endemic in chicken flocks. Reassortment events might have occurred in domestic ducks or chickens in the Pearl River Delta area in southern China. The novel H3N8 viruses possess the ability to bind to both avian-type and human-type sialic acid receptors, which pose a threat to human health. No poultry worker in our study was positive for antibodies against the H3N8 virus. INTERPRETATION: The novel H3N8 virus that caused human infection had originated from chickens, a typical spillover. The virus is a triple reassortment strain with the Eurasian avian H3 gene, North American avian N8 gene, and dynamic internal genes of the H9N2 viruses. The virus already possesses binding ability to human-type receptors, though the risk of the H3N8 virus infection in humans was low, and the cases are rare and sporadic at present. Considering the pandemic potential, comprehensive surveillance of the H3N8 virus in poultry flocks and the environment is imperative, and poultry-to-human transmission should be closely monitored. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, Hunan Provincial Innovative Construction Special Fund: Emergency response to COVID-19 outbreak, Scientific Research Fund of Hunan Provincial Health Department, and the Hunan Provincial Health Commission Foundation.

Friend or Foe? Implication of the autophagy-lysosome pathway in SARS-CoV-2 infection and COVID-19.

There is increasing amount of evidence indicating the close interplays between the replication cycle of SARS-CoV-2 and the autophagy-lysosome pathway in the host cells. While autophagy machinery is known to either assist or inhibit the viral replication process, the reciprocal effects of the SARS-CoV-2 on the autophagy-lysosome pathway have also been increasingly appreciated. More importantly, despite the disappointing results from the clinical trials of chloroquine and hydroxychloroquine in treatment of COVID-19, there is still ongoing effort in discovering new therapeutics targeting the autophagy-lysosome pathway. In this review, we provide an update-to-date summary of the interplays between the autophagy-lysosome pathway in the host cells and the pathogen SARS-CoV-2 at the molecular level, to highlight the prognostic value of autophagy markers in COVID-19 patients and to discuss the potential of developing novel therapeutic strategies for COVID-19 by targeting the autophagy-lysosome pathway. Thus, understanding the nature of such interactions between SARS-CoV-2 and the autophagy-lysosome pathway in the host cells is expected to provide novel strategies in battling against this global pandemic.

Superimmunity by pan-sarbecovirus nanobodies.

Vaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observe superimmunity in a camelid extensively immunized with the SARS-CoV-2 receptor-binding domain (RBD). We rapidly isolate a large repertoire of specific ultra-high-affinity nanobodies that bind strongly to all known sarbecovirus clades using integrative proteomics. These pan-sarbecovirus nanobodies (psNbs) are highly effective against SARS-CoV and SARS-CoV-2 variants, including Omicron, with the best median neutralization potency at single-digit nanograms per milliliter. A highly potent, inhalable, and bispecific psNb (PiN-31) is also developed. Structural determinations of 13 psNbs with the SARS-CoV-2 spike or RBD reveal five epitope classes, providing insights into the mechanisms and evolution of their broad activities. The highly evolved psNbs target small, flat, and flexible epitopes that contain over 75% of conserved RBD surface residues. Their potencies are strongly and negatively correlated with the distance of the epitopes from the receptor binding sites.

Spatial and Temporal Differences in the Health Expenditure Efficiency of China: Reflections Based on the Background of the COVID-19 Pandemic.

The outbreak of the COVID-19 pandemic has brought several challenges to China's national health services, causing great risks and uncertainties to people's lives. Considering China's huge population and relatively small medical investment and its good performance in the COVID-19 pandemic, this research utilizes the hybrid meta-frontier model to analyze health expenditure efficiencies of 30 provinces in China from 1999 to 2018 and compares spatial and temporal differences of the efficiencies in regards to regional forward position and national common frontier. The results show an obvious difference in health expenditure efficiency in different provinces along the regional frontier, in which the efficiency gap in the eastern region is the largest. Moreover, the room for improvement in health expenditure efficiency varies from region to region. For the national common frontier, Beijing is the most efficient, while Guizhou is the least. The eastern region owns the most efficient technical level of health expenditure efficiency, and there is a large efficiency distance between it and the western region. The findings offer effective guidance for elevating the expenditure structure and spatial resource allocation of public health and for promoting the equalization of high quality basic medical services.

The burden and trend of gastric cancer and possible risk factors in five Asian countries from 1990 to 2019.

The burdens and trends of gastric cancer are poorly understood, especially in high-prevalence countries. Based on the Global Burden of Disease Study 2019, we analyzed the incidence, death, and possible risk factors of gastric cancer in five Asian countries, in relation to year, age, sex, and sociodemographic index. The annual percentage change was calculated to estimate the trends in age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR). The highest ASIR per 100,000 person-years in 2019 was in Mongolia [44 (95% uncertainty interval (UI), 34 to 55)], while the lowest was in the Democratic People's Republic of Korea (DPRK) [23 (95% UI, 19 to 29)]. The highest ASDR per 100,000 person-years was in Mongolia [46 (95% UI, 37 to 57)], while the lowest was in Japan [14 (95% UI, 12 to 15)]. Despite the increase in the absolute number of cases and deaths from 1990 to 2019, the ASIRs and ASDRs in all five countries decreased with time and improved sociodemographic index but increased with age. Smoking and a high-sodium diet were two possible risk factors for gastric cancer. In 2019, the proportion of age-standardized disability-adjusted life-years attributable to smoking was highest in Japan [23% (95% UI, 19 to 28%)], and the proportions attributable to a high-sodium diet were highest in China [8.8% (95% UI, 0.21 to 33%)], DPRK, and the Republic of Korea. There are substantial variations in the incidence and death of gastric cancer in the five studied Asian countries. This study may be crucial in helping policymakers to make better decisions and allocate appropriate resources.

Influence of Hospital Outdoor Rest Space on the Eye Movement Measures and Self-Rating Restoration of Staff.

Objective: To investigate the effect of hospital outdoor rest space on the eye movement measures and self-rating restoration of staff. Background: Relieving the pressure of hospital staff through exposure to hospital outdoor rest space is essential, but there is a scarcity of research on the impact of hospital outdoor rest space on the eye movement measures and self-rating restoration of staff, especially for large Chinese hospitals. Methods: Cross-analysis was conducted based on the eye movement measures of 76 staff members obtained by eye movement tracking equipment in combination with the self-rating restoration scale and hospital outdoor rest space picture attributes (element proportion and position, brightness and saturation). Results: The differences in eye movement measures of different staff attributes (occupation, age, and gender) were identified, and the effects of hospital outdoor rest space picture attributes on the eye movement measures and self-rating restoration scale of staff were summarized. A number of proposals were also formulated: hospital outdoor rest space should be set up close to the working area of the group of medical staff; attention should be paid to the actual needs of senior staff members and the work pressure of junior nurses; the exposure to natural environment should be increased and the proportion of hard artificial elements should be reduced; the natural environment should be placed in the visual center; the saturation and brightness of hospital outdoor rest space should be increased; and staff members should have access to the sky environment in a variety of ways. Conclusion: The present study is an empirical study of evidence-based design on hospital outdoor rest space in China, and the results reveal the effects of hospital outdoor rest space on the eye movement measures and self-rating restoration of staff.

A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19.

Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10-15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10-3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10-16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Analysis of SARS-CoV-2 variants B.1.617: host tropism, proteolytic activation, cell-cell fusion, and neutralization sensitivity.

SARS-CoV-2 has caused the COVID-19 pandemic. B.1.617 variants (including Kappa and Delta) have been transmitted rapidly in India. The transmissibility, pathogenicity, and neutralization characteristics of these variants have received considerable interest. In this study, 22 pseudotyped viruses were constructed for B.1.617 variants and their corresponding single amino acid mutations. B.1.617 variants did not exhibit significant enhanced infectivity in human cells, but mutations T478K and E484Q in the receptor binding domain led to enhanced infectivity in mouse ACE2-overexpressing cells. Furin activities were slightly increased against B.1.617 variants and cell-cell fusion after infection of B.1.617 variants were enhanced. Furthermore, B.1.617 variants escaped neutralization by several mAbs, mainly because of mutations L452R, T478K, and E484Q in the receptor binding domain. The neutralization activities of sera from convalescent patients, inactivated vaccine-immunized volunteers, adenovirus vaccine-immunized volunteers, and SARS-CoV-2 immunized animals against pseudotyped B.1.617 variants were reduced by approximately twofold, compared with the D614G variant.

Impact of new variants on SARS-CoV-2 infectivity and neutralization: A molecular assessment of the alterations in the spike-host protein interactions.

The emergence of SARS-CoV-2 variants necessitates rational assessment of their impact on the recognition and neutralization of the virus by the host cell. We present a comparative analysis of the interactions of Alpha, Beta, Gamma, and Delta variants with cognate molecules (ACE2 and/or furin), neutralizing nanobodies (Nbs), and monoclonal antibodies (mAbs) using in silico methods, in addition to Nb-binding assays. Our study elucidates the molecular origin of the ability of Beta and Delta variants to evade selected antibodies, such as REGN10933, LY-CoV555, B38, C105, or H11-H4, while being insensitive to others including REGN10987. Experiments confirm that nanobody Nb20 retains neutralizing activity against the Delta variant. The substitutions T478K and L452R in the Delta variant enhance associations with ACE2, whereas P681R promotes recognition by proteases, thus facilitating viral entry. The Ab-specific responses of variants highlight how full-atomic structure and dynamics analyses are required for assessing the response to newly emerging variants.

Longitudinal analysis of antibody dynamics in COVID-19 convalescents reveals neutralizing responses up to 16 months after infection.

Elucidating the dynamics of the neutralizing antibody (nAb) response in coronavirus disease 2019 (COVID-19) convalescents is crucial in controlling the pandemic and informing vaccination strategies. Here we measured nAb titres across 411 sequential plasma samples collected during 1-480 d after illness onset or laboratory confirmation (d.a.o.) from 214 COVID-19 convalescents, covering the clinical spectrum of disease and without additional exposure history after recovery or vaccination against SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. Forty-eight samples were also tested for neutralizing activities against the circulating variants using pseudotyped neutralization assay. Results showed that anti-RBD IgG and MN titres peaked at ~120 d.a.o. and subsequently declined, with significantly reduced nAb responses found in 91.67% of COVID-19 convalescents (≥50% decrease in current MN titres compared with the paired peak MN titres). Despite this decline, majority of the COVID-19 convalescents maintained detectable anti-RBD IgG and MN titres at 400-480 d.a.o., with undetectable neutralizing activity found in 14.41% (16/111) of the mild and 50% (5/10) of the asymptomatic infections at 330-480 d.a.o. Persistent antibody-dependent immunity could provide protection against circulating variants after one year, despite significantly decreased neutralizing activities against Beta, Delta and Mu variants. In conclusion, these data show that despite a marked decline in neutralizing activity over time, nAb responses persist for up to 480 d in most convalescents of symptomatic COVID-19, whereas a high rate of undetectable nAb responses was found in convalescents from asymptomatic infections.

Biomaterial-assisted biotherapy: A brief review of biomaterials used in drug delivery, vaccine development, gene therapy, and stem cell therapy.

Biotherapy has recently become a hotspot research topic with encouraging prospects in various fields due to a wide range of treatments applications, as demonstrated in preclinical and clinical studies. However, the broad applications of biotherapy have been limited by critical challenges, including the lack of safe and efficient delivery systems and serious side effects. Due to the unique potentials of biomaterials, such as good biocompatibility and bioactive properties, biomaterial-assisted biotherapy has been demonstrated to be an attractive strategy. The biomaterial-based delivery systems possess sufficient packaging capacity and versatile functions, enabling a sustained and localized release of drugs at the target sites. Furthermore, the biomaterials can provide a niche with specific extracellular conditions for the proliferation, differentiation, attachment, and migration of stem cells, leading to tissue regeneration. In this review, the state-of-the-art studies on the applications of biomaterials in biotherapy, including drug delivery, vaccine development, gene therapy, and stem cell therapy, have been summarized. The challenges and an outlook of biomaterial-assisted biotherapies have also been discussed.

Llamanade: An open-source computational pipeline for robust nanobody humanization.

Nanobodies (Nbs) have emerged as a promising class of biologics. Despite having marked physicochemical properties, Nbs are derived from camelids and may require humanization to improve translational potentials. By systematically analyzing the sequence and structural properties of Nbs, we found substantial framework diversities and revealed the key differences between Nbs and human immunoglobulin G antibodies. We identified conserved residues that may contribute to enhanced solubility, structural stability, and antigen binding, providing insights into Nb humanization. Based on big data analysis, we developed "Llamanade," an open-source software to facilitate rational humanization of Nbs. Using sequence as input, Llamanade can rapidly extract sequence features, model structures, and optimize solutions to humanize Nbs. Finally, we used Llamanade to successfully humanize a cohort of structurally diverse and potent SARS-CoV-2 neutralizing Nbs. Llamanade is freely available and will be easily accessible on a server to support the development of therapeutic Nbs into safe and effective trials.