Divided When Crisis Comes: How Perceived Self-Partner Disagreements over COVID-19 Prevention Measures Relate to Employee Work Outcomes at Home.

As a response to the COVID-19 pandemic, our societies went into a lockdown model and many organizations required or permitted their employees to work from home. As a result, employees need to deal with the COVID-19 pandemic while they work from home, providing an opportunity to examine how COVID-19 prevention experiences influence those who are working from home. Based on the interpersonal self-regulation perspective, we propose that employees who perceive having more disagreements with their partners over COVID-19 prevention measures are more likely to experience a reduction in their identification with the partner which is subsequently associated with their negative work outcomes through emotional exhaustion. Results from a two-wave survey study with a sample of 282 employees who worked from home during the COVID-19 pandemic supported our predictions: perceived self-partner disagreements over COVID-19 prevention measures related to a reduction in identification with the partner, which was subsequently associated with exhausted regulatory resources and undermined work outcomes. Furthermore, these negative effects were particularly salient for individuals who were not married. Theoretical and practical implications for family-to-work interference and working from home in times of crisis are discussed.

Acute reactions after a homologous primary COVID-19 vaccination series: Analysis of Taiwan V-Watch data.

INTRODUCTION: The ChAdOx1 nCoV-19 (ChAd), mRNA-1273 (m1273), MVC-COV1901 (MVC), and BNT162b2 (BNT) COVID-19 vaccines received authorization for emergency use in Taiwan beginning in February 2021. We investigated acute reactions to homologous primary COVID-19 vaccination series in adults aged ≥ 18 years. METHODS: In this prospective observational study based on smartphone data (Taiwan V-Watch), we calculated the frequencies of self-reported local and systemic acute reactions within 7 days of a COVID-19 vaccination, and the health effects up to 3 weeks after each dose. Those who reported adverse reactions after both doses were assessed by the McNemar test. RESULTS: During 22 March 2021-13 December 2021, 77,468 adults were enrolled; 59.0 % were female and 77.8 % were aged 18-49 years. For both doses of all four vaccines, the local and systemic reactions were minor in severity and highest on days 1 and 2 after vaccination, and declined markedly until day 7. For 65,367 participants who provided data after the first and second doses, systemic reactions were more frequent after dose 2 of the BNT and m1273 vaccines (McNemar tests: both p < 0.001), while local reactions were more frequent after dose 2 of the m1273 and MVC vaccines (both p < 0.001), compared with dose 1 of the homologous vaccine. Among the participants aged 18-49 years, the percentage who missed work on the day after vaccination was slightly higher among women (9.3 %) than among men (7.0 %). CONCLUSIONS: Acute reactogenicity and impact of work absenteeism for the four COVID vaccines in the V-Watch survey were mild and of short duration.

Acute Reactions After a Homologous Primary COVID-19 Vaccination Series: Analysis of Taiwan V-Watch Data

Introduction The ChAdOx1 nCoV-19 (ChAd), mRNA-1273 (m1273), MVC-COV1901 (MVC), and BNT162b2 (BNT) COVID-19 vaccines received authorization for emergency use in Taiwan beginning in February 2021. We investigated acute reactions to homologous primary COVID-19 vaccination series in adults aged ≥18 years. Methods In this prospective observational study based on smartphone data (Taiwan V-Watch), we calculated the frequencies of self-reported local and systemic acute reactions within 7 days of a COVID-19 vaccination, and the health effects up to 3 weeks after each dose. Those who reported adverse reactions after both doses were assessed by the McNemar test. Results During 22 March 2021–13 December 2021, 77,468 adults were enrolled;59.0% were female and 77.8% were aged 18–49 years. For both doses of all four vaccines, the local and systemic reactions were minor in severity and highest on days 1 and 2 after vaccination, and declined markedly until day 7. For 65,367 participants who provided data after the first and second doses, systemic reactions were more frequent after dose 2 of the BNT and m1273 vaccines (McNemar tests: both p < 0.001), while local reactions were more frequent after dose 2 of the m1273 and MVC vaccines (both p < 0.001), compared with dose 1 of the homologous vaccine. Among the participants aged 18–49 years, the percentage who missed work on the day after vaccination was slightly higher among women (9.3%) than among men (7.0%). Conclusions Acute reactogenicity and impact of work absenteeism for the four COVID vaccines in the T-Watch survey were mild and of short duration.

Media Exposure to COVID-19 Predicted Acute Stress: A Moderated Mediation Model of Intolerance of Uncertainty and Perceived Social Support.

Background: Previous studies have found that disaster-related media exposure could predict acute stress responses. However, few studies have investigated the relationship between media exposure to COVID-19 and acute stress, and less is known about the mechanisms that translate media exposure to COVID-19 into acute stress. The current study explored the impact of media exposure to COVID-19 on acute stress, and examined the mediating role of intolerance of uncertainty (IU) and the moderating role of perceived social support (PSS). Methods: A total of 1,483 Chinese participants (M age = 27.93 years, SD = 8.45) completed anonymous online questionnaires regarding media exposure to COVID-19, IU, PSS, and acute stress during the COVID-19 outbreak in China. Results: Media exposure to COVID-19 was positively related to acute stress, and IU partially mediated this relationship. The direct effect of media exposure to COVID-19 on acute stress, and the relationship between IU and acute stress, were both moderated by PSS. The impacts of both media exposure to COVID-19 and IU on acute stress were stronger for individuals with low PSS. Limitations: This study collected data in a shorter timeframe, and no assessments occurred during the follow-up, which may prevent us from detecting the changes of the relationships between variables over time. Meanwhile, the self-report method limited the validity of the data due to subjective reporting bias. Conclusions: These findings contribute to a better understanding of how and when pandemic-related media exposure affects acute stress, and provide new perspectives for the prevention to reduce psychological problems following traumatic events.

A Polysaccharide-RBD-Fc-Conjugated COVID-19 Vaccine, SCTV01A, Showed High Immunogenicity and Low Toxicity in Animal Models.

We previously developed a polysaccharide--RBD-conjugated nanoparticle vaccine which induced protective efficacy against SARS-CoV-2 in a mouse model. Here, we newly developed a vaccine, SCTV01A, by chemically conjugating recombinant SARS-CoV-2 RBD-Fc and PPS14 (Streptococcus pneumoniae serotype type 14 capsular polysaccharide). The immunogenicity and toxicity of SCTV01A were evaluated in animal models. The PPS14 conjugation enhanced the immunogenicity of RBD-Fc in C57BL/6 mice whether formulated with SCT-VA02B or Alum adjuvant. SCTV01A also induced high opsonophagocytic activity (OPA) against S. pneumoniae serotype 14. In addition, SCTV01A stimulated potent neutralizing titers in rhesus macaques and effectively reduced lung inflammation after SARS-CoV-2 infection with neither antibody-dependent enhancement (ADE) nor vaccine-enhanced diseases (VED) phenomenon. Importantly, the long-term toxicity study of SCTV01A in rhesus macaques did not cause any abnormal toxicity and was tolerated at the highest tested dose (120 µg). The existing immunogenicity and toxicological evaluation results have demonstrated the safety and efficacy of SCTV01A, which will be a promising and feasible vaccine to protect against SARS-CoV-2 infection.

Minimalist Nanocomplex with Dual Regulation of Endothelial Function and Inflammation for Targeted Therapy of Inflammatory Vascular Diseases.

Vascular disorders, characterized by vascular endothelial dysfunction combined with inflammation, are correlated with numerous fatal diseases, such as coronavirus disease-19 and atherosclerosis. Achieving vascular normalization is an urgent problem that must be solved when treating inflammatory vascular diseases. Inspired by the vascular regulatory versatility of nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) catalyzing l-arginine (l-Arg), the eNOS-activating effects of l-Arg, and the powerful anti-inflammatory and eNOS-replenishing effects of budesonide (BUD), we constructed a bi-prodrug minimalist nanoplatform co-loaded with BUD and l-Arg via polysialic acid (PSA) to form BUD-l-Arg@PSA. This promoted vascular normalization by simultaneously regulating vascular endothelial dysfunction and inflammation. Mediated by the special affinity between PSA and E-selectin, which is highly expressed on the surface of activated endothelial cells (ECs), BUD-l-Arg@PSA selectively accumulated in activated ECs, targeted eNOS expression and activation, and promoted NO production. Consequently, the binary synergistic regulation of the NO/eNOS signaling pathway occurred and improved vascular endothelial function. NO-induced nuclear factor-kappa B alpha inhibitor (IκBα) stabilization and BUD-induced nuclear factor-kappa B (NF-κB) response gene site occupancy achieved dual-site blockade of the NF-κB signaling pathway, thereby reducing the inflammatory response and inhibiting the infiltration of inflammation-related immune cells. In a renal ischemia-reperfusion injury mouse model, BUD-l-Arg@PSA reduced acute injury. In an atherosclerosis mouse model, BUD-l-Arg@PSA decreased atherosclerotic plaque burden and improved vasodilation. This represents a revolutionary therapeutic strategy for inflammatory vascular diseases.

Serinc2 deficiency causes susceptibility to sepsis-associated acute lung injury.

BACKGROUND: Severe sepsis and its subsequent complications cause high morbidity and mortality rates worldwide. The lung is one of the most vulnerable organs sensitive to the sepsis-associated inflammatory storm and usually develops into acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). The pathogenesis of sepsis-associated ALI is accompanied by coordinated transmembrane signal transduction and subsequent programmed cell death; however, the underlying mechanism remains largely unclear. RESULTS: Here we find that the expression of serine incorporator 2 (Serinc2), a protein involved in phosphatidylserine synthesis and membrane incorporation, is upregulated in cecal ligation and puncture (CLP)-induced ALI. Furthermore, the Serinc2-knockout (KO) mouse line is generated by the CRISPR-cas9 approach. Compared with wild-type mice, the Serinc2-KO mice exhibit exacerbated ALI-related pathologies after CLP. The expressions of pro-inflammatory factors, including IL1ß, IL6, TNFα, and MCP1, are significantly enhanced by Serinc2 deficiency, concurrent with over-activation of STAT3, p38 and ERK pathways. Conversely, Serinc2 overexpression in RAW264.7 cells significantly suppresses the inflammatory responses induced by lipopolysaccharide (LPS). Serinc2 KO aggravates CLP-induced apoptosis as evidenced by increases in TUNEL-positive staining, Bax expression, and cleaved caspase-3 and decreases in BCL-2 expression and Akt phosphorylation, whereas these changes are suppressed by Serinc2 overexpression in LPS-treated RAW264.7 cells. Moreover, the administration of AKTin, an inhibitor of Akt, abolishes the protective effects of Serinc2 overexpression against inflammation and apoptosis. CONCLUSIONS: Our findings demonstrate a protective role of Serinc2 in the lung through activating the Akt pathway, and provide novel insight into the pathogenesis of sepsis-induced ALI.

Experience Pandemic Fatigue? Social Media Use May Play a Role: Testing a Model of Pandemic Fatigue Development from a Social Media Perspective.

Recently, the World Health Organization noted the increasing signs of pandemic fatigue around the world and repeatedly warned the public to continue to stay cautious. The current study explores whether social media use plays a role in the formation and development of pandemic fatigue. Drawing on a survey of 849 social media users in China, the findings indicated that different social media behaviors play different roles in affecting pandemic fatigue. Specifically, social interaction use is negatively associated with pandemic fatigue, mediated by more social support and reduced hopelessness. Active content use contributes to pandemic fatigue development, an association explained by information overload and desensitization. Notably, passive content use is found to trigger reactance but is negatively associated with pandemic fatigue, which is fully mediated by reduced information overload. This study seeks to understand how pandemic fatigue is associated with social media use and to explicate the underlying mechanism. The implications of the findings and directions for future research are discussed.

Immune Persistence against SARS-CoV-2 after Primary and Booster Immunization in Humans: A Large-Scale Prospective Cohort Study.

Amid the ongoing global COVID-19 pandemic, limited literature exists on immune persistence after primary immunization and the immunogenic features of booster vaccines administered at different time intervals. Therefore, this study aimed to determine the immune attenuation of neutralizing antibodies against the SARS-CoV-2 wild-type strain, and Delta and Omicron variants 12 months after the primary administration of the COVID-19 inactivated vaccine and evaluate the immune response after a booster administration at different time intervals. A total of 514 individuals were followed up after primary immunization and were vaccinated with a booster. Neutralizing antibodies against the wild-type strain and Delta and Omicron variant spike proteins were measured using pseudovirus neutralization assays. The geometric mean titers (GMTs) after the primary and booster immunizations were 12.09 and 61.48 for the wild-type strain, 11.67 and 40.33 for the Delta variant, and 8.51 and 29.31 for the Omicron variant, respectively. The GMTs against the wild-type strain declined gradually during the 12 months after the primary immunization, and were lower against the two variants. After implementing a booster immunization with a 6 month interval, the GMTs against the wild-type strain were higher than those obtained beyond the 7 month interval; however, the GMTs against the two variants were not statistically different across 3-12 month intervals. Overall, SARS-CoV-2 variants showed remarkable declines in immune persistence, especially against the Omicron variant. The booster administration interval could be shortened to 3 months in endemic areas of the Omicron variant, whereas an appropriate prolonging of the booster administration interval did not affect the booster immunization effect.

Neuropilin-1 Facilitates Pseudorabies Virus Replication and Viral Glycoprotein B Promotes Its Degradation in a Furin-Dependent Manner.

Pseudorabies virus (PRV), which is extremely infectious and can infect numerous mammals, has a risk of spillover into humans. Virus-host interactions determine viral entry and spreading. Here, we showed that neuropilin-1 (NRP1) significantly potentiates PRV infection. Mechanistically, NRP1 promoted PRV attachment and entry, and enhanced cell-to-cell fusion mediated by viral glycoprotein B (gB), gD, gH, and gL. Furthermore, through in vitro coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays, NRP1 was found to physically interact with gB, gD, and gH, and these interactions were C-end Rule (CendR) motif independent, in contrast to currently known viruses. Remarkably, we illustrated that the viral protein gB promotes NRP1 degradation via a lysosome-dependent pathway. We further demonstrate that gB promotes NRP1 degradation in a furin-cleavage-dependent manner. Interestingly, in this study, we generated gB furin cleavage site (FCS)-knockout PRV (Δfurin PRV) and evaluated its pathogenesis; in vivo, we found that Δfurin PRV virulence was significantly attenuated in mice. Together, our findings demonstrated that NRP1 is an important host factor for PRV and that NRP1 may be a potential target for antiviral intervention. IMPORTANCE Recent studies have shown accelerated PRV cross-species spillover and that PRV poses a potential threat to humans. PRV infection in humans always manifests as a high fever, tonic-clonic seizures, and encephalitis. Therefore, understanding the interaction between PRV and host factors may contribute to the development of new antiviral strategies against PRV. NRP1 has been demonstrated to be a receptor for several viruses that harbor CendR, including SARS-CoV-2. However, the relationships between NRP1 and PRV are poorly understood. Here, we found that NRP1 significantly potentiated PRV infection by promoting PRV attachment and enhanced cell-to-cell fusion. For the first time, we demonstrated that gB promotes NRP1 degradation via a lysosome-dependent pathway. Last, in vivo, Δfurin PRV virulence was significantly attenuated in mice. Therefore, NRP1 is an important host factor for PRV, and NRP1 may be a potential target for antiviral drug development.

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.

Wide-Bandwidth Nanocomposite-Sensor Integrated Smart Mask for Tracking Multiphase Respiratory Activities.

Wearing masks has been a recommended protective measure due to the risks of coronavirus disease 2019 (COVID-19) even in its coming endemic phase. Therefore, deploying a "smart mask" to monitor human physiological signals is highly beneficial for personal and public health. This work presents a smart mask integrating an ultrathin nanocomposite sponge structure-based soundwave sensor (≈400 µm), which allows the high sensitivity in a wide-bandwidth dynamic pressure range, i.e., capable of detecting various respiratory sounds of breathing, speaking, and coughing. Thirty-one subjects test the smart mask in recording their respiratory activities. Machine/deep learning methods, i.e., support vector machine and convolutional neural networks, are used to recognize these activities, which show average macro-recalls of ≈95% in both individual and generalized models. With rich high-frequency (≈4000 Hz) information recorded, the two-/tri-phase coughs can be mapped while speaking words can be identified, demonstrating that the smart mask can be applicable as a daily wearable Internet of Things (IoT) device for respiratory disease identification, voice interaction tool, etc. in the future. This work bridges the technological gap between ultra-lightweight but high-frequency response sensor material fabrication, signal transduction and processing, and machining/deep learning to demonstrate a wearable device for potential applications in continual health monitoring in daily life.

SMRI: A New Method for siRNA Design for COVID-19 Therapy.

First discovered in Wuhan, China, SARS-CoV-2 is a highly pathogenic novel coronavirus, which rapidly spread globally and became a pandemic with no vaccine and limited distinctive clinical drugs available till March 13th, 2020. Ribonucleic Acid interference (RNAi) technology, a gene-silencing technology that targets mRNA, can cause damage to RNA viruses effectively. Here, we report a new efficient small interfering RNA (siRNA) design method named Simple Multiple Rules Intelligent Method (SMRI) to propose a new solution of the treatment of COVID-19. To be specific, this study proposes a new model named Base Preference and Thermodynamic Characteristic model (BPTC model) indicating the siRNA silencing efficiency and a new index named siRNA Extended Rules index (SER index) based on the BPTC model to screen high-efficiency siRNAs and filter out the siRNAs that are difficult to take effect or synthesize as a part of the SMRI method, which is more robust and efficient than the traditional statistical indicators under the same circumstances. Besides, to silence the spike protein of SARS-CoV-2 to invade cells, this study further puts forward the SMRI method to search candidate high-efficiency siRNAs on SARS-CoV-2's S gene. This study is one of the early studies applying RNAi therapy to the COVID-19 treatment. According to the analysis, the average value of predicted interference efficiency of the candidate siRNAs designed by the SMRI method is comparable to that of the mainstream siRNA design algorithms. Moreover, the SMRI method ensures that the designed siRNAs have more than three base mismatches with human genes, thus avoiding silencing normal human genes. This is not considered by other mainstream methods, thereby the five candidate high-efficiency siRNAs which are easy to take effect or synthesize and much safer for human body are obtained by our SMRI method, which provide a new safer, small dosage and long efficacy solution for the treatment of COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s11390-021-0826-x.

The kinetics of IgG subclasses and contributions to neutralizing activity against SARS-CoV-2 wild-type strain and variants in healthy adults immunized with inactivated vaccine.

Neutralizing antibody is an important indicator of vaccine efficacy, of which IgG is the main component. IgG can be divided into four subclasses. Up to now, studies analysing the humoral response to SARS-CoV-2 vaccination have mostly focused on measuring total IgG, and the contribution of specific IgG subclasses remains elusive. The aim of this study is to investigate the kinetics of neutralizing antibodies and IgG subclasses, and to explore their relationships in people vaccinated with inactivated COVID-19 vaccine. We conducted a prospective cohort study in 174 healthy adults aged 18-59 years old who were administrated 2 doses of CoronaVac 14 days apart and a booster dose 1 year after the primary immunization, and followed up for 15 months. Blood samples were collected at various time points after primary and booster immunization. We used live SARS-CoV-2 virus neutralizing assay to determine neutralizing ability against the wild-type strain and 4 variants (Beta, Gamma, Delta and Omicron) and ELISA to quantify SARS-CoV-2 RBD-specific IgG subclasses. The results showed that the 2-dose primary immunization only achieved low neutralizing ability, while a booster shot can significantly enhance neutralizing ability against the wild-type strain, Beta, Gamma, Delta and Omicron variants. IgG1 and IgG3 were the most abundant serum antibodies, and IgG2 and IgG4 were hardly detected at any time. The ratio of IgG1/IgG3 was positively associated with the neutralization ability. The underlying mechanism requires further exploration.

Genomic Epidemiology of Imported Cases of COVID-19 in Guangdong Province, China, October 2020 - May 2021.

Objective: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been engendering enormous hazards to the world. We obtained the complete genome sequences of SARS-CoV-2 from imported cases admitted to the Guangzhou Eighth People's Hospital, which was appointed by the Guangdong provincial government to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 diversity was analyzed, and the mutation characteristics, time, and regional trend of variant emergence were evaluated. Methods: In total, 177 throat swab samples were obtained from COVID-19 patients (from October 2020 to May 2021). High-throughput sequencing technology was used to detect the viral sequences of patients infected with SARS-CoV-2. Phylogenetic and molecular evolutionary analyses were used to evaluate the mutation characteristics and the time and regional trends of variants. Results: We observed that the imported cases mainly occurred after January 2021, peaking in May 2021, with the highest proportion observed from cases originating from the United States. The main lineages were found in Europe, Africa, and North America, and B.1.1.7 and B.1.351 were the two major sublineages. Sublineage B.1.618 was the Asian lineage (Indian) found in this study, and B.1.1.228 was not included in the lineage list of the Pangolin web. A reasonably high homology was observed among all samples. The total frequency of mutations showed that the open reading frame 1a (ORF1a) protein had the highest mutation density at the nucleotide level, and the D614G mutation in the spike protein was the commonest at the amino acid level. Most importantly, we identified some amino acid mutations in positions S, ORF7b, and ORF9b, and they have neither been reported on the Global Initiative of Sharing All Influenza Data nor published in PubMed among all missense mutations. Conclusion: These results suggested the diversity of lineages and sublineages and the high homology at the amino acid level among imported cases infected with SARS-CoV-2 in Guangdong Province, China.

A Bivalent COVID-19 Vaccine Based on Alpha and Beta Variants Elicits Potent and Broad Immune Responses in Mice against SARS-CoV-2 Variants.

With the emergence and rapid spread of new pandemic variants, especially variants of concern (VOCs), the development of next-generation vaccines with broad-spectrum neutralizing activities is of great importance. In this study, SCTV01C, a clinical stage bivalent vaccine based on trimeric spike extracellular domain (S-ECD) of SARS-CoV-2 variants Alpha (B.1.1.7) and Beta (B.1.351) with a squalene-based oil-in-water adjuvant was evaluated in comparison to its two corresponding (Alpha and Beta) monovalent vaccines in mouse immunogenicity studies. The two monovalent vaccines induced potent neutralizing antibody responses against the antigen-matched variants, but drastic reductions in neutralizing antibody titers against antigen-mismatched variants were observed. In comparison, the bivalent vaccine SCTV01C induced relatively higher and broad-spectrum cross-neutralizing activities against various SARS-CoV-2 variants, including the D614G variant, VOCs (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.1.529), variants of interest (VOIs) (C.37, B.1.621), variants under monitoring (VUMs) (B.1.526, B.1.617.1, B.1.429, C.36.3) and other variants (B.1.618, 20I/484Q). All three vaccines elicited potent Th1-biased T-cell immune responses. These results provide direct evidence that variant-based multivalent vaccines could play important roles in addressing the critical issue of reduced protective efficacy against the existing and emerging SARS-CoV-2 variants.

Status of Humoral and Cellular Immune Responses within 12 Months following CoronaVac Vaccination against COVID-19.

Understanding immune memory to COVID-19 vaccines is critical for the design and optimal vaccination schedule for curbing the COVID-19 pandemic. Here, we assessed the status of humoral and cellular immune responses at 1, 3, 6, and 12 months after two-dose CoronaVac vaccination. A total of 150 participants were enrolled, and 136 of them completed the study through the 12-month endpoint. Our results show that, at 1 month after vaccination, both binding and neutralizing antibodies could be detected; the seropositive rate of binding antibodies and seroconversion rate of neutralizing antibodies were 99% and 50%, respectively. From 3 to 12 months, the binding and neutralizing antibodies declined over time. At 12 months, the binding and neutralizing antibodies were still detectable and significantly higher than the baseline. Gamma interferon (IFN-γ) and interleukin 2 (IL-2) secretion specifically induced by the receptor-binding domain (RBD) persisted at high levels until 6 months and could be observed at 12 months, while the levels of IL-5 and granzyme B (GzmB) were hardly detected, demonstrating a Th1-biased response. In addition, specific CD4+ T central memory (TCM), CD4+ effector memory (TEM), CD8+ TEM, and CD8+ terminal effector (TE) cells were all detectable and functional up to 12 months after the second dose, as the cells produced IFN-γ, IL-2, and GzmB in response to stimulation of SARS-CoV-2 RBD. Our work provides evidence that CoronaVac induced not only detectable binding and neutralizing antibody responses, but also functional SARS-CoV-2-specific CD4+ and CD8+ memory T cells for up to 12 months. IMPORTANCE CoronaVac is an inactivated vaccine containing whole-virion SARS-CoV-2, which has been approved in 43 countries for emergency use as of 26 November 2021. However, the long-term immune persistence of the CoronaVac vaccine is still unknown. Here, we reported the status of the persistence of antibodies and cellular responses within 12 months after two doses of CoronaVac. Such data are crucial to inform ongoing and future vaccination strategies to combat COVID-19.

Hydrophilic rhodamine B-loaded / boronic acid-modified graphene oxide nanocomposite as a substitute of enzyme-labeled second antibody for ultrasensitive detection of antibodies.

Enzyme-labeled secondary antibody is often used to amplify the output signal in the process of antibody detection. However, its preparation process is complex and time-consuming. Herein, we fabricated an innovative hydrophilic rhodamine B-loaded / boronic acid-modified graphene oxide (HRBGO) nanocomposite, used as a substitute of enzyme-labeled second antibody. The synthetic HRBGO was loaded with generous rhodamine B and modified with boronic acid. Therefore, the HRBGO could selectively label the carbohydrate chains of Fc fragment of primary antibody through specific boronate affinity recognition, and then perform signal output and amplification by releasing rhodamine B. To verify the practicability of HRBGO, trastuzumab as a humanized monoclonal antibody targeting human epidermal growth factor receptor-2 (HER2) was selected as model antibody. A glycosylation site-blocked / HER2-immobilized magnetic nanoparticles (GHMN) was also prepared for selectively capturing trastuzumab from complex samples via specific immunoaffinity. Because the glycosylation sites of HER2 can also be labeled with the HRBGO by boronate affinity recognition, these sites were blocked by a masking agent to minimize the background signal. For specific and ultrasensitive detection of trastuzumab, the integration of GHMN and HRBGO was proposed and optimized in detail. Trastuzumab detection based on HRBGO consisted of three steps: specific capture, selective labeling, and output signal. The proposed strategy provided ultrahigh sensitivity with limit of detection of 0.35 fg mL-1 and was successfully applied in the detection of trastuzumab in spiked serum sample with recovery and relative standard deviation in the range of 98.7-103.8% and 3.8-6.0%, respectively. To assess universal applicability, the HRBGO was also successfully used for the determination of anti-SARS-COV2 RBD antibody in human serum sample.

A Novel Virus Detection Strategy Enabled by TR512-Peptide-Based Bioorthogonal Capture and Enrichment of Preamplified Nucleic Acid.

High-cost viral nucleic acid detection devices (e.g., qPCR system) are limited resources for developing counties and rural areas, leading to underdiagnosis or even pandemics of viral infectious diseases. Herein, a novel virus detection strategy is reported. Such detection method is enabled by TR512-peptide-based biorthogonal capture and enrichment of commercially available Texas red fluorophore labeled nucleic acid on the functionalized paper. The GST-TR512 fusion protein electrostatically immobilized on the paper is constructed to retain the binding affinity of TR512-peptide toward Texas red fluorophore labeled nucleic acid released in the preamplification process, then the enrichment of analytes enhances fluorescence signal for rapid detection as volume of sample filters through the paper. The method is generally applicable to different nucleic acid preamplification strategies (PCR, RAA, CRISPR) and different virus types (Hepatitis B virus (HBV), African swine fever virus (ASFV), human papillomavirus (HPV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 or 2019 nCoV)). Finally, a full-set virus detection device is developed in house to detect the presence of Hepatitis B virus (HBV) viral gene in patients' blood samples. Taken together, we first apply TR512-peptide in the signal enrichment and the novel detection strategy may offer an inexpensive, rapid, and portable solution for areas with limited access to a standard diagnosis laboratory.

Evaluation of Immunogenicity by Pseudovirus Neutralization Assays for SARS-CoV-2 Variants after Primary and Booster Immunization.

OBJECTIVES: To determine the status of immune responses after primary and booster immunization for SARS-CoV-2 variants and evaluate the differences in disease resistance based upon titers of neutralizing antibodies (NAbs) against the variants. METHODS: Participants aged 18-59 years received 2 doses of inactivated COVID-19 vaccine, 14 days apart, and a booster dose after 12 months. Blood samples were collected before vaccination (baseline), 1 and 6 months after primary immunization, and at multiple instances within 21 days of the booster dose. NAbs against the spike protein of Wuhan-Hu-1 and 3 variants were measured using pseudovirus neutralization assays. RESULTS: Of 400 enrolled participants, 387 completed visits scheduled within 6 months of the second dose and 346 participants received the booster dose in the follow-up research. After 1 month of primary immunization, geometric mean titers (GMTs) of NAbs peaked for Wuhan-Hu-1, whereas GMTs of other variants were <30. After 6 months of primary immunization, GMTs of NAbs against all strains were <30. After 3 days of booster immunization, GMTs were unaltered, seroconversion rates reached approximately 50% after 7 days, and GMTs of NAbs against all strains peaked at 14 days. CONCLUSION: Two-dose of inactivated COVID-19 vaccine induced the formation of NAbs and memory-associated immune responses, and high titers of NAbs against the variants obtained after booster immunization may further improve the effectiveness of the vaccine.