Safety and immunogenicity of SW-BIC-213, a modified COVID-19 Lipo-Polyplex mRNA vaccine, in Laotian healthy adults aged 18 years and above: a Phase 1/2 trial (preprint)

Background The mRNA vaccine against SARS-CoV-2 has demonstrated remarkable efficacy in protecting against coronavirus disease 2019 (COVID-19), including providing high protection against severe disease during the emergence of variant waves. In this study, we aimed to investigate the safety and immunogenicity of a 2-dose regimen of the LPP-based mRNA vaccine, SW-BIC-213, in Laos. Methods For this phase 1/2 clinical trial, we recruited healthy adults aged 18-60 years (phase 1) or [≥]18 years (phase 2) from Mahosot Hospital (Vientiane) and Champhone District Hospital (Savannakhet). Participants with SARS-CoV-2 infection, previous COVID-19 vaccination, known allergies to any vaccine component, or pregnancy were excluded. In the phase 1 trial, 41 eligible participants were sequentially assigned to either the 25 g dose group (25 g) or the 45 g dose group (45 g) in accordance with their enrollment order, with 21 participants in 45 g dose group and 20 participants in 25 g dose group. In the phase 2 trial, 480 participants were randomly allocated (2:2:1 ratio) to either the 25 g dose group, 45 g dose group, or placebo group. The primary endpoints for the phase 1 trial were the incidence of local/systemic solicited adverse reactions/events (0-6 days after each vaccination dose), unsolicited adverse events (0-21 days and 0-28 days after the first and second dose of immunization, respectively), and serious adverse events from the first dose of vaccination to 28 days after completing the full course of immunization. In the phase 2 trial, the primary endpoints were the seroconversion rate and geometric mean titer (GMT) of SARS-CoV-2 S-protein specific IgG antibodies and neutralizing antibodies 14 days after the second dose in participants. As for neutralizing antibodies, we detected pseudo-virus neutralizing antibody against wild type (WT), Delta, BA.1 and BA.2. We also detected live viral neutralizing antibody against WT strain 14 days after the second dose. Furthermore, the safety endpoints were also measured during the trial. This seamless phase 1/2 trial was registered with ClinicalTrials.gov under the identifier NCT05144139. Results Between December 3, 2021, and March 31, 2022, a total of 41 participants were recruited in the phase 1 trial, while the phase 2 trial enrolled 480 participants from January 20 to July 6, 2022. In the phase 1 trial, a total of 32 subjects (80.0%) reported 103 cases of adverse reactions. All adverse reactions were limited to Grade 1-2. In the phase 2 trial, a total of 479 subjects, 372 subjects (77.7%) reported 929 cases of adverse reactions. All adverse reactions in severity of Grade 3 were manifested as fever (3.4%, 2.1% and 2.9% in 45 g dose, 25 g dose and placebo group respectively, only observed in adults), except which all other reactions were limited to Grade 1-2. All adverse reactions noted during the study were tolerable, predominantly transient, and resolved spontaneously. No serious adverse events (SAEs) related to vaccination were observed. In Phase 2 study, SW-BIC-213 could elicit a high level of seroconversion rate of pseudo-virus neutralizing antibody against WT (100.0% in 25 g dose group, 99.3% in 45 g dose group), Delta (99.2% in 25 g dose group, 98.0% in 45 g dose group), Omicron BA.1 (84.1% in 25 g dose group, 84.7% in 45 g dose group) and Omicron BA.2 (96.0% in 25 g dose group, 88.8% in 45 g dose group) at 14 days after the second dose. The pseudo-virus neutralizing antibody titer against WT, Delta, BA.1 and BA.2 was all significant higher (P<0.0001) in both 45 g dose group (1175.02, 620.62, 72.39 and 172.80) and 25 g dose group (885.80, 579.40, 47.24 and 101.96) compared with the placebo group (9.67, 10.66, 13.99 and 29.53) at 14 days after the second dose. As for live viral neutralizing antibodies against WT strain, the seroconversion rate could reach more than 94% at 14 days after second dose. The neutralizing antibody titer against WT strain was significantly higher (P<0.0001) in both 45 g dose group (315.00) and 25 g dose group (323.18) compared with the placebo group (8.51) at 14 days after second dose. Conclusion: COVID-19 mRNA vaccine SW-BIC-213 manifests a favorable safety profile and is highly immunogenic in eligible subjects aged [≥]18 years.

Diagnostic value and characteristic analysis of serum nucleocapsid antigen in COVID-19 patients.

Background: To date, several types of laboratory tests for coronavirus disease 2019 (COVID-19) diagnosis have been developed. However, the clinical importance of serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antigen (N-Ag) remains to be fully elucidated. In this study, we sought to investigate the value of serum SARS-CoV-2 N-Ag for COVID-19 diagnosis and to analyze N-Ag characteristics in COVID-19 individuals. Methods: Serum samples collected from 215 COVID-19 patients and 65 non-COVID-19 individuals were used to quantitatively detect N-Ag via chemiluminescent immunoassay according to the manufacturer's instructions. Results: The sensitivity and specificity of the N-Ag assay were 64.75% (95% confidence interval (95% CI) [55.94-72.66%]) and 100% (95% CI [93.05-100.00%]), respectively, according to the cut-off value recommended by the manufacturer. The receiver operating characteristic (ROC) curve showed a sensitivity of 100.00% (95% CI [94.42-100.00%]) and a specificity of 71.31% (95% CI [62.73-78.59%]). The positive rates and levels of serum SARS-CoV-2 N-Ag were not related to sex, comorbidity status or disease severity of COVID-19 (all P < 0.001). Compared with RT‒PCR, there was a lower positive rate of serum N-Ag for acute COVID-19 patients (P < 0.001). The positive rate and levels of serum SARS-CoV-2 N-Ag in acute patients were significantly higher than those in convalescent patients (all P < 0.001). In addition, the positive rate of serum SARS-CoV-2 N-Ag in acute COVID-19 patients was higher than that of serum antibodies (IgM, IgG, IgA and neutralizing antibodies (Nab)) against SARS-CoV-2 (all P < 0.001). However, the positive rate of serum SARS-CoV-2 N-Ag in convalescent COVID-19 patients was significantly lower than that of antibodies (all P < 0.001). Conclusion: Serum N-Ag can be used as a biomarker for early COVID-19 diagnosis based on appropriate cut-off values. In addition, our study also demonstrated the relationship between serum N-Ag and clinical characteristics.

Factors Associated with Primary Care Provider's Job Satisfaction and Organizational Commitment in China: A Machine Learning-Based Random Forest Analysis.

The objective of the study is to explore the factors that influence the job satisfaction and organizational commitment of primary care providers in China, with a focus on the impact of the COVID-19 pandemic and the rescission of restriction policies. We utilized the 20-item Minnesota Satisfaction Questionnaire (MSQ) and the 25-item organizational commitment survey to assess job satisfaction and organizational commitment. In total, 435 valid responses were included in our analysis. The average scores for job satisfaction and organizational commitment were 80.6 and 90.8. After a two-step tuning process, we built random forest models by machine learning. The results show income change, working years, working years in the current institute, and age were the four most important features associated with job satisfaction, organizational commitment, and most of their dimensions. The number of professional fields engaged, gender, job status, and types of endowment insurance were least associated. During pandemic time, income-related factors remain a core concern for primary care providers, whereas job security may lose its importance. These findings suggest that financial bonuses may be an effective way to boost morale, and age-specific motivation plans may be necessary.

Nirmatrelvir/Ritonavir for hemodialysis patients with COVID-19.

Background: Hemodialysis patients have a high risk of severe/critical COVID-19 and related high mortality, but nirmatrelvir/ritonavir is not recommended for hemodialysis patients with COVID-19 infection because of lack of evidence of safety. Objectives: Our study aims to evaluate the minimum plasma concentration (Cmin) of nirmatrelvir and its safety of different doses of nirmatrelvir/ritonavir in hemodialysis patients with mild COVID-19. Method: This was a prospective, two step, nonrandomized, open-label study. Participants were treated with nirmatrelvir 150 mg or 300 mg once a day (another 75 mg or 150 mg supplied after hemodialysis) and ritonavir 100 mg twice daily for 5 days, respectively. The primary outcome was the safety of nirmatrelvir/ritonavir, including the Cmin of nirmatrelvir and the number of adverse events (AE). The secondary outcome was the time of viral elimination in hemodialysis patients. Results: Adverse events were happened in 3 and 7 participants in the step 1 and step 2 group, respectively (p = 0.025). Among them, 2 and 6 participants were identified as drug-related adverse events (p = 0.054). No SAE or liver function damage happened. The Cmin of nirmatrelvir in step 1 and step 2 group were 5,294.65 ± 2,370.59 ng/mL and 7,675.67 ± 2,745.22 ng/mL (p = 0.125). The Cmin of the control group was 2,274.10 ± 1,347.25 ng/mL (p = 0.001 compared to step 2 and p = 0.059 compared to step 1). Compared to hemodialysis patients without nirmatrelvir/ritonavir, there were no statistical differences in overall viral elimination time (p = 0.232). Conclusion: In our study, two doses of nirmatrelvir/ritonavir appeared to be excessive for hemodialysis patients. Although all of the patients tolerated 5-day administration, nearly half of the patients experienced drug-related adverse events. In addition, the medication group did not show a significant advantage in the time of viral elimination.

Incidence of myopericarditis after mRNA COVID-19 vaccination: A meta-analysis with focus on adolescents aged 12-17 years.

BACKGROUND: The incidence of myopericarditis after mRNA COVID-19 vaccination among adolescents aged 12-17 years remains unknown. Therefore, we conducted a study to pool the incidence of myopericarditis following COVID-19 vaccination in this age group. METHODS: We did a meta-analysis by searching 4 electronic databases until February 6, 2023. The following main keywords were used: "COVID-19", "vaccines", "myocarditis", "pericarditis", and "myopericarditis". Observational studies reporting on adolescents aged 12-17 years who had myopericarditis in temporal relation to receiving mRNA COVID-19 vaccines were included. The pooled incidence of myopericarditis and 95 % confidence interval (CI) were calculated using a single-group meta-analysis. RESULTS: Fifteen studies were included. The pooled incidences of myopericarditis after mRNA COVID-19 vaccination among adolescents aged 12-17 years were 43.5 (95 % CI, 30.8-61.6) cases per million vaccine doses for both BNT162b2 and mRNA-1273 (39 628 242 doses; 14 studies), and 41.8 (29.4-59.4) cases for BNT162b2 alone (38 756 553 doses; 13 studies). Myopericarditis was more common among males (66.0 [40.5-107.7] cases) than females (10.1 [6.0-17.0] cases) and among those receiving the second dose (60.4 [37.6-96.9] cases) than those receiving the first dose (16.6 [8.7-31.9] cases). The incidences of myopericarditis did not differ significantly when grouped by age, type of myopericarditis, country, and World Health Organization region. None of the incidences of myopericarditis pooled in the current study were higher than those after smallpox vaccinations and non-COVID-19 vaccinations, and all of them were significantly lower than those in adolescents aged 12-17 years after COVID-19 infection. CONCLUSIONS: The incidences of myopericarditis after mRNA COVID-19 vaccination among adolescents aged 12-17 years were very rare; they were not higher than other important reference incidences. These findings provide an important context for health policy makers and parents with vaccination hesitancy to weight the risks and benefits of mRNA COVID-19 vaccination among adolescents aged 12-17 years.

Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants.

Mucosal immunity plays a significant role in the first-line defense against viruses transmitted and infected through the respiratory system, such as SARS-CoV-2. However, the lack of effective and safe adjuvants currently limits the development of COVID-19 mucosal vaccines. In the current study, we prepare an intranasal vaccine containing cationic crosslinked carbon dots (CCD) and a SARS-CoV-2 antigen, RBD-HR with spontaneous antigen particlization. Intranasal immunization with CCD/RBD-HR induces high levels of antibodies with broad-spectrum neutralization against authentic viruses/pseudoviruses of Omicron-included variants and protects immunized female BALB/c mice from Omicron infection. Despite strong systemic cellular immune response stimulation, the intranasal CCD/RBD-HR vaccine also induces potent mucosal immunity as determined by the generation of tissue-resident T cells in the lungs and airway. Moreover, CCD/RBD-HR not only activates professional antigen-presenting cells (APCs), dendritic cells, but also effectively targets nasal epithelial cells, promotes antigen binding via sialic acid, and surprisingly provokes the antigen-presenting of nasal epithelial cells. We demonstrate that CCD is a promising intranasal vaccine adjuvant for provoking strong mucosal immunity and might be a candidate adjuvant for intranasal vaccine development for many types of infectious diseases, including COVID-19.

Cost-effectiveness of COVID-19 vaccination: A systematic review.

OBJECTIVE: The COVID-19 vaccination strategy has been widely used to protect population health worldwide. This study aims to summarize the cost-effectiveness evidence of economic evaluation of COVID-19 vaccination strategies to provide evidence supporting the usage of COVID-19 vaccination, especially where the supply of COVID-19 vaccine is limited. METHODS: A systematic literature review was performed by searching both English and Chinese databases, including PubMed, Embase, Science Direct, Web of Science, Medline, Scopus, and CNKI. Articles published from January 1, 2020 to August 1, 2022 (PROSPERO registration number: CRD42022355442). RESULTS: Of the 1035 papers identified, a total of 28 English studies that met the preset criteria were included. COVID-19 vaccination and booster vaccination were cost-effective or cost-saving regardless of the vaccine type; vaccine efficacy, vaccine price, vaccine supply or prioritization, and vaccination pace were the influential factors of cost-effectiveness among different population groups. When supply is adequate, mass vaccination should be encouraged, while when supply is inadequate, prioritizing the high risk and the elderly is more cost-effective. CONCLUSIONS: COVID-19 vaccination strategies are economically favorable in a wide range of countries and population groups, and further research on suitable strategies for booster COVID-19 vaccination is needed.

Clinicopathological and immunological features of new onset kidney disease: a rare event after SARS-CoV-2 vaccination.

The onset of various kidney diseases has been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, detailed clinical and pathological features are lacking. We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021, and compared them with the reported cases in the literature. We obtained samples of blood, urine and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observations, were described. The SARS-CoV-2 spike protein and nucleoprotein were stained using the immunofluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay. The study group included 17 patients with a range of conditions including immune-complex-mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil-cytoplasmic-antibody-associated vasculitis, anti-glomerular basement membrane nephritis, acute tubulointerstitial nephritis and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and ten (58.82%) after the second dose. The kidney disease spectrum as well as clinicopathological features are similar across different types of SARS-CoV-2 vaccines. We found no definitive evidence of SARS-CoV-2 spike protein or nucleoprotein deposition in the kidney biopsy samples. Seropositive markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients. In conclusion, we observed various kidney diseases following SARS-CoV-2 vaccine administration, which show a high consistency across different types of SARS-CoV-2 vaccines. Our findings provide evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of SARS-CoV-2 vaccine renal safety.

Does online–offline channel integration matter for supply chain resilience? The moderating role of environmental uncertainty

PurposeDrawing on dynamic capability theory, this study investigates how online–offline channel integration (OOCI) affects a firm's supply chain resilience and how such an effect is moderated by market turbulence and regulatory uncertainty.Design/methodology/approachA sample of 273 Chinese firms that conduct online and offline business and hierarchical regression analysis were used to examine the research model.FindingsThe results suggest that the effect of OOCI on supply chain resilience differs in terms of its dimensions (i.e. information integration, transaction integration and service integration). While information integration and service integration were positively associated with supply chain resilience, transaction integration had a non-significant relationship with supply chain resilience. Moreover, market turbulence negatively moderated the effect of transaction integration and positively moderated the effect of service integration. Regulatory uncertainty positively moderated the effect of transaction integration and negatively moderated the effect of service integration. Implications and suggestions for future research are discussed.Originality/valueThis study examines the effect of OOCI on supply chain resilience. It further explores the influence of market turbulence and regulatory uncertainty on the relationship between OOCI and supply chain resilience.

A recombinant spike‐XBB.1.5 protein vaccine induces broad‐spectrum immune responses against XBB.1.5‐included Omicron variants of SARS‐CoV‐2

The XBB.1.5 subvariant has drawn great attention owing to its exceptionality in immune evasion and transmissibility. Therefore, it is essential to develop a universally protective coronavirus disease 2019 vaccine against various strains of Omicron, especially XBB.1.5. In this study, we evaluated and compared the immune responses induced by six different spike protein vaccines targeting the ancestral or various Omicron strains of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in mice. We found that spike‐wild‐type immunization induced high titers of neutralizing antibodies (NAbs) against ancestral SARS‐CoV‐2. However, its activity in neutralizing Omicron subvariants decreased sharply as the number of mutations in receptor‐binding domain (RBD) of these viruses increased. Spike‐BA.5, spike‐BF.7, and spike‐BQ.1.1 vaccines induced strong NAbs against BA.5, BF.7, BQ.1, and BQ.1.1 viruses but were poor in protecting against XBB and XBB.1.5, which have more RBD mutations. In sharp contrast, spike‐XBB.1.5 vaccination can activate strong and broadly protective immune responses against XBB.1.5 and other common subvariants of Omicron. By performing correlation analysis, we found that the NAbs titers were negatively correlated with the number of RBD mutations in the Omicron subvariants. Vaccines with more RBD mutations can effectively overcome the immune resistance caused by the accumulation of RBD mutations, making spike‐XBB.1.5 the most promising vaccine candidate against universal Omicron variants.

Study on basic and clinical application of Shufeng Jiedu Capsule in treating respiratory tract infection.

Shufeng Jiedu Capsule (SFJDC), composed of eight herbs, is a big brand traditional Chinese medicine (TCM) for the treatment of different respiratory tract infectious diseases with good clinical efficacy and few side effects. It is clinically applied to acute upper respiratory tract infection(URI), influenza, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), community-acquired pneumonia(CAP) and other diseases, due to its antibacterial, antiviral, anti-inflammatory, immunoregulatory and antipyretic activities. In particular, it has shown good clinical effects for COVID-19, and was included in the fourth to tenth editions of the 'Diagnosis and Treatment Protocol for COVID-19 (Trial)' by the National Health Commission. In recent years, studies on the secondary development which focus on the basic and clinical application of SFJDC have been widely reported. In this paper, chemical components, pharmacodynamic material basis, mechanisms, compatibility rule and clinical application were systematically summarized, in order to provide theoretical and experimental basis for further research and clinical application of SFJDC.

Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccine

BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is in desperate need of the third booster. It has been reported that heterologous boosters might produce more effective immunity against wild‐type SARS‐CoV‐2 and the variants. Additionally, the third heterologous protein subunit booster should be considered potentially. In the present study, we prepared a Delta full‐length spike protein sequence‐based mRNA vaccine as the "priming” shot and developed a recombinant trimeric receptor‐binding domain (RBD) protein vaccine referred to as RBD–HR/trimer as a third heterologous booster. Compared to the homologous mRNA group, the heterologous group (RBD–HR/trimer vaccine primed with two mRNA vaccines) induced higher neutralizing antibody titers against BA.4/5‐included SARS‐CoV‐2 variants. In addition, heterologous vaccination exhibited stronger cellular immune response and long‐lasting memory response than the homologous mRNA vaccine. In conclusion, a third heterologous boosting with RBD–HR/trimer following two‐dose mRNA priming vaccination should be a superior strategy than a third homologous mRNA vaccine. The RBD–HR/trimer vaccine becomes an appropriate candidate for a booster immune injection. We prepared a Delta full‐length spike protein sequence‐based mRNA vaccine (Figure A, B) and developed a recombinant trimeric receptor‐binding domain (RBD) protein vaccine (Figure C). Later, the mRNA vaccine was injected as the "priming” shot, and the RBD–HR/trimer vaccine was used as a third heterologous booster (Figure D).

Clinical characteristics and severity prediction score of Adenovirus pneumonia in immunocompetent adult.

BACKGROUND: Compared with children and immunocompromised patients, Adenovirus pneumonia in immunocompetent adults is less common. Evaluation of the applicability of severity score in predicting intensive care unit (ICU) admission of Adenovirus pneumonia is limited. METHODS: We retrospectively reviewed 50 Adenovirus pneumonia inpatients in Xiangtan Central Hospital from 2018 to 2020. Hospitalized patients with no pneumonia or immunosuppression were excluded. Clinical characteristics and chest image at the admission of all patients were collected. Severity scores, including Pneumonia severity index (PSI), CURB-65, SMART-COP, and PaO2/FiO2 combined lymphocyte were evaluated to compare the performance of ICU admission. RESULTS: Fifty inpatients with Adenovirus pneumonia were selected, 27 (54%) non-ICU and 23 (46%) ICU. Most patients were men (40 [80.00%]). Age median was 46.0 (IQR 31.0-56.0). Patients who required ICU care (n = 23) were more likely to report dyspnea (13[56.52%] vs 6[22.22%]; P = 0.002) and have lower transcutaneous oxygen saturation ([90% (IQR, 90-96), 95% (IQR, 93-96)]; P = 0.032). 76% (38/50) of patients had bilateral parenchymal abnormalities, including 91.30% (21/23) of ICU patients and 62.96% (17/27) of non-ICU patients. 23 Adenovirus pneumonia patients had bacterial infections, 17 had other viruses, and 5 had fungi. Coinfection with virus was more common in non-ICU patients than ICU patients (13[48.15%]VS 4[17.39%], P = 0.024), while bacteria and fungi not. SMART-COP exhibited the best ICU admission evaluation performance in Adenovirus pneumonia patients (AUC = 0.873, p < 0.001) and distributed similar in coinfections and no coinfections (p = 0.26). CONCLUSIONS: In summary, Adenovirus pneumonia is not uncommon in immunocompetent adult patients who are susceptible to coinfection with other etiological illnesses. The initial SMART-COP score is still a reliable and valuable predictor of ICU admission in non-immunocompromised adult inpatients with adenovirus pneumonia.

Trimeric protein vaccine based on Beta variant elicits robust immune response against BA.4/5-included SARS-CoV-2 Omicron variants.

The current Coronavirus Disease 2019 (COVID-19) pandemic, induced by newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants, posed great threats to global public health security. There is an urgent need to design effective next­generation vaccines against Omicron lineages. Here, we investigated the immunogenic capacity of the vaccine candidate based on the receptor binding domain (RBD). An RBDß-HR self-assembled trimer vaccine including RBD of Beta variant (containing K417, E484 and N501) and heptad repeat (HR) subunits was developed using an insect cell expression platform. Sera obtained from immunized mice effectively blocked RBD-human angiotensin-converting enzyme 2 (hACE2) binding for different viral variants, showing robust inhibitory activity. In addition, RBDß-HR/trimer vaccine durably exhibited high titers of specific binding antibodies and high levels of cross-protective neutralizing antibodies against newly emerging Omicron lineages, as well as other major variants including Alpha, Beta, and Delta. Consistently, the vaccine also promoted a broad and potent cellular immune response involving the participation of T follicular helper (Tfh) cells, germinal center (GC) B cells, activated T cells, effector memory T cells, and central memory T cells, which are critical facets of protective immunity. These results demonstrated that RBDß-HR/trimer vaccine candidates provided an attractive next-generation vaccine strategy against Omicron variants in the global effort to halt the spread of SARS-CoV-2.

Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5-included SARS-CoV-2 variants than homologous vaccination of mRNA vaccine.

BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in desperate need of the third booster. It has been reported that heterologous boosters might produce more effective immunity against wild-type SARS-CoV-2 and the variants. Additionally, the third heterologous protein subunit booster should be considered potentially. In the present study, we prepared a Delta full-length spike protein sequence-based mRNA vaccine as the "priming" shot and developed a recombinant trimeric receptor-binding domain (RBD) protein vaccine referred to as RBD-HR/trimer as a third heterologous booster. Compared to the homologous mRNA group, the heterologous group (RBD-HR/trimer vaccine primed with two mRNA vaccines) induced higher neutralizing antibody titers against BA.4/5-included SARS-CoV-2 variants. In addition, heterologous vaccination exhibited stronger cellular immune response and long-lasting memory response than the homologous mRNA vaccine. In conclusion, a third heterologous boosting with RBD-HR/trimer following two-dose mRNA priming vaccination should be a superior strategy than a third homologous mRNA vaccine. The RBD-HR/trimer vaccine becomes an appropriate candidate for a booster immune injection.

Experiences investigation for COVID-19 vaccination in patients with epilepsy.

OBJECTIVE: This study aimed to investigate the safety of COVID-19 vaccination in patients with epilepsy (PWE) and their willingness to undergo vaccination. METHODS: This was a survey study. A questionnaire was completed by patients of the outpatient clinic and hospital ward at The Third Xiangya Hospital in 2021. The survey included general, epilepsy-specific, and COVID-specific questions. RESULTS: In total, 120 valid questionnaires were returned. Eighty-nine of 120 patients (74.2%) were not vaccinated, and 31 (25.8%) received the COVID-19 vaccine. Of the 31 vaccinated PWE, one (3.2%) had worsening of seizures and four (12.9%) had adverse reactions that were characteristic of the COVID-19 vaccine. The other 26 patients (83.9%) reported no adverse reactions, Moreover, there was no significant difference between the 18 PWE with well-controlled seizureand the 13 PWE with poorly-controlled seizure. Of the 89 unvaccinated PWE, 69.7% (62/89) were willing to receive the COVID-19 vaccine, 28.1% (25/89) were unsure, and 2.2% (2/89) declined to be vaccinated. SIGNIFICANCE: Among PWE, few adverse reactions occurred following the COVID-19 vaccination. Most PWE were willing to receive the COVID-19 vaccine. COVID-19 vaccination is safe for PWE.

Ultrasound-Guided Capsular Thyroid Injection Therapy With Dexamethasone and Lidocaine Mixture for Subacute Thyroiditis: A Single-Center Study.

OBJECTIVES: Subacute thyroiditis (SAT) is a self-limiting, inflammatory thyroid disease possibly caused by viral infection. In recent years, the incidence of SAT is increasing, especially during the pandemic of the COVID-19. This study aimed to evaluate the efficacy, safety, and recovery time of capsular thyroid injection therapy under ultrasound guidance for SAT. METHODS: A total of 73 patients with SAT were divided into two groups. Patients in group A (n = 48) received an ultrasound-guided capsular injection consisting of dexamethasone (DEX) and lidocaine in the thyroid lesion area, while patients in group B (n = 25) received oral prednisolone (PSL). The two groups were compared for pain relief and treatment duration, the recovery time of thyroid function, recurrence rates, hypothyroidism incidence, and drug-related side effects. RESULTS: The follow-up time was 1 year. In group A, the duration of pain relief, treatment, and recovery time of thyroid function were significantly shorter than that in group B (P < .05), and no statistically significant differences in recurrence rate or incidence of hypothyroidism were observed (P > .05). Weight gain was significantly higher in group A at the end of treatment (P < .001). CONCLUSIONS: Compared with oral PSL treatment, ultrasound-guided local injection of DEX and lidocaine into the capsular thyroid is a safe and effective procedure that can significantly reduce the treatment time of SAT.

Impactful publications of critical care medicine research in China: A bibliometric analysis.

Background: Although publications have been increasing rapidly, the research quality has yet to improve in the field of critical care medicine (CCM) in China. This study aimed at investigating the current status of and the influential factors for impactful publications in CCM research by Chinese authors. Methods: Publications by authors with the affiliation of critical care medicine department or intensive care unit (CCM/ICU) in Chinese as well as American hospitals from 2001 to 2020 were retrieved from the Web of Science Core Collection (WoSCC) database for this bibliometric analysis. Moreover, statistical analyses to test factors affecting impactful publications by Chinese authors were performed. Results: Of 13,487 articles retrieved by this search strategy, 6,622 were published by Chinese authors as first or corresponding authors. The annual publications by Chinese authors have been rapidly increasing from 2001 to 2020, and so did the citations to these articles. However, the proportion in the world of publications by Chinese authors was much less than that by American authors each year [M (IQR): 1.85 (9.592) vs. 27.77 (7.3), p < 0.001]. In addition, impactful articles were significantly less published by Chinese than by American authors, including articles either in journals with a high impact factor (p < 0.001) or in the top 10 journals in the field of CCM (5.4 vs 13.4%, p < 0.001), and articles with high citation frequency as well (p < 0.001). Moreover, the percentage of impactful publications by Chinese authors was likely associated with academic background and regions of the author's affiliations, funds support, public health events of COVID-19, and collaboration between authors. Conclusion: Our results demonstrated that CCM research in China grew rapidly in the recent 20 years. However, the impactful publications remained limited, largely owing to the shortage of comprehensive research training, inactive collaboration, and underfunded CCM research.

Single-cell transcriptomics identifies different immune signatures between macrophage activation-like syndrome and immune paralysis in sepsis (preprint)

Different immune phenotypes characterize sepsis patients, including hyperinflammation and/or immunosuppression, but the biological mechanisms driving this heterogeneity remain largely unknown. We used single-cell RNA sequencing to profile circulating leukocytes of healthy controls and sepsis patients classified as either hyperinflammatory (macrophage activation-like syndrome [MALS]), immune paralysis, or unclassified (when criteria for neither of these two immune subgroups were applicable). Pronounced differences were detected in the transcriptional signature of monocytes from sepsis patients, with clear distinction between MALS and immune paralysis patients. Unsupervised clustering analysis revealed the existence of MALS-specific monocyte clusters, as well as one sepsis-specific monocyte cluster that was linked to disease severity. In separate cohorts, urosepsis was characterized by heterogeneous MALS and immunosuppression monocyte signatures, while MALS-specific monocyte clusters showed overlapping transcriptional signatures with severe COVID-19. In conclusion, our findings shed light on the heterogeneous immune landscape underlying sepsis, and provide opportunities for patient stratification for future therapeutic development.

Analysis of network public opinion on COVID-19 epidemic based on the WSR theory.

Objective: To obtain the influencing factors of public opinion reactions and to construct a basic framework of the factors causing the occurrence of online public opinion in the epidemic area. Methods: The hot news comments on microblogs during the epidemic in Shanghai were collected and analyzed with qualitative analysis, grounded theory, and the "Wuli-Shili-Renli" (WSR) methodology as an auxiliary method. Results: (1) Three core categories of the Wuli system, the Shili system, and the Renli system, 15 main categories, and 86 categories that influence the development of network public opinion are obtained. (2) WSR Elements Framework Of Network Public Opinion (WSR-EFONPO) is established. (3) The WSR-EFONPO is explained. Conclusion: The framework of factors for the occurrence of network public opinion is proposed, and the development process of network public opinion under COVID-19 is sorted out, which is of great theoretical value in guiding the public in the epidemic area to form reasonable behavior.