Heterologous boost with mRNA vaccines against SARS-CoV-2 Delta/Omicron variants following an inactivated whole-virus vaccine.

The coronavirus SARS-CoV-2 has mutated quickly and caused significant global damage. This study characterizes two mRNA vaccines ZSVG-02 (Delta) and ZSVG-02-O (Omicron BA.1), and associating heterologous prime-boost strategy following the prime of a most widely administrated inactivated whole-virus vaccine (BBIBP-CorV). The ZSVG-02-O induces neutralizing antibodies that effectively cross-react with Omicron subvariants. In naïve animals, ZSVG-02 or ZSVG-02-O induce humoral responses skewed to the vaccine's targeting strains, but cellular immune responses cross-react to all variants of concern (VOCs) tested. Following heterologous prime-boost regimes, animals present comparable neutralizing antibody levels and superior protection against Delta and Omicron BA.1variants. Single-boost only generated ancestral and omicron dual-responsive antibodies, probably by "recall" and "reshape" the prime immunity. New Omicron-specific antibody populations, however, appeared only following the second boost with ZSVG-02-O. Overall, our results support a heterologous boost with ZSVG-02-O, providing the best protection against current VOCs in inactivated virus vaccine-primed populations.

Management experience of a designated hospital for children with coronavirus disease 2019. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žå„¿ç«¥å®šç‚¹åŒ»é™¢ç®¡ç†ç»éªŒåˆ†äº«.

The global pandemic of coronavirus disease 2019 (COVID-19) has brought great challenges to the traditional medical model. During the outbreak of COVID-19 in Shanghai, China, from March to May, 2022, there was a significant increase in the number of pediatric cases due to high transmissibility, immune escape, and vaccine breakthrough capacity of Omicron variants. The designated hospitals for children with COVID-19 served as a connecting link between children's specialized hospitals and mobile cabin hospitals. From April 7 to June 2, 2022, a total of 871 children with COVID-19 were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine (South Branch), a designated hospital for children with COVID-19. Among these patients, 568 (65.2%) were children under 3 years old, 870 (99.9%) were mild or moderate, and 1 was severe. This article reports the experience in the management of pediatric cases in this designated hospital, which included the following aspects: establishing an optimal case-admission process; strengthening multidisciplinary standardized diagnosis and treatment; optimizing the management, warning, and rescue system for severe COVID-19; implementing family-centered nursing care; formulating an individualized traditional Chinese medicine treatment regimen; optimizing the discharge process and strengthening bed turnover; implementing strict whole-process control to reduce the risk of nosocomial infection; constructing a structured medical record system and using information platforms to adapt to the work mode of large-volume cases; conducting scientific research and sharing the experience in diagnosis and treatment.

Rapid Antigen Diagnostics as Frontline Testing in the COVID-19 Pandemic.

The ongoing global COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in significant loss of life since December 2019. Timely and precise virus detection has been proven as an effective solution to reduce the spread of the virus and to track the epidemic. Rapid antigen diagnostics has played a significant role in the frontline of COVID-19 testing because of its convenience, low cost, and high accuracy. Herein, different types of recently innovated in-lab and commercial antigen diagnostic technologies with emphasis on the strengths and limitations of these technologies including the limit of detection, sensitivity, specificity, affordability, and usability are systematically reviewed. The perspectives of assay development are looked into.

Handheld Microfluidic Filtration Platform Enables Rapid, Low-Cost, and Robust Self-Testing of SARS-CoV-2 Virus (Small 52/2021)

COVID-19 Diagnostics In article number 2104009, Jiang Xu, Yan Zhang, Taotao Lao, and co-workers present a handheld microfluidic filtration platform that enables rapid, low-cost and robust self-testing of the SARS-CoV-2 virus. The cover design emphasizes its important advantages: (1) Equipment-free handheld injection, represented by the hands manipulation;(2) Visible and easy readout: a Taichi diagram is used to distinguish the negative/positive results, which is in line with the meaning of Taichi (Yin/Yang) in traditional Chinese culture. The Taichi eyes are filled with illustrational structures of negative/positive nanocomplexes;(3) Reusable chips: the flow arrows at both inlet and outlet indicate that the chip can be repeatedly cleaned and injected.

Handheld Microfluidic Filtration Platform Enables Rapid, Low-Cost, and Robust Self-Testing of SARS-CoV-2 Virus.

Here, a novel microfluidic test kit combining ultrahigh throughput hydrodynamic filtration and sandwich immunoassay is reported. Specifically, nano and microbeads coated with two different, noncompetitive antibodies, are used to capture the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) proteins simultaneously, forming larger complexes. Microfluidic filtration discards free nanobeads but retains antigen-bridged complexes in the observation zone, where a display of red color indicates the presence of antigen in the sample. This testing platform exhibits high throughput separation (<30 s) and enrichment of antigen that exceeds the traditional lateral flow assays or microfluidic assays, with a low limit of detection (LoD) < 100 copies mL-1 . In two rounds of clinical trials conducted in December 2020 and August 2021, the assays demonstrate high sensitivities of 95.4% and 100%, respectively, which proves this microfluidic test kit is capable of detecting SARS-CoV-2 virus variants evolved over significant periods of time. Furthermore, the mass-produced chip can be fabricated at a cost of $0.98/test and the robust design allows the chip to be reused for over 50 times. All of these features make the microfluidic test kit particularly suitable for areas with inadequate medical infrastructure and a shortage of laboratory resources.

Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study.

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.

Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis

BACKGROUND: Celastrol has been proven effective in anti-inflammatory but was limited in the clinic due to the poor solubility and side effects induced by low bioavailability. Osteoarthritis has acidic and inflammatory environment. Our aim was to load celastrol into HMSNs and capped with chitosan to construct a pH-responsive nanoparticle medicine (CSL@HMSNs-Cs), which is of high solubility for osteoarthritis intra-articular injection treatment. METHODS: The CSL@HMSNs-Cs were assembled and the characteristics were measured. The CSL@HMSNs-Cs was applied in vitro in the chondrocytes collected from rats cartilage tissue and in vivo in the MIA induced knee osteoarthritis rats via intra-articular injection. Cytotoxicity assay, pH-responsive release, pain behavior, MRI, safranin o fast green staining, ELISA and western blot analysis were applied to evaluate the bioavailability and therapeutic effect of CSL@HMSNs-Cs. RESULTS: CSL@HMSNs-Cs was stable due to the protection of the chitosan layers in alkaline environment (pH = 7.7) but revealed good solubility and therapeutic effect in acidic environment (pH = 6.0). The cytotoxicity assay showed no cytotoxicity at relatively low concentration (200 µg/mL) and the cell viability of chondrocytes stimulated by IL-1ß was increased in CSL@HMSNs-Cs group. Paw withdrawal threshold in CSL@HMSNs-Cs group is increased, and MRI and Safranin O Fast Green staining showed improvements in articular surface erosion and joint effusion. The upregulated expression levels of IL-1ß, TNF-α, IL-6, MMP-3 and MMP-13 and NF-κB signaling pathway of chondrocytes were inhibited in CSL@HMSNs-Cs group. CONCLUSION: Hollow mesoporous silica nanoparticles were an ideal carrier for natural drugs with poor solubility and were of high biocompatibility for intra-articular injection. These intra-articular injectable CSL@HMSNs-Cs with improved solubility, present a pH-responsive therapeutic strategy against osteoarthritis.

Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in Patients With Coronavirus Disease 2019.

Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported in almost all countries globally. No effective therapy has been documented for COVID-19, and the role of convalescent plasma therapy is unknown. In the current study, 6 patients with COVID-19 and respiratory failure received convalescent plasma a median of 21.5 days after viral shedding was first detected, all tested negative for SARS-CoV-2 RNA within 3 days after infusion, and 5 eventually died. In conclusion, convalescent plasma treatment can end SARS-CoV-2 shedding but cannot reduce the mortality rate in critically ill patients with end-stage COVID-19, and treatment should be initiated earlier.

Clinical course and treatment efficacy of COVID-19 near Hubei Province, China: A multicentre, retrospective study.

Currently, COVID-19 has been reported in nearly all countries globally. To date, little is known about the viral shedding duration, clinical course and treatment efficacy of COVID-19 near Hubei Province, China. This multicentre, retrospective study was performed in 12 hospitals in Henan and Shaanxi Provinces from 20 January to 8 February 2020. Clinical outcomes were followed up until 26 March 2020. The viral shedding duration, full clinical course and treatment efficacy were analysed in different subgroups of patients. A total of 149 COVID-19 patients were enrolled. The median age was 42 years, and 61.1% (91) were males. Of them, 133 (89.3%) had fever, 131 of 144 (91%) had pneumonia, 27 (18.1%) required intensive care unit (ICU) management, 3 (2%) were pregnant, and 3 (2%) died. Two premature newborns were negative for SARS-CoV-2. In total, the median SARS-CoV-2 shedding period and clinical course were 12 (IQR: 9-17; mean: 13.4, 95% CI: 12.5, 14.2) and 20 (IQR: 16-24; mean: 21.2, 95% CI: 20.1, 22.3) days, respectively, and ICU patients had longer median viral shedding periods (21 [17-24] versus 11 [9-15]) and clinical courses (30 [22-33] vs. 19 [15.8-22]) than non-ICU patients (both p < .0001). SARS-CoV-2 clearances occurred at least 2 days before fatality in 3 non-survivors. Current treatment with any anti-viral agent or combination did not present the benefit of shortening viral shedding period and clinical course (all p > .05) in real-life settings. In conclusion, the viral shedding duration and clinical course in Henan and Shaanxi Provinces were shorter than those in Hubei Province, and current anti-viral therapies were ineffective for shortening viral shedding duration and clinical course in real-world settings. These findings expand our knowledge of the SARS-CoV-2 infection and may be helpful for management of the epidemic outbreak of COVID-19 worldwide. Further studies concerning effective anti-viral agents and vaccines are urgently needed.