COVID-19 vaccines based on viral nanoparticles displaying a conserved B-cell epitope show potent immunogenicity and a long-lasting antibody response.

The COVID-19 pandemic caused by SARS-CoV-2 sparked intensive research into the development of effective vaccines, 50 of which have been approved thus far, including the novel mRNA-based vaccines developed by Pfizer and Moderna. Although limiting the severity of the disease, the mRNA-based vaccines presented drawbacks, such as the cold chain requirement. Moreover, antibody levels generated by these vaccines decline significantly after 6 months. These vaccines deliver mRNA encoding the full-length spike (S) glycoprotein of SARS-CoV-2, but must be updated as new strains and variants of concern emerge, creating a demand for adjusted formulations and booster campaigns. To overcome these challenges, we have developed COVID-19 vaccine candidates based on the highly conserved SARS CoV-2, 809-826 B-cell peptide epitope (denoted 826) conjugated to cowpea mosaic virus (CPMV) nanoparticles and bacteriophage Qß virus-like particles, both platforms have exceptional thermal stability and facilitate epitope delivery with inbuilt adjuvant activity. We evaluated two administration methods: subcutaneous injection and an implantable polymeric scaffold. Mice received a prime-boost regimen of 100 µg per dose (2 weeks apart) or a single dose of 200 µg administered as a liquid formulation, or a polymer implant. Antibody titers were evaluated longitudinally over 50 weeks. The vaccine candidates generally elicited an early Th2-biased immune response, which stimulates the production of SARS-CoV-2 neutralizing antibodies, followed by a switch to a Th1-biased response for most formulations. Exceptionally, vaccine candidate 826-CPMV (administered as prime-boost, soluble injection) elicited a balanced Th1/Th2 immune response, which is necessary to prevent pulmonary immunopathology associated with Th2 bias extremes. While the Qß-based vaccine elicited overall higher antibody titers, the CPMV-induced antibodies had higher avidity. Regardless of the administration route and formulation, our vaccine candidates maintained high antibody titers for more than 50 weeks, confirming a potent and durable immune response against SARS-CoV-2 even after a single dose.

External Supports Are Associated With the COVID-19 Vaccination in Chinese Breast Cancer Patients: A Cross-Sectional Survey.

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic. Breast cancer is the most commonly diagnosed malignant cancer in China. Considering the specific national conditions, no evidence is available for factors associated with COVID-19 vaccination in patients with breast cancer. Methods: This was a cross-sectional survey, fielded from June 21 through June 27, 2021. A total of 944 nationally representative samples of Chinese breast cancer patients participating in the survey were included. Participant surveys included questions addressing who finished COVID-19 vaccination with the question "Have you taken the COVID-19 vaccine?", and response options were "Yes" and "No". Results: Overall, 730 (77.33%) women with breast cancer were unvaccinated, and only 214 (22.67%) were vaccinated with the COVID-19 vaccine. After adjusting for potential confounders, including both sociodemographic and clinical characteristics, we found that external support, including positive doctor suggestions (odds ratio (OR): 5.52; 95% confidence interval (CI): 3.50 - 8.71; P < 0.0001), positive support from surrounding people (OR: 11.65; 95% CI: 7.57 - 17.91; P < 0.0001), and negative initiative from the community (OR: 0.15; 95% CI: 0.06 - 0.35; P < 0.0001), was associated with COVID-19 vaccination rates among breast cancer patients. These results remain stable in subgroup analyses. We found that most participants (82.52%) understood the necessity of COVID-19 vaccinations in China was strong; however, the recognition regarding the COVID-19 vaccine showed different patterns between vaccinated and unvaccinated participants. Conclusions: Our findings suggest external support, including vaccination suggestions from surgeons or oncologists, vaccination suggestions from associated people, and residents' committee mandated vaccinations, was associated with the COVID-19 vaccination rates. Interventions regarding these factors and improving publicity as well as education regarding COVID-19 vaccines among breast cancer patients are warranted.

Age-Specific Transmissibility Change of COVID-19 and Associations With Breathing Air Volume, Preexisting Immunity, and Government Response.

Background: The comprehensive impacts of diverse breathing air volumes and preexisting immunity on the host susceptibility to and transmission of COVID-19 at various pandemic stages have not been investigated. Methods: We classified the US weekly COVID-19 data into 0-4, 5-11, 12-17, 18-64, and 65+ age groups and applied the odds ratio (OR) of incidence between one age group and the 18-64 age group to delineate the transmissibility change. Results: The changes of incidence ORs between May, 2020 and November, 2021 were 0.22-0.66 (0-4 years), 0.20-1.34 (5-11 years), 0.39-1.04 (12-17 years), and 0.82-0.73 (65+ years). The changes could be explained by age-specific preexisting immunity including previous infection and vaccination, as well as volumes of breathing air. At the early pandemic, the ratio that 0-4-year children exhaled one-fifth of air and discharge a similar ratio of viruses was closely associated with incidence OR between two age groups. While, after a rollout of pandemic and vaccination, the much less increased preexisting immunity in children resulted in rapidly increased OR of incidence. The ARIMA model predicted the largest increase of relative transmissibility in 6 coming months in 5-11-year children. Conclusions: The volume of breathing air may be a notable factor contributing to the infectivity of COVID-19 among different age groups of patients. This factor and the varied preexisting greatly shape the transmission of COVID-19 at different periods of pandemic among different age groups of people.

Associations Between Short-Term Ambient Particulate Matter Exposure and The Risk of Severe COVID-19 (preprint)

Background: Previous studies have suggested the relation between outdoor air pollution and the onset risk of Corona Virus Disease 2019 (COVID-19). However, there is a lack of data related to the severity of the disease, especially in China. Methods We recruited a group of COVID-19 patients diagnosed in a recent large-scale outbreak caused by Delta variants in eastern China. We collected ambient air pollution data of the same period where the case occurred and applied a generalized linear model (GLM) to analyze the effects of short-term outdoor ambient particulate matter (PM) exposure on the risk of severe COVID-19. Results A total of 476 confirmed adult patients were recruited, of which 42 (8.82%) had a severe illness. With a unit increase in PM 10 , the risk of severe COVID-19 increased by 47.64% (95% confidence interval [CI]: 27.67, 70.73) at lag 0-14 days, 65.00% (95% CI: 35.18, 101.40) at lag 0-21 days, and 69.44% (95% CI: 37.03, 109.50) at lag 0-28 days, respectively. The association remained significant at lag 0-14 days or 0-28 days in the multi-pollutant models. With a unit increase in PM 2.5 , the risk of severe COVID-19 increased by 49.47% (95% CI: 19.61, 86.78) at lag 0-14 days, 97.61% (95% CI: 45.92, 167.60) at lag 0-21 days, and 120.27% (95% CI: 56.53, 209.98) at lag 0-28 days, respectively. The association remained significant at lag 0-21 days or 0-28 days in the multi-pollutant models. Conclusions Our results indicated that short-term exposure to outdoor PM was positively related to the risk of severe COVID-19, and reducing air pollution may contribute to the control of COVID-19.

Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia.

AIMS: We recently reported five cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) 7-10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against corona virus disease 2019 (COVID-19). We aimed to investigate the pathogenic immunological responses operating in these patients. METHODS AND RESULTS: We assessed circulating inflammatory markers by immune assays and immune cell phenotyping by flow cytometry analyses and performed immunoprecipitation with anti-platelet factor (PF)4 antibody in plasma samples followed by mass spectrometry from all five patients. A thrombus was retrieved from the sinus sagittal superior of one patient and analysed by immunohistochemistry and flow cytometry. Precipitated immune complexes revealed multiple innate immune pathway triggers for platelet and leucocyte activation. Plasma contained increased levels of innate immune response cytokines and markers of systemic inflammation, extensive degranulation of neutrophils, and tissue and endothelial damage. Blood analyses showed activation of neutrophils and increased levels of circulating H3Cit, dsDNA, and myeloperoxidase-DNA complex. The thrombus had extensive infiltration of neutrophils, formation of neutrophil extracellular traps (NETs), and IgG deposits. CONCLUSIONS: The results show that anti-PF4/polyanion IgG-mediated thrombus formation in VITT patients is accompanied by a massive innate immune activation and particularly the fulminant activation of neutrophils including NETosis. These results provide novel data on the immune response in this rare adenoviral vector-induced VITT.

Xuebijing injection in the treatment of COVID-19: a retrospective case-control study.

BACKGROUND: Neither a vaccine nor specific therapeutic drugs against 2019 novel coronavirus have been developed. Some studies have shown that Xuebijing injection (XBJ) can exert an anti-inflammatory effect by inhibiting the production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and other cytokines. This study aimed to investigate the effect of XBJ on coronavirus disease 2019 (COVID-19) and its effects on IL-6 and tumor necrosis alpha TNF-α. METHODS: A total of 42 patients, who were diagnosed with COVID-19 and treated with XBJ combined with routine treatment at Chongqing University Three Gorges Hospital between January 20, 2020, and March 11, 2020, were selected as the observation group. A control group comprising 16 patients who received routine treatment was also established, and cases were matched from the observation group on a 1:1 basis according to age, comorbidities, and mild and severe disease. The clinical symptoms, laboratory test indexes, and changes in computed tomography (CT) scans of patients in the two groups were observed at the time of admission and 7 days after treatment, and the time taken for the patients to produce a negative nucleic acid test was also recorded. RESULTS: There were no significant differences in baseline data between the two groups. After treatment, there were significant improvements in IL-6 levels and body temperature in the observation group as compared with the control group. Particularly in severe patients, the reduction in body temperature in the observation group was greater than that in the control group (P<0.05). A higher number of patients in the observation group showed improved CT imaging results compared with the control group, and the time taken to produce a negative nucleic acid test was shorter in the observation group than in the control group; however, the differences were not statistically significant (P>0.05). Furthermore, there were no significant differences in TNF-α and IL-10 between the two groups. CONCLUSIONS: The results of this study suggest that routine treatment combined with XBJ can better improve the clinical outcomes of COVID-19 patients.

Decontamination of surgical face masks and N95 respirators by dry heat pasteurization for one hour at 70°C.

BACKGROUND: The need for protective masks greatly exceeds their global supply during the current COVID-19 pandemic. METHODS: We optimized the temperature used in the dry heat pasteurization method to destroy pathogens and decontaminate masks while retaining their filtering capacity. RESULTS: The current study showed that dry heat at both 60°C and 70°C for 1 hour could successfully kill 6 species of respiratory bacteria and one fungi species, and inactivate the H1N1 indicator virus. After being heated at 70°C for 1, 2, and 3 hours, the N95 respirators and surgical face masks showed no changes in their shape and components. The filtering efficiency of bacterial aerosol for N95 respirators were 98%, 98%, and 97% after being heated for 1, 2, and 3 hour, respectively, all of which were over the 95% efficiency required and similar to the value before being heated (99%). The filtering efficiency for surgical face masks was 97%, 97%, and 96% for 1, 2, and 3 hours of heating, respectively, all of which were also similar to the value before being heated (97%). CONCLUSIONS: This method can be used at home and can significantly resolve the current shortage of masks.

Clinical features and treatment of COVID-19 patients in northeast Chongqing.

The outbreak of the novel coronavirus in China (SARS-CoV-2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID-19 were enrolled. The median age was 47 years (interquartile range, 36-55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty-three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d-dimer, lactate dehydrogenase, PCT, ALB, C-reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID-19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID-19.