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1.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-330621

ABSTRACT

Background: Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity has raised the need for booster vaccinations. However, which combination of COVID-19 vaccines offers the strongest immune response against Omicron variant is unknown. Methods: This randomized, subject-blinded, controlled trial assess the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2+BNT162b2+BNT162b2;‘BBB’) or heterologous mRNA booster vaccine (BNT162b2+BNT162b2+mRNA-1273;‘BBM’). Primary endpoint was the level of neutralizing antibodies against SARS-CoV-2 wild-type and VOCs at Day 28. Results: 51 participants were allocated to BBB and 49 to BBM;50 and 48 respectively were analyzed for safety and immunogenicity outcomes. At Day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22,382 IU/mL 95% CI, 18,210 to 27,517) vs BBM (29,751 IU/mL 95% CI, 25,281 to 35,011, p=0·034) as was the median level of neutralizing antibodies: BBB 99.0% (IQR 97·9 to 99·3%) vs BBM 99.3% (IQR 98·8 to 99·5%, p=0·021). On sub-group analysis, significant differences in mean spike antibody titer and live Omicron neutralization titer was only observed in older adults. Median surrogate neutralizing antibody level against all VOCs was also significantly higher with BBM in older adults, and against Omicron was BBB 72·8% (IQR 54·0 to 84·7%) vs BBM 84·3% (IQR 78·1 to 88·7%, p=0·0073). Both vaccines were well tolerated. Conclusions: Heterologous mRNA-1273 booster vaccination induced a stronger neutralizing response against the Omicron variant in older individuals compared with homologous BNT123b2.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310725

ABSTRACT

Background: In December 2019, COVID-19 emerged in Wuhan, China. By 8 July 2020, the cumulative number of infected people worldwide had exceeded 11.50 million. It has been reported that a variety of indicators, including lymphocytes, can predict the progression of COVID-19 disease, but the clinical application value of eosinophils has not received widespread attention. It’s specific changes in the course of the disease, as well as the relationship with severity and prognosis of COVID-19 patients, need to be further studied.Method: In this multicenter, retrospective study, we collected data on laboratory-confirmed 482 COVID-19 patients from three hospitals in Wuhan, China, who died or were discharged between February 1, 2020, and February 20, 2020. By collecting the clinical data and laboratory examination results of the patients, we analyzed the changes of eosinophil and lymphocyte count in patients with different severity and outcomes, so as to study their relationship with the severity and prognosis, to compare the diagnostic effects of lymphocytes and eosinophils on severe COVID-2019 patients.Result: A total of 482 patients were enrolled in this study. Of those, 39.0% were severe patients and 13.3% were nonsurvivors. All the nonsurvivors were from the severe group. The count of eosinophil remained relatively lower levels during hospitalization in the severe and nonsurvival groups compared with the nonsevere and survival groups (all P < 0.05). Patients with the lowest eosinophil count during hospitalization reduced to <0.02×10⁹/L and =0.00×10⁹/L had higher rates of severity and fatality (all P < 0.05). The lowest counts of lymphocyte and eosinophil during hospitalization were used to analyze the diagnostic efficacy of severe COVID-19, and their diagnostic effects were similar. The cutoff values were ≤0.72×10⁹/L and =0.00×10⁹/L, and the areas under the curve were 0.768 and 0.740, respectively. Multivariate Cox regression model showed that the older age, the emergence of dyspnea, the increase of the white blood cell count on admission, the decrease of lymphocyte count on admission, and eosinophil count reduced to =0.00×10⁹/L on admission were associated with fatal outcome.Conclusion: Eosinophil and lymphocyte count remained relatively lower levels during hospitalization in the severe and nonsurvival COVID-19 patients, and patients with eosinophil decline had higher rates of severity and fatality. Eosinophils = 0.00×10⁹/L and lymphocytes ≤0.72×10⁹/L had the similar efficacy to diagnosis the severe COVID-19 patients. Compared with lymphocytes, eosinophils could also be used to diagnose severe COVID-19 patients and predict prognosis.Funding Statement: This study is funded by grants from the Natural Science Foundation of China (81974383 and 81772607 to W.Y.;81770554 and 81570501 to Y.F.)Declaration of Interests: None.Ethics Approval Statement: The study was approved by the Ethics Commission of Wuhan Tongji Hospital, Union Hospital, and Jin Yin-tan Hospital, and written informed consent was waived.

3.
Journal of Molecular Structure ; : 132588, 2022.
Article in English | ScienceDirect | ID: covidwho-1670923

ABSTRACT

Cocktail therapy is one of the leading approaches for treating some complex diseases. Herein, a pH-triggered supramolecular cocktail drug delivery system assembled by the medium-strength complexes of pillar[5]arene-based schiff base (P5SB) with methylene blue (MB). Molecular modeling suggest that noncovalent interactions between schiff base side chain of P5SB and MB were mainly responsible for the stability of the complex. The amphiphilic P5SB⊃MB complex assembled into stable vesicles with an average diameter of 244.1 nm in conventional physiological environment (pH=7.4). Drug loading experiments demonstrated that doxorubicin (DOX) could be efficiently encapsulated into the hollow vesicles, and the drug would be rapidly released under acidic environment (pH=6.0). Moreover, the anti-cancer efficiency of DOX-loaded P5SB⊃MB vesicles was significantly enhanced because of the synergistic effect of P5SB, MB and DOX. Nonetheless, the live-cell imaging property of DOX was maintained after encapsulation.

4.
Journal of Intensive Medicine ; 2021.
Article in English | ScienceDirect | ID: covidwho-1157520

ABSTRACT

Background : The outbreak of coronavirus disease 2019 (COVID-19) has posed a huge threat to human health. However, little is known regarding the risk factors associated with COVID-19 severity. We aimed to explore early-stage disease risk factors associated with eventual disease severity. Methods : This study enrolled 486 hospitalized, non-intensive care unit (ICU)-admitted adult patients with COVID-19 (age ≥ 18 years) treated at Wuhan Jinyintan Hospital, who were divided into three groups according to disease severity. The demographic, clinical, and laboratory data at admission and clinical outcomes were compared among severity groups, and the risk factors for disease severity were identified by multiple regression analysis. Results : Of 486 patients with COVID-19, 405 (83.33%) were discharged, 33 (6.71%) died outside of the ICU, and 48 (7.20%) were still being treated in the ICU by the time the study period ended. Significant differences in age, lymphocyte counts, and the levels of procalcitonin, aspartate aminotransferase, and D-dimer (P < 0.001 for all) among the three groups. Further analysis showed that older age, decreased lymphocyte counts, and increased procalcitonin, aspartate aminotransferase, and D-dimer levels were significantly associated with disease progression. Conclusion : Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may impair the immune system, the blood coagulation system, and hepatic and cardiac function. Some clinical characteristics and laboratory findings can help identify patients with a high risk of disease severity, which can be significant for appropriate resource allocation during the COVID-19 pandemic.

5.
Preprint in English | medRxiv | ID: ppmedrxiv-20153106

ABSTRACT

ObjectivesThe prevalence of antibodies to SARS-CoV-2 among blood donors in China remains unknown. To reveal the missing information, we investigated the seroprevalence of SARS-CoV-2 antibodies among blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang of China. DesignCross-sectional study SettingThree blood centers, located in the central, south and north China, respectively, recruiting from January to April 2020. Participants38,144 healthy blood donors donated in Wuhan, Shenzhen and Shijiazhuang were enrolled, who were all met the criteria for blood donation during the COVID-19 pandemic in China. Main outcome measuresSpecific antibodies against SARS-CoV-2 including total antibody (TAb), IgG antibody against receptor-binding domain of spike protein (IgG-RBD) and nucleoprotein (IgG-N), and IgM. Pseudotype lentivirus-based neutralization test was performed on all TAb-positive samples. In addition, anonymous personal demographic information, including gender, age, ethnicity, occupation and educational level, and blood type were collected. ResultsA total of 519 samples from 410 donors were confirmed by neutralization tests. The SARS-CoV-2 seroprevalence among blood donors was 2.29% (407/17,794, 95%CI: 2.08% to 2.52%) in Wuhan, 0.029% (2/6,810, 95%CI: 0.0081% to 0.11%) in Shenzhen, and 0.0074% (1/13,540, 95%CI: 0.0013% to 0.042%) in Shijiazhuang, respectively. The earliest emergence of SARS-CoV-2 seropositivity in blood donors was identified on January 20, 2020 in Wuhan. The weekly prevalence of SARS-CoV-2 antibodies in Wuhans blood donors changed dynamically and were 0.08% (95%CI: 0.02% to 0.28%) during January 15 to 22 (before city lockdown), 3.08% (95%CI: 2.67% to 3.55%) during January 23 to April 7 (city quarantine period) and 2.33% (95%CI: 2.06% to 2.63%) during April 8 to 30 (after lockdown easing). Female and older-age were identified to be independent risk factors for SARS-CoV-2 seropositivity among donors in Wuhan. ConclusionsThe prevalence of antibodies to SARS-CoV-2 among blood donors in China was low, even in Wuhan city. According to our data, the earliest emergence of SARS-CoV-2 in Wuhans donors should not earlier than January, 2020. As most of the population of China remained uninfected during the early wave of COVID-19 pandemic, effective public health measures are still certainly required to block viral spread before a vaccine is widely available.

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