Repeat-Dose Toxicity of Candidate Omicron COVID-19 Vaccine in Sprague-Dawley Rats

Due to a large number of mutations in the spike protein and immune escape, the Omicron variant (B.1.1.529) has become a predominant variant of concern (VOC) strain. To prevent the disease, we developed a candidate inactivated vaccine (Omicron COVID-19 Vaccine (Vero Cell), Inactivated). To evaluate the safety of the vaccine, we tested the repeat-dose toxicity in Sprague-Dawley (SD) rats. The doses were administered randomly to three groups: physiological saline solution (control), aluminum adjuvant in PBS solution adjuvant (adjuvant group), and low-dose and high-dose omicron vaccines (vaccine group) for 6 weeks. The SD rats were allowed to recover for 4 weeks after withdrawal. We evaluated the physiological condition of the rats, including their ophthalmological condition, body weight, food intake, body temperature, blood biochemistry, urine, neutralizing antibody, inflammation at the injection site, and organs weight. In summary, no dose-dependent adverse toxicological changes were observed, and a recovery trend was obvious, which proved the preclinical safety of the candidate omicron vaccine and provided evidence for clinical trials in humans. [ FROM AUTHOR] Copyright of COVID is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Frequency and Type of Outpatient Visits for Patients With Cardiovascular Ambulatory-Care Sensitive Conditions During the COVID-19 Pandemic and Subsequent Outcomes: A Retrospective Cohort Study.

Background Because the impact of changes in how outpatient care was delivered during the COVID-19 pandemic is uncertain, we designed this study to examine the frequency and type of outpatient visits between March 1, 2019 to February 29, 2020 (prepandemic) and from March 1, 2020 to February 28, 2021 (pandemic) and specifically compared outcomes after virtual versus in-person outpatient visits during the pandemic. Methods and Results Population-based retrospective cohort study of all 3.8 million adults in Alberta, Canada. We examined all physician visits and 30- and 90-day outcomes, with a focus on those adults with the cardiovascular ambulatory-care sensitive conditions heart failure, hypertension, and diabetes. Our primary outcome was emergency department visit or hospitalization, evaluated using survival analysis accounting for competing risk of death. Although in-person outpatient visits decreased by 38.9% in the year after March 1, 2020 (10 142 184 versus 16 592 599 in the prior year), the introduction of virtual visits (7 152 147; 41.4% of total) meant that total outpatient visits increased by 4.1% in the first year of the pandemic for Albertan adults. Outpatient visit frequency (albeit 41.4% virtual, 58.6% in-person) and prescribing patterns were stable in the first year after pandemic onset for patients with the cardiovascular ambulatory-care sensitive conditions we examined, but laboratory test frequency declined by 20% (serum creatinine) to 47% (glycosylated hemoglobin). In the first year of the pandemic, virtual outpatient visits were associated with fewer subsequent emergency department visits or hospitalizations (compared with in-person visits) for patients with heart failure (adjusted hazard ratio [aHR], 0.90 [95% CI, 0.85-0.96] at 30 days and 0.96 [95% CI, 0.92-1.00] at 90 days), hypertension (aHR, 0.88 [95% CI, 0.85-0.91] and 0.93 [95% CI, 0.91-0.95] at 30 and 90 days), or diabetes (aHR, 0.90 [95% CI, 0.87-0.93] and 0.93 [95% CI, 0.91-0.95] at 30 and 90 days). Conclusions The adoption and rapid uptake of virtual outpatient care during the COVID-19 pandemic did not negatively impact frequency of follow-up, prescribing, or short-term outcomes, and could have potentially positively impacted some of these for adults with heart failure, diabetes, or hypertension in a setting where there was an active reimbursement policy for virtual visits. Given declines in laboratory monitoring and screening activities, further research is needed to evaluate whether long-term outcomes will differ.

Repeat-Dose Toxicity of Candidate Omicron COVID-19 Vaccine in Sprague-Dawley Rats

Due to a large number of mutations in the spike protein and immune escape, the Omicron variant (B.1.1.529) has become a predominant variant of concern (VOC) strain. To prevent the disease, we developed a candidate inactivated vaccine (Omicron COVID-19 Vaccine (Vero Cell), Inactivated). To evaluate the safety of the vaccine, we tested the repeat-dose toxicity in Sprague-Dawley (SD) rats. The doses were administered randomly to three groups: physiological saline solution (control), aluminum adjuvant in PBS solution adjuvant (adjuvant group), and low-dose and high-dose omicron vaccines (vaccine group) for 6 weeks. The SD rats were allowed to recover for 4 weeks after withdrawal. We evaluated the physiological condition of the rats, including their ophthalmological condition, body weight, food intake, body temperature, blood biochemistry, urine, neutralizing antibody, inflammation at the injection site, and organs weight. In summary, no dose-dependent adverse toxicological changes were observed, and a recovery trend was obvious, which proved the preclinical safety of the candidate omicron vaccine and provided evidence for clinical trials in humans.

Awe experience trigged by fighting against COVID-19 promotes prosociality through increased feeling of connectedness and empathy

The promoter of prosocial behavior in fighting against the COVID-19 pandemic needs to be examined. Here, we examined the effect of experienced awe through cross-sectional (Study 1), a 3-wave longitudinal (Study 2) and experimental (Study 3–4) approaches. Study 1 showed that dispositional awe positively predicted one’s prosocial behavior in the pandemic (N = 1281). Study 2 (N = 332) observed that experienced awe predicted higher prosociality, and this relationship was serially mediated by connectedness and empathy. Study 3 (N = 153) and 4 (N = 156) confirmed that elicited awe, compared to that of amusement and neutrality, promoted multiple types of prosociality (Study 3) and willingness of blood donation (Study 4) via serial mediation of connectedness and empathy. These findings suggest that the experience of awe increases one’s connectedness to the world, which in turn enhances empathic concern and prosociality in pandemic fighting. [ FROM AUTHOR] Copyright of Journal of Positive Psychology is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

The risk of death or unplanned readmission after discharge from a COVID-19 hospitalization in Alberta and Ontario.

BACKGROUND: The frequency of readmissions after COVID-19 hospitalizations is uncertain, as is whether current readmission prediction equations are useful for discharge risk stratification of COVID-19 survivors or for comparing among hospitals. We sought to determine the frequency and predictors of death or unplanned readmission after a COVID-19 hospital discharge. METHODS: We conducted a retrospective cohort study of all adults (≥ 18 yr) who were discharged alive from hospital after a nonpsychiatric, nonobstetric, acute care admission for COVID-19 between Jan. 1, 2020, and Sept. 30, 2021, in Alberta and Ontario. RESULTS: Of 843 737 individuals who tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction during the study period, 46 412 (5.5%) were adults admitted to hospital within 14 days of their positive test. Of these, 8496 died in hospital and 34 846 were discharged alive (30 336 discharged after an index admission of ≤ 30 d and 4510 discharged after an admission > 30 d). One in 9 discharged patients died or were readmitted within 30 days after discharge (3173 [10.5%] of those with stay ≤ 30 d and 579 [12.8%] of those with stay > 30 d). The LACE score (length of stay, acuity, Charlson Comorbidity Index and number of emergency visits in previous 6 months) for predicting urgent readmission or death within 30 days had a c-statistic of 0.60 in Alberta and 0.61 in Ontario; inclusion of sex, discharge locale, deprivation index and teaching hospital status in the model improved the c-statistic to 0.73. INTERPRETATION: Death or readmission after discharge from a COVID-19 hospitalization is common and had a similar frequency in Alberta and Ontario. Risk stratification and interinstitutional comparisons of outcomes after hospital admission for COVID-19 should include sex, discharge locale and socioeconomic measures, in addition to the LACE variables.

Large Screening Identifies ACE2 Positively Correlates With NF-κB Signaling Activity and Targeting NF-κB Signaling Drugs Suppress ACE2 Levels.

Coronaviruses SARS-CoV-2 infected more than 156 million people and caused over 3 million death in the whole world, therefore a better understanding of the underlying pathogenic mechanism and the searching for more effective treatments were urgently needed. Angiotensin-converting enzyme 2 (ACE2) was the receptor for SARS-CoV-2 infection. In this study, we found that ACE2 was an interferon-stimulated gene (ISG) in human cell lines. By performing an ISG library screening, we found that ACE2 levels were positively regulated by multiple ISGs. Interestingly, ACE2 levels were highly correlated with ISGs-induced NF-κB activities, but not IFNß levels. Furthermore, using an approved clinical durgs library, we found two clinical drugs, Cepharanthine and Glucosamine, significantly inhibited ACE2 level, IFNß level, and NF-κB signaling downstream TNFα and IL6 levels. Our finding suggested the possible inhibitory effects of Cepharanthine and Glucosamine during SARS-CoV-2 infection and the subsequent inflammatory cytokine storm.

Development of a europium nanoparticles lateral flow immunoassay for NGAL detection in urine and diagnosis of acute kidney injury.

BACKGROUND: AKI is related to severe adverse outcomes and mortality with Coronavirus Disease 2019 (COVID-19) patients, that early diagnosed and intervened is imperative. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most promising biomarkers for detection of acute kidney injury (AKI), but current detection methods are inadequacy, so more rapid, convenient and accuracy methods are needed to detect NGAL for early diagnosis of AKI. Herein, we established a rapid, reliable and accuracy lateral flow immunoassay (LFIA) based on europium nanoparticles (EU-NPS) for the detection of NGAL in human urine specimens. METHODS: A double-antibody sandwich immunofluorescent assay using europium doped nanoparticles was employed and the NGAL monoclonal antibodies (MAbs) conjugate as labels were generated by optimizing electric fusion parameters. Eighty-three urine samples were used to evaluate the clinical application efficiency of this method. RESULTS: The quantitative detection range of NGAL in AKI was 1-3000 ng/mL, and the detection sensitization was 0.36 ng/mL. The coefficient of variation (CV) of intra-assay and inter-assay were 2.57-4.98 % and 4.11-7.83 %, respectively. Meanwhile, the correlation coefficient between europium nanoparticles-based lateral fluorescence immunoassays (EU-NPS-LFIA) and ARCHITECT analyzer was significant (R2 = 0.9829, n = 83, p < 0.01). CONCLUSIONS: Thus, a faster and easier operation quantitative assay of NGAL for AKI has been established, which is very important and meaningful to diagnose the early AKI, suggesting that the assay can provide an early warning of final outcome of disease.