Comparison of the immunogenicity of nasal-spray rVSV vector, adenovirus vector, and inactivated COVID-19-based vaccines in rodent models.

Intranasal (i.n.) vaccines can induce mucosal and systemic immunity against respiratory pathogens. Previously, we demonstrated that the recombinant vesicular stomatitis virus (rVSV)-based COVID-19 vaccine rVSV-SARS-CoV-2, with poor immunogenicity via the intramuscular route (i.m.), is more suitable for i.n. administration in mice and nonhuman primates. Here, we found that the rVSV-SARS-CoV-2 Beta variant was more immunogenic than the wild-type strain and other variants of concern (VOCs) in golden Syrian hamsters. Furthermore, the immune responses elicited by rVSV-based vaccine candidates via the i.n. route were significantly higher than those of two licensed vaccines: the inactivated vaccine KCONVAC delivered via the i.m. route and the adenovirus-based Vaxzevria delivered i.n. or i.m. We next assessed the booster efficacy of rVSV following two i.m. doses of KCONVAC. Twenty-eight days after receiving two i.m. doses of KCONVAC, hamsters were boosted with a third dose of KCONVAC (i.m.), Vaxzevria (i.m. or i.n.), or rVSVs (i.n.). Consistent with other heterologous booster studies, Vaxzevria and rVSV elicited significantly higher humoral immunity than the homogenous KCONVAC. In summary, our results confirmed that two i.n. doses of rVSV-Beta elicited significantly higher humoral immune responses than commercial inactivated and adeno-based COVID vaccines in hamsters. As a heterologous booster dose, rVSV-Beta induced potent, persistent, and broad-spectrum humoral and mucosal neutralizing responses against all VOCs, highlighting its potential to be developed into a nasal-spray vaccine.

Efficiency of nicotinamide-based supportive therapy in lymphopenia for patients with ordinary or severe COVID-19: A randomized controlled trial.

BACKGROUND: This study aimed to investigate the efficiency of nicotinamide-based supportive therapy for lymphopenia in patients with coronavirus disease-2019 (COVID-19). METHODS: Twenty four patients diagnosed with COVID-19 were randomly divided into 2 groups (n = 12) during hospitalization in a ratio of 1:1. Based on conventional treatment, the treatment group was administered 100 mg nicotinamide 5 times a day for 2 days. The control group received routine treatment only. The primary endpoint was the change in the absolute lymphocyte count. The secondary endpoints included both in-hospital death and the composite endpoint of aggravation, according to upgraded oxygen therapy, improved nursing level, and ward rounds of superior physicians for changes in conditions. RESULTS: Full blood counts before and after nicotinamide administration were comparable in each group (all P > .05). Before and after receiving nicotinamide, mean absolute lymphocyte counts were similar between the two groups ([0.94 ± 0.26] × 109/L vs [0.89 ± 0.19] × 109/L, P = .565; [1.15 ± 0.48] × 109/L vs [1.02 ± 0.28] × 109/L, P = .445, respectively). Therefore, there was no statistically significant difference in the lymphocyte improvement rate between the two groups (23.08 ± 46.10 vs 16.52 ± 24.10, P = .67). There was also no statistically significant difference in the secondary endpoints between the two groups. CONCLUSION: Among patients with COVID-19, there was no statistically significant difference in the change of whole blood counts and absolute lymphocyte counts before and after intervention in both groups. Therefore, no new evidence has been found regarding the effect of niacinamide on lymphopenia in COVID-19 patients.

Highly Sensitive Detection Method for HV69-70del in SARS-CoV-2 Alpha and Omicron Variants Based on CRISPR/Cas13a.

As SARS-CoV-2 variants continue to evolve, identifying variants with adaptive diagnostic tool is critical to containing the ongoing COVID-19 pandemic. Herein, we establish a highly sensitive and portable on-site detection method for the HV69-70del which exist in SARS-CoV-2 Alpha and Omicron variants using a PCR-based CRISPR/Cas13a detection system (PCR-CRISPR). The specific crRNA (CRISPR RNA) targeting the HV69-70del is screened using the fluorescence-based CRISPR assay, and the sensitivity and specificity of this method are evaluated using diluted nucleic acids of SARS-CoV-2 variants and other pathogens. The results show that the PCR-CRISPR detection method can detect 1 copies/µL SARS-CoV-2 HV69-70del mutant RNA and identify 0.1% of mutant RNA in mixed samples, which is more sensitive than the RT-qPCR based commercial SARS-CoV-2 variants detection kits and sanger sequencing. And it has no cross reactivity with ten other pathogens nucleic acids. Additionally, by combined with our previously developed ERASE (Easy-Readout and Sensitive Enhanced) lateral flow strip suitable for CRISPR detection, we provide a novel diagnosis tool to identify SARS-CoV-2 variants in primary and resource-limited medical institutions without professional and expensive fluorescent detector.

A comparison between manual and artificial intelligence-based automatic positioning in CT imaging for COVID-19 patients.

OBJECTIVE: To analyze and compare the imaging workflow, radiation dose, and image quality for COVID-19 patients examined using either the conventional manual positioning (MP) method or an AI-based automatic positioning (AP) method. MATERIALS AND METHODS: One hundred twenty-seven adult COVID-19 patients underwent chest CT scans on a CT scanner using the same scan protocol except with the manual positioning (MP group) for the initial scan and an AI-based automatic positioning method (AP group) for the follow-up scan. Radiation dose, patient positioning time, and off-center distance of the two groups were recorded and compared. Image noise and signal-to-noise ratio (SNR) were assessed by three experienced radiologists and were compared between the two groups. RESULTS: The AP operation was successful for all patients in the AP group and reduced the total positioning time by 28% compared with the MP group. Compared with the MP group, the AP group had significantly less patient off-center distance (AP 1.56 cm ± 0.83 vs. MP 4.05 cm ± 2.40, p < 0.001) and higher proportion of positioning accuracy (AP 99% vs. MP 92%), resulting in 16% radiation dose reduction (AP 6.1 mSv ± 1.3 vs. MP 7.3 mSv ± 1.2, p < 0.001) and 9% image noise reduction in erector spinae and lower noise and higher SNR for lesions in the pulmonary peripheral areas. CONCLUSION: The AI-based automatic positioning and centering in CT imaging is a promising new technique for reducing radiation dose and optimizing imaging workflow and image quality in imaging the chest. KEY POINTS: • The AI-based automatic positioning (AP) operation was successful for all patients in our study. • AP method reduced the total positioning time by 28% compared with the manual positioning (MP). • AP method had less patient off-center distance and higher proportion of positioning accuracy than MP method, resulting in 16% radiation dose reduction and 9% image noise reduction in erector spinae.