Immune response enhancement with GLS-5310 DNA primary vaccine against SARS-CoV-2 followed by administration of an mRNA vaccine heterologous boost.

Heterologous boost regimens are being increasingly considered against SARS-CoV-2. We report results for the 32 of 45 participants in the Phase 1 CoV2-001 clinical trial (Kim et al., Int J Iinfect Dis 2023, 128:112-120) who elected to receive an EUA-approved SARS-CoV-2 mRNA vaccine 6 to 8 months following a two-dose primary vaccination with the GLS-5310 bi-cistronic DNA vaccine given intradermally and followed by application of suction using the GeneDerm device. Receipt of EUA-approved mRNA vaccines after GLS-5310 vaccination was well-tolerated, with no reported adverse events. Immune responses were enhanced such that binding antibody titers, neutralizing antibody titers, and T-cell responses increased 1,187-fold, 110-fold, and 2.9-fold, respectively. This paper is the first description of the immune responses following heterologous vaccination with a DNA primary series and mRNA boost.

Clinical implications of gut microbiota and cytokine responses in coronavirus disease prognosis.

Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gut luminal cells through the angiotensin-converting enzyme-2 receptor and disrupts the gut microbiome. We investigated whether the gut microbiome in the early stage of SARS-CoV-2 infection was associated with the prognosis of coronavirus disease (COVID-19). Methods: Thirty COVID-19 patients and 16 healthy controls were prospectively enrolled. Blood and stool samples and clinical details were collected on days 0 (enrollment), 7, 14, and 28. Participants were categorized into four groups by their clinical course. Results: Gut microbiota composition varied during the clinical course of COVID-19 and was closely associated with cytokine levels (p=0.003). A high abundance of the genus Dialister (linear discriminant analysis [LDA] effect size: 3.97856, p=0.004), species Peptoniphilus lacrimalis (LDA effect size: 4.00551, p=0.020), and Anaerococcus prevotii (LDA effect size: 4.00885, p=0.007) was associated with a good prognosis. Starch, sucrose, and galactose metabolism was highly activated in the gut microbiota of the poor prognosis group. Glucose-lowering diets, including whole grains, were positively correlated with a good prognosis. Conclusion: Gut microbiota may mediate the prognosis of COVID-19 by regulating cytokine responses and controlling glucose metabolism, which is implicated in the host immune response to SARS-CoV-2.

Safety and immunogenicity of the bi-cistronic GLS-5310 COVID-19 DNA vaccine delivered with the GeneDerm suction device.

OBJECTIVES: The CoV2-001 phase I randomized trial evaluated the safety and immunogenicity of the GLS-5310 bi-cistronic DNA vaccine through 48 weeks of follow-up. DESIGN: A total of 45 vaccine-naïve participants were recruited between December 31, 2020, and March 30, 2021. GLS-5310, encoding for the SARS-CoV-2 spike and open reading frame 3a (ORF3a) proteins, was administered intradermally at 0.6 mg or 1.2 mg per dose, followed by application of the GeneDerm suction device as part of a two-dose regimen spaced either 8 or 12 weeks between vaccinations. RESULTS: GLS-5310 was well tolerated with no serious adverse events reported. Antibody and T cell responses were dose-independent. Anti-spike antibodies were induced in 95.5% of participants with an average geometric mean titer of ∼480 four weeks after vaccination and declined minimally through 48 weeks. Neutralizing antibodies were induced in 55.5% of participants with post-vaccination geometric mean titer of 28.4. T cell responses were induced in 97.8% of participants, averaging 716 site forming units/106 cells four weeks after vaccination, increasing to 1248 at week 24, and remaining greater than 1000 through 48 weeks. CONCLUSION: GLS-5310 administered with the GeneDerm suction device was well tolerated and induced high levels of binding antibodies and T-cell responses. Antibody responses were similar to other DNA vaccines, whereas T cell responses were many-fold greater than DNA and non-DNA vaccines.

Ciclesonide Inhaler Treatment for Mild-to-Moderate COVID-19: A Randomized, Open-Label, Phase 2 Trial.

Although some intravenous drugs have been used to treat coronavirus disease 2019 (COVID-19), no effective antiviral agents are currently available in the outpatient setting. We aimed to evaluate the efficacy and adverse events of 14-day ciclesonide treatment vs. standard care for patients with mild-to-moderate COVID-19. A randomized, open-label, multicenter clinical trial of ciclesonide inhalers was conducted in patients with mild-to-moderate COVID-19. Patients were enrolled within 3 days of diagnosis or within 7 days from symptom onset and randomly assigned to receive either ciclesonide (320 µg inhalation twice per day for 14 days) or standard care. The primary endpoint was the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) eradication rate on day 14 from study enrollment. Clinical status was assessed once daily, and serial nasopharyngeal viral load was evaluated by quantitative reverse transcription polymerase chain reaction. There were 35 and 26 patients in the ciclesonide and standard care groups, respectively. The SARS-CoV-2 eradication rate at day 14 was significantly higher in the ciclesonide group (p = 0.021). In multivariate analysis, SARS-CoV-2 negative conversion within 14 days was 12 times more likely in the ciclesonide group (95% confidence interval, 1.187-125.240). Additionally, the clinical failure rate (high-flow nasal oxygen therapy or mechanical ventilation) was significantly lower in the ciclesonide group (p = 0.034). In conclusion, ciclesonide inhalation shortened SARS-CoV-2 viral shedding duration, and it may inhibit the progression to acute respiratory failure in patients with mild-to-moderate COVID-19. Clinical Trial Registration NCT04330586.

Correlation between the Level of Social Distancing and Activity of Influenza Epidemic or COVID-19 Pandemic: A Subway Use-Based Assessment.

Social distancing is an effective measure to mitigate the spread of novel viral infections in the absence of antiviral agents and insufficient vaccine supplies. Subway utilization density may reflect social activity and the degree of social distancing in the general population.; This study aimed to evaluate the correlations between subway use density and the activity of the influenza epidemic or coronavirus disease 2019 (COVID-19) pandemic using a time-series regression method. The subway use-based social distancing score (S-SDS) was calculated using the weekly ridership of 11 major subway stations. The temporal association of S-SDS with influenza-like illness (ILI) rates or the COVID-19 pandemic activity was analyzed using structural vector autoregressive modeling and the Granger causality (GC) test. During three influenza seasons (2017-2020), the time-series regression presented a significant causality from S-SDS to ILI (p = 0.0484). During the COVID-19 pandemic in January 2020, S-SDS had been suppressed at a level similar to or below the average of the previous four years. In contrast to the ILI rate, there was a negative correlation between COVID-19 activity and S-SDS. GC analysis revealed a negative causal relationship between COVID-19 and S-SDS (p = 0.0098).; S-SDS showed a significant time-series association with the ILI rate but not with COVID-19 activity. When public transportation use is sufficiently suppressed, additional social mobility restrictions are unlikely to significantly affect COVID-19 pandemic activity. It would be more important to strengthen universal mask-wearing and detailed public health measures focused on risk activities, particularly in enclosed spaces.

Comparison of the second and third waves of the COVID-19 pandemic in South Korea: Importance of early public health intervention.

OBJECTIVES: To compare epidemiologic features of the second and third waves of the coronavirus disease 2019 (COVID-19) pandemic in South Korea. METHODS: Nationwide COVID-19 data were collected between 6 May and 30 December 2020. The degree of social activity was estimated using an Internet search trend analysis program for leisure-related keywords, including 'eating-out', 'trip' and 'get directions' (transportation). Demographics, transmission chains, case fatality rates, social activity levels and public health responses were compared between the second (13 August-18 September 2020) and third (4 November 2020-present) waves. RESULTS: In comparison with the second wave, the third wave was characterized by delayed strengthening of social distancing policies (3 vs. 15 days), longer duration (36 vs. >56 days) and a higher case fatality rate (0.91% vs. 1.26%). There were significant differences in transmission chains between the second and third waves (P < 0.01). In comparison with the second wave, the proportion of local clusters (24.8% vs. 45.7%) was lower in the third wave, and personal contact transmission (38.5% vs. 25.9%) and unknown routes of transmission (23.5% vs. 20.8%) were higher in the third wave. CONCLUSION: Early and timely interventions with strengthened social distancing policies should be implemented to suppress and control the COVID-19 pandemic effectively.