Safety and immunogenicity of the ChAdOx1, MVA-MERS-S, and GLS-5300 DNA MERS-CoV vaccines.

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a pathogen associated with an acute respiratory infection that has a high mortality rate in humans. It was first identified in June of 2012 in the Arabian Peninsula. The success of the COVID-19 vaccines has shown that it is possible to take advantage of medical and scientific advances to produce safe and effective vaccines for coronaviruses. This study aimed to examine the safety and immunogenicity of MERS-CoV vaccines. METHODS: The research method Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used as the guideline for this study. RevMan 5.4 software was used to perform a meta-analysis of the included studies. The safety was assessed by recording adverse events following vaccination, and the immunogenicity was assessed by using seroconversion. RESULTS: The study included five randomized controlled trials that met the inclusion criteria after screening. The studies had 173 participants and were performed in four countries. The vaccines examined were the ChAdOx1 MERS vaccine, MVA-MERS-S vaccine, and GLS-5300 DNA MERS-CoV vaccine. The meta-analysis showed no significant differences in local adverse effects (all local adverse effects and pain) or systemic adverse effects (all systemic adverse effects, fatigue, and headache) among participants in groups receiving a high-dose vaccine or a low-dose vaccine. There were, however, higher levels of seroconversion in high-dose groups than in low-dose groups (OR 0.16 [CI 0.06, 0.42, p = 0.0002]). CONCLUSION: The findings showed that high doses of current MERS-CoV vaccine candidates conferred better immunogenicity than low doses and that there were no differences in the safety of the vaccines.

The Safety and Efficacy of the Protease Inhibitors Lopinavir/Ritonavir as Monotherapy or Combined with Interferon in COVID-19 Patients

Enzyme inhibitors are frequently used to treat viral illnesses. Protease inhibitors are a promising class for combating novel and life-threatening viral infections. This research aimed to evaluate the efficacy and safety of lopinavir/ritonavir monotherapy or lopinavir/ritonavir plus interferon for the treatment of COVID-19. The PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for English articles with full texts available online. ReviewManager software was used to conduct a meta-analysis, subgroup analysis, and sensitivity analysis. Following the creation of the protocol, the collected sources were sorted into categories and evaluated for quality. Risk and hazard ratios and the random effects model were implemented, with statistical heterogeneity assigned using the Higgins I2 statistic. Lopinavir/ritonavir, with or without interferon, was associated with a nonsignificant higher mortality rate (odds ratio [OR] 1.29;95% confidence interval [CI] 0.95 to 1.761;p = 0.1), as was clinical improvement (OR 1.2;95% CI 0.8 to 1.84;p = 0.36). The difference in the length of hospital stay was in favor of the control group but statistically insignificant (standardized mean difference [SMD] 0.07;95% CI -0.44 to 0.57;p = 0.79). The pooled data showed that lopinavir/ritonavir, with or without interferon, was associated with a significantly higher number of adverse events than placebo (OR 1.2;95% CI 1.09 to 2.34;p = 0.02). Serious adverse events were insignificantly increased in the treated group over the control group (OR 1.2;95% CI 0.96 to 2.12;p = 0.08). In the subgroup analysis, it was found that interferon used with lopinavir/ritonavir did not have a statistically significant effect on mortality rates (OR 1.75;95% CI 0.87 to 3.55;p = 0.37), adverse effects (OR 1.20;95% CI 0.75 to 1.91;p = 0.27), or serious adverse effects (OR 1.86;95% CI 1.17 to 2.96;p = 0.33). Treatment with lopinavir/ritonavir alone or in combination with interferon for COVID-19 did not significantly outperform placebo in this study. Large randomized clinical trials are required to evaluate lopinavir/ritonavir in conjunction with interferon for the treatment of COVID-19. Such studies would benefit greatly from being conducted in a double-blind fashion at multiple locations.

Omicron variant genome evolution and phylogenetics.

Following the discovery of the SARS-CoV-2 Omicron variant (B.1.1.529), the global COVID-19 outbreak has resurfaced after appearing to be relentlessly spreading over the past 2 years. This new variant showed marked degree of mutation, compared with the previous SARS-CoV-2 variants. This study investigates the evolutionary links between Omicron variant and recently emerged SARS-CoV-2 variants. The entire genome sequences of SARS-CoV-2 variants were obtained, aligned using Clustal Omega, pairwise comparison was computed, differences, identity percent, gaps, and mutations were noted, and the identity matrix was generated. The phylogenetics of Omicron variants were determined using a variety of evolutionary substitution models. The ultrametric and metric clustering methods, such as UPGMA and neighbor-joining (NJ), using nucleotide substitution models that allowed the inclusion of nucleotide transitions and transversions as Kimura 80 models, revealed that the Omicron variant forms a new monophyletic clade that is distant from other SARS-CoV-2 variants. In contrast, the NJ method using a basic nucleotide substitution model such as Jukes-Cantor revealed a close relationship between the Omicron variant and the recently evolved Alpha variant. Based on the percentage of sequence identity, the closest variants were in the following order: Omicron, Alpha, Gamma, Delta, Beta, Mu, and then the SARS-CoV-2 USA isolate. A genome alignment with other variants indicated the greatest number of gaps in the Omicron variant's genome ranging from 43 to 63 gaps. It is possible, given their close relationship to the Alpha variety, that Omicron has been around for much longer than predicted, even though they created a separate monophyletic group. Sequencing initiatives in a systematic and comprehensive manner is highly recommended to study the evolution and mutations of the virus.