A phase 3, randomised, double-blind, placebo-controlled clinical trial evaluation of the efficacy and safety of a SARS-CoV-2 recombinant spike RBD protein vaccine in adults (ABDALA-3 study).

Background: The pandemic of COVID-19 raised the urgent need for safe and efficacious vaccines against SARS-CoV-2. We evaluated the efficacy and safety of a new SARS-CoV-2 virus receptor-binding domain (RBD) vaccine. Methods: A phase 3, multicentre, randomised, double-blind, placebo-controlled trial was carried out at 18 clinical sites in three provinces of the south-eastern region of Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1, in blocks) to two groups: placebo, and 50 µg RBD vaccine (Abdala). The product was administered intramuscularly, 0.5 mL in the deltoid region, in a three-dose immunization schedule at 0-14-28 days. The organoleptic characteristics and presentations of the vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained blinded during the study period. The main endpoint was to evaluate the efficacy of the Abdala vaccine in the prevention of symptomatic COVID-19. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000359. Findings: Between March 22 to April 03, 2021, 48,290 subjects were included (24,144 and 24,146 in the placebo and Abdala groups, respectively) in the context of predominant D614G variant circulation. The evaluation of the main efficacy outcomes occurred during May-June 2021, starting at May 3rd, in the context of high circulation of mutant viruses, predominantly VOC Beta. The incidence of adverse reactions for individuals in the placebo and Abdala vaccine groups were 1227/24,144 (5.1%) and 1621/24,146 (6.7%), respectively. Adverse reactions were mostly mild, and from the injection site, which resolved in the first 24-48 h. No severe adverse events with demonstrated cause-effect relationship attributable to the vaccine were reported. Symptomatic COVID-19 disease was confirmed in 142 participants in the placebo group (78.44 incidence per 1000 person-years, 95% confidence interval [CI], 66.07-92.46) and in 11 participants in Abdala vaccine group (6.05 incidence per 1000 person years; 95% CI 3.02-10.82). The Abdala vaccine efficacy against symptomatic COVID-19 was 92.28% (95% CI 85.74-95.82). Moderate/serious forms of COVID-19 occurred in 30 participants (28 in the placebo group and only 2 in the Abdala vaccine group) for a vaccine efficacy of 92.88% (95% CI 70.12-98.31). There were five critical patients (of which four died), all in the placebo group. Interpretation: The Abdala vaccine was safe, well tolerated, and highly effective, fulfilling the WHO target product profile for COVID-19 vaccines. Those results, along with its immunization schedule and the advantage of easy storage and handling conditions at 2-8 °C, make this vaccine an option for the use in immunization strategies as a key tool for the control of the pandemic. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.

Phenolic compounds versus SARS-CoV-2: An update on the main findings against COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 remains an international concern. Although there are drugs to fight it, new natural alternatives such as polyphenols are essential due to their antioxidant activity and high antiviral potential. In this context, this review reports the main findings on the effect of phenolic compounds (PCs) against SARS-CoV-2 virus. First, the proven activity of PCs against different human viruses is briefly detailed, which serves as a starting point to study their anti-COVID-19 potential. SARS-CoV-2 targets (its proteins) are defined. Findings from in silico, in vitro and in vivo studies of a wide variety of phenolic compounds are shown, emphasizing their mechanism of action, which is fundamental for drug design. Furthermore, clinical trials have demonstrated the effectiveness of PCs in the prevention and as a possible therapeutic management against COVID-19. The results were complemented with information on the influence of polyphenols in strengthening/modulating the immune system. It is recommended to investigate compounds such as vitamins, minerals, alkaloids, triterpenes and fatty acids, and their synergistic use with PCs, many of which have been successful against SARS-CoV-2. Based on findings on other viruses, synergistic evaluation of PCs with accepted drugs against COVID-19 is also suggested. Other recommendations and limitations are also shown, which is useful for professionals involved in the development of efficient, safe and low-cost therapeutic strategies based on plant matrices rich in PCs. To the authors' knowledge, this manuscript is the first to evaluate the relationship between the antiviral and immunomodulatory (including anti-inflammatory and antioxidant effects) activity of PCs and their underlying mechanisms in relation to the fight against COVID-19. It is also of interest for the general population to be informed about the importance of consuming foods rich in bioactive compounds for their health benefits.

Phenolic compounds versus SARS-CoV-2: An update on the main findings against COVID-19

The COVID-19 pandemic caused by SARS-CoV-2 remains an international concern. Although there are drugs to fight it, new natural alternatives such as polyphenols are essential due to their antioxidant activity and high antiviral potential. In this context, this review reports the main findings on the effect of phenolic compounds (PCs) against SARS-CoV-2 virus. First, the proven activity of PCs against different human viruses is briefly detailed, which serves as a starting point to study their anti-COVID-19 potential. SARS-CoV-2 targets (its proteins) are defined. Findings from in silico, in vitro and in vivo studies of a wide variety of phenolic compounds are shown, emphasizing their mechanism of action, which is fundamental for drug design. Furthermore, clinical trials have demonstrated the effectiveness of PCs in the prevention and as a possible therapeutic management against COVID-19. The results were complemented with information on the influence of polyphenols in strengthening/modulating the immune system. It is recommended to investigate compounds such as vitamins, minerals, alkaloids, triterpenes and fatty acids, and their synergistic use with PCs, many of which have been successful against SARS-CoV-2. Based on findings on other viruses, synergistic evaluation of PCs with accepted drugs against COVID-19 is also suggested. Other recommendations and limitations are also shown, which is useful for professionals involved in the development of efficient, safe and low-cost therapeutic strategies based on plant matrices rich in PCs. To the authors' knowledge, this manuscript is the first to evaluate the relationship between the antiviral and immunomodulatory (including anti-inflammatory and antioxidant effects) activity of PCs and their underlying mechanisms in relation to the fight against COVID-19. It is also of interest for the general population to be informed about the importance of consuming foods rich in bioactive compounds for their health benefits. Polyphenols;SARS-CoV-2;COVID-19;coronavirus;medicine natural;immune system.

Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial.

Importance: Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit. Objective: To determine whether ivermectin is an efficacious treatment for mild COVID-19. Design, Setting, and Participants: Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state's health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020. Intervention: Patients were randomized to receive ivermectin, 300 µg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200). Main Outcomes and Measures: Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected. Results: Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group). Conclusion and Relevance: Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04405843.

Dengue and COVID-19, overlapping epidemics? An analysis from Colombia.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout Latin America, a region swept by multiple previous and ongoing epidemics. There are significant concerns that the arrival of COVID-19 is currently overlapping with other viruses, particularly dengue, in various endo-epidemic regions across South America. In this report, we analyzed trends for both viral infections in Colombia during the first 20 epidemiological weeks (EWs) of 2020. From 1st January to 16th May 2020 (EWs, 1-20), a total of 52 679 cases of dengue and 14 943 cases of COVID-19 have been confirmed in Colombia. As both conditions may potentially lead to fatal outcomes, especially in patients with chronic co-morbidities, overlapping infections, and co-occurrence may increase the number of patients requiring intensive care and mechanical ventilation. In regions, such as Valle del Cauca, intensified preparation for such scenarios should be pondered, and further studies should be performed to address this critical issue in a timely matter.