Safety and immunogenicity of SCB-2019, an adjuvanted, recombinant SARS-CoV-2 trimeric S-protein subunit COVID-19 vaccine in healthy 12-17 year-old adolescents.

We previously demonstrated the efficacy of the COVID-19 vaccine candidate, SCB-2019, in adults in the SPECTRA phase 2/3 efficacy study. We extended the study to include 1278 healthy 12-17-year-old adolescents in Belgium, Colombia, and the Philippines who received either two doses of SCB-2019 or placebo 21 days apart, to assess immunogenicity as neutralizing antibodies against prototype SARS-CoV-2 and variants of concern, and safety and reactogenicity as solicited and unsolicited adverse events with a comparator group of young adults (18-25 years). In participants with no evidence of prior SARS-CoV-2 infection SCB-2019 immunogenicity in adolescents was non-inferior to that in young adults; respective geometric mean neutralizing titers (GMT) against prototype SARS-CoV-2 14 days after the second vaccination were 271 IU/mL (95% CI: 211-348) and 144 IU/mL (116-178). Most adolescents (1077, 84.3%) had serologic evidence of prior SAR-CoV-2 exposure at baseline; in these seropositive adolescents neutralizing GMTs increased from 173 IU/mL (135-122) to 982 IU/mL (881-1094) after the second dose. Neutralizing titers against Delta and Omicron BA SARS-CoV-2 variants were also increased, most notably in those with prior exposure. SCB-2019 vaccine was well tolerated with generally mild or moderate, transient solicited and unsolicited adverse events that were comparable in adolescent vaccine and placebo groups except for injection site pain - reported after 20% of SCB-2019 and 7.3% of placebo injections. SCB-2019 vaccine was highly immunogenic against SARS-CoV-2 prototype and variants in adolescents, especially in those with evidence of prior exposure, with comparable immunogenicity to young adults. Clinical trial registration: EudraCT 2020-004272-17; ClinicalTrials.gov NCT04672395.

Factors Associated With Hospitalization or Intensive Care Admission in Children With COVID-19 in Latin America.

Background: Limited data is available from low-middle and upper-middle income countries of the factors associated with hospitalization or admission to pediatric intensive care unit (PICU) for children with COVID-19. Objective: To describe the factors associated with hospitalization or PICU admission of children with COVID-19 in Latin America. Method: Multicenter, analytical, retrospective study of children reported from 10 different Latin American countries to the Latin-American Society of Pediatric Infectious Diseases (SLIPE-COVID) research network from June 1, 2020, and February 28, 2021. Outpatient or hospitalized children <18 years of age with COVID-19 confirmed by polymerase chain reaction or antigen detection from the nasopharynx were included. Children with multisystem inflammatory syndrome in children (MIS-C) were excluded. Associations were assessed using univariate and multivariable logistic regression models. Results: A total of 1063 children with COVID-19 were included; 500 (47%) hospitalized, with 419 (84%) to the pediatric wards and 81 (16%) to the ICU. In multivariable analyses, age <1 year (Odds Ratio [OR] 1.78; 95% CI 1.08-2.94), native race (OR 5.40; 95% CI 2.13-13.69) and having a co-morbid condition (OR 5.3; 95% CI 3.10-9.15), were associated with hospitalization. Children with metabolic or endocrine disorders (OR 4.22; 95% CI 1.76-10.11), immune deficiency (1.91; 95% CI 1.05-3.49), preterm birth (OR 2.52; 95% CI 1.41-4.49), anemia at presentation (OR 2.34; 95% CI 1.28-4.27), radiological peribronchial wall thickening (OR 2.59; 95% CI 1.15-5.84) and hypoxia, altered mental status, seizures, or shock were more likely to require PICU admission. The presence of pharyngitis (OR 0.34; 95% CI 0.25-0.48); myalgia (OR 0.47; 95% CI 0.28-0.79) or diarrhea (OR 0.38; 95% CI 0.21-0.67) were inversely associated with hospital admission. Conclusions: In this data analysis reported to the SLIPE research network in Latin America, infants, social inequalities, comorbidities, anemia, bronchial wall thickening and specific clinical findings on presentation were associated with higher rates of hospitalization or PICU admission. This evidence provides data for prioritization prevention and treatment strategies for children suffering from COVID-19.

Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019. METHODS: This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0·5 mL intramuscular doses of SCB-2019 (30 µg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020-004272-17) and ClinicalTrials.gov (NCT04672395). FINDINGS: 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44·4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67·2% (95·72% CI 54·3-76·8), 83·7% (97·86% CI 55·9-95·4) against moderate-to-severe COVID-19, and 100% (97·86% CI 25·3-100·0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78·7% (95% CI 57·3-90·4) for delta, 91·8% (44·9-99·8) for gamma, and 58·6% (13·3-81·5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63-103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35·7% [287 of 803] vs 10·3% [81 of 786]) and second (26·9% [189 of 702] vs 7·4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups. INTERPRETATION: Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant. FUNDING: Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations.

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.