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.

Immunogenicity of an adjuvanted SARS-CoV-2 trimeric S-protein subunit vaccine (SCB-2019) in SARS-CoV-2-naïve and exposed individuals in a phase 2/3, double-blind, randomized study.

BACKGROUND: We evaluated immunogenicity of SCB-2019, a subunit vaccine candidate containing a pre-fusion trimeric form of the SARS-CoV-2 spike (S)-protein adjuvanted with CpG-1018/alum. METHODS: The phase 2/3, double-blind, randomized SPECTRA trial was conducted in five countries in participants aged ≥ 18 years, either SARS-CoV-2-naïve or previously exposed. Participants were randomly assigned to receive two doses of SCB-2019 or placebo administered intramuscularly 21 days apart. In the phase 2 part of the study, on days 1, 22, and 36, neutralizing antibodies were measured by pseudovirus and wild-type virus neutralization assays to SARS-CoV-2 prototype and variants, and ACE2-receptor-binding antibodies and SCB-2019-binding antibodies were measured by ELISA. Cell-mediated immunity was measured by intracellular cytokine staining via flow cytometry. RESULTS: 1601 individuals were enrolled between 24 March and 13 September 2021 and received at least one vaccine dose. Immunogenicity analysis was conducted in a phase 2 subset of 691 participants, including 428 SARS-CoV-2-naïve (381 vaccine and 47 placebo recipients) and 263 SARS-CoV-2-exposed (235 vaccine and 28 placebo recipients). In SARS-CoV-2-naïve participants, GMTs of neutralizing antibodies against prototype virus increased 2 weeks post-second dose (day 36) compared to baseline (224 vs 12.7 IU/mL). Seroconversion rate was 82.5 %. In SARS-CoV-2-exposed participants, one SCB-2019 dose increased GMT of neutralizing antibodies by 48.3-fold (1276.1 IU/mL on day 22) compared to baseline. Seroconversion rate was 92.4 %. Increase was marginal post-second dose. SCB-2019 also showed cross-neutralization capability against nine variants, including Omicron, in SARS-CoV-2-exposed participants at day 36. SCB-2019 stimulated Th1-biased cell-mediated immunity to the S-protein in both naïve and exposed participants. The vaccine was well tolerated, no safety concerns were raised from the study. CONCLUSIONS: A single dose of SCB-2019 was immunogenic in SARS-CoV-2-exposed individuals, whereas two doses were required to induce immune response in SARS-CoV-2-naïve individuals. SCB-2019 elicited a cross-neutralizing response against emergent SARS-CoV-2 variants at antibody levels associated with clinical protection, underlining its potential as a booster. CLINICALTRIALS: gov: NCT04672395; EudraCT: 2020-004272-17.

Reporte de cuatro casos COVID-19 hospitalizados en unidad de cuidados intensivos en una institución hospitalaria en Barranquilla, Colombia / Original article: Case-Serie of 4 COVID-19 patients hospitalized in an intensive care unit in a hospital institution in Barranquilla, Colombia

Resumen Presentar una serie de casos de COVID-19 con requerimiento de ingreso a Unidad de Cuidados Intensivos. La información fue tomada de las historias clínicas, y su evaluación y diagnóstico fue realizado mediante estudios paraclínicos en sangre, orina, PCR e imágenes diagnósticas en 4 pacientes con diferentes comorbilidades y nexo epidemiológico presente para desarrollo de la enfermedad. Los cuatro casos fueron manejados con cloroquina 300 mg vía oral, cada 12 horas, y azitromicina 1 gr vía oral, cada 24 horas, durante 5 días, sin complicaciones ni toxicidad asociada. El caso 1 desarrolló falla orgánica múltiple, incluyendo injuria renal aguda con una estancia en UCI de 4 días antes de su fallecimiento, mientras los casos 2, 3 y 4 tuvieron una evolución favorable y fueron dados de alta de UCI. Se requieren estudios multicéntricos rápidos que orienten científicamente hacia un mejor abordaje diagnóstico y manejo, en el contexto de una enfermedad con un comportamiento clínico-epidemiológico que debe estudiarse en profundidad y que probablemente cobrará muchas vidas; además, debido a la ausencia de pruebas diagnósticas rápidas, la utilización de una clasificación basada en la severidad de lesiones radiológicas llamada CO-RADS (Covid-19 Imaging Reporting and Data System) podría ser de gran importancia para instalar de manera temprana los tratamientos farmacológicos disponibles y la asistencia respiratoria mecánica precoz.

Abstract To present a COVID-19 case series with clinical admission criteria to Intensive Care Unit. Patients information was obtained from medical records, and daily clinical evaluation whereas diagnosis was carried out through paraclinical studies in blood, urine, PCR and diagnostic images in 4 patients with different comorbidities and epidemiological link for the development of COVID-19. All four cases were managed with chloroquine 300 mg orally every 12 hours and azithromycin orally every 24 hours for 5 days without complications or associated toxicity. The case 1 developed multiple organ failure, including acute kidney injury with an ICU stay of 4 days before his death, while cases 2, 3 and 4 had a favorable evolution and were discharged from the ICU. Rapid multicenter studies are required to scientifically guide a better diagnostic and management approach, in the context of a disease with a clinical-epidemiological behavior that must be studied in depth and will probably take many lives. In addition, due to the absence of sufficiently rapid tests, the use of a classification based on the severity of radiological lesions called CO-RADS (Covid-19 Imaging Reporting and Data System) could be of great importance to install available pharmacological treatments early and early mechanical respiratory support.