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BackgroundMultiple vaccines against SARS-CoV-2 have been evaluated in clinical trials, but very few include the pediatric population. The inactivated vaccine CoronaVac(R) has shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. This study is an interim safety and immunogenicity report of a phase 3 clinical trial for CoronaVac(R) in healthy children and adolescents in Chile. MethodsParticipants aged 3 to 17 years old received two doses of CoronaVac(R) in a four-week interval. Local and systemic adverse reactions were registered in 699 participants that received the first dose and 381 that received the second dose until December 31st, 2021. Whole blood samples were collected from 148 participants for humoral and cellular immunity analyses. ResultsThe primary adverse reaction reported after the first and second dose was pain at the injection site. The adverse reactions observed were primarily mild and local, and no severe adverse events were reported. Four weeks after the second dose, a significant increase in the levels of total and neutralizing antibodies was observed. Increased activation of specific CD4+ T cells was also observed four weeks after the second dose. Although antibodies induced by vaccination neutralize variants Delta and Omicron, titers were lower than the D614G variant. Importantly, comparable T cell responses were detected against these variants of concern. ConclusionsCoronaVac(R) is safe and immunogenic in subjects aged 3-17 years old and is thus likely to confer protection against infection caused by SARS-CoV-2 variants in this target population.
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BackgroundSeveral vaccines have been developed to control the COVID-19 pandemic. CoronaVac(R) (Sinovac Life Sciences), an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity in previous studies, preventing severe COVID-19 cases. We further investigated the safety and efficacy of two immunization schedules of CoronaVac(R) in a non-inferiority trial in healthy adults. MethodsThis is a multi-center and randomized clinical trial. Healthy adults were enrolled at eight centers in Chile. Participants were randomly assigned to two vaccination schedules, receiving two doses with either 14 (0-14) or 28 (0-28) days between each. 2302 participants were vaccinated. The primary safety and efficacy endpoints were solicited adverse events (AE) within 7 days after each dose and compared the number of cases of SARS-CoV-2 infection 14 days after the second dose between schedules, respectively. FindingsThe most frequent local AE was pain at the injection site, which was less frequent in participants aged [≥]60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. The remaining AEs were minor allergic reactions and fever. Most AEs were mild and transient. There were no significant differences for local and systemic AE between schedules. No anaphylactic reactions or vaccine-related severe AEs were observed. 58 COVID-19 cases were confirmed, and all but two of them were mild. No differences were observed in protection between schedules. InterpretationCoronaVac(R) is safe, especially in [≥]60 years-old participants. Both schedules protected against COVID-19 hospitalizations. FundingMINSAL, Chile, CPC & IMII, Chile. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSCoronaVac(R) (an inactivated SARS-CoV-2 vaccine) was approved on June 1st, 2021, by the WHO for its use in humans. Sinovac Life Sciences generated this vaccine in China and conducted phase 1/2 trials. Good safety, efficacy, and immunogenicity profiles were reported. The results from this study led to the use of CoronaVac(R) in other countries, such as Brazil, Turkey, and Chile, with phase 3 trials being held on them. Added-value of this studyThis work compares the safety and efficacy of two immunization schedules with CoronaVac(R), with each dose administrated two or four weeks after the first dose on healthy Chilean adults. To date, no studies showing the safety and efficacy of these two immunization schedules with CoronaVac(R) in healthy adults in a population other than the Chinese have been published. We show that CoronaVac(R) is safe and prevents hospitalization due to COVID-19 in both immunization schedules. No differences were found in the incidence of adverse events between both schedules, and no related severe adverse events were reported. These results give further insight into the immune response induced by CoronaVac(R) and are relevant when deciding on the immunization schedule chosen for vaccination. Implications of all the available evidenceThe data reported here show that using either immunization schedule with two doses of CoronaVac(R) protects against SARS-CoV-2. The data also indicate that CoronaVac(R) does not induce severe adverse events in either immunization schedule, and the adverse events registered are mild and transient, confirming the safety of this vaccine.
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Background: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. Methods: Open-label, single-center, randomized clinical trial performed in an academic center in Santiago, Chile from May 10, 2020, to July 18, 2020, with final follow-up August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptoms onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted in immediate CP (early plasma group) versus no CP unless developing pre-specified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days or death. Key secondary outcomes included: time to respiratory failure, days of mechanical ventilation, hospital length-of-stay, mortality at 30 days, and SARS-CoV-2 RT-PCR clearance rate. Results: Of 58 randomized patients (mean age, 65.8 years, 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We found no benefit in the primary outcome (32.1% vs 33.3%, OR 0.95, 95% CI 0.32-2.84, p>0.99) in the early versus deferred CP group. In-hospital mortality rate was 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), mechanical ventilation 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), and prolonged hospitalization 21.4% vs 30% (OR 0.64, 95%CI, 0.19-2.1, p=0.55) in early versus deferred CP group, respectively. Viral clearance rate on day 3 (26% vs 8%, p=0.20) and day 7 (38% vs 19%, p=0.37) did not differ between groups. Two patients experienced serious adverse events within 6 or less hours after plasma transfusion. Conclusion: Immediate addition of CP therapy in early stages of COVID-19 -compared to its use only in case of patient deterioration- did not confer benefits in mortality, length of hospitalization or mechanical ventilation requirement.
