Half dose ChAdOx1 nCoV-19 vaccine was equivalent to full doses to reduce moderate and severe COVID-19 cases.

Objectives: Previously, we presented the effectiveness of ChAdOx1 nCoV-19 half-dose (HD) immunization for preventing new COVID-19 cases. Here, we evaluated the administration of an HD of ChAdOx1 nCoV-19 in the primary immunization protocol (up to two doses) in reducing moderate and severe cases, hospitalizations, and deaths when compared to the administration of full doses (FD) after a long-term follow-up. Methods: We evaluated data from 29,469 participants between January 2021 and November 2022 who received an HD or FD vaccine and crossed this information with their medical records to identify those who developed moderate or severe cases. All participants were classified into four groups according to their immunization status and followed 500 days after the last vaccine administration. Results: The propensity-score matching analysis indicates that the administration of the two HDs of ChAdOx1 nCoV-19 was equivalent to the use of two FDs to reduce moderate and severe COVID-19 cases. The relative risk of being infected and developing moderate or severe conditions after the administration of at least one HD or FD was similar 150 or 500 days after the administration of the immunizers. Conclusion: Administering two HDs can be used safely as a cost-effective alternative to the primary immunization protocol.

Timeline kinetics of protective immunity to SARS-CoV-2 upon primary vaccination and humoral response to variants after booster dose.

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, imposing the need for periodic booster doses. However, whether booster doses should be applied to the entire population or groups, and the booster doses interval, remains unclear. In this study, we evaluated humoral reactivity kinetics from before the first dose to 180 days after the third booster dose in different schedules in a well-controlled health worker cohort. Among the 2,506 employees, the first 500 vaccinated health workers were invited to participate. The third booster dose was administered 8 months after the first dose. Among the invited participants, 470 were included in the study; 258 received inactivated vaccine CoronaVac (VAC group) and 212 received viral vector vaccine ChAdOx1 (AZV group). The groups were homogeneous in terms of age and sex. 347 participants were followed up after the booster dose with AZV or BNT162b2 (Pfizer, BNT group): 63 with VAC/AZV, 117 with VAC/BNT, 72 with the AZV/AZV and 95 with AZV/BNT schedules. Blood samples were collected immediately before, 28 days after each dose and 180 days after the primary vaccination and booster dose. Anti-SARS-CoV-2 antibodies were measured by chemiluminescence and plaque reduction neutralization test (PRNT). Plasma immune mediators were quantified using a multiplex immunoassay. Geometric mean of antibodies increased 28 days after the second dose with 100 % seroconversion rate in both groups and decreased 180 days after the first dose. In the baseline-seropositive VAC group, the levels of plasma immune mediators increased after the second dose. Booster dose was applied at 4-6 months after the primary vaccination. Heterologous booster in VAC or AZV primary vaccinees were effective maintaining the titers of anti-SARS-CoV-2 antibodies even after 6 months of follow-up. The heterologous schedule induced higher and stable antibody reactivity, even after 180 days, protecting to ancestral (Wuhan), Delta, and Omicron variants.

Effectiveness, safety, and immunogenicity of half dose ChAdOx1 nCoV-19 COVID-19 Vaccine: Viana project.

Fractional dose is an important strategy to increase access to vaccines. This study evaluated the effectiveness, safety, and immunogenicity of half dose of ChAdOx1 nCoV-19 vaccine. A non-inferiority non-randomized controlled trial compared a half dose of ChAdOx1 nCoV-19 with the full dose, with an interval of 8 to 10 weeks, in individuals aged 18-49 years. The primary endpoints were the incidence rate of new cases/1,000 person-year at 90 days after 14 days of the second dose, confirmed by RT-PCR and new cases registered at SUS National Health Surveillance Database (e-SUS VS). The anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) by chemiluminescence and the neutralizing antibodies by plaque reduction neutralization test (PRNT) were titrated. The soluble biomarkers were quantified with a multiplex immunoassay. Follow-up was 90 days after 14 days of the second dose. A total of 29,598 individuals were vaccinated. After exclusion, 16,570 individuals who received half a dose and 6,402 who received full doses were analyzed. The incidence of new cases confirmed by RT-PCR of half dose was non-inferior to full dose (23.7 vs. 25.7 cases per 1,000 persons-year [coefficient group -0.09 CI95%(-0.49 to 0.31)], even after adjusting for age and sex. There were no deaths or hospitalization after immunization of either group. Immunogenicity was evaluated in a subsample (N=558) compared to 154 healthcare workers who received a full dose. The seroconversion rate in seronegative individuals at baseline half dose was 99.8%, similar to that of the full dose (100%). Geometric mean concentration (95% CI; BAU/mL) were half dose = 188 (163-217) and full dose = 529 (423-663) (p < 0.001). In seropositive subjects at baseline (pre-immune individuals), the first dose induced very high and similar IgG-S in half dose 1,359 (1,245-1,483) and full dose 1,354 (1,048-1,749) BAU/mL. A half dose induced a high increase in plasma chemokines, pro-inflammatory/regulatory cytokines, and growth factors. The frequency of adverse events was similar. No serious adverse events or deaths were reported. A half dose of ChAdOx1 nCoV-19 is as effective, safe, and immunogenic as the full dose. The immune response in pre-immune (seropositive in the baseline) individuals indicates that the half dose may be a booster dose schedule.

Covert cases of Severe Acute Respiratory Syndrome Coronavirus 2: An obscure but present danger in regions endemic for Dengue and Chikungunya viruses.

BACKGROUND: The impact of SARS-CoV-2 in regions endemic for both Dengue and Chikungunya is still not fully understood. Considering that symptoms/clinical features displayed during Dengue, Chikungunya and SARS-CoV-2 acute infections are similar, undiagnosed cases of SARS-CoV-2 in co-endemic areas may be more prevalent than expected. This study was conducted to assess the prevalence of covert cases of SARS-CoV-2 among samples from patients with clinical symptoms compatible with either Dengue or Chikungunya viral infection in the state of Espírito Santo, Brazil. METHODS: Presence of immunoglobulin G (IgG) antibody specific to SARS-CoV-2 nucleoprotein was detected using a chemiluminescent microparticle immunoassay in samples from 7,370 patients, without previous history of COVID-19 diagnosis, suspected of having either Dengue (n = 1,700) or Chikungunya (n = 7,349) from December 1st, 2019 to June 30th, 2020. FINDINGS: Covert cases of SARS-CoV-2 were detected in 210 (2.85%) out of the 7,370 serum samples tested. The earliest undiagnosed missed case of COVID-19 dated back to a sample collected on December 18, 2019, also positive for Dengue Virus. Cross-reactivity with either Dengue virus or other common coronaviruses were not observed. INTERPRETATION: Our findings demonstrate that concomitant Dengue or Chikungunya outbreaks may difficult the diagnosis of SARS-CoV-2 infections. To our knowledge, this is the first study to demonstrate, with a robust sample size (n = 7,370) and using highly specific and sensitive chemiluminescent microparticle immunoassay method, that covert SARS-CoV-2 infections are more frequent than previously expected in Dengue and Chikungunya hyperendemic regions. Moreover, our results suggest that SAR-CoV-2 cases were occurring prior to February, 2020, and that these undiagnosed missed cases may have contributed to the fast expansion of SARS-CoV-2 outbreak in Brazil. Data presented here demonstrate that in arboviral endemic regions, SARS-CoV-2 infection must be always considered, regardless of the existence of a previous positive diagnosis for Dengue or Chikungunya.