Phase II/III Double-Blind Study Evaluating Safety and Immunogenicity of a Single Intramuscular Booster Dose of the Recombinant SARS-CoV-2 Vaccine "Patria" (AVX/COVID-12) Using an Active Newcastle Disease Viral Vector (NDV) during the Omicron Outbreak in Healthy Adults with Elevated Baseline Antibody Titers from Prior COVID-19 and/or SARS-CoV-2 Vaccination (preprint)

Background: The urgent need for safe, effective, and economical coronavirus disease 2019 (COVID-19) vaccines, especially for booster campaigns targeting vulnerable populations, prompted the development of the AVX/COVID-12 vaccine candidate. AVX/COVD-12 is based in a Newcastle disease virus La Sota (NDV-LaSota) recombinant viral vector. This vaccine expresses a stabilized version of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), specifically the ancestral Wuhan strain. The study aimed to assess its safety, immunogenicity, and potential efficacy as an anti-COVID-19 booster vaccine. Methods: In a phase II/III clinical trial conducted from November 9, 2022, to September 11, 2023, a total of 4,056 volunteers were enrolled. Participants received an intramuscular booster dose of either AVX/COVID-12 or AZ/ChAdOx-1-S vaccines. Safety, immunogenicity, and potential efficacy were assessed through various measures, including neutralizing antibody titers, interferon (IFN)-γ-producing CD4+ T cells, and CD8+ T cells. The evaluation also involved immunobridging, utilizing the AZ/ChAdOx-1-S vaccine as an active comparator, and monitoring the incidence of COVID-19 cases. Findings: The AVX/COVID-12 vaccine induced neutralizing antibodies against both the ancestral SARS-CoV-2 and the BA.2 and BA.5 Omicron variants. The geometric mean ratio of neutralizing antibody titers between individuals immunized with the AVX/COVID-12 vaccine and those with the AZ/ChAdOx-1-S vaccine at 14 days is 0.96, with a confidence interval (CI) of 0.85-1.06. The outcome aligns with the non-inferiority criterion recommended by the World Health Organization (WHO), indicating a lower limit of the CI greater than or equal to 0.67. Induction of IFN-γ-producing CD8+ T cells at day 14 post-immunization was exclusively observed in the AVX/COVID-12 group. Finally, a trend suggested a potentially lower incidence of COVID-19 cases in AVX/COVID-12 boosted volunteers compared to AZ/ChAdOx-1-S recipients. Conclusion: The AVX/COVID-12 vaccine proved safe, well-tolerated, and immunogenic. AVX/COVID-12 meets the WHO non-inferiority standard compared to AZ/ChAdOx-1-S. These results strongly advocate for AVX/COVID-12 as a viable booster dose, supporting its utilization in the population.

Seroepidemiology of SARS-CoV-2 in Healthcare Personnel Working at the Largest Tertiary COVID-19 Referral Hospitals in Mexico City (preprint)

Background: We performed a longitudinal SARS-CoV-2 seroepidemiologic study in healthcare personnel of the two largest tertiary referral hospitals in Mexico City. Methods: Participants answered a computer-assisted self-administered interview and donated blood samples for antibody testing every three weeks from October 2020 to June 2021. Findings: 290/883 participants had a positive result in any of the antibody tests, yielding an overall adjusted prevalence in the study period of 33·5%. 235 positive tests were identified at baseline (prevalent cases), the remaining 55 positive tests were incident cases. Prevalent cases showed associations with both occupational (institution 2 vs. 1: adjusted odds ratio [aOR]=2·24, 95% confidence interval [CI]: 1·54, 3·25; laboratory technician vs. medical doctor: aOR=4·38, 95% CI: 1·75, 10·93) and community risk (municipality of residence Xochimilco vs. Tlalpan: aOR=2·03, 95% CI: 1·09, 3·79). The incidence rate was 3·0 cases per 100 person-months. Incident cases were mainly associated with community-acquired risk, due to contact with suspect/confirmed COVID-19 cases (HR=2·45, 95% CI: 1·21, 5·00).Interpretation: We observed similar level of exposure to SARS-CoV-2 in healthcare workers of the two largest tertiary COVID-19 referral centers in Mexico City to the general population. Most variables associated with exposure in this setting pointed toward community rather than occupational risk.Funding: Consejo Nacional de Ciencia y Tecnología (CONACyT) (Fondo FORDECYT-PRONACES) and the Mexican Government (Programa Presupuestal P016; Anexo 13 del Decreto del Presupuesto de Egresos de la Federación).Declaration of Interest: None to declare. Ethical Approval: The study was reviewed and approved by the Institutional Review Boards of both participating institutions.

EVALUATION OF A RAPID ANTIGEN TEST FOR SARS-COV-2 IN SYMPTOMATIC PATIENTS AND THEIR CONTACTS: A MULTICENTER STUDY (preprint)

BACKGROUND Point-of-care rapid tests to identify SARS-CoV-2 can be of great help because, in principle, they allow decisions to be made at the site of care for treatment, or for the separation of cohorts avoiding cross-infection, especially in emergency situations. METHODS A cross sectional study in adults requesting care in Emergency Rooms (ER), or the outpatient clinics of referral hospitals for COVID-19, to define the diagnostic characteristics of a rapid antigen test for SARS-CoV-2 (the Abbott PanbioTM) having as a gold standard the RT-PCR for SARS-CoV-2. Health personnel in a routine situation within an active pandemic in several cities of Mexico performed the tests. RESULTS A total of 1,069 participants with a mean age of 47 years (SD 16 years), 47% with a self-reported comorbidity, and an overall prevalence of a positive RT-PCR test of 45%, were recruited from eight hospitals in Mexico. Overall sensitivity of the Panbio test was 54.4% (95%CI 51-57) with a positive likelihood ratio of 35.7, a negative likelihood ratio of 0.46 and a Receiver-Operating Characteristics curve area of 0.77. Positivity for the rapid test depended strongly on an estimate of the viral load (Cycle threshold of RT-PCR, Ct), and the days of symptoms. With a Ct 25, sensitivity of the rapid test was 0.82 (95%CI, 0.76-0.87). For patients during the first week of symptoms sensitivity was 69.6% (95%CI 66-73). On the other hand, specificity of the rapid test was above 97.8% in all groups. CONCLUSIONS The PanbioTM rapid antigen test for SARS-CoV-2 has a good specificity, but due to low and heterogeneous sensitivity in real life, a negative test in a person with suggestive symptoms at a time of community transmission of SARS-CoV-2 requires confirmation with RT-PCR, and after the first week of symptoms, sensitivity decreases considerably.

Epicardial adipose tissue thickness is associated with increased severity and mortality related to SARS-CoV-2 infection (preprint)

BACKGROUNDIncreased adiposity and visceral obesity have been linked to adverse COVID-19 outcomes. The amount of epicardial adipose tissue (EAT) may have relevant implications given its proximity to the heart and lungs. Here, we explored the role of EAT in increasing the risk for COVID-19 adverse outcomes. METHODSWe included 748 patients with COVID-19 attending a reference center in Mexico City. EAT thickness, sub-thoracic and extra-pericardial fat were measured using thoracic CT scans. We explored the association of each thoracic adipose tissue compartment with COVID-19 mortality and severe COVID-19 (defined as mortality and need for invasive mechanical ventilation), according to the presence or absence of obesity. Mediation analyses evaluated the role of EAT in facilitating the effect of age, body mass index and cardiac troponin levels with COVID-19 outcomes. RESULTSEAT thickness was associated with increased risk of COVID-19 mortality (HR 1.18, 95%CI 1.01-1.39) independent of age, gender, comorbid conditions and BMI. Increased EAT was associated with lower SpO2 and PaFi index and higher levels of cardiac troponins, D-dimer, fibrinogen, C-reactive protein, and 4C severity score, independent of obesity. EAT mediated 13.1% (95%CI 3.67-28.0%) and 5.1% (95%CI 0.19-14.0%) of the effect of age and 19.4% (95%CI 4.67-63.0%) and 12.8% (95%CI 0.03-46.0%) of the effect of BMI on requirement for intubation and mortality, respectively. EAT also mediated the effect of increased cardiac troponins on myocardial infarction during COVID-19. CONCLUSIONEAT is an independent risk factor for severe COVID-19 and mortality independent of obesity. EAT partly mediates the effect of age and BMI and increased cardiac troponins on adverse COVID-19 outcomes.