Immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) using two-dose primary protocol in children and adolescents (Immunita-002, Brazil): A phase IV six-month follow up (preprint)

Introduction: Vaccines are essential for the prevention and control of several diseases, indeed, monitoring the immune response generated by vaccines is crucial. The immune response generated by vaccination against SARS-CoV-2 in children and adolescents is not well defined regarding to the intensity and medium to long-term duration of a protective immune response, which may point out the need of booster doses and might support the decisions in public health.Objective The study aims to evaluate the immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) in a two-dose primary protocol in children and adolescent aging from 3 to 17 years old in Brazil.Methods Participants were invited to participate in the research at two public healthcare centers located in Serrana (São Paulo) and Belo Horizonte (Minas Gerais), Brazil. Participants underwent medical interviews to gather their medical history, including COVID-19 history and medical records. Physical exams were conducted, including weight, blood pressure, temperature, and pulse rate measurements. Blood samples were obtained from the participants before vaccination, 1 month after the first dose, and 1, 3, and 6 months after the second dose and were followed by a virtual platform for monitoring post-vaccination reactions and symptoms of COVID-19. SARS-CoV-2 genome from Swab samples of COVID-19 positive individuals were sequenced by NGS. Total antibodies were measured by ELISA and neutralizing antibodies to B.1 lineage and Omicron variant (BA.1) quantified by PRNT and VNT. The cellular immune response was evaluated by flow cytometry by the quantification of systemic soluble immune mediators.Results The follow-up of 640 participants showed that the CoronaVac vaccine (Sinovac/Butantan Institute) was able to significantly induce the production of total IgG antibodies to SARS-CoV-2 and the production of neutralizing antibodies to B.1 lineage and Omicron variant. In addition, a robust cellular immune response was observed with wide release of pro-inflammatory and regulatory mediators in the early post-immunization moments. Adverse events recorded so far have been mild and transient except for seven serious adverse events reported on VigiMed.Conclusions The results indicate a robust and sustained immune response induced by the CoronaVac vaccine in children and adolescents up to six months, providing evidences to support the safety and immunogenicity of this effective immunizer.

COVID-19 INDUCES SENESCENCE AND EXHAUSTION OF T CELLS IN PATIENTS WITH MILD/MODERATE AND SEVERE DISEASE DURING A SEVEN-DAY INTERVAL (preprint)

Risk factors for the development of severe COVID 19 include several comorbidities, but age was the most striking one since elderly people were disproportionately affected by SARS Cov 2 Major drivers that can explain this markedly unfavourable response in the elderly are inflammaging and immunosenescence Recent reports have shown that the relationship between immunosenescence and COVID 19 can be bidirectional, since hospitalized patients with severe COVID 19 have an accumulation of senescent T cells suggesting that immunosenescence can be also exacerbated by SARSC oV 2 infection Therefore, the present work was designed to examine the emergence of immunosenescence in a longitudinal study in two distinct cohorts of COVID 19 patients, and to determine whether the senescence alterations were restricted to severe cases of the disease Our data, with patients from Portugal and Brazil, identified their distinctive inflammatory profile and provided evidence of increased frequencies of senescent and exhausted T cells within a seven day period in patients with mild to severe COVID 19 These results support the view that SARS CoV 2 infection can accelerate immunosenescence in both CD4 and CD8 T cell compartments in a short period of time Key words COVID 19, immunosenescence, T cell exhaustion, T cell senescence, inflammatory cytokines, inflammaging

Airway epithelial cells and macrophages trigger IL-6-CD95/CD95L axis and mediate initial immunopathology of COVID-19 (preprint)

Airway epithelial cells (AEC) are the first in contact with SARS-CoV-2 and drive the interface with macrophage to generate inflammation. To elucidate how those initial events contribute to the immunopathology or to dysregulate the immune response observed in severe and critical COVID-19, we determined the direct and indirect interactions of these cells. AEC lineage (Calu-3) infected with SARS-CoV-2 and epithelial cells (CD45-EpCAM+) from intubated COVID-19 patients showed high expression of CD95L. Infected-Calu-3 cells secreted IL-6, and expressed annexin V and caspase-3, apoptosis markers. The direct interaction of macrophages with sorted apoptotic Calu-3 cells, driven by SARS-CoV-2 infection, resulted in macrophage death and increased expression of CD95, CD95L and CD163. Macrophages exposed to tracheal aspirate supernatants from intubated COVID-19 patients or to recombinant human IL-6 exhibited decreased HLA-DR and increased CD95 and CD163 expression. IL-6 effects on macrophages were prevented by tocilizumab (anti-IL-6 receptor mAb) and Kp7-6 (CD95/CD95L antagonist). Similarly, lung inflammation and death of AEC were decreased in CD95 and IL-6 knockout mice infected with SARS-CoV-2. Our results show that the AEC-macrophage interaction via CD95/CD95L signaling is an initial key step of immunopathology of severe COVID-19 and should be considered as a therapeutic target.