Project description:To evaluate the gene expression profiling of peripheral leukocytes in different outcomes of SARS-CoV-2 infections, whole blood samples were collected from individuals with positive SARS-CoV-2 nasopharyngeal swab by RT-PCR (54 patients) and healthy uninfected individuals (12 volunteers). Infected patients were classified into mild, moderate, severe and critical groups according to a modified statement in the Novel Coronavirus Pneumonia Diagnosis and Treatment Guideline. Blood were collected into EDTA tubes and the buffy coat samples were stored in TRIzol reagent at -80 °C until use for RNA extraction. Affymetrix Clariom S array was used to perform the high-throughput gene expression profiling. Microarray analyses were performed using APT Affymetrix software, R packages and Bioconductor libraries. This systemic view of SARS-CoV-2 infections through blood transcriptomics will foster the understanding about molecular mechanisms and immunopathological processes involved in COVID-19 disease and its different outcomes.
Project description:The COVID-19 pandemic was severely aggravated in Brazil due to its politicization by the country's federal government. However, the impact of diffuse political forces on the fatality of an epidemic is notoriously difficult to quantify. Here we introduce a method to measure this effect in the Brazilian case, based on the inhomogeneous distribution throughout the national territory of political support for the federal government. This political support is quantified by the voting rates in the last general election in Brazil. This data is correlated with the fatality rates by COVID-19 in each Brazilian state as the number of deaths grows over time. We show that the correlation between fatality rate and political support grows as the government's misinformation campaign is developed. This led to the dominance of such political factor for the pandemic impact in Brazil in 2021. Once this dominance is established, this correlation allows for an estimation of the total number of deaths due to political influence as 350±70 thousand up to the end of 2021, corresponding to (57±11)% of the total number of deaths.
Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.
Project description:Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk-factor for severe disease. Inflammation is central to the aetiology of both conditions where immune responses influence disease course. Identifying at-risk groups through immuno-inflammatory signatures can direct personalised care and help develop potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leukocyte populations in circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia, of CD8+ lymphocytes, was associated with severe COVID-19 and intensive care admission in non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia of classical monocytes were specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Over-expression of inflammatory markers reminiscent of the type-1 interferon pathway underlaid the immunophenotype associated with T2D. These changes may contribute to severity of COVID-19 in T2D. These findings show characteristics of severe COVID-19 in T2D as well as provide evidence that type-1 interferons may be actionable targets for future studies.