The impact of cyclin-dependent kinases 4 and 6 inhibitors in the immune response to mRNA SARS-CoV-2 vaccine in women with breast cancer. (preprint)

Introduction: Patients with cancer have a higher risk of complications and death from coronavirus disease 2019 (COVID19), thus vaccination is crucial in this population. Oncologic therapies can affect vaccination response, but few data are available about the immune response to mRNA SARS-CoV-2 vaccines in patients with breast cancer receiving cyclin-dependent kinases 4/6 inhibitors (CDK4/6i). Our study aimed to assess the immunogenicity and safety of the mRNA-1273 vaccine in patients treated with CDK4/6i in comparison with a group of volunteer health workers.Methods: We conducted a prospective, single-center study including patients with breast cancer treated with CDK4/6i and a comparative group of health care workers (HCW). Blood samples were collected before and after first dose administration, and after second dose. The primary endpoint was to compare the rate and magnitude of humoral and T-cell responses after full vaccination. Neutralizing antibodies titers, the correlation between neutralizing and anti-S antibodies, the incidence of COVID-19 after vaccination, and safety were defined as secondary objectives.Results: No differences were observed in the rate of either anti-S or neutralizing antibodies after full vaccination, being 100% in both groups. A positive correlation was found between neutralizing and anti-S antibodies. However, the rate of anti-S CD4 and CD8 T-cell response after complete vaccination was a 15% lower in the CDK4/6i group, although differences were not statistically significant (CD4 T-cell response 69.2% vs 84.6%; p 0.324; anti-S T-cell CD8 response 69.2% vs 84.6%; p 0.324). No differences in the incidence of COVID-19 after vaccination were found (19.2% vs 11.5%, p 0.703). Patients with vaccine breakthrough showed lower levels of anti-S antibody after the first dose (492.29 vs 157.96; p 0.029) and lower titers of neutralizing antibodies after full vaccination (p 0.068). The rate of adverse events was higher in patients treated with CDK4/6i. No serious adverse events were reported in any of the two groups.Conclusion: While a robust humoral response was observed in the CDK4/6i group, a limited T cell response was found, without differences in the rate of subsequent COVID-19. Further insight into the underlying mechanisms is crucial to improve breast cancer patients’ protection and to adjust vaccination strategies in this specific population.

Impact of SARS-CoV-2-specific memory B cells on the immune response after mRNA-based Comirnaty vaccine in seronegative health care workers (preprint)

Purpose To analyze the impact of SARS-COV-2-specific memory B cells (MBC) on the immune response after two doses of mRNA-based Comirnaty COVID-19 vaccine in seronegative health care workers. This study is seeking a rationale for boosting vaccines.Methods Longitudinal study including 31 seronegative health care workers with undetectable MBCs (IgG-MBC- group), 24 seronegative with detectable MBCs (IgG-MBC + group), and 24 seropositive with detectable MBCs (IgG + MBC + group). The level of neutralizing, anti-S IgG, IgA, and IgM antibodies was quantified by ELISA. In addition, specific memory B and T cells were quantified by flow cytometry.Results The level of specific MBCs, and isotypes, in the IgG-MBC- group was lower compared to that found in IgG-MBC+ (p = 0.0001) and IgG + MBC+ (p < 0.0001) groups, respectively. Neutralizing and anti-S IgG antibodies were at lower levels in the IgG-MBC- group after the vaccine. Specific MBCs directly correlated with specific CD4 + T cells (although not significant, p = 0.065), while no correlation was found with specific CD8 + T cells (p = 0.156) after the vaccine. In parallel, neutralizing antibodies only positively correlated with specific CD4 + T cells (p = 0.034).Conclusions IgG-MBC- individuals showed the worst humoral and cellular responses, both in frequency and magnitude, after vaccine. Individuals whose antibodies wane and become undetectable after a given period of time post vaccine and show no specific MBCs are less protected and hence are good candidates for boosting vaccine. On the other hand, seronegative individuals with specific MBC showed faster and higher responses compared to the IgG-MBC- group.

Exponential magnetophoretic gradient for the direct isolation of basophils from whole blood in a microfluidic system (preprint)

Despite their rarity in peripheral blood, basophils play important roles in allergic disorders and other diseases including sepsis and COVID-19. Existing basophil isolation methods require many manual steps and suffer from significant variability in purity and recovery. We report an integrated basophil isolation device (i-BID) in microfluidics for negative immunomagnetic selection of basophils directly from 100 μL of whole blood within 10 minutes. We use a simulation-driven pipeline to design a magnetic separation module to apply an exponentially increasing magnetic force to capture magnetically tagged non-basophils flowing through a microtubing sandwiched between magnetic flux concentrators sweeping across a Halbach array. The exponential profile captures non-basophils effectively while preventing their excessive initial buildup causing clogging. The i-BID isolates basophils with a mean purity of 93.9%±3.6% and recovery of 95.6%±3.4% without causing basophil degradation or unintentional activation. Our i-BID has the potential to enable basophil-based point-of-care diagnostics such as rapid allergy assessment.

Analysis of the Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Breast Cancer Patients Treated With Cyclin-Dependent Kinases 4 and 6 Inhibitors (CDKi): Limited T-Cell Immunity Despite Satisfactory Humoral Response. (preprint)

SARS-CoV-2 vaccination in cancer patients has become crucial because of their higher risk of complications and death from COVID19. We performed a prospective study to assess the immunogenicity of SARS-CoV-2 vaccine in cancer patients treated with CDKi and compared their immune response with patients treated with chemotherapy. While a robust humoral response was observed in the CDKi patients compared with chemotherapy patients, limited T-cell immunity was achieved in both groups.

Vision-based Autonomous Disinfection of High Touch Surfaces in Indoor Environments (preprint)

Autonomous systems have played an important role in response to the Covid-19 pandemic. Notably, there have been multiple attempts to leverage Unmanned Aerial Vehicles (UAVs) to disinfect surfaces. Although recent research suggests that surface transmission is less significant than airborne transmission in the spread of Covid-19, surfaces and fomites can play, and have played, critical roles in the transmission of Covid-19 and many other viruses, especially in settings such as child daycares, schools, offices, and hospitals. Employing UAVs for mass spray disinfection offers several potential advantages, including high-throughput application of disinfectant, large scale deployment, and the minimization of health risks to sanitation workers. Despite these potential benefits and preliminary usage of UAVs for disinfection, there has been little research into their design and effectiveness. In this work, we present an autonomous UAV capable of effectively disinfecting indoor surfaces. We identify relevant parameters such as disinfectant type and concentration, and application time and distance required of the UAV to disinfect high-touch surfaces such as door handles. Finally, we develop a robotic system that enables the fully autonomous disinfection of door handles in an unstructured and previously unknown environment. To our knowledge, this is the smallest untethered UAV ever built with both full autonomy and spraying capabilities, allowing it to operate in confined indoor settings, and the first autonomous UAV to specifically target high-touch surfaces on an individual basis with spray disinfectant, resulting in more efficient use of disinfectant