Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trial.

Background: Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. Many healthcare regulatory agencies recommend administering 'booster' doses of COVID-19 vaccines beyond the standard two-dose series, for this group of patients. Therefore, studying the efficacy of these additional vaccine doses against SARS-CoV-2 and variants of concern is of utmost importance in this immunocompromised patient population. Methods: We conducted a prospective single arm clinical trial enrolling patients with cancer that had received two doses of mRNA or one dose of AD26.CoV2.S vaccine and administered a third dose of mRNA vaccine. We further enrolled patients that had no or low responses to three mRNA COVID vaccines and assessed the efficacy of a fourth dose of mRNA vaccine. Efficacy was assessed by changes in anti-spike antibody, T-cell activity, and neutralization activity, which were again assessed at baseline and 4 weeks. Results: We demonstrate that a third dose of COVID-19 vaccine leads to seroconversion in 57% of patients that were seronegative after primary vaccination series. The immune response is durable as assessed by anti-SARS-CoV-2 (anti-S) antibody titers, T-cell activity, and neutralization activity against wild-type (WT) SARS-CoV2 and BA1.1.529 at 6 months of follow-up. A subset of severely immunocompromised hematologic malignancy patients that were unable to mount an adequate immune response (titer <1000 AU/mL) after the third dose and were treated with a fourth dose in a prospective clinical trial which led to adequate immune boost in 67% of patients. Low baseline IgM levels and CD19 counts were associated with inadequate seroconversion. Booster doses induced limited neutralization activity against the Omicron variant. Conclusions: These results indicate that third dose of COVID vaccine induces durable immunity in cancer patients and an additional dose can further stimulate immunity in a subset of patients with inadequate response. Funding: Leukemia Lymphoma Society, National Cancer Institute. Clinical trial number: NCT05016622.

People with cancer have a higher risk of death or severe complications from COVID-19. As a result, vaccinating cancer patients against COVID-19 is critical. But patients with cancer, particularly blood or lymphatic system cancers, are less likely to develop protective immunity after COVID-19 vaccination. Immune suppression caused by cancer or cancer therapies may explain the poor vaccine response. Booster doses of the vaccine may improve the vaccine response in patients with cancer. But limited information is available about how well booster doses protect patients with cancer against COVID-19. Thakkar et al. show that a third dose of a COVID-19 vaccine can induce a protective immune response in half of the patients with cancer with no immunity after the first two doses. In the experiments, Thakkar et al. tracked the immune reaction to COVID-19 booster shots in 106 cancer patients. A third booster dose protected patients for up to four to six months and reduced breakthrough infection rates to low levels. Eighteen patients with blood cancers and severe immune suppression had an inadequate immune response after three doses of the vaccine; a fourth dose boosted the immune response for two-thirds of them, which for some included neutralization of variants such as Omicron. The experiments show that booster doses can increase COVID-19 vaccine protection for patients with cancer, even those who do not respond to the initial vaccine series. Thakkar et al. also show that pre-vaccine levels of two molecules linked to the immune system, (immunoglobin M and the CD19 antigen) predicted the patients' vaccine response, which might help physicians identify which individuals would benefit from booster doses.

Long-term Cardiovascular Manifestations and Complications of COVID-19: Spectrum and Approach to Diagnosis and Management.

Survivors of coronavirus disease 2019 (COVID-19) may experience persistent symptoms, abnormal diagnostic test findings, incident disease in specific organ systems, or progression of existing disease. Post-acute COVID-19 syndrome (PACS) is defined by persistent, recurrent, or new symptoms, findings, or diagnoses beyond four weeks after the initial infection. PACS has been characterized as a multi-organ syndrome, often with cardiopulmonary symptoms that include fatigue, dyspnea, chest pain, and palpitations. Cardiovascular pathologies in PACS include new-onset arrhythmia, myocarditis, unmasked coronary artery disease, and diastolic dysfunction as well as abnormal findings on electrocardiogram, troponin testing, and cardiac magnetic resonance imaging. In this review, we discuss the cardiovascular symptoms, pathophysiology, clinical investigation, and management strategies for cardiopulmonary symptoms of PACS. We offer a treatment algorithm for primary care clinicians encountering patients with cardiopulmonary PACS and discuss ongoing research on this topic.

PICAndro: Packet InspeCtion-Based Android Malware Detection

The post-COVID epidemic world has increased dependence on online businesses for day-to-day life transactions over the Internet, especially using the smartphone or handheld devices. This increased dependence has led to new attack surfaces which need to be evaluated by security researchers. The large market share of Android attracts malware authors to launch more sophisticated malware (12000 per day). The need to detect them is becoming crucial. Therefore, in this paper, we propose PICAndro that can enhance the accuracy and the depth of malware detection and categorization using packet inspection of captured network traffic. The identified network interactions are represented as images, which are fed in the CNN engine. It shows improved performance with the accuracy of 99.12% and 98.91% for malware detection and malware class detection, respectively, with high precision.

Efficacy of booster doses in augmenting waning immune responses to COVID-19 vaccine in patients with cancer.

Anti-COVID-19 immunity dynamics were assessed in patients with cancer in a prospective clinical trial. Waning of immunity was detected 4-6 months post-vaccination with significant increases in anti-spike IgG titers after booster dosing, and 56% of seronegative patients seroconverted post-booster vaccination. Prior anti-CD20/BTK inhibitor therapy was associated with reduced vaccine efficacy.

Outcomes of coronavirus disease-2019 among veterans with pre-existing diagnosis of heart failure.

AIMS: Pre-existing cardiovascular disease in general and related risk factors have been associated with poor coronavirus disease-2019 (COVID-19) outcomes. However, data on outcomes of COVID-19 among people with pre-existing diagnosis of heart failure (HF) have not been studied in sufficient detail. We aimed to perform detailed characterization of the association of pre-existing HF with COVID-19 outcomes. METHODS AND RESULTS: A retrospective cohort study based on Veterans Health Administration (VHA) data comparing 30 day mortality and hospital admission rates after COVID-19 diagnosis among Veterans with and without pre-existing diagnosis of HF. Cox-regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for covariates. Among 31 051 veterans (97% male) with COVID-19, 6148 had pre-existing diagnosis of HF. The mean (SD) age of patients with HF was 70 (13) whereas the mean (SD) age of patients without HF was 57 (17). Within the HF group with available data on left ventricular ejection fraction (EF), 1844 patients (63.4%) had an EF of >45%, and 1063 patients (36.6%) had an EF of ≤45%. Patients in the HF cohort had higher 30 day mortality (5.4% vs. 1.5%) and admission (18.5% vs. 8.4%) rates after diagnosis of COVID-19. After adjustment for age, sex, and race, HRs (95% CIs) for 30 day mortality and for 30 day hospital admissions were 1.87 (1.61-2.17) and 1.79 (1.66-1.93), respectively. After additional adjustment for medical comorbidities, HRs for 30 day mortality and for 30 day hospital admissions were 1.37 (1.15-1.64) and 1.27 (1.16-1.38), respectively. The findings were similar among HF patients with preserved vs. reduced EF, among those taking vs. not taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, and among those taking vs. not taking anticoagulants. CONCLUSIONS: Patients with COVID-19 and pre-existing diagnosis of HF had a higher risk of 30 day mortality and hospital admissions compared to those without history of HF. The findings were similar by EF categories and by angiotensin-converting enzyme inhibitors/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitors or anticoagulant use.

Association of poor housing conditions with COVID-19 incidence and mortality across US counties.

OBJECTIVE: Poor housing conditions have been linked with worse health outcomes and infectious disease spread. Since the relationship of poor housing conditions with incidence and mortality of COVID-19 is unknown, we investigated the association between poor housing condition and COVID-19 incidence and mortality in US counties. METHODS: We conducted cross-sectional analysis of county-level data from the US Centers for Disease Control, US Census Bureau and John Hopkins Coronavirus Resource Center for 3135 US counties. The exposure of interest was percentage of households with poor housing conditions (one or greater of: overcrowding, high housing cost, incomplete kitchen facilities, or incomplete plumbing facilities). Outcomes were incidence rate ratios (IRR) and mortality rate ratios (MRR) of COVID-19 across US counties through 4/21/2020. Multilevel generalized linear modeling (with total population of each county as a denominator) was utilized to estimate relative risk of incidence and mortality related to poor housing conditions with adjustment for population density and county characteristics including demographics, income, education, prevalence of medical comorbidities, access to healthcare insurance and emergency rooms, and state-level COVID-19 test density. We report incidence rate ratios (IRRs) and mortality ratios (MRRs) for a 5% increase in prevalence in households with poor housing conditions. RESULTS: Across 3135 US counties, the mean percentage of households with poor housing conditions was 14.2% (range 2.7% to 60.2%). On April 21st, the mean (SD) number of cases and deaths of COVID-19 were 255.68 (2877.03) cases and 13.90 (272.22) deaths per county, respectively. In the adjusted models standardized by county population, with each 5% increase in percent households with poor housing conditions, there was a 50% higher risk of COVID-19 incidence (IRR 1.50, 95% CI: 1.38-1.62) and a 42% higher risk of COVID-19 mortality (MRR 1.42, 95% CI: 1.25-1.61). Results remained similar using earlier timepoints (3/31/2020 and 4/10/2020). CONCLUSIONS AND RELEVANCE: Counties with a higher percentage of households with poor housing had higher incidence of, and mortality associated with, COVID-19. These findings suggest targeted health policies to support individuals living in poor housing conditions should be considered in further efforts to mitigate adverse outcomes associated with COVID-19.