Efficacy and longevity of immune response to 3rd COVID-19 vaccine and effectiveness of a 4th dose in severely immunocompromised patients with cancer (preprint)

Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. We demonstrate that a 3 rd dose of COVID-19 vaccine leads to seroconversion in 57% of patients that were seronegative after primary vaccination. The immune response is durable as assessed by anti-S antibody titers, T-cell activity and neutralization activity against wild-type SARS-CoV2 and BA1.1.529 at 6 months of follow up. A subset of severely immunocompromised hematologic malignancy patients were unable to mount adequate immune response after the 3 rd dose and were treated with a 4 th 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. These results indicate that vaccine booster-induced immunity is durable in cancer patients and additional doses can further stimulate immunity in a subset of hematologic malignancy patients. Statement of significance We demonstrate that a 3 rd dose of vaccine leads to seroconversion in 57% of negative patients with durable immune responses at 6 months. A 4 th dose of vaccine can seroconvert hematologic malignancy patients with higher baseline IgM and CD19 levels.

Specifying uniform eligibility criteria to strengthen causal inference studies of long-term outcomes of COVID-19 (preprint)

Background: Causal interpretation of findings from existing epidemiological studies on long-term clinical outcomes of coronavirus disease 2019 (COVID-19) may be limited by the choice of comparator (control) group. Objective: We compare two approaches to control group selection (based on requirement for negative SARS-CoV-2 test for eligibility) in long-term clinical outcomes after COVID-19 in patients with history of heart failure (HF). Design: Retrospective cohort study using data from February 1, 2020 to July 31, 2021. Setting: Veteran Health Administration (VHA). Participants: We studied two cohorts of Veterans with COVID-19 and history of HF which selected comparison group using two different approaches. In Cohort I, Veterans with HF who tested for positive for SARS-CoV-2 were age, sex, and race matched to Veterans with no evidence of COVID-19 in 1:5 ratio. In Cohort II Veterans with HF who tested positive for SARS-CoV-2 were age, sex, and race matched with Veterans with HF who tested negative for SARS-CoV-2 within +/-15 days of the positive test date within the same VHA facility. Exposure: COVID-19 as determined by a positive SARS-CoV-2 test. Main Outcomes and Measures: 1-year all-cause mortality and hospital admissions beyond the first 30 days after COVID-19 diagnosis. Adjusted hazard ratios (HRs) accounting for comorbidity and 95% confidence intervals were calculated. Results: Cohort I comprised 13,722 Veterans with HF with COVID-19 (mean [SD] age 72.0 [10.2] years, 2.4% female, 71.1% White) and 60,956 matched controls not known to have COVID-19. Cohort II comprised 6,725 Veterans with HF with COVID-19 (mean [SD] age 72.5 [7.5] years, 0.1% female, 80.8% White) and 6,726 matched controls with negative SARS-CoV-2 test. The adjusted HRs for 1-year mortality and hospital admission beyond the first 30 days after diagnosis of COVID-19 were 1.40 (1.32-1.49) and 1.34 (1.28-1.41), respectively, in analysis of Cohort-I (where the comparator group was not required to test negative for SARS-CoV-2). However, in Cohort-II (using the second comparator group specifying negative SARS-CoV-2 test for eligibility), the associations were markedly attenuated; adjusted HRs 1.05 (0.95-1.17) and 1.07 (0.96-1.19), respectively. Conclusions: We found significant attenuation of associations between COVID-19 and long-term risk of mortality and hospital admissions beyond the first 30 days among patient with existing HF, when comparing with a control group selected based on a negative SARS-CoV-2 test versus control group not known to have COVID-19. The findings have implications for the design of studies of long-term CVD (and non-CVD) outcome of COVID-19.

Association of Poor Housing Conditions with COVID-19 Incidence and Mortality Across US Counties (preprint)

ObjectivePoor housing conditions have been linked with worse health outcomes and infectious spread in communities but its relationship with incidence and mortality of COVID-19 is unknown. Therefore, we undertook this study to determine the association between poor housing condition and COVID-19 incidence and mortality in US counties. MethodsWe 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 3141 US counties. The exposure of interest was percentage of households with poor housing conditions (one or more 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 was utilized 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. ResultsAcross 3135 US counties, the mean percentage of households with poor housing conditions was 14.2% (range 2.7% to 60.2%). The mean (SD) incidence and mortality of COVID-19 were 255.68 (2877.03) cases and 13.90 (272.22) deaths per county, respectively. In the fully adjusted models, 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 RelevanceCounties 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.